REVIEW | doi:10.20944/preprints202308.0074.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: HFNC; COPD; NIV; respiratory failure; respiratory support; critical care; LTOT
Online: 2 August 2023 (02:13:02 CEST)
High-flow Nasal Cannula (HFNC) oxygen therapy is gaining traction globally as a treatment for respiratory failure. There are several physiological benefits and there may be a growing patient preference for HFNC. In this narrative review, we aim to outline the basic mechanisms of HFNC, who can use it and review the literature regarding its utility both in the critical care setting, as well as in the home setting for chronic hypercapnic respiratory failure with an emphasis on Chronic Obstructive Pulmonary Disease (COPD). The role of non-pharmacological interventions like non-invasive ventilation (NIV) and HFNC in the prevention of hospital readmissions following acute exacerbations of COPD (AECOPD) is an area of increasing importance because randomised controlled trials and systematic reviews have found measures like nurse-led predischarge bundles to be clinically ineffective and to have a high cost per quality adjusted life year. This review therefore considers the evidence of NIV vs HFNC in the context of AECOPD and the application of HFNC at home in the prevention of AECOPD. We also look at applications of HFNC in specific settings, such as in the peri-operative period, emergency department, acute (mainly Critical Care) setting including in immunocompromised patients and palliative care.
CASE REPORT | doi:10.20944/preprints202008.0640.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: VIP; COVID-19; respiratory failure; vasoactive intestinal peptide; aviptadil; ARDS
Online: 28 August 2020 (11:38:23 CEST)
Background: Vasoactive Intestinal Peptide (VIP) is known to bind to and protect the Alveolar Type II cell by blocking replication of the SARS-CoV-2 virus, upregulating surfactant production, blocking apoptosis, and blocking cytokine effects. RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) has been granted Fast Track Designation and is currently in phase 2/3 placebo-controlled trials. FDA has granted Emergency Use IND and Expanded Access Protocol approval for the use of RLF-100 in patients whose comorbidities render them ineligible for inclusion in the ongoing pivotal trial. Methods: This report describes the first 6 patients with Acute Respiratory Failure in Critical COVID-19, enrolled under Emergency Use IND were treated with three successive 12-hour infusions of intravenous Aviptadil at 50/100/150 pmol/kg/hr, while continuing to receive maximal ICU care. Results: Median patient follow-up time is 14 days. So far, all treated patients have survived. Improved radiographic appearance of typical “ground glass” COVID-19 features to varying degrees is seen in all patients within 72 hours. Improvement in blood oxygenation is seen in all patients, with complete remission from respiratory failure in 4 of 6 patients. An average 56% reduction in inflammatory markers was seen, together with a median 4 point reduction in the NIAID Ordinal Scale. 2/6 patients were discharged from the hospital and 1 patient was downgraded to the general medicine floor. Comment: The short term survival of 6/6 patients with respiratory failure in the setting of COVID-19 and major comorbidity is the most dramatic response ever seen with an antiviral agent. Improvement in radiographic appearance, oxygenation requirement, and inflammatory markers is consistent with in vitro evidence of direct anti-viral effect.
ARTICLE | doi:10.20944/preprints202309.2082.v1
Subject: Medicine And Pharmacology, Internal Medicine Keywords: Non-invasive respiratory support 1; SARS-CoV-2 2; Hospitalization 3; CPAP 4; HFNO 5; Bilevel 6
Online: 29 September 2023 (10:41:45 CEST)
Introduction: The objective of the study is to assess the failure of therapies with HFNO (High-Flow Nasal Oxygen), CPAP, Bilevel or combined therapy in patients with hypoxemic acute respiratory failure due to SARS-CoV-2 during their hospitalization. Methods: Retrospective and observational study of SARS-CoV-2 positive patients who required non-invasive respiratory support (NIRS), at the Reina Sofía General University Hospital of Murcia between March 2020 and May 2021. Results: Of 7355 patients, 197 (11,8%) were included. 95 of them failed this therapy (48,3%). We objectivated that during hospitalization in the ward the combined therapy with HFNO and CPAP had a lower failure rate overall and the highest treatment purely with Bilevel (p = 0,005). In the comparison of failure in therapy without two levels of airway pressure, HFNO, CPAP and combined therapy of HFNO with CPAP, (35,6% of patients) presented a 24,2% failure compared to those who did have two levels of pressure with Bilevel and combined therapy of HFNO with Bilevel (64,4% of patients) with 75,8% associated failure (OR: 0, 374; CI 95%: 0,203-0,688. p=0,001).Conclusions: The use of NIRS in conventional hospitalization is safe and effective in patients with respiratory failure secondary to SARS-CoV-2 infection. The therapeutic strategy with Bilevel increases the probability of failure, with the combined therapy strategy with CPAP and HFNO being the most promising option.
ARTICLE | doi:10.20944/preprints202305.1916.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: High flow nasal cannula oxygen therapy; acute respiratory failure; geriatrics; acute non-intensive hospital setting
Online: 26 May 2023 (10:22:17 CEST)
Background. There are scant data about the effectiveness of high flow nasal cannula (HFNC) oxygen therapy in patients hospitalized with severe acute respiratory failure (ARF) in non-intensive medical wards, particularly regarding the effect on arterial oxygenation compared to conventional oxygen therapy (COT) and non-invasive ventilation (NIV) or continuous positive airway pressure (CPAP). Methods. In a retrospective observational study, oxygenation parameters were measured before and immediately after HFNC initiation in 37 consecutive patients hospitalized in a geriatric ward in 2017. Results. HFNC was used as escalation therapy for untreatable hypoxia after failure of NIV/CPAP (n=18) or COT (n=19). Twenty-two patients died, 2 were transferred to the intensive care unit, while 13 were discharged alive. A “do not intubate” status was identified in 17 of the 22 deceased patients. Partial pressure of oxygen (pO2, p< 0.0001), oxygen saturation (SO2, p< 0.0001), pO2/fraction of inspired oxygen ratio (p=0.004) and peripheral SO2 measured by pulse oximetry (p< 0.0001) significantly increased soon after HFNC application. Oxygenation improvements were greater after escalation from NIV/CPAP and in patients discharged alive. Conclusion. HFNC significantly improved oxygenation in severe ARF after failure of COT or NIV/CPAP and may be particularly suitable for older patients hospitalized in non-intensive medical wards.
ARTICLE | doi:10.20944/preprints202306.1455.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Acute respiratory illness; critical care; recombinant tissue plasminogen activator; nebulization, fibrinolytics, COVID-19 pandemic, inhaled medication, targeted therapy
Online: 20 June 2023 (14:59:12 CEST)
Nebulized thrombolysis offers locally targeted therapy with potentially lower bleeding risk than systemic administration for coronavirus disease 2019 (COVID-19) respiratory failure. In a proof-of-concept safety study, adult patients with COVID-19-induced respiratory failure and a <300mmHg PaO2/FiO2 (P/F) ratio, requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care during the first two UK COVID-19 waves. Matched historical controls (MHC; n=18) were used in C1. Safety co-primary endpoints were treatment-related bleeds and fibrinogen reduction to <1.0–1.5 g/L. A dose escalation strategy for improved efficacy with the least safety concerns was determined in C1 for use in C2; patients were stratified by ventilation type to receive 40–60 mg rt-PA per day for ≤14 days. Nine patients in C1 (IMV, 6/9; NIRS, 3/9) and 26 in C2 (IMV, 12/26; NIRS, 14/26) received nebulized rt-PA for a mean (SD) of 6.7 (4.6) and 9.1(4.6) days, respectively. Four bleeding events (one severe and three mild) in three patients were considered treatment-related. No significant fibrinogen reductions were reported. Greater improvement in mean P/F ratio from baseline to end of study was observed in C1 compared with MHC [C1; 154 to 299 vs MHC; 154 to 212). In C2, there was no difference in the baseline P/F ratio of NIRS and IMV patients. However, a larger improvement in P/F ratio was observed in NIRS patients [NIRS; 126 to 240 vs IMV; 120 to 188) and they required fewer treatment days (NIRS; 7.86 vs IMV; 10.5). Nebulized rt-PA appears to be well-tolerated, showing a trend of improved oxygenation and faster recovery in patients with acute COVID-19-induced respiratory failure requiring respiratory support; this effect was more pronounced in the NIRS group. Further investigation is required to study the potential of this novel treatment approach.
CASE REPORT | doi:10.20944/preprints202007.0178.v2
Subject: Medicine And Pharmacology, Internal Medicine Keywords: Aviptadil; Vasoactive Intestinal Peptide; VIP; SARS-CoV-2; COVID-19; Corona Virus; Acute Respiratory Distress Syndrome; ARDS; Acute Lung Injury; ALI; surfactant; Alveolar Type II; ATII
Online: 2 August 2020 (18:16:20 CEST)
RLF-100 (Aviptadil), a synthetic form of Vasoactive Intestinal Peptide (VIP) is shown to block replication of the SARS-CoV-2 virus and has been granted Fast Track Designation by the US FDA for the treatment of Critical COVID-19 with Respiratory Failure. We describe the clinical course of the first patient treated with this investigational medication in an open label manner -- a 54 year old patient suffering antibody-mediated rejection of his double lung transplant who contracted COVID-19 with respiratory failure refractory to all currently available therapies. He received three infusions of RLF-100 under an FDA-approved emergency use IND. Within 24 hours of the third infusion, substantial improvement in oxygen saturation and radiographic improvement in characteristic COVID-19 pneumonitis was noted. He was discharged from intensive care at that point and scheduled for discharge to home at 1 week on room air. Despite an intervening hospitalization for trauma, he remains alive and free of respiratory failure at 28 days post treatment.
BRIEF REPORT | doi:10.20944/preprints202101.0416.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Respiratory Syncytial Virus, Molecular Diagnostic, Respiratory Viruses, Coronavirus, Bronchiolitis
Online: 21 January 2021 (12:12:25 CET)
Over two years (2012-2014), 719 nasopharyngeal samples were collected from 6 weeks to 12 months old infants presenting at emergency department with moderate to severe acute bronchiolitis. Viral testing was performed and we found 98% positive samples including 90% Respiratory Syncytial Virus, 34% Human Rhino Virus, and 55% viral co-detections with predominance of RSV/HRV co-infections (30%). Interestingly, we found that the risk of being infected by HRV is higher in the absence of RSV, suggesting interferences or exclusion mechanisms between these two viruses. Conversely, Coronavirus infection had no impact on the likelihood of co-infection involving HRV and RSV. Bronchiolitis is the leading cause of hospitalizations in infants before 12 months of age, and many questions about its role in the later chronic respiratory diseases (asthma and chronic obstructive pulmonary disease) do exist. Role of virus detection and burden of viral codetections need to be further explored, in order to understand the physiopathology of chronic respiratory diseases, a major public health issue.
REVIEW | doi:10.20944/preprints202004.0291.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: respiratory acidosis; CO2 narcosis; acute respiratory distress syndrome; hyperoxia
Online: 17 April 2020 (01:59:51 CEST)
Since 1991, there has been an alarming increase in the number of unexplained physiological events (UPEs) reported and experienced by pilots of jet fighters across different fleets. The UPEs have resulted in grounding some airframes, loss of aircraft, and even loss of life. There is no single agreed-upon root cause of UPEs that has been identified, and therefore there is no reliable corrective action. This author analyzed the literature related to other industries where artificial hyperoxic gas mixes are employed and where similar adverse reports have been reported. I hypothesize that UPEs are caused by high-dose oxygen delivery in excess of officially approved oxygen schedules while airflow rates are often inadequate, at a time when the positive pressure breathing feature of their oxygen regulator is not used. In a setting where pulmonary vital capacity is adversely affected by G-maneuvers and oxygen- and G-induced atelectasis, tidal volume is reduced by flight gear, and effective gas exchange is not supported by adequate ventilation, these factors combine to produce respiratory acidosis, followed by acute respiratory distress syndrome, CO2 narcosis, and coma. Reports from field data related to incidents in F-18S/H, showing that emergency oxygen did not correct the hypoxia-like symptoms including long-lasting periods of incapacitation and prolonged headaches, lend support to our hypothesis.
ARTICLE | doi:10.20944/preprints201711.0198.v2
Subject: Biology And Life Sciences, Virology Keywords: human coronavirus; MERS-CoV; clinical features; upper respiratory tract infections; lower respiratory tract infections; respiratory viruses
Online: 30 January 2018 (09:52:03 CET)
Human coronaviruses cause both upper and lower respiratory tract infections in humans. In 2012 a sixth human coronavirus (hCoV) was isolated from a patient presenting with severe respiratory illness. The 60-year-old man died as a result of renal and respiratory failure after admission to a hospital in Jeddah, Saudi Arabia. The aetiological agent was eventually identified as a coronavirus and designated Middle East respiratory syndrome coronavirus (MERS-CoV). MERS-CoV has now been reported in more than 27 countries across the Middle East, Europe, North Africa and Asia. As of July 2017, 2040 MERS-CoV laboratory confirmed cases, resulting in 712 deaths, were reported globally, with a majority of these cases from the Arabian Peninsula. This review summarises the current understanding of MERS-CoV, with special reference to the (i) genome structure, (ii) clinical features, (iii) diagnosis of infection and (iv) treatment and vaccine development.
ARTICLE | doi:10.20944/preprints202008.0008.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Respiratory Rate; Growth
Online: 2 August 2020 (10:38:52 CEST)
Background: Elevated respiratory rates (RR) have been described in several disease states, such as pneumonia, asthma and bronchiolitis. Despite this, there are few studies defining the range of RR found in healthy children. Available age percentiles for RR have been generated using methods that have the potential themselves to alter the rate. Aim: The aim of this study was to develop accurate percentile charts of RR specific for age in healthy children for potential use in pre-hospital care (first-aid), clinical medicine and for reference in respiratory research. Method: A newly developed optical respiratory sensor was used to measure RR which placed no restrictions on respiratory excursion. This technique enabled recording in awake children without the artefact of the observer’s presence on the subject’s RR. A cross-sectional sample of healthy children was obtained from maternity wards, childcare centres and schools in Brisbane, Queensland, Australia. Results: RR were observed in 560 awake and 103 sleeping children of which data from 343 awake and 94 sleeping children was used to create reference ranges for healthy children from newborn to 13 years of age. The recorded rates were significantly higher when children were awake compared to asleep. During quiet sleep, RR decreased from 40 (interquartile range 7) bpm at one month to 20 (interquartile range 3) in children aged 3 years. In awake children, RR ranged from a median of 40 bpm (interquartile range 18) at 1 year to 12 bpm (interquartile range 11) at 13 years respectively. Conclusion: The optical sensor was found to be an appropriate respiratory transducer, capable of measuring RR and reducing artefact by the subjective responses of alert children. The centile charts will be helpful as an aid to detecting abnormal RR in children and will contribute to further systematic reviews related to this vital sign.
BRIEF REPORT | doi:10.20944/preprints202311.1033.v1
Subject: Public Health And Healthcare, Primary Health Care Keywords: coinfection; population; respiratory viruses.
Online: 15 November 2023 (15:49:46 CET)
The 2021/2022 influenza season was not characterised by a well-defined incidence peak. A high value of incidence was recorded in week 13, but it was still lower than in other influenza seasons. This abnormal circulation was probably due to relaxation of the COVID-19 pandemic restriction measures, which greatly reduced the circulation of respiratory-transmitted viruses, including human respiratory syncytial virus (HRSV). The symptoms of SARS-CoV-2 and influenza are quite similar, sharing the human-to-human transmission route via respiratory droplets. The aim of this study was to estimate the rate of coinfection with influenza viruses and/or HRSV in SARS-CoV-2-positive subjects (N=940) in a population of central Italy during the 2021/2022 season. A total of 54 cases of coinfection were detected during the study period, 51 cases (5.4%) of SARS-CoV-2 and influenza virus and three cases (0.3%) of SARS-CoV-2 and HRSV coinfection. These results highlight the importance of continuous monitoring of the circulation of influenza virus and other respiratory viruses in the context of the COVID-19 pandemic.
REVIEW | doi:10.20944/preprints202001.0256.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Pompe Disease; Breathing; Respiratory
Online: 22 January 2020 (09:24:53 CET)
Pompe disease is a glycogen storage disease caused by a deficiency in acid α-glucosidase (GAA) – a hydrolase necessary for the degradation of lysosomal glycogen. This deficiency in GAA results in muscle and neuronal glycogen accumulation, which causes respiratory insufficiency. Pompe disease rodent models provide a means of assessing respiratory pathology and are important for pre-clinical studies of novel therapies that aim to treat respiratory dysfunction and improve quality of life. This review aims to compile and summarize existing manuscripts which characterize the respiratory phenotype of Pompe rodent models. Manuscripts included in this review were selected utilizing specific search terms and exclusion criteria. Analysis of these findings demonstrate that Pompe disease rodent models have respiratory physiological defects as well as pathologies in the diaphragm, tongue, phrenic and hypoglossal motor nucleus, phrenic and hypoglossal nerves, neuromuscular junctions, and airway smooth muscle and higher order respiratory control centers. Overall, the culmination of these pathologies contributes to severe respiratory dysfunction, underscoring the importance of characterizing the respiratory phenotype while developing effective therapies for patients.
ARTICLE | doi:10.20944/preprints202106.0173.v1
Subject: Medicine And Pharmacology, Veterinary Medicine Keywords: Fade abruptly, abnormal respiratory noise, dynamic overground endoscopy, upper respiratory tract, horse.
Online: 7 June 2021 (12:41:43 CEST)
The purpose of the study was to find the source of complaints and to diagnose dynamic upper respiratory tract problems, which were derived from the horse owners, trainers, and jockeys, and to evaluate the overground endoscopic examination efficiency to determine the subclinical upper respiratory tract (URT) abnormalities, which were unable to diagnose with resting endoscopy. In the study, overground endoscopy has been used which nowadays there is a more useful and safe technique of performing endoscopy during ridden exercise in the natural field to diagnose dynamic upper respiratory tract (URT) abnormalities in comparison with the more traditional method of resting endoscopy. This study focused on 25 racehorses (Thoroughbred, n:22 and Arabian n: 3), which were admitted to Racehorse Hospital with complaints of fade abruptly and/or abnormal respiratory noise during the last meters of the race. All horses were examined for the complaints to be associated with systemic disorders and/or lameness, the racehorses with lameness and/or systemic disorders findings were excluded. Resting (post-exercise) and overground endoscopy by using Dr. Fritz® ETL-Equine Overground Endoscopy was performed on a polytrack racecourse in all racehorses. Observed abnormalities were recorded as simple and complex cases and the results of resting and dynamic examination were compared. It was concluded the overground endoscopic examination has a useful diagnostic value in determining the cause of abnormal respiratory noise and/or fade abruptly.
REVIEW | doi:10.20944/preprints202004.0467.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: respiratory acidosis; CO2 narcosis; acute respiratory distress syndrome; hyperoxia; unexplained physiological event
Online: 26 April 2020 (03:26:09 CEST)
Over the last 20 years, there has been a significant increase in the number of unexplained physiological events (UPEs) reported by pilots of fighter jets across different fleets. The UPEs have resulted in grounding some types of aircraft, loss of airplanes, and even loss of life. Despite considerable research, no single agreed-upon root cause has been found that explains UPEs, and therefore no reliable corrective actions exist. The purpose of this review was to analyze the literature related to other industries in which artificial hyperoxic gas mixes are employed and similar adverse reports have been reported. Based on analysis of the literature, it is hypothesized that UPEs are caused by unlimited delivery of high-dose oxygen in excess of officially approved oxygen schedules in the presence of inadequate airflow rates, at a time when the positive pressure breathing feature of their oxygen regulator system is not used. During flight maneuvers such as climbs, turns, and descents, pulmonary vital capacity is impaired by G-maneuvers and oxygen- and G-induced atelectasis. At the same time, tidal volume is reduced by flight gear, and effective gas exchange is not supported by adequate ventilation. These factors combine to produce hypercarbia, respiratory acidosis, acute respiratory distress syndrome, CO2 narcosis, and coma. In fact, reports from field data related to incidents in F-18S/H, showing that emergency oxygen did not correct the hypoxia-like symptoms including long-lasting periods of incapacitation and prolonged headaches, lend support to this hypothesis.
ARTICLE | doi:10.20944/preprints202310.0863.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: canine; respiratory; virus; disease; diagnostics
Online: 13 October 2023 (08:12:33 CEST)
Canine infectious respiratory disease complex (CIRDC) is caused by different viruses and bacteria. Viruses associated with CIRDC include canine adenovirus-2 (CAV-2), canine distemper virus (CDV), canine influenza virus (CIV), canine herpesvirus (CHV), canine coronavirus (CCoV) and canine parainfluenza virus (CPIV). Bacteria associated with CIRDC include Bordetella bronchiseptica, Streptococcus equi subspecies zooepidemicus, and Mycoplasma spp. The present study examined the prevalence of pathogens associated with CIRDC in specimens received by a Veterinary Diagnostic Laboratory in Georgia from 2018 to 2022. Out of 459 cases, viral agents were detected in 34% cases and bacterial agents were detected in 58% cases. A single pathogen was detected in 31% cases, while two or more pathogens were identified in 24% cases. The percentages of viral agents identified were CAV-2 (4%), CDV (3%), CPIV (16%), CCoV (7%), and CIV (2%). The percentages of bacterial agents were Bordetella bronchiseptica (10%), Mycoplasma canis (24%), Mycoplasma cynos (21%), and S treptococcus zooepidemicus (2%). Positive viral cases ranged from 2-4% for CAV-2, 1-7% for CDV, 1-4% for CHV, 9-22% for CPIV, 4-13% for CCoV, and 1-4% for CIV. Overall, the study showed that the most prevalent pathogens associated with CIRDC during the study period were CPIV, M. canis, and M. cynos.
REVIEW | doi:10.20944/preprints202306.2165.v1
Subject: Medicine And Pharmacology, Otolaryngology Keywords: sobrerol; mucolytic agent; respiratory infections
Online: 29 June 2023 (14:42:35 CEST)
Respiratory infections are usually characterized by mucus hypersecretion. This condition may worsen and prolong symptoms and signs. Mucoactive agents include different molecules with different mechanisms of action. Sobrerol is a monoterpene able to fluidify mucus, increase mucociliary clearance, and exert antioxidant activity. Sobrerol is available in various formulations (granules, syrup, nebulized, and suppository). Sobrerol has been on the market for over 50 years. Several studies investigated its efficacy and safety in acute and chronic respiratory diseases characterized by mucus hyperproduction. Seven pediatric studies have been conducted with favorable outcomes. Recently, regulatory agencies reduced the treatment duration to three days. Therefore, a future study will test the hypothesis that a combination of oral and topical sobrerol could benefit children and adults with frequent respiratory infections. The rationale considers that mucus accumulation could be a risk factor for increased susceptibility to have infections.
REVIEW | doi:10.20944/preprints202101.0575.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: wearable respiratory monitors; smart garment; lung volume; respiratory inductance plethysmography; chest expansion; inhalation topography
Online: 27 January 2021 (21:27:53 CET)
Background: Natural environment inhalation topography provides useful information for toxicant exposure, risk assessment and cardiopulmonary performance. Commercially available Wearable Respiratory Monitors (WRM), which are currently used to measure a variety of physiological parameters such as heart rate and breathing frequency, can be leveraged to obtain inhalation topography, yet little work has been done. This paper assesses the feasibility of adapting these WRMs for measuring inhalation topography. Methods: Commercially available WRMs were compiled and assessed for the ability to report chest motion, data analysis software features, ambulatory observation capabilities, participant acceptability, purchasing constraints and affordability. Results: The following WRMs were found: LifeShirt, Equivital EQ02 LifeMonitor, Smartex WWS, Hexoskin Smart Garment, Zephyr BioHarness, Nox T3&A1, BioRadio, SleepSense Inductance Band, and ezRIP & zRIP Durabelt. None of the WRMs satisfied all six assessment criteria in a manner enabling them to be used for inhalation topography without modification and development. Conclusion: The results indicate that there are WRMs with core technologies and characteristics that can be built upon for ambulatory inhalation topography measurement in the NE.
REVIEW | doi:10.20944/preprints202004.0330.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: SARS-CoV-2 (CoV-2); COVID-19; coronavirus; pandemic; respiratory distress; brainstem; respiratory center
Online: 19 April 2020 (05:37:30 CEST)
Covid-19 pandemic has captivated scientists to investigate if this new disease can affect the central nervous system (CNS). The most challenging symptoms of Covid-19 are related to respiratory distress, and most patients admitted in intensive care units cannot breathe by their own. Therefore, a crucial question is if respiratory distress can be partially explained by the CNS affection. SARS-Cov-2 is a beta-coronavirus that shares high similarities with SARS-CoV. The infection of SARS‐CoV has been reported in the brains from both patients and experimental animals, where the brainstem was heavily infected. Those coronaviruses have been able to invade the brainstem via a synapse‐connected route to the medullary respiratory center, where the infected regions included the nucleus of the solitary tract and nucleus ambiguous. The vagal afferent nerves from receptors in the lung communicate with the medulla and pons respiratory control centers to coordinate inspiration and expiration. This suggests that neuroinvasion of SARS‐CoV‐2 might play a role in the acute respiratory failure of Covid-19. Therefore, acute respiratory distress in Covid-19 can be partially explained by brainstem dysfunction, suggesting the needs of more specific and aggressive treatments with the direct participation of neurologists and neurointensivists.
ARTICLE | doi:10.20944/preprints202309.1161.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COPD; respiratory; viruses; rhinovirus; Middle East
Online: 18 September 2023 (14:50:16 CEST)
Purpose: This study aimed to describe the molecular epidemiology and seasonality of human rhinovirus (HRV) in chronic obstructive pulmonary disease (COPD) and its association with COPD exacerbations in Abu Dhabi, the United Arab Emirates (UAE). Methods: Sputum specimens were collected for analysis from all COPD patients who visited a medical center from November 2021 to October 2022. The real-time quantitative polymerase chain reaction (qPCR) test was used to detect HRV. Results: Of the 78 COPD patients included in the study, 58 (74%) pa-tients presented with one or more exacerbation episodes. The incidence of COPD exacerbation peaked over the winter and substantially decreased during the summer. HRV positivity in pa-tients during exacerbation (E1) was 11/58 (19%) and 15/58 (26%) two weeks after the exacerbation episode (E2). There was no significant difference in the HRV load in these patients. No statistically significant difference was observed in the detection of HRV during exacerbation compared to patients with stable COPD. Conclusion: This is the first study to assess the association between HRV detection by qPCR and COPD exacerbations in the UAE. The high sensitivity of the detec-tion technology helped collect reliable epidemiologic data. Few studies have provided similar Middle East data. This study's pattern of COPD exacerbations and HRV detection parallels that of temperate countries. This information can help with future, more extensive surveillance of res-piratory viruses in the UAE and the Middle East and their association with COPD exacerbations.
ARTICLE | doi:10.20944/preprints202309.0695.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: respiratory health; ammonia; ventilation; smart farming
Online: 12 September 2023 (04:08:36 CEST)
This study aimed to assess the feasibility of employing audio and vision technologies as an integrated monitoring system to monitor the health and behavior of pigs under different environmental conditions and to associate these factors. A total of 81 growing pigs ((Landrace x Largewhite) x Duroc) with distinct weight categories (10.47 ± 2.57 kg and 28.81 ± 5.03 kg) were distributed into two distinct housing conditions: Control (characterized by low NH3 levels and low stocking density) and Treatment (marked by elevated NH3 levels and varying stocking densities). Each house was installed with a SoundTalks monitor for automated daily evaluation of respiratory health status (ReHS), and a camera with a microphone to facilitate manual tracking of respiratory symptoms and behavioral patterns. Results showed that the Treatment group encountered significantly high room temperature, NH3 concentration, and carbon dioxide levels, resulting in compromised growth performance—a phenomenon further exacerbated in high stocking density conditions. Pigs within the treatment exhibited increases (p < 0.05) in lateral and total lying behaviors, and incidences of ear and tail injuries, increases screaming frequency, conjunctivitis incidences, coughing frequency, elevated respiration rates, and a decrease in ReHS. The environmental conditions affect the behavior and health of the pigs. Moreover, the behavioral patterns of the pigs are associated with their health conditions. The SoundTalks system did not trigger any warnings during the experimental period. Nevertheless, trend analysis indicated a significant reduction in respiratory health in the treatment. In conclusion, this study underscores the efficacy of merging audio and visual technologies to holistically monitor pig health and behavior, enabling enhanced management strategies. Findings emphasize that monitoring the ReHS trend serves as a pivotal marker for identifying respiratory health problems, complementing the system's innate alarm functions.
ARTICLE | doi:10.20944/preprints202306.1055.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: respirator; fit testing; tuberculosis; respiratory protection
Online: 14 June 2023 (14:18:37 CEST)
Background: The COVID-19 pandemic has promoted a shortage of filtering facepiece respirators (FFRs) and the emergence of new FFRs brands. We aimed to determine the fit provided by in-use FFRs in Peruvian healthcare workers (HCWs) during the COVID-19 pandemic. Methods: We enrolled 279 HCWs from 37 primary healthcare centers with highest burden of care for TB in Peru, of which 263 were assessed using quantitative fit tests (QNFT). Results were expressed as real-time fit factor (rt-FF) and overall fit factor (overall-FF), which was categorized as ≥100 (optimal result), 50-99, and <50. Results: We identified 3M 1860 FFRs (33.1%), Xiantao Zhong Yi ZYB-11 FFRs (24.7%) and Makrite 9500 FFRs (20.5%), mainly. Eighty-seven HCWs (33.1%) had an optimal overall-FF, 27 (10.3%) between 50-99, and 149 (56.7%) less than 50. Of the 87 HCWs with optimal over-all-FF, 73 (83.9%) were 3M 1860 FFR. Of the 27 participants with overall-FF between 50-99, 7 (25.9%) were Makrite 9500, while of the 149 with overall-FF less than 50, 58 (38.9%), and 47 (31.5%) were Xiantao Zhong Yi ZYB-11 and Makrite 9500, respectively. Conclusion: The Xiantao Zhong Yi and Makrite FFRs do not adapt adequately to the face of Peruvian HCWs, most having fit factors less than 50.
REVIEW | doi:10.20944/preprints202305.0581.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: multiomics; lung, respiratory; models; integration; outcomes
Online: 9 May 2023 (07:38:25 CEST)
Diseases of the lung account for more than 5 million deaths worldwide and are a burden to healthcare. Improving clinical outcomes including mortality and quality of life involves a holistic understanding the etiopathogenesis, which can be provided by multi-omics integration of lung data. An enhanced understanding of large comprehensive datasets provides opportunities to mine those datasets for features that contribute to prevention and amelioration of disease. In this review, we evaluate lung disease models including animal models, organoids and single cell lines as mechanisms to study multiomics in lung health and disease. We provide examples of lung diseases where multi-omics investigations have provided a deeper insight into pathogenesis that has resulted in improved preventive and therapeutic interventions.
ARTICLE | doi:10.20944/preprints202304.0969.v1
Subject: Biology And Life Sciences, Cell And Developmental Biology Keywords: Mitochondrion; respiratory chain; mitochondrial translation; chaperone
Online: 26 April 2023 (07:40:36 CEST)
Insulin-degrading enzyme (IDE) is a highly conserved metalloprotease mainly localized in the cytosol. Although IDE can degrade insulin and some other low molecular weight substrates efficiently, its ubiquitous expression suggests additional functions supported by experimental findings, such as a role in stress responses, cellular protein homeostasis. Translation of full-length (Met1) IDE transcripts has reported to result in targeting to mitochondria but the role of IDE in this compartment is unknown. To obtain initial leads on the function of IDE in mitochondria, here we used a proximity biotinylation approach to identify proteins interacting with wild-type and protease-dead IDE targeted to the mitochondrial matrix. We find that mitochondrial IDE interacts strongly with mitochondrial ribosomes as well as with proteins of the respiratory chain. The mitochondrial interactomes of wild type and mutant IDE are highly similar and do not reveal any proteolytic IDE substrates. We speculate that IDE could adopt similar functions in mitochondria as in the cytosol, acting as a chaperone and contributing to protein homeostasis and stress responses.
ARTICLE | doi:10.20944/preprints202204.0105.v1
Subject: Biology And Life Sciences, Virology Keywords: respiratory care; covid; ICU; cost-effectiveness
Online: 12 April 2022 (08:49:09 CEST)
OBJETIVES: During the COVID-19 pandemic, the risk of collapse of the health system created great difficulties. We will demonstrate that Intermediate Respiratory Care Units (IRCU) provide adequate management of patients with non-invasive respiratory support, which is particularly important in patients with SARS-CoV-2 pneumonia. METHODS: A prospective observational study of patients with COVID-19 admitted to the ICU of a tertiary hospital. Sociodemographic data, comorbidities, pharmacological, respiratory support, laboratory and blood gas variables were collected. The overall cost of the unit was subsequently analyzed. RESULTS: 991 patients were admitted, 56 to the IRCU (of the 81 a critical care unit). Mean age was 65 years (SD 12.8), Barthel Index 75 (SD 8.3), Charlson 3.1 (SD 2.2), HTN 27%, COPD 89% and obesity 24%. Significant relationship (p <0.05) with higher mortality of the following: fever greater than or equal to 39oC [OR 5.6; 95% CI (1.2-2.7); p = 0.020], protocolized pharmacological treatment [OR 0.3; 95% CI (0.1-0.9); p = 0.023] and IOI [OR 3.7; 95% CI (1.1-12.3); p = 0.025]. NIMV showed less of a negative impact [OR 1.8; 95% CI (0.4-8.4); p = 0.423] than IOI. The total cost of the IRCUs amounted to €66,233. The cost per day of stay in the IRCU was €164 per patient. The total cost avoided was €214,865. CONCLUSION: The pandemic has highlighted the importance of IRCUs in facilitating the management of a high patient volume. The treatment carried out in IRCUs is effective and efficient, reducing both admissions to and stays in the ICU.
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: metabolic flexibility, respiratory quotient, energy expenditure
Online: 24 May 2021 (13:48:29 CEST)
Metabolic flexibility is the ability of an organism to adapt its energy source based on nutrient availability and energy requirements. In humans, this ability has been linked to cardio-metabolic health and healthy aging. Genome-scale metabolic models have been employed to simulate metabolic flexibility by computing the Respiratory Quotient (RQ), which is defined as the ratio of carbon dioxide produced to oxygen consumed, and varies between values of 0.7 for pure fat metabolism and 1.0 for pure carbohydrate metabolism. While the nutritional determinants of metabolic flexibility are known, the role of low energy expenditure and sedentary behavior in the development of metabolic inflexibility is less studied. In this study we present a new description of metabolic flexibility in genome-scale metabolic models which accounts for energy expenditure, and we study the interactions between physical activity and nutrition in a set of patient-derived models of skeletal muscle metabolism in older adults. The simulations show that fuel choice is sensitive to ATP consumption rate in all models tested. The ability to adapt fuel utilization to energy demands is an intrinsic property of the metabolic network
ARTICLE | doi:10.20944/preprints202105.0345.v1
Subject: Chemistry And Materials Science, Biomaterials Keywords: Respiratory Failure; COVID19; Intravenous Immunoglobulin Therapy
Online: 14 May 2021 (15:04:29 CEST)
Adjunctive therapy with polyclonal intravenous immunoglobins (IVIg) is currently used for preventing or managing infections and sepsis, especially in immunocompromised patients. The pathobiology of COVID19 and the mechanisms of action of Ig led to consider this adjunctive therapy also in patients with respiratory failure by SARS-CoV2 infection. This manuscript report the rationale, the available data and the results of a structured consensus on intravenous Ig therapy in patients with severe COVID19. METHODS A panel of multidisciplinary experts defined the clinical phenotypes of COVID19 patients with severe respiratory failure and, after literature review, voted for the agreement on the rationale and the potential role of IVIg therapy for each phenotype. Due to the scarce evidence available, a modified RAND/UCLA appropriateness method was used. RESULTS Three different phenotypes of COVID19 patients with severe respiratory failure were identified: patients with an abrupt and dysregulated hyperinflammatory response (early phase), patients with suspected immune-paralysis (late phase), and patients with sepsis by hospital-acquired superinfection (sepsis by bacterial superinfection). The rationale for intravenous Ig therapy in the early phase was considered uncertain whereas the panellists considered appropriate its use in the late phase and patients with sepsis/septic shock by bacterial superinfection. CONCLUSION As with other immunotherapies, IVIg adjunctive therapy may a potential role in the managing of COVID19 patients. The ongoing trials will clarify the appropriate target population and the true effectiveness.
REVIEW | doi:10.20944/preprints202006.0074.v1
Subject: Medicine And Pharmacology, Neuroscience And Neurology Keywords: COVID-19; myasthenia gravis; respiratory management
Online: 7 June 2020 (09:28:09 CEST)
The outbreak of COVID-19 has brought unprecedented risks and challenges to everyone in the world. Myasthenia gravis is an autoimmune disease of the nervous system. Infection can worsen it and cause severe symptoms such as myasthenia crisis and respiratory failure. At present, the pandemic of COVID-19 may promote the aggravation of patients with MG. This article focuses on the respiratory management of MG patients during the epidemic of COVID-19.
BRIEF REPORT | doi:10.20944/preprints202004.0452.v1
Subject: Medicine And Pharmacology, Other Keywords: respiratory failure; stethoscope; ultrasound; COVID-19
Online: 25 April 2020 (02:31:18 CEST)
The current Covid-19 pandemic has hugely disrupted the delivery of routine and established medical care. Patients can develop a wide range of clinical signs and symptoms from a cough and fever to severe respiratory failure. There is an ongoing argument on a concise investigative pathway to ensure the safety of all healthcare workers. The stethoscope can help with any clinical respiratory assessment but the risk of cross infection is high. Computer tomography should not be routinely performed. There is a potential place for lung ultrasound but outcomes are not yet determined.
HYPOTHESIS | doi:10.20944/preprints202004.0317.v2
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2); COVID19; Middle East Respiratory Syndrome Coronavirus; bioaerosol; aerosol
Online: 30 April 2020 (05:30:30 CEST)
A short review of the important studies was conducted to evaluate the potential of aerosol transmission of the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The minimum size of droplets potentially carrying the SARS-CoV-2 was newly estimated and discussed in this review.
ARTICLE | doi:10.20944/preprints202310.1128.v1
Subject: Public Health And Healthcare, Physical Therapy, Sports Therapy And Rehabilitation Keywords: covid-19; diaphragm; chest mobilization; respiratory fucntion
Online: 18 October 2023 (08:14:01 CEST)
This study aims to investigate the effects of chest mobilization and breathing exercises on respiratory function, trunk stability, and endurance in chronic stroke patients who have contracted coronavirus disease (COVID-19). Thirty inpatients of a tertiary hospital in South Korea, who had a history of COVID-19 and were diagnosed with stroke within the last 6 months were randomly assigned to either the Chest Mobilization Exercise with Breathing Exercise (CMEBE) or Conservative Physical Therapy with Breathing Exercise (CPTBE) groups. The respiratory function, trunk stability, and endurance were measured at baseline and 6 weeks after the interventions. Both CMEBE and CPTBE groups showed improvements in respiratory function, trunk stability, and endurance after the intervention (p<0.05). However, the CMEBE group showed significantly greater improvements in forced expiratory volume in 1 second (p<0.05), trunk stability (p<0.05), and endurance (p<0.05) than the CPTBE group. No significant intergroup difference was observed in forced vital capacity and peak expiratory flow. Conclusion: The combination of chest mobilization and breathing exercises improved respiratory muscle mobility and endurance, stabilized the trunk, and enhanced balance and transfer of weight. The findings suggest that this intervention could be beneficial in improving respiratory function and endurance in stroke patients.
ARTICLE | doi:10.20944/preprints202309.1415.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COVID-19; COPD; smoking; mortality; respiratory failure
Online: 21 September 2023 (07:09:02 CEST)
Background: The global pandemic of coronavirus disease 2019 (COVID-19) resulted to many deaths from fulminant respiratory failure. Chronic obstructive pulmonary disease (COPD) is the leading cause of morbidity and mortality worldwide. There has been great concern regarding the impact of COPD on COVID-19 illness. Methods: Data from the Philippine CORONA Study were analyzed to determine the association of COPD and COVID-19 in terms of mortality, disease severity, respiratory failure, mechanical ventilation, and lengths of stay in the intensive care unit (ICU) and hospital. The influence of smoking on COVID-19 disease severity and mortality were also reviewed. Results: A total of 10,881 patients were included in the study and 156 (1.4%) patients had been diagnosed with COPD. Majority of COVID-19 patients with COPD had other existing comorbidities: hypertension, diabetes mellitus, chronic cardiac disease, and chronic kidney disease. COPD patients more commonly present with severe or critical COVID-19. COPD patients with COVID-19 were at higher risk to experience in-hospital mortality, respiratory failure, and to be admitted in the ICU. Smokers were more likely to present with higher COVID-19 severity and experience in-hospital mortality. Conclusion: Our study supports that the growing evidence that COPD among COVID-19 patients is a risk for higher mortality, more severe form of COVID-19, higher ICU admission, and higher respiratory failure needing ventilatory support. Smoking increases risk for developing severe COVID-19 and mortality.
ARTICLE | doi:10.20944/preprints202306.1646.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: respiratory syncytial virus; RSV; ELISA; Vaccine; Immunogenicity
Online: 23 June 2023 (08:36:32 CEST)
Recently, two respiratory syncytial virus (RSV) vaccines based on the prefusion F (pre-F) antigen were approved in the United States. We developed and validated an enzyme-linked immunosorbent assay (ELISA)-based protocol for the practical and large-scale evaluation of RSV vaccines. Two modified pre-F proteins (DS-Cav1 and SC-TM) were produced by genetic recombination and replication using an adenoviral vector. The protocol was established by optimizing the concentrations of the coating antigen (pre-F proteins), secondary antibodies, and choice of blocking buffer. To validate the protocol, we examined its accuracy, precision, and specificity using serum samples from 150 participants across various age groups and the standard serum provided by the National Institute of Health. In the linear correlation analysis, coating concentrations of 5 and 2.5 μg/mL of DS-Cav1 and SC-TM, respectively, showed high coefficients of determination (r2 = 0.90). Concentrations of secondary antibodies (alkaline phosphatase-conjugated anti-human immunoglobulin G, diluted 1:2000) and blocking reagents (5% skim milk/PBS-T) were optimized to minimize non-specific reactions. High accuracy was observed for DS-Cav1 (r2 = 0.90) and SC-TM (r2 = 0.86). Further, both antigens showed high precision (coefficient of variation < 15%). Inhibition ELISA revealed cross-reactivity of antibodies against DS-Cav1 and SC-TM but not with the attachment protein.
BRIEF REPORT | doi:10.20944/preprints202212.0525.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Respiratory Syncytial Virus Infections; Child; Bronchiolitis; Survival.
Online: 28 December 2022 (02:37:39 CET)
Background: The respiratory syncytial virus infection (RSV) spread has been unusually high during 2022 and increasing trends have been documented We aimed to assess the survival experience of children hospitalized due bronchiolitis by laboratory-confirmed RSV. Methods: A nationwide and retrospective cohort was conducted in Mexico and data from 436 children aged 5 years and younger, with symptoms onset from August 2021 to November 2022, were analyzed. Survivor functions and 95% confidence intervals (CI) were computed by using the Kaplan-Meier method. Results: The survival rates were high, particularly within the first three weeks of admission. The 3-day survival was 99.8% (CI 95% 98.4-99.9%) and went to 98.9% (CI 95% 96.5-99.7%), 97.5% (CI 95% 91.9-99.3%), 86.7% (95% CI 48.2-97.2%), and 69.4% (95% CI 24.2-91.0%) on days 7, 14, 21 and 28 of hospital stay, respectively. We documented 5 fatal outcomes, and the mortality rate was 2.1 per 1,000 person-days. Conclusions: We analyzed a large set of pediatric patients with bronchiolitis by RSV and the presented results contribute to achieving a better understanding of the in-hospital evolution of this disease.
ARTICLE | doi:10.20944/preprints202207.0331.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COVID-19; diagnose; primary care; respiratory disease
Online: 22 July 2022 (03:12:31 CEST)
Objective: Several authors have analyzed the impact of the pandemic on the incidence rates of different conditions. Our aim was to analyze the impact of the COVID-19 pandemic on primary care new diagnoses of respiratory diseases. Methods: This was an observational retrospective study performed to describe the impact of COVID-19 pandemic on primary care new diagnosis of respiratory diseases other than lung cancer. Incidence rate ratio between pre-pandemic and pandemic period was calculated. Results: We found an decrease in the incidence of respiratory conditions (IRR 0.65) during the pandemic period. When we compared the different groups of diseases according to ICD-10, we found a significant decrease in the number of new cases during the pandemic period, except in the case of pulmonary tuberculosis, abscesses or necrosis of the lungs and other respiratory complications. Instead, we found increases in new diagnoses of flu and pneumonia (IRR 2.17) and respiratory interstitial diseases (IRR 1.41). Conclusion: There has been a decrease in new diagnosis of most respiratory diseases during the COVID-19 pandemic. The real clinical impact of this situation is still unknown. Large-scale real-life studies will make it possible to evaluate the long-term true impact of COVID-19 pandemic on the respiratory diseases management.
REVIEW | doi:10.20944/preprints202108.0082.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: vaccines; vaccination; bovine respiratory disease; antigen; adjuvants
Online: 3 August 2021 (13:39:11 CEST)
Vaccination is widely regarded as a cornerstone in animal or herd health and infectious disease management. Nineteen vaccines against the major pathogens implicated in bovine respiratory disease are registered for use in the UK by the Veterinary Medicines Directorate (VMD). However, despite annual prophylactic vaccination, bovine respiratory disease is still conservatively estimated to cost the UK economy approximately £80 million per annum. This review examines the vaccine types available, discusses the surrounding literature and scientific rationale of the limitations and assesses the potential of novel vaccine technologies.
ARTICLE | doi:10.20944/preprints202103.0602.v2
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: COVID-19; hospitalization period; respiratory disease; Hormozgan
Online: 10 May 2021 (12:34:09 CEST)
Abstract Introduction: COVID-19 has a relationship with patients’ demographic characteristics as well as their underlying diseases. This research has been conducted to evaluate factors' effect on Covid-19 patient's hospitalization rate and period in Hormozgan, Iran. Materials and Methods: The inclusion criteria of this retrospective study included all patients diagnosed as COVID-19 Patients after PCR who were referred to Covid-19 hospitals from February 2020 to June 2020 in Hormozgan province, Iran. After the completion of the consent form and observing ethical principles, 3480 patients' information was collected through the interview by Medical care monitoring center unit experts. The checklist was designed according to COVID-19 guidelines and approved by the World Health Organization and Iran Ministry of Health and Medical Education. The studied variables included gender, age, patients’ residence place, smoking history and medications use history, pregnancy, referral type to hospital, contact history with COVID-19 patients, early symptoms, gastrointestinal symptoms, intubation, Po2 level, history of cancer, chronic liver diseases, diabetes, chronic blood diseases, HIV/AIDS, acquired or congenital immunodeficiency, cardiovascular diseases, chronic kidney diseases, dialysis status, asthma and other chronic lung diseases, and chronic neurological disorders. These data were analyzed using descriptive (average-standard deviation-percentage) and analytical (including Chi-square, t-test, and regression tests) statistics with SPSS Ver.23 software. Results: In this study, 3480 COVID-19 patients including 1852 male patients (53.20%) with a median age of 43.11±21.72 and 1628 female patients (46/80%) with a median age of 44.86±22.40. The median age of men was significantly lower than the women's median age (P= 0.02). The duration of hospitalization of male and female patients was reported 2.64±4.14 and 2.76±4.297, respectively which was not statistically significant. The death rate of patients in our study was 6.6%. Conclusion: The results of this study also showed that the hospitalization period of HIV-positive patients and patients with cardiovascular and pulmonary diseases is much longer than other people, which imposes many human and financial costs on the country's health care system. Therefore, to maintain individual health and help improve the critical condition of the virus, it is better to develop and apply stricter protocols to prevent further outbreaks of the disease and check underlying diseases of people suspected to have Covid-19. These results can improve health care system planning and improving medical services presented to covid-19 patients.
REVIEW | doi:10.20944/preprints202006.0045.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: ARDS; COVID-19; Berlin Criteria; Respiratory Failure
Online: 5 June 2020 (13:54:36 CEST)
Introduction: The exponential growth of the SARS-CoV-2 virus transmission during the first months of 2020 has placed substantial pressure on health systems worldwide. The complications derived from the novel coronavirus disease (COVID-19) vary in due to comorbidities, sex and age, with more than 50% of the patients who require some level of intensive care developing acute respiratory distress syndrome (ARDS). Areas covered: Various complications caused by SARS-CoV-2 infection have been identified, the most lethal being the acute respiratory distress syndrome, caused most likely by the presence of severe immune cell response and the concomitant alveolus inflammation. The authors carried out an extensive and comprehensive literature review on SARS-CoV-2 infection, the clinical, pathological and radiological presentation as well as the current treatment strategies. Expert Opinion Elevation of inflammatory biomarkers is a common trend among seriously ill patients. The information available strongly suggests that in COVID-19 patients, their altered immune response, including a massive cytokine storm, is responsible for the further damage evidenced among ARDS patients. The increasingly high number of scientific articles and evidence available can only suggest that the individualization of each case is the norm, not all patients with acute respiratory failure due to COVID-19 meet the Berlin definition and therefore ARDS should be considered as a heterogeneous disease, with a wide range in the expression of its severity and clinical manifestations.
REVIEW | doi:10.20944/preprints201810.0002.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Probiotics, Upper Respiratory Infections, Network Meta-Analysis
Online: 1 October 2018 (10:22:49 CEST)
Background. Upper respiratory infections (URIs) remains as significant cause of morbidity in children. Evidence on efficacy of probiotics to prevent URIs in children is increasing. This systematic review was assembled to analyze evidence about the efficacy of probiotics to reduce duration of upper respiratory infections in ambulatory children. Methods. Randomized controlled trials (RCTs) comparing probiotics vs. placebo to prevent URIs, published between 2001 and 2016 were considered. Quality evaluation was evaluated using CONSORT. Standard mean difference (SMD) or risk ratio (RR) was calculated. Network Meta-Analysis (NMA), using a random effect model was assembled. Results. 31 RCTs were evaluated and 20 studies were included with 3,635 children randomized to probiotics and 3,433 to placebo. Lactobacillus reuteri [SMD -0.56 CI95% (-0.72 to -0.41), p 0.0001] and Lactobacillus acidophillus [SMD -0.33 CI95% (-0.60 to -0.06), p 0.01] were superior to placebo to reduce duration of URIs. L. rhamnosus GG showed tendency [SMD -0.14 CI95% (-0.28 to 0.0), p 0.048]. On the network forest plot L. reuteri showed preventive equivalence when was compared to L. rhamnosus GG, L. casei and BB12. Conclusions. Lactobacillus reuteri, Lactobacillus rhamnosus GG and Bifidobacterium BB12 are evidence-based alternatives to be considered to prevent URIs in children.
ARTICLE | doi:10.20944/preprints202311.0966.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: influenza-like illness; respiratory virus; respiratory viral infection; direct medical cost; non-direct medical cost; social determinants of health
Online: 16 November 2023 (10:35:52 CET)
Respiratory viral infections (RVI) are common reasons for healthcare consultations. The inpatient management of RVI consumes significant resources. From 2009-2014, we assessed the costs of RVI management in 4776 hospitalized chil-dren aged 0-18 years participating in a quality improvement program, where all ILI patients underwent virologic testing at the National Reference Centre followed by de-tailed recording of their clinical course. The direct (medical or non-medical) and indirect costs of inpatient management outside the ICU (“non-ICU”) versus management requiring ICU-care (“ICU”) added up to 2,767.14€ (non-ICU) vs. 29,941.71€ (ICU) for Influenza, 2,713.14€ (non-ICU) vs. 16,951.06€ (ICU) for RSV infections, and 2,767.33€ (non-ICU) vs. 14,394.02€ (ICU) for human rhinovirus (hRV) infections, respectively. Non-ICU inpatient costs were similar for all 8 RVI studied: Influenza, RSV, hRV, ade-novirus (hAdV), metapneumovirus (hMPV), parainfluenzavirus (hPIV), bocavirus (hBoV) and seasonal coronavirus (hCoV) infections. ICU-costs for Influenza however, ex-ceeded all other RVI. At the time of the study, Influenza was the only RVI with antivi-ral treatment options available for children, but only 9.8% of Influenza patients (non-ICU) and 1.5% of ICU-patients with Influenza received antivirals; only 2.9% were vac-cinated. Future studies should investigate the economic impact of treatment and pre-vention of Influenza-, COVID-19-, and RSV post vaccine introduction.
ARTICLE | doi:10.20944/preprints202307.0938.v1
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: major depressive disorder; bipolar disorder; infectious diseases; upper respiratory infections; lower respiratory infections; lung-brain axis; gut-brain axis
Online: 13 July 2023 (12:23:28 CEST)
Mood disorders are among the commonest mental disorders worldwide. Epidemiological and clinical evidence suggests that there are close links between infectious diseases and mood disorders, but the strength and direction of these association remain largely unknown. Theoretical models have attempted to explain this link based on evolutionary or immune-related factors, but these have not been empirically verified. The current study examined cross-sectional and longitudinal associations between the incidence of infectious diseases and mood disorders, while correcting for climate and economic factors, based on data from the Global Burden of Disease Studies, 1990-2019. It was found that major depressive disorder was positively associated with lower respiratory infections, while bipolar disorder was positively associated with upper respiratory infections and negatively associated with enteric and tropical infections, both cross-sectionally and over a period of thirty years. These results suggest that a complex, bidirectional relationship exists between these disorders. This relationship may be mediated through the immune system as well as through the gut-brain and lung-brain axes. Understanding the mechanisms that link these groups of disorders could lead to advances in the prevention and treatment of both.
REVIEW | doi:10.20944/preprints202308.0995.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Respiratory infection; etiology; viruses; bacteria; sub-Saharan Africa
Online: 14 August 2023 (08:44:59 CEST)
(1) Background: Respiratory infections are a major public health problem worldwide, with potentially serious consequences. Indeed, these infections remain one of the main causes of morbidity and mortality in children under 5 years old in developing countries. Etiological information on respiratory infections is crucial for prevention and case management strategies. This systematic review aims to describe the etiology of respiratory infections reported in studies carried out in sub-Saharan African countries; (2) Methods: Using PubMed, HINARI and Google scholar search engines, a systematic search was carried out to identify published articles on the etiology of viral and/or bacterial respiratory infections in sub-Saharan Africa in patients of all ages. We have only considered data from sub-Saharan Africa. Papers published from 2010 to 2021, in English or French have been included in this review; (3) Results: After reviewing 115 articles reporting studies carried out in the African continent, only 32 articles were selected of which, studies were conducted in 15 sub-Saharan African countries, including 6/32 (18.75%) in Cameroon. Twenty (62.5%) were cross-sectional studies, and twenty-four (75%) were hospital-based investigations. In these studies, RT-PCR and culture methods were respectively used for viruses and bacteria investigations. Respiratory syncytial virus was the most frequently identified, with prevalence ranging from 0.6% to 59%, followed by rhinovirus (9.3% -73%), influenza virus (flu) A/B (0.9%-69.1%), and human adenovirus (0.9% - 30.8%). Streptococcus pneumoniae (14.2% - 96%), followed by Haemophilus influenzae type b (2.5% - 54%), and Klebsiella pneumoniae (1.4% - 49.9%) were the most frequently detected bacteria; (4) Conclusions: This review has reported that many pathogens, mainly viruses, are associated with acute respiratory infections in sub-Saharan Africa in both children and adults. Unfortunately, the limited geographical distribution of data across sub-Saharan Africa does not allow most of countries to develop an effective strategy for the prevention and treatment of respiratory infections.
REVIEW | doi:10.20944/preprints202307.1733.v1
Subject: Biology And Life Sciences, Virology Keywords: RSV; respiratory virus; tracheobronchitis; bronchiolitis; pneumonia; apnea; infants
Online: 26 July 2023 (08:43:20 CEST)
Respiratory syncytial virus (RSV) is a common respiratory virus that can cause mild to severe illness in people of all ages. The most common symptoms of an RSV infection are cough, runny nose, and fever. However, RSV can also cause more serious complications, such as tracheobronchitis, bronchiolitis, pneumonia, and apnea. RSV is especially dangerous for infants, young children, and older adults. RSV is a seasonal virus, with peak incidence in the winter months. The virus spreads through respiratory droplets produced when an infected person coughs or sneezes. The virus can also be spread through contact with contaminated surfaces. Treatment is aimed at relieving symptoms and preventing complications. This review will provide an overview of the medical significance, virology, pathogenesis, immunity, epidemiology, symptoms, risk factors, and complications associated with RSV, and the diagnosis and management of RSV infections.
ARTICLE | doi:10.20944/preprints202304.1085.v1
Subject: Medicine And Pharmacology, Clinical Medicine Keywords: SARS-CoV-2; pandemic; children infection; respiratory failure
Online: 28 April 2023 (03:02:24 CEST)
Background: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild course; however, about 1% of affected children require a stay in the pediatric intensive care unit (PICU) due to the severe life-threatening course. The risk of respiratory failure, as in adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyze patients admitted to PICUs due to severe course of SARS-CoV-19 infection. Methods: A retrospective multi-center study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection, who were admitted to PICUs, in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, and the endpoint – survival or death. Results: The study analyzed 45 patients (0.075% of all children hospitalized in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n=18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system, Lung Injury Score and Pediatric Sequential Organ Failure Assessment . A significant correlation between disease severity and the patient's prognosis was shown by the liver function parameter AST (p=0.028). Analyzing patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalization, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. Conclusions: As in adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis.
REVIEW | doi:10.20944/preprints202212.0448.v2
Subject: Medicine And Pharmacology, Orthopedics And Sports Medicine Keywords: moderate exercise; vigorous exercise; upper respiratory infection; immunity
Online: 10 January 2023 (02:31:03 CET)
The practice of physical activity is an effective non-pharmacological strategy for preventing and treating chronic diseases. A large body of evidence has contributed to establishing a positive correlation between a physically active lifestyle and health benefits, including enhanced vaccination responses, lower numbers of senescent T-cells, increased T-cell proliferative capacity, lower levels of inflammatory cytokines, and improved neutrophil and macrophage function. While females are generally thought to exert more robust immune responses than males in response to a variety of challenges, and both male and female sex hormones have been suggested as mediators of immune function, research on this topic has not always been designed with a sex-specific lens. The goal of this review is to summarize the available experimental and clinical evidence linking exercise and immune function in male and female subjects, with an emphasis on sex differences and sex-specific mechanisms. Overall, the available evidence indicates that moderate exercise and physical activity improves immune function in both sexes, whereas prolonged and high-intensity exercise temporarily impairs immune responses at a higher degree in females. A role of male and female sex hormones in these sex-specific effects is also discussed.
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: Bovine respiratory disease; Pasteurella multocida; resistance; tolerance; satP.
Online: 20 July 2021 (14:48:06 CEST)
Under the pressure of fluoroquinolones, Pasteurella multocida (PM) can easily develop resistance to fluoroquinolones mediated by QRDR target mutation. It is imperative to find new drug resistance inhibitor targets to combat the rapid development of drug resistance. In order to overcome these problems, we sequenced the transcriptome of PM with different levels of resistance to ENR(0.03 μg/mL; 8 μg/mL; 32μg/Ml, Enrofloxacin). The results showed that with the increase of resistance to fluoroquinolones, the expression of satP gene was significantly up-regulated. The satP gene deletion strain and replenishment strain were constructed, and their drug resistance and tolerance were determined. The results showed that the deletion of satP gene did not affect the resistance of PM to fluoroquinolones, rather affected the time when PM developed resistance to fluoroquinolones. After 10 generations of drug induction, the MIC (minimum inhibitory concentration) of fluoroquinolones for wild strain was 64 μg/mL, while the MIC for satP gene deletion strain was only 8 μg/mL. The MDK99 test (time to kill 99% bacteria),agar diffusion test and mutation frequency test showed that the tolerance of satP gene deletion strain was significantly lower than that of wild strain. At the same time, the virulence of gene deletion strain and wild strain was tested, and about 400 times decreased virulence was observed for satP gene deletion strain. The mouse infection model confirmed that mice infected with satP gene deletion strains were more likely to be treated with ENR than mice infected with wild-type bovine PM strains. The results show that satP has potential to be a target of fluoroquinolone resistance inhibitors.
ARTICLE | doi:10.20944/preprints202106.0630.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Exercise; Runners; Near-infrared spectroscopy; Respiratory muscles; Respiration.
Online: 28 June 2021 (09:44:55 CEST)
The study aimed to evaluate the association between the changes in ventilatory variables (tidal volume (Vt), respiratory rate (RR), and lung ventilation (VE)) and deoxygenation of m.intescostales (∆SmO2-m.intercostales) during a maximal incremental exercise in nineteen male competitive marathon runners. The ventilatory variables and oxygen-consumption (VO2) were recorded breath-by-breath by exhaled gas analysis. A near-infrared spectroscopy device (MOXY) located in the right-hemithorax allowed recording SmO2-m.intercostales. To explore changes in oxygen levels in muscles with high demand during exercise, a second MOXY records SmO2-m.vastus laterallis. The triphasic model of exercise intensity was used for evaluating changes in SmO2 in both muscle groups. We found that ∆SmO2-m.intercostales correlated with VO2-peak (r=0.65; p=0.002) and the increase of VE (r=0.78; p=0.001), RR (r=0.54; p=0.001), but not Vt (p=0.210). The interaction of factors (muscles X exercise-phases) in SmO2 expressed as an arbitrary unit (a.u) was significant (p=0.005). At VT1 were no difference (p=0.177), but SmO2-m.intercostales was higher at VT1 (p<0.001) and VO2-peak (p<0.001). In competitive marathon runners, the m.intercostales deoxygenation during incremental exercise is directly associated with the aerobic capacity and increased lung ventilation and respiratory rate, but not tidal volume. Besides, it shows less deoxygenation than m.vastus laterallis at intensities above the aerobic ventilatory threshold.
ARTICLE | doi:10.20944/preprints202005.0216.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: children; infectious disease; lower respiratory tract infections; gastrointestinal
Online: 12 May 2020 (12:59:25 CEST)
The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Pediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 83.98% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. 12.0% were transferred to the Vietnam National Children’s Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time PCR assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.
ARTICLE | doi:10.20944/preprints201808.0435.v1
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: Respiratory tract infections (RTI); antibiotic; sensitivity; resistant; bacteria
Online: 24 August 2018 (11:46:41 CEST)
1) Background: Respiratory tract infections (RTI) has been known to be a significant health concern for mortality and morbidity since many years. This study was aimed at determining the prevalence of bacterial pathogen causing upper respiratory tract (URTIs) and the susceptibility patterns to frequently used antibiotics among patients attending Abusetta hospital in Tripoli district; 2) Methods: A total of 1,110 throat swabs were collected between Jan, 2011 to December, 2014 and inoculated onto Blood agar, MacCkonkey agar and Chocolate agar then incubated at 37 oC for 24 hours. Bacterial pathogens were determined by bacteriological culture methods and antibiotic susceptibility of the isolates was identified following Clinical Laboratory Standard Institute guidelines (CLSI); 3) Results: Of the 1,110 respiratory samples tested, 71.1% (n = 789) of specimens were positive cultures with the dominant bacterial pathogens being streptococcus pneumonia 43.3% (n = 342), followed by pseudomonas aeruginosa 22.8% (n = 180), staphylococcus aurous 13.8% (n = 109), Escherichia Coli 6.9% (n = 55), Enterobacter spp 6.2% (n = 49), Citrobacter 4.5% (n = 36), and Klebsiella 2.2% (n = 18). Most isolates exhibited resistance against the commonly used antibiotics and to at least one antibiotic; and 4) Conclusions: The level of antibiotic resistance in this study is alarming and brings to light the timely and suitable diagnosis of the common bacteria causes of URTIs and proper antibiotic administration based on susceptibility test.
ARTICLE | doi:10.20944/preprints201808.0318.v1
Subject: Biology And Life Sciences, Virology Keywords: respiratory syncytial virus; phylogenetics; evolution; multi-year persistence
Online: 18 August 2018 (05:14:42 CEST)
There is an ongoing global pandemic of human respiratory syncytial virus (RSV) infection that results in substantial annual morbidity and mortality. In Australia, RSV is the major cause of acute lower respiratory tract infections (ALRI). Nevertheless, little is known about the extent and origins of genetic diversity of RSV in Australia, nor the factors that shape this diversity. We conducted a genome-scale analysis of RSV infections in New South Wales (NSW). RSV genomes were successfully sequenced for 144 specimens collected between 2010-2016. Of these, 64 belonged to the RSVA and 80 to the RSVB subtype. Phylogenetic analysis revealed a wide diversity of RSV lineages within NSW and that both subtypes evolved rapidly in a strongly clock-like manner, with mean rates of approximately 6-8 x 10-4 nucleotide substitutions per site per year. There was only weak evidence for geographic clustering of sequences, indicative of fluid patterns of transmission within the infected population, and no evidence of any clustering by patient age such that viruses in the same lineages circulate through the entire host population. Importantly, we show that both subtypes circulated concurrently in NSW with multiple introductions into the Australian population in each year, and only limited evidence for multi-year persistence.
ARTICLE | doi:10.20944/preprints201610.0030.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: respiratory symptoms; PM exposure; residential location; Namibia; Windhoek
Online: 10 October 2016 (09:59:29 CEST)
The study aimed to estimate the prevalence of respiratory symptoms and to assess respiratory health risks associated with Particulate Matter (PM) exposure among the residents of Windhoek, Namibia. Objectives: To measure particulate pollution concentration in Windhoek through monitoring of particulate matter concentration and to identify any associations between particulate pollution, individual location and respiratory health among the Windhoek resident’s. Methods: an adapted standardized self-administered questionnaire was used to collect respiratory health related data as well as previous exposure, while PM monitoring was done using ASTM D1739 reference method. Results: A high prevalence was observed for cough (43%), breathlessness (25%), and Asthma (11.2%). PM was found to be a significant risk factor for episode of cough and phlegm, while high PM exposure category had increased odds ratio for episode of phlegm and cough (OR: 2.5, 95% CI: 0.8-8.0). No association was observed between location and respiratory health outcomes. Conclusion: The study found high levels of PM concentration across all Windhoek suburbs which were above the German, American and EPA. Enactment of legislation relating to the control and monitoring of PM related emissions at point of generation is required at country and city level.
ARTICLE | doi:10.20944/preprints202112.0128.v1
Subject: Medicine And Pharmacology, Emergency Medicine Keywords: ECMO; ECLS; ECCO2R; ARDS; respiratory failure, LTx, DIN EN ISO 7199; Extracorporeal membrane oxygenation, acute respiratory distress syndrome, animal model
Online: 8 December 2021 (14:16:25 CET)
Extracorporeal membrane oxygenation (ECMO) is an established rescue therapy for patients with chronic respiratory failure waiting for lung transplantation (LTx). The therapy inherent immobilization may result in fatigue, consecutive deteriorated prognosis and even lost eligibility for transplantation. We conducted a feasibility study on a novel system designed for the deployment of a mobile ECMO device, enabling physical exercise of awake patients prior to LTx. The system comprises a novel mobile oxygenator with a directly connected blood pump, a double lumen cannula, gas blender and supply, as well as control, and energy management. In-vitro experiments included tests regarding performance, efficiency, and blood damage. A reduced system was tested in vivo for feasibility using a novel large animal model. Six anesthetized pigs were first positioned in supine position, followed by a 45° angle, simulating an upright position of the patients. We monitored performance and vital parameters. All in-vitro experiments showed good performance for the respective subsystems and the integrated system. The acute invivo trials of 8h duration confirmed the results. The novel mobile ECMO-system enables adequate oxygenation and decarboxylation sufficient for, e.g., physical exercise of designated LTx-recipients. These results are promising and suggest further preclinical studies on safety and efficacy to facilitate translation into clinical application.
ARTICLE | doi:10.20944/preprints202309.0269.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: Asthma; Forest atmosphere; Monoterpenes; Respiratory functions; Volatile organic compounds.
Online: 5 September 2023 (08:02:04 CEST)
Increasing evidence supports the direct healing effects of forests, partly attributed to the exposure to plant-emitted monoterpenes available in the forest atmosphere. The potential benefits on respiratory functions from inhaling monoterpenes have gained attention, especially due to the global rise in respiratory diseases. This study involved 42 asthmatic adolescents attending a summer rehabilitation camp at an Altitude Pediatric Asthma Center within a densely forested area in the Eastern Italian Alps. Volatile organic compound measurements indicated a pristine atmosphere, enabling modeling of continuous hourly monoterpenes concentration. Monoterpene concentration exposure and total inhaled dose were assessed over a 14-day stay, during which spirometry, lung oscillometry, and fractional exhaled nitric oxide were measured. Statistically significant correlations were observed between modifications in lung function parameters among asthmatic adolescents and monoterpenes exposure. These findings suggest a potential localized airway effect specific to monoterpenes. This pilot cohort study might pave the way for further investigations into the therapeutic effects of forest monoterpenes on lung function tests, asthma, and the broader healing potential of forest environments.
ARTICLE | doi:10.20944/preprints202306.2168.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Acute respiratory distress syndrome; PEEP; Mechanical ventilation; Oleic acid
Online: 30 June 2023 (07:11:12 CEST)
Abstract: To compare the use of variable mechanical ventilation with conventional mechanical ventilation in porcine model of ARDS. Methods: Animals were divided into two groups (n = 6), conventional ventilation and variable ventilation with bi-oscillatory PEEP. For induction of ARDS, intravenous oleic acid was used until a P/F ratio of 200 to 300 mmHg. The animals were ventilated with pressure control, FiO2 1.0, inspiration-expiration ratio = 1:2, tidal volume 6 ml/kg with the initial respiratory rate adjusted to maintain an end tidal CO2 tension of 35 to 45 mmHg. Variable ventilation was characterized by the oscillation of PEEP from 5 to 10 cmH2O every 4 respiratory cycles, in convencional ventilation group PEEP was set from 5 cmH2O. Ventilatory, hemodynamic parameters, oxidative stress, antioxidant enzymes, Interleukin 8 (IL8) and 17-a (IL17a) and histological analyzes were evaluated; Results: The use of BiPEEP demonstrated improvement in lung compliance and PaO2 in relation to control. The levels of oxidative stress and antioxidant enzymes showed no significant difference. There was no difference in IL17a between groups. In IL8 there was a significant increase in the lung base of control in relation to BiPEEP, and a reduction in the apex of BiPEEP in relation to control. The control group showed changes in lung morphology characterized by cellular infiltrates, a thickening of the alveolar septae and atelectasis, which were attenuated in BiPEEP group; (4) Conclusions: The use of variable ventilation with bi-oscillatory level of PEEP demonstrates a potential ventilatory strategy in an experimental model of ARDS.
ARTICLE | doi:10.20944/preprints202306.1534.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: IR-UWB radar; polysomnography; spectrograms; respiratory rate; heartbeat rate
Online: 25 June 2023 (08:33:47 CEST)
The last decade the impulse-radio ultra-wideband (IR-UWB) radar sensors have tended to substitute the gold standard, polysomnography (PSG), for the acquisition of the primary vital signs of the human body. However, the main drawback of the radar sensor is its sensitivity to the environmental noise and body motion. In this work, we aim to investigate whether radar sensor recordings of the chest and heart motion can be accurate substitutes to the PSG chest and heartbeat signals measurements. In terms of this scientific issue, we develop an innovative pipeline of handling the radar-based recordings, which includes: (a) the motion detection, (b) the extraction of the respiration, heartbeat and activity vital signs and (c) the estimation of the respiratory and heartbeat rates, i.e., the RR and HR, respectively. Our experimental results, applying our proposed methodology to 5 subjects during their sleep, showed that the radar sensor’s measurements can be comparative to the those producted by the PSG. Moreover, the corresponding RR and HR frequencies were proven to have Pearson’s correlation, between the radar and the PSG, greater than 0.9 and 0.78, respectively. Finally, the relative errors between the PSG, and the radar-based RR and HR rates were proven to be less than 6% and 10%, respectively.
ARTICLE | doi:10.20944/preprints202306.1006.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: COPD; Dyspnea; Health Status; Respiratory Symptoms; Surveys and Questionnaires
Online: 14 June 2023 (07:47:07 CEST)
The hypothesis that health status is the highest-ranking concept, followed by respiratory symptoms and dyspnea as the lowest-ranking concepts in subjects with chronic obstructive pulmonary disease (COPD) was tested in a real clinical setting with 157 subjects with stable COPD. Spearman's rank correlation coefficients for scores of health status using the COPD assessment test (CAT), respiratory symptoms using the COPD Evaluating Respiratory Symptoms (E-RS) and dyspnea using the Dyspnoea-12 (D-12) between any two were 0.6 to 0.7. Upon categorizing the patients as "abnormal" or "normal" according to the threshold, it was found that 30 patients (19.1%) had dyspnea, respiratory symptoms, and impaired the health status. Dyspnea was considered an important part of respiratory symptoms though seven patients had dyspnea but no respiratory symptoms. There were 10 patients who had respiratory symptoms without dyspnea but without health status problems. Furthermore, there were six patients who had both dyspnea and respiratory symptoms but whose health status was classified as fine. Thus, the hypothesis was correct in approximately 85% of cases.
ARTICLE | doi:10.20944/preprints202305.0533.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: Respiratory syncytial virus; Nrf2; collagen; micro-CT; airway remodeling
Online: 8 May 2023 (11:21:24 CEST)
Severe respiratory syncytial virus (RSV) infections in early life have been linked to the development of chronic airway disease. RSV is a potent inducer of reactive oxygen species (ROS) which contributes to inflammation and enhanced clinical disease. NF-E2-related factor 2 (Nrf2) is an evolutionary conserved redox-responsive protein that helps to protect cells and whole organisms from oxidative stress and injury. The role of Nrf2 in the context of viral-mediated chronic lung injury is not known. Herein, we show that RSV experimental infection of adult Nrf2 deficient BALB/c mice (Nrf2-/-; Nrf2 KO) is characterized by enhanced disease, increased inflammatory cell recruitment to the bronchoalveolar compartment, and a more robust upregulation of innate and inflammatory genes and proteins, compared to wild type Nrf2+/+ competent mice (WT). These events that occur at very early time points, lead to increased peak RSV replication in Nrf2 KO compared to WT mice (day 5). To evaluate longitudinal changes of the lung architecture, mice were scanned weekly by high-resolution micro-computed tomography (micro-CT) imaging up to 28 days after initial viral inoculation. Based on micro-CT qualitative 2D imaging and quantitative reconstructed histogram-based analysis of lung volume and density, we found that RSV infected Nrf2 KO mice developed significantly greater and prolonged fibrosis compared to WT mice. Results of this study underscore the critical role of Nrf2-mediated protection from oxidative injury not only in acute pathogenesis of RSV infection, but also in its long-term consequences of chronic airway injury.
ARTICLE | doi:10.20944/preprints202305.0521.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Aircraft; Wastewater; Surveillance; Indicator viruses; Enteric viruses; Respiratory viruses
Online: 8 May 2023 (10:39:58 CEST)
The effective detection of viruses in aircraft wastewater is crucial to establish surveillance programs for monitoring virus spread via aircraft passengers. This study aimed to compare the performance of two virus concentration workflows, adsorption-extraction (AE) and Nanotrap® Microbiome A Particles (NMAP), in detecting the prevalence and concentrations of 15 endogenous viruses in aircraft lavatory wastewater samples. The viruses tested include two indicator viruses, four enteric viruses, and nine respiratory viruses. The results showed that cross-assembly phage (crAssphage), human polyomavirus (HPyV), rhinovirus A (RhV A), and rhinovirus B (RhV B) were detected in all wastewater samples using both workflows. However, enterovirus (EV), human norovirus (HNoV GII), human adenovirus (HAdV), bocavirus (BoV), parechovirus (PeV), epstein-barr virus (EBV), influenza A virus (IAV), and respiratory syncytial virus B (RsV B) were infrequently detected by both workflows, and hepatitis A virus (HAV), influenza B virus (IBV), and respiratory syncytial virus B (RsV A) were not detected in any samples. The NMAP workflow had greater detection rates of EV, PeV, and RsV B than the AE workflow, while the AE workflow had greater detection rates of HAdV, BoV, and EBV than the NMAP workflow. The concentration of each virus was also analyzed, and the results showed that CrAssphage had the highest mean concentration (6.76 log10 GC/12.5 mL) followed by HPyV (5.46 log10 GC/12.5 mL using the AE workflow, while the mean concentrations of enteric and respiratory viruses ranged from 2.48 to 3.63 log10 GC/12.5 mL. Using the NMAP workflow, the mean concentration of crAssphage was 5.18 log10 GC/12.5 mL and the mean concentration of HPyV was 4.20 log10 GC/12.5 mL, while mean concentrations of enteric and respiratory viruses ranged from 2.55 to 3.74 log10 GC/12.5 mL. The mean concentrations of CrAssphage, HPyV, RhV A, and RhV B between the two workflows were statistically significant (p < 0.05). In summary, the present study provides valuable insights into the performance of virus concentration workflows in detecting and quantifying different viruses in aircraft lavatory wastewater samples. The findings can aid in the selection of an appropriate concentration workflow for virus surveillance studies and contribute to the development of efficient and reliable virus detection methods.
BRIEF REPORT | doi:10.20944/preprints202211.0436.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Kawasaki disease; febrile convulsions; respiratory virus; filmarray; multiplex PCR
Online: 23 November 2022 (07:02:54 CET)
In Kawasaki disease (KD), convulsions are rare and mostly attributed to latent and coexisting encephalitis/encephalopathy due to KD itself. Therefore, we retrospectively investigated concomitant viral infections in patients with KD. Between January 2012 and December 2020, among 523 patients with KD, 7 (1.53%), 1 (0.19%), 6 and 1 (1.15% and 0.19%) were positive for adenovirus (AdV-Ag), respiratory syncytial virus (RSV-Ag), and influenza A or B (Flu A-Ag or Flu B-Ag) antigens, respectively. Among them, two were positive for both AdV-Ag and FluA-Ag. Seven patients with KD (1.3%) presented febrile convulsions, and only one was diagnosed with encephalitis/encephalopathy. Between January 2021 and August 2022, 57 patients with KD were newly diagnosed among whom FilmArray® respiratory panel (FARP) was applied on 24 patients, and 14 (58.3%) were positive for at least one virus. During the same period, 32 out of 45 patients (71.1%) with febrile convulsions examined using the FARP were positive for at least one virus. The trend of viruses in patients with KD and febrile convulsion reflected the regional epidemic viral infection. Respiratory virus detected at a much higher rate using the FARP suggests that most convulsions in patients with KD might be related to concomitant viral infection. The possible involvement and association of concomitant respiratory viral infections in patients with KD with prognosis or encephalopathy/encephalitis remain to be investigated.
REVIEW | doi:10.20944/preprints202103.0597.v2
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: viral respiratory infections; severe asthma; immune response; biologicals; omalizumab
Online: 26 March 2021 (10:55:06 CET)
Viral respiratory infections are recognized risk factors for the loss of control of allergic asthma and the induction of exacerbations, both in adults and children. Severe asthma is more susceptible to virus-induced asthma exacerbations, especially in the presence of high IgE levels. In the course of immune responses to viruses, an initial activation of innate immunity typically occurs and the production of type I and III interferons is essential in the control of viral spread. However, the Th2 inflammatory environment still appears to be protective against viral infections in general and in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections as well. As for now, literature data, although very limited and preliminary, show that severe asthma patients treated with biologics don’t have an increased risk of SARS-CoV-2 infection or progression to severe forms compared to the non-asthmatic population. Omalizumab, an anti-IgE monoclonal antibody, exerts a profound cellular effect, which is able to stabilize the effector cells becoming much more efficient from the point of view of innate immunity in contrasting respiratory viral infections. In addition to the antiviral effect, clinical efficacy and safety of this biological allows a great improvement in the management of asthma.
ARTICLE | doi:10.20944/preprints201804.0375.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: pesticides; spirometry; respiratory symptoms; cholinesterase; rural workers; family farmers
Online: 29 April 2018 (10:25:38 CEST)
Pesticide exposure is a growing concern for public health. Although Brazil is the world's largest consumer of pesticides, few studies addressed the health effects among farmers. This study aimed to evaluate whether pesticide exposure is associated with respiratory outcomes among rural workers and relatives in Brazil during the crop and off-seasons. 82 family farmers were interviewed about occupational history and respiratory symptoms, and cholinesterase tests were conducted in the crop-season. Spirometry was performed during the crop and off-season. Respiratory outcomes were compared between seasons and multiple regressions were conducted to search for associations with exposure indicators. Participants were occupationally and environmentally exposed to multiple pesticides from an early age. During the crop and off-season, respectively, they presented a prevalence of 40% and 30.7% for cough, 30.7% and 24% for nasal allergies, and 24% and 17.3% for chest tightness. Significant relations between spirometry impairments and exposure indicators were found both during the crop and off-season. These findings provide complementary evidence about the association of pesticide exposure with adverse respiratory effects among family farmers in Brazil. This situation requires special attention as it may increase the risk of pulmonary dysfunctions, and the morbidity and mortality burden associated with these diseases.
ARTICLE | doi:10.20944/preprints202310.1733.v1
Subject: Biology And Life Sciences, Virology Keywords: Respiratory syncytial virus; Retro-2.2; fusion protein; retrograde transport; antiviral
Online: 26 October 2023 (16:10:47 CEST)
Human respiratory syncytial virus (hRSV) is the most common cause of bronchiolitis and pneumonia in new-borns, with all children being infected before the age of two. Reinfections are very common throughout life, and can cause severe respiratory infections in the elderly and immunocompromised adults. Although vaccines and preventive antibodies have recently been licensed for use in specific subpopulations of patients, there is still no therapeutic treatment commonly available for these infections. Here, we investigated the potential antiviral activity of Retro-2.2, a derivative of the cellular retrograde transport inhibitor Retro-2, against hRSV. We show that Retro-2.2 inhibits hRSV replication in cell culture, and impairs the ability of hRSV to form syncytia. Our results suggest that Retro-2.2 treatment affects virus spread by disrupting the trafficking of the viral de novo synthetized F and G glycoproteins to the plasma membrane, leading to a defect in virion morphogenesis. Taken together, our data show that targeting intracellular transport may be an effective strategy against hRSV infection.
REVIEW | doi:10.20944/preprints202310.1097.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Nanobodies; respiratory viral infections; spray and aerosol particles; targeted delivery.
Online: 18 October 2023 (03:04:54 CEST)
Respiratory viral infections, including influenza, respiratory syncytial virus (RSV), and, more recently, the coronavirus disease 2019 (COVID-19) pandemic, continue to pose significant global health threats. Conventional treatments for these infections often face challenges such as limited efficacy, the emergence of drug-resistant strains, and the requirement for frequent administration. In recent years, nanobodies have emerged as a promising class of therapeutic agents due to their unique properties, including small size, high stability, and specific binding capabilities. This mini-review article focuses on the application of nanobodies as spray and aerosol particles for the treatment of respiratory viral infections. Furthermore, we highlight the remarkable efficacy of nanobodies in preclinical and clinical studies against respiratory viruses, including their ability to neutralize viral particles, inhibit viral replication, and modulate the host immune response. We discuss the potential advantages of using nanobodies as inhalable formulations, including their improved delivery to the respiratory tract, enhanced stability in aerosol form, and reduced systemic side effects. Additionally, we explore the various strategies employed to engineer nanobodies for optimal aerosol delivery, such as conjugation to carrier particles or formulation as dry powders. We also examine the potential challenges and limitations associated with the development of nanobody-based aerosol therapies, including production scalability, cost-effectiveness, and regulatory considerations.
REVIEW | doi:10.20944/preprints202305.0906.v2
Subject: Biology And Life Sciences, Virology Keywords: Respiratory viruses; Anosmia; Olfaction Disorders; loss of smell; Covid-19
Online: 16 October 2023 (08:54:50 CEST)
Acute respiratory viruses (ARVs) are leading cause of diseases in human worldwide. High risk individuals including children and elderly could potentially develop severe illness that could result in hospitalization or death in the worst case. Most common ARVs are Human respiratory syncytial virus, Human Metapneumovirus, Human Parainfluenza Virus, rhinovirus, coronaviruses (including SARS and MERS CoV), adenoviruses, Human Bocavirus, enterovirus (-D68 and 71), and influenza viruses. The olfactory deficits due to ARVs infection is a common symptom among patients. This mini review provides an overview of the role of SARS-CoV-2 and other common ARVs in the development of human olfactory pathophysiology. We highlight the critical need for understanding the signaling underlying the olfactory dysfunction and the development of therapeutics for this wide-ranging category of AVRs to restore the altered or loss of smell in affected patients.
COMMUNICATION | doi:10.20944/preprints202308.1124.v1
Subject: Physical Sciences, Optics And Photonics Keywords: respiratory carbon dioxide; absorption theory; micro-nano fiber; optical sensor
Online: 16 August 2023 (08:54:07 CEST)
In the field of clinical medicine, the real-time monitoring of carbon dioxide gas exhaled by the human body is of great significance. At present, the detection devices in the market are mainly detected by sucking a small amount of gas in the nasal cavity to the detection device, and there are some problems such as too long sampling tubes, easy blockage or distortion, and abnormal gas dispersion. In this paper, a micro-nano optical fiber sensor that can directly detect the concentration of end-tidal carbon dioxide is proposed. The measurement is achieved by using the principle of high evanescent field absorption, and the operating band is 2.004 μm. The sensor uses micro-nano optical fiber as the sensing area, and then detects the presence of carbon dioxide gas exhaled by human body through optical power attenuation. The function of micro-nano fiber is to realize the transmission of signal light and also serve as the absorption medium of the gas to be measured. In addition, the variation of light power also reflects the respiratory cycle of the human body. The sensor can realize rapid real-time response to carbon dioxide gas detection, with small size, low cost, and easy to replace. It has great application potential in clinical scenarios such as Gastrointestinal Endoscopes that require real-time monitoring of human respiration.
ARTICLE | doi:10.20944/preprints202304.0996.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Convolutional Neural Network; Deep Learning; Photoplethysmography; Respiratory Rate; Time Series
Online: 26 April 2023 (13:17:24 CEST)
Respiratory rate is an important biomarker that indicates changes in the clinical condition of critically ill patients, so a surveillance tool that can accurately monitor the changing respiratory rate in real time is needed. Through investigating various pairs of machine learning models, we proposed new machine learning model for real-time respiratory rate estimation using photoplethysmogram. New photoplethysmogram-driven respiratory rate dataset(StMary) was collected from surgical intensive care unit of a tertiary referral hospital, using photoplethysmogram signal collector. For 50patients and 50healthy volunteers, 2-minute photoplethysmogram was collected for each subject twice. To evaluate the respiratory rate of subject, it was inputted into the deep neural network model we built, and dataset was splitted into training, validation, testing dataset, then 4-fold cross validation was exploited. Our deep neural network model trained with StMary and two public datasets(BIDMC and CapnoBase) individually, or selectively merged dataset had shown a low error rate in respiration rate measurements. Our model trained with StMary showed low mean absolute error score(1.0273±0.8965), and trained with 3 datasets(CapnoBase, BIDMC and StMary) showed a lower error rate(1.7359±1.6724) than the model trained with CapnoBase and BIDMC(1.9480±1.6751). We could verify the performance of model evaluating respiratory rate from photoplethysmogram, and our dataset could contribute as the clinical research data that supports artificial intelligence models evaluating respiratory rate and surveillance tools to test whether their monitoring function works properly.
ARTICLE | doi:10.20944/preprints202212.0196.v1
Subject: Biology And Life Sciences, Anatomy And Physiology Keywords: SARS-CoV-2; PCR persistent positive; respiratory infection; COVID-19
Online: 12 December 2022 (09:04:59 CET)
Background and Objectives: Most individuals infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are asymptomatic or have mild symptoms of COVID-19, which usually resolve after few days. Regardless of symptoms, infected people can transmit the virus to others especially on the first days of infection. Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) is used to confirm SARS-CoV-2 infection; some individuals show persistent PCR-positivity after recovering from COVID-19. In this study, 12 individuals who showed persistence of COVID-19 symptoms and of SARS-CoV-2 PCR-positivity were followed-up. Methods: nasopharyngeal samples were collected for SARS-CoV-2 detection by RT-qPCR; clinical and epidemiological data were analyzed. Results: that persistence of SARS-CoV-2 PCR positivity was associated with duration of symptoms (rs 0.81338), which varied between one and 49 days, with 75% of the individuals reporting symptoms for more than two weeks; 83.33% of cases remained positive after two weeks of onset of symptoms, despite decreases in viral load. Conclusion: neither RT-qPCR test nor a symptom-based approach alone are sufficient to evaluate discontinuation of patient isolation; other factors such as viral loads and symptom severity should also be considered. Additional studies are needed to understand how RT-PCR-positivity is related to symptoms and the risk of viral transmission, and to better support isolation guidelines.
REVIEW | doi:10.20944/preprints202104.0633.v2
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: viral transmission; causation; evidence hierarchy; SARS-CoV-2; respiratory pathogens
Online: 30 June 2022 (03:33:13 CEST)
Systematic reviews of 591 primary studies of the modes of transmission for SARS-CoV-2 show significant methodological shortcomings and heterogeneity in the design, conduct, testing and reporting of SARS-CoV-2 transmission. While this is partly understandable at the outset of a pandemic, evidence rules of proof for assessing the transmission of this virus are needed for pre-sent and future pandemics of viral respiratory pathogens. We review the history of causality as-sessment related to microbial etiologies with a focus on respiratory viruses and suggest a hierar-chy of evidence to integrate clinical, epidemiologic, molecular and laboratory perspectives on transmission. The hierarchy, if applied to future studies, should narrow the uncertainty over the twin concepts of causality and transmission of human respiratory viruses. We attempt to address the translational gap between the current research evidence and the assessment of causality in the transmission of respiratory viruses with a focus on SARS-CoV-2. Experimentation, consistency and independent replication of research alongside our proposed framework provide a chain of evidence that can reduce the uncertainty over the transmission of respiratory viruses and increase the level of confidence in specific modes of transmission, informing the measures that should be undertaken to prevent transmission.
ARTICLE | doi:10.20944/preprints202203.0187.v2
Subject: Biology And Life Sciences, Virology Keywords: human parechovirus; HPeV; PeV-A; Panama; gastrointestinal infection; respiratory infection
Online: 27 April 2022 (08:07:52 CEST)
Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.
ARTICLE | doi:10.20944/preprints202110.0094.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: nutrition; pediatrics; geographic information systems; acute respiratory infections; diarrhea; growth
Online: 6 October 2021 (09:00:12 CEST)
Infectious disease is the leading cause of mortality in children under five. This study has investigated environmental factors related to the morbidity of acute respiratory infections (ARIs), diarrhea, and growth using geographical information systems (GIS) technology. Anthropometric, address and disease prevalence data were collected through the SEEM study in Matiari, Pakistan. Publicly available map data was used to compile coordinates of healthcare facilities. A Pearson correlation coefficient (r) was used to calculate the correlation between distance from healthcare facilities and participant growth and morbidity. Other continuous variables influencing these outcomes were analyzed using a random forest regression model. In this study of 416 children, we found participants living closer to secondary hospitals had lower prevalence of ARI (r=0.154, p<0.010) and diarrhea (r=0.228, p<0.001) as well as participants living closer to Maternal Health Centers (MHCs): ARI (r=0.185, p<0.002) and diarrhea (r=0.223, p<0.001) compared to those living near primary facilities. Our random forest model showed distance to have high variable importance in the context of disease prevalence. Our results indicated that participants closer to more basic healthcare facilities reported a higher prevalence of both diarrhea and ARI than those near more urban facilities, highlighting potential public policy gaps in ameliorating rural health.
ARTICLE | doi:10.20944/preprints202105.0706.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: alcohol; brain networks; heart rate variability; abstinence; respiratory sinus arrhythmia
Online: 28 May 2021 (13:45:25 CEST)
Alcohol consumption is now common practice worldwide, and functional brain networks are beginning to reveal the complex interactions observed with alcohol consumption and abstinence. The autonomic nervous system (ANS) has a well-documented relationship with alcohol use, and a growing body of research is finding links between the ANS and functional brain networks. This study recruited everyday drinkers in an effort to uncover the relationship between alcohol abstinence, ANS function, and whole brain functional brain networks. Participants (n=29), 24-60 years-of-age, consumed moderate levels of alcohol regularly (males 2.4 (±0.26) drinks/day, females 2.3 (±0.96) drinks/day). ANS function, specifically cardiac vagal tone, was assessed using the Porges-Bohrer method for calculating respiratory sinus arrhythmia (PBRSA). Functional brain networks were generated from resting-state MRI scans obtained following 3-day periods of typical consumption and abstinence. A multi-task mixed-effects regression model determined the influences of HRV and drinking state on functional network connectivity. Results showed differences in the relationship between the strength of network connections and clustering coefficients across drinking states, moderated by PBRSA. Increases in connection strength between highly clustered nodes during abstinence as PBRSA increases demonstrates a greater possible range of topological configurations at high PBRSA values. This novel finding begins to shed light on the complex interactions between typical alcohol abstinence and physiological responses of the central and autonomic nervous system.
ARTICLE | doi:10.20944/preprints202105.0004.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Appeasing Pheromone; Bovine; Respiratory Infections; Immune Response; Average Daily Gain
Online: 3 May 2021 (09:15:45 CEST)
Bovine respiratory disease is still a major concern in feedlots and has major economic impact. Another consequence of respiratory infections is the use of antimicrobial molecules to control bacterial pathogens. This can participate to the emergence and shedding of antimicrobial re-sistance that can threaten animal as well as human health. Appeasing pheromones with their capacity to reduce stress and thus their ability to preserve the functions of the immune system have been proposed to reduce the use of antimicrobial substances. In the current report we as-sessed the effect of appeasing pheromone administration on bovine health and performance during the fattening period. Zootechnical and health parameters as well as whole blood immune transcript expressions were measured over weeks in young bulls to determine the effect of the pheromone. We observed a reduction of clinical signs at day 30 in young bulls who received the pheromone and a higher expression of interleukin 8 transcripts in this group than in the control group. Our results are in line with previous reports in bovine and other mammals and ask for further studies to shed more light on the beneficial impact of appeasing pheromones and to de-cipher their exact mechanisms of action.
ARTICLE | doi:10.20944/preprints202104.0409.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: Reflux; Laryngopharyngeal; Clinical; Atypical; Nasal; Otological; Respiratory; Management; Treatment; Diagnosis
Online: 15 April 2021 (12:08:19 CEST)
Background: Laryngopharyngeal reflux (LPR) is a common disease in otolaryngology characterized by an inflammatory reaction of the mucosa of the upper aerodigestive tract caused by digestive refluxate enzymes. LPR has been identified as etiological or favoring factor of laryngeal, oral, sinonasal or otological diseases. In this case-series, we reported atypical clinical presentation of LPR in patients presenting in our clinic with reflux. Methods: A retrospective medical chart review of 351 patients with LPR treated in the European Reflux Clinic in Brussels, Poitiers and Paris was performed. In order to be included, patients had to report atypical clinical presentation of LPR, consisting of symptoms or findings that are not described in reflux symptom score and reflux sign assessment. The LPR diagnosis was confirmed with 24-hour hypopharyngeal-esophageal impedance pH-study and patients were treated with a combination of diet, proton pump inhibitors and alginates. The atypical symptoms or findings had to be resolved from pre- to posttreatment Results: From 2017 to 2021, 21 patients with atypical LPR were treated in our center. The clinical presentation consisted of recurrent aphthosis or burning mouth (N=9), recurrent burps and abdominal disorders (N=2), posterior nasal obstruction (N=2), recurrent acute suppurative otitis media (N=2), severe vocal fold dysplasia (N=2), and recurrent acute rhinopharyngitis (N=1), tearing (N=1), aspirations (N=1) or tracheobronchitis (N=1). Abnormal upper aerodigestive tract reflux events were identified in all of these patients. Atypical clinical findings resolved and did not recur after an adequate anti-reflux treatment. Conclusion: LPR may present with various clinical presentations including mouth, eye, tracheobronchial, nasal or laryngeal findings, which may all regress with an adequate treatment. Future studies are needed to better specify the relationship between LPR and these atypical findings through analyses identifying gastroduodenal enzyme in the enflamed tissue.
ARTICLE | doi:10.20944/preprints202012.0258.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: co-infection; SARS-CoV-2; Covid-19; seasonal respiratory viruses
Online: 10 December 2020 (12:53:28 CET)
Background: Co-infections of SARS-CoV-2 with respiratory viruses, bacteria and fungi have been reported to cause a wide range of illness. Objectives: We asses s the prevalence of co-infection of SARS-CoV-2 with seasonal respiratory viruses, document the respiratory viruses detected among individuals tested for SARS-CoV-2, and describe characteristics of individuals with respiratory virus co-infection detected. Methods: Specimens included in this study were submitted as part of routine clinical testing to Public Health Ontario Laboratory from individuals requiring testing for SARS-CoV-2 and/or seasonal respiratory viruses. Results: Co-infection was detected in a smaller proportion (2.5%) of individuals with laboratory confirmed SARS-CoV-2 than those with seasonal respiratory viruses (4.3%); this difference was not significant. Individuals with any respiratory virus co-infection were more likely to be younger than 65 years of age and male than those with single infection. Those with SARS-CoV-2 co-infection manifested mostly mild respiratory symptoms. Conclusions: Findings of this study may not support routine testing for seasonal respiratory viruses among all individuals tested for SARS-CoV-2, as they were rare during the study period nor associated with severe disease. However, testing for seasonal respiratory viruses should be performed in severely ill individuals, in which detection of other viruses may assist with patient management.
BRIEF REPORT | doi:10.20944/preprints202007.0569.v1
Subject: Medicine And Pharmacology, Immunology And Allergy Keywords: SARS-CoV-2; COVID-19; respiratory failure; ARDS; ventilation; ECMO
Online: 24 July 2020 (04:44:14 CEST)
The rapidly evolving understanding of Coronavirus Disease 2019 (COVID-19) respiratory failure pathogenesis, limited disease-specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. In this single-centre retrospective cohort study we describe the outcomes of COVID-19 patients admitted to Guy’s and St. Thomas’ NHS Foundation Trust (GSTT) critical care service. Patients were managed according to a local respiratory failure management pathway that was predicated on timely invasive ventilation when indicated and tailored ventilatory strategies according to pulmonary mechanics. Between 2nd March and 25th May 2020 GSTT critical care service admitted 316 patients with confirmed COVID-19. Of the 201 patients admitted directly through the Emergency Department with a completed critical care outcome, 71.1% survived to critical care discharge. These favourable outcomes may serve to inform the wider debate on the optimal ventilatory management in COVID-19.
ARTICLE | doi:10.20944/preprints202007.0453.v1
Subject: Medicine And Pharmacology, Pulmonary And Respiratory Medicine Keywords: ARDS; VIP; Aviptadil; RLF-100; Acute Respiratory Distress Syndrome; Sepsis
Online: 20 July 2020 (03:46:11 CEST)
Purpose: To assess the clinical safety and possible effectiveness of Vasoactive Intestinal Peptide in the treatment of Acute Respiratory Distress Syndrome (ARDS) related to sepsis. Methods: Under FDA Investigational New Drug clearance, 8 patients with ARDS related to sepsis were treated with 50 pmole/kg/hr – 100 pmole/kg/hr of Vasoactive Intestinal Peptide by intravenous infusion for 12 hours. All patients were on mechanical ventilation and full telemetery. Results: No drug-related serious adverse events were seen. Hypotension was seen in association with two infusions and diarrhea in association with one, but did not necessitate cessation of therapy. Bigeminy was seen in association with one infusion without sequelae. Seven of eight patients demonstrated a successful course during intensive care and were successfully removed from mechanical ventilation and discharged from intensive care. The eighth patient succumbed to purulent secretions in the lungs. Of those who were discharged from the ICU, six demonstrated successful 30 day survival. The seventh died from a cerebral infract at day 30, deemed unrelated to treatment with VIP. Serum levels of Tumor Necrosis Factor α were obtained in 6 patients at baseline and 24 hours and were seen to decrease with treatment in five patients. Conclusions: Initial clinical results of treatment with VIP in patients with ARDS demonstrated a safety profile consistent with previous studies in normal volunteers. The successful clinical course seen in 7 of 8 patients in the setting of an expected 50% survival may suggest that VIP shows promise in the treatment of other infectious conditions that damage the pulmonary epithelium, particularly COVID-19.
REVIEW | doi:10.20944/preprints202006.0248.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: probiotic; upper respiratory tract infection (URTI); infection; prevention; common cold
Online: 21 June 2020 (10:07:31 CEST)
Background: Probiotics can provide health benefits to an individual by regulation of the immune system. Many clinical trials have found that probiotics can prevent upper respiratory tracts infections. Aim: To perform a systematic review and meta-analysis of available trials to investigate the effectiveness of probiotics in the prevention of upper respiratory tract infections in individuals of all ages. Conclusion: Probiotics were found to be better in reducing the number of participants who experienced acute URTI, the average duration per episode of acute URTI, use of antibiotics in URTI related cases and absence due to URTI. Side effects were found to be minor, making probiotics a good candidate for clinical use. This shows that probiotics are effective in preventing acute URTIs. However, due to limited studies and small sample size, the results are subjected to bias and should be interpreted with care.
REVIEW | doi:10.20944/preprints202004.0069.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: coronavirus; SARS-CoV-2; COVID-19; respiratory diseases; air pollution
Online: 6 April 2020 (15:48:46 CEST)
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), known to cause 2019-coronavirus disease (COVID-19) pandemic is a zoonotic coronavirus and crosses species to infect human populations, where an efficient transmission of virus occurs human-to-human. Nationwide lockdown is being adopted to stop public transport, keep people at their homes and out of their work, and maintain social distancing. In turn, large geographic areas in the world (including China, Italy, Spain, and USA) has been almost halted. This temporary halt is significantly slashing down the air pollution (air pollutants and warming gases) in most cities across the world. This paper: (i) introduces both COVID-19 and air pollution; (ii) overviews the relation of air pollution with respiratory/lung diseases; (iii) compiles and highlights major data appeared in media and journals reporting lowering of air pollution in major cities those have been highly impacted by the COVID-19; and also (iv) lists the way forward in the present context. Because COVID-19 is an ongoing pandemic and currently far from over, strong conclusions could not be drawn with very limited data at present. The temporary slashed down global air pollution as a result of COVID-19 restrictions are expected to stimulate the researchers, policy makers and governments for the judicious use of resources; thereby minimise the global emissions, and maintain their economies once the pandemic eases. On the other, lifting of the nationwide lockdown and eventual normalisation of the temporarily halted sectors may also reverse the currently COVID-19 pandemic-led significantly slashed down global air pollution that could make the future respiratory health crisis grimmer.
ARTICLE | doi:10.20944/preprints201807.0026.v1
Subject: Engineering, Electrical And Electronic Engineering Keywords: non-invasive respiratory monitoring; diaphragm motion monitoring; breathing disorder; ultrasound
Online: 3 July 2018 (06:16:35 CEST)
This paper introduces a novel respiratory detection system based on diaphragm wall motion tracking using an embedded ultrasound sensory system. We assess the utility and accuracy of this method in evaluating diaphragmatic function and its contribution to respiratory workload. The developed system is able to monitor the diaphragm wall activities when the sensor is placed in the zone of apposition (ZOA). This system allows the direct measurements with only one ultrasound PZT5 piezo transducer. The system both generates pulsed ultrasound waves at 2.2 MHz and amplifies reflected echoes. According to the diaphragmatic motions, the respiratory signals of the proposed system is insensitive to human motion artifacts. Promising results were obtained from six subjects on six different tests with an average sensitivity and specificity of 84% and 93% of respiration detection, respectively. Measurements are referenced to a SPR-BTA commercial spirometer. In this study, we also evaluated inertial and photoplethysmography (PPG) sensors as other conventional methods in this area.
TECHNICAL NOTE | doi:10.20944/preprints201803.0243.v1
Subject: Computer Science And Mathematics, Other Keywords: respiratory sinus arrhythmia (RSA); R-peak amplitude (RPA); QRS amplitude
Online: 29 March 2018 (05:17:58 CEST)
We propose an electrocardiogram (ECG) signal-based algorithm to estimate the respiratory rate is a significant informative indicator of physiological state of a patient. The consecutive ECG signals reflect the information about the respiration because inhalation and exhalation make transthoracic impedance vary. The proposed algorithm extracts the respiration-related signal by finding out the commonality between the frequency and amplitude features in the ECG pulse train. The respiration rate can be calculated from the principle components after the procedure of the singular spectrum analysis. We achieved 1.7569 breaths per min of root-mean-squared error and 1.7517 of standard deviation with a 32-seconds signal window of the Capnobase dataset, which gives notable improvement compared with the conventional Autoregressive model based estimation methods.
ARTICLE | doi:10.20944/preprints201611.0068.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: particulate matter; AirQ model; hospital admission respiratory disease; Athens; Greece
Online: 14 November 2016 (04:13:34 CET)
The main objective of this work is the assessment of the annual number of hospital admissions for respiratory disease (HARD) due to the exposure to in-healable particulate matter (PM10), within the greater Athens area (GAA), Greece. Towards this aim, the time series of the particulate matter with aerodynamic diameter less than 10μm (PM10) recorded in six monitoring stations located in the GAA, for a 13-year period 2001-2013, is used. Initially, a descriptive statistical treatment of PM10 concentrations took place. Furthermore, the AirQ2.2.3 software developed by the WHO was used to evaluate adverse health effects by PM10 in the GAA during the examined period. The results show that, during the examined period PM10 concentrations present a significant decreasing trend. Also, the mean annual HARD cases per 100,000 inhabitants ranged between 20 (suburban location) and 40 (city centre location). Approximately 70% of the annual HARD cases are due to city centre residents. In all examined locations, a declining trend in the annual number of HARD cases is appeared. Moreover, a strong relation between the annual number of HARD cases and the annual number of days exceeding the European Union daily PM10 threshold value was found.
ARTICLE | doi:10.20944/preprints202212.0438.v1
Subject: Biology And Life Sciences, Animal Science, Veterinary Science And Zoology Keywords: bovine respiratory disease; virome; bovine nidovirus; bovine coronavirus; bovine herpesvirus 1; bovine viral diarrhea virus 1; bovine respiratory syncytial virus; case control; odds ratio
Online: 23 December 2022 (03:30:02 CET)
Bovine respiratory disease (BRD) is a major health problem within the global cattle industry. This disease has a complex aetiology, with viruses playing an integral role. In this study, metagenomics was used to sequence viral nucleic acids in the nasal swabs of BRD affected cattle. Viruses detected included those well known for their association with BRD in Australia (bovine viral diarrhea virus 1), as well as viruses known to be present but not fully characterised (bovine coronavirus) and viruses that have not been reported in BRD affect cattle in Australia (bovine rhinitis, bovine influenza D, and bovine nidovirus). Nasal swabs from a case control study were subsequently tested for 10 viruses and the presence of at least one virus was found to be significantly associated with BRD. Some of the more recently detected viruses had inconsistent association with BRD. Full genome sequences for bovine coronavirus, a virus increasingly associated with BRD, and bovine nidovirus were complete. Both viruses belong to the Coronaviridae family, which are frequently associated with disease in mammals. This study has provided greater insights into the viral pathogens associated with BRD and highlighted the need for further studies to elucidate more precisely the roles viruses play in BRD.
ARTICLE | doi:10.20944/preprints202312.0003.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: Respiratory Distress Syndrome; Chest X-ray; Diagnostics; Image Segmentation; Performance Evaluation
Online: 1 December 2023 (04:59:28 CET)
This research addresses the respiratory distress syndrome (RDS) in preterm newborns, caused by insufficient surfactant synthesis, which can lead to serious complications, including pneumothorax, pulmonary hypertension, and pulmonary hemorrhage, increasing the risk of a fatal outcome. By analyzing chest radiographs and blood gases, we specifically focus on the significant contributions of these parameters to the diagnosis and analysis of the recovery of patients with RDS. The study involved 32 preterm newborns, and the analysis of gas parameters before and after the administration of surfactants and inhalation corticosteroid therapy revealed statistically significant changes in values of parameters such as FiO2, pH, pCO2, HCO3 and BE (Sig.<0.05), ehile the pO2 parameter showed a potential change (Sig.=0.061). Parallel to this, the research emphasizes the development of a lung segmentation algorithm implemented in the MATLAB programming environment. The key steps of the algorithm include preprocessing, segmentation, and visualization for a more detailed understanding of the recovery dynamics after RDS. These algorithms have achieved promising results, with a global accuracy of 0.93±0.06, precision 0.81±0.16 and an F-score of 0.82±0.14. These results highlight the potential application of algorithms in the analysis and monitoring of recovery in newborns with RDS, also underscoring the need for further development of software solutions in medicine, particularly in neonatology, to enhance the diagnosis and treatment of preterm newborns with respiratory distress syndrome.
ARTICLE | doi:10.20944/preprints202311.1356.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: bronchiolitis; children; respiratory syncytial virus; high flow nasal cannula; acute bronchiolitis
Online: 21 November 2023 (17:18:53 CET)
Bronchiolitis is an acute viral infection of the lower respiratory tract that affects infants and young children. Respiratory syncytial virus (RSV) is the most common causative agent, however other viruses can be the reason of the disease. We retrospectively reviewed the clinical features of infants aged less than 12 months referred to our Pediatric Units of Chivasso, Cirié and Ivrea for acute bronchiolitis requiring hospitalization over two consecutive bronchiolitis seasons. Patient-, disease- and treatment related variables were analyzed in this retrospective study. We were able to show how with the high flow oxygen support (HFNC) only a very low number of children (8 out of 192) need to be trasferred to our HUB referral centers. The probability of success were 96% for all patients and 93% for RSV vs. 98% for non-RSV patients (P=NS). Factor associated to failure of treatment were age below 1 months and the failure of HFNC. The wide and increasing use of HFNC in pediatric inpatients improved management of bronchiolitis in Spoke hospitals, reducing transfer to a Hub hospital provided with Intensive Care Units.
ARTICLE | doi:10.20944/preprints202311.0888.v1
Subject: Biology And Life Sciences, Virology Keywords: Respiratory syncytial virus; RSV; COVID-19 pandemic; Children; SARI death; Bangladesh
Online: 14 November 2023 (10:10:30 CET)
Respiratory syncytial virus (RSV) is a leading cause of acute lower respiratory infections in young children worldwide. RSV-associated deaths in children are underreported in Bangladesh. We analyzed hospital-based surveillance data on severe acute respiratory infections (SARI) in under-five children before (August 2009–February 2020) and during the COVID-19 pandemic (March 2020–March 2022). Using the World Health Organization definition, we identified SARI cases in 14 tertiary-level hospitals. Nasopharyngeal and oropharyngeal swabs were collected for real-time reverse transcriptase-polymerase chain reaction (rRT-PCR) testing of six respiratory viruses, including RSV. SARI deaths during the pandemic (2.6%, 66) were higher than pre-pandemic (1.8%, 159; p<0.001). Nearly half of pandemic deaths (47%) had underlying respiratory viruses, similar to the pre-pandemic rate (45%). RSV detection in deaths was consistent pre-pandemic (13%, 20/159) and during the pandemic (12%, 8/66). Children aged <6 months constituted 57% (16) of RSV-related deaths. Evaluating interventions like maternal vaccination and infant monoclonal antibody prophylaxis is crucial to address RSV, a major contributor to under-five SARI deaths.
DATA DESCRIPTOR | doi:10.20944/preprints202310.0082.v1
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: Precision Metagenomics; Next Generation Sequencing (NGS), Respiratory infections, Microbiome, Targeted Sequencing
Online: 3 October 2023 (03:06:42 CEST)
Understanding microbial composition in upper respiratory infections (URIs) is critical for effective diagnosis and treatment. Precision Metagenomic next-generation sequencing p(mNGS) can provide a comprehensive yet clinically relevant profile of respiratory infection. The hybridization capture-based targeted sequencing generated a precision metagenomics profile of 29 patients with acute URIs. Nasopharyngeal samples were collected from the subjects suspected of respiratory infection, and p(mNGS) was performed using the Illumina®/IDbyDNA Respiratory Pathogen ID/AMR Panel (RPIP). The dataset obtained from the mNGS analysis contains a wealth of information on the composition of acute URI microbiota, including the relative abundance of known pathogens and potential clinical implications. The dataset represents a valuable resource for future research endeavors in respiratory medicine, infectious disease epidemiology, and therapeutic interventions. In addition, the dataset offers significant potential for reuse and integration with other omics datasets. The comprehensive nature of the mNGS data allows the exploration of associations between the respiratory microbiota and host factors such as clinical outcomes, immune responses, or genetic predisposition. Combining this dataset with other relevant datasets, such as transcriptomics or metabolomics, could provide a deeper understanding of the complex interactions between the microbiota and the host in acute URIs.
ARTICLE | doi:10.20944/preprints202308.0024.v2
Subject: Public Health And Healthcare, Public Health And Health Services Keywords: respiratory health; real-time air-quality monitoring; lung functionality; alert system
Online: 8 August 2023 (07:12:49 CEST)
Asthma is a chronic respiratory disease that impairs breathing. Management of asthma presents a significant challenge due to its inherent variability; that is, its symptoms can substantially differ among individuals, thereby complicating the prediction and management of exacerbations. Furthermore, individuals with asthma often have unique triggers that precipitate symptoms or attacks. The identification of these triggers can often prove to be a challenging, and at times, an impractical attempt. To address this, our research proposes a practical, personalized alert system, predicated on individual lung function tests conducted under varying environmental conditions classified by air-quality sensors. To validate this concept, we conducted an observational pilot study involving healthy individuals. We recruited twelve healthy participants and monitored their responses across a broad spectrum of environments, characterized by varying air quality, temperature, and humidity conditions. The lung function for each participant, assessed using peak expiratory flow (PEF) values, was recorded in each of these environments. Our results highlighted substantial variability in pulmonary responses to different environments. Utilizing these insights, we proposed a personalized alarm system that provides real-time air-quality monitoring and issues alerts when environmental conditions may potentially become unfavorable. We also explored the feasibility of employing basic machine learning techniques to predict PEF values in the aforementioned environmental conditions. This proposed system has the potential to empower individuals in actively safeguarding their respiratory health and mitigating discomfort caused by environmental conditions, especially in cases of asthma patients. By enabling timely and personalized interventions, the system aims to provide individuals with the necessary tools to minimize exposure to asthma’s possible triggers.
ARTICLE | doi:10.20944/preprints202306.0293.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: Pseudomonas aeruginosa; chronic infection; respiratory; murine model; in vivo; S. aureus
Online: 5 June 2023 (09:50:00 CEST)
Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen and is the leading cause of infection in patients with cystic fibrosis (CF). The ability of P. aeruginosa to evade host responses and develop into chronic infection causes significant morbidity and mortality. Several mouse models have been developed to study chronic respiratory infections induced by P. aeruginosa, with the bead agar model being the most widely used. However, this model has several limitations, including the requirement for surgical procedures and high mortality rates. Herein, we describe novel and adapted biologically relevant models of chronic lung infection caused by P. aeruginosa. Three methods are described, a clinical isolate infection model, utilizing isolates obtained from patients with CF, an incomplete antibiotic clearance model, leading to bacterial bounce-back and the establishment of chronic infection, and an adapted water bottle chronic infection model. These models circumvent the requirement for surgical procedure and importantly, can be induced with clinical isolates of P. aeruginosa and in wild-type mice. We also demonstrate successful induction of chronic infection in the transgenic βENaC murine model of CF. We envisage that the models described will facilitate the investigations of host and microbial factors, and the efficacy of novel antimicrobials, during chronic P. aeruginosa respiratory infections.
ARTICLE | doi:10.20944/preprints202211.0116.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: 2-year-old children; respiratory diseases; influenza; OH-PAHs; metabolites; urine
Online: 7 November 2022 (10:12:30 CET)
Aim: Exposure to polycyclic aromatic hydrocarbons (PAHs) has been in the past associated with adverse effects on human health among which belong also respiratory diseases. Our study is focused on the evaluation of PAH exposure by measuring the concentrations of their monohydroxylated metabolites (OH-PAHs) in urine and comparing their concentrations with the incidence of respiratory diseases in 2-year-old children from two locations of the Czech Republic – a control locality Ceske Budejovice and a previously highly contaminated mining district Most. Methods: The total number of 248 participants were sampled for urine samples that were analysed for the presence of 11 OH-PAHs using liquid-liquid extraction with ethyl acetate and clean-up employing dispersive solid phase extraction with a sorbent Z-Sep. Separation, identification and quantification of the target compounds was achieved by ultra-high performance liquid chromatography coupled to tandem mass spectrometry. The incidence of respiratory diseases was evaluated according to the questionnaires provided by the paediatricians. Results and discussion: The concentrations of measured OH-PAHs were higher in the urine samples collected from 2-year-old children living in Most compared to 2-year-old children from Ceske Budejovice. The same trend was observed also when the urine samples were analysed when these children were studied as newborns in our previous study. From all of the monitored respiratory diseases, only influenza due to unidentified influenza virus showed a difference between tested locations where the 2-year-old children living in Most were more frequently diagnosed with this disease. Conclusion: Even though the air pollution and lifestyle in both cities is very similar, we have observed higher incidence of respiratory diseases as well as higher concentration of OH-PAHs in urine of the 2-year-old children from Most. Therefore, we hypothesize that the population living in this previously highly contaminated location (in 1970s and 1980s) can carry some long-term health burden.
REVIEW | doi:10.20944/preprints202206.0421.v1
Subject: Biology And Life Sciences, Biology And Biotechnology Keywords: Mitochondria; Respiratory chain; Krebs cycle; Succinate; Cancer; Encephalopathy; SDH, SDHI; pesticides
Online: 30 June 2022 (08:31:22 CEST)
Research focused on succinate dehydrogenase (SDH) and its substrate, succinate, culminated in the 50’s accompanying the rapid development of research dedicated to bioenergetics and intermediary metabolism. This allowed to uncover the implication of the SDH in both the mitochondrial respiratory chain and the Krebs cycle. Nowadays this theme is experiencing a real revival following the discovery of the role of SDH and succinate in a subset of tumors and cancers in human. The aim of this review is to enlighten the many questions yet unanswered, ranging from fundamental to clinically oriented aspects, up to the danger of the current use of SDH as a target for a sub class of pesticides.
ARTICLE | doi:10.20944/preprints202201.0118.v2
Subject: Environmental And Earth Sciences, Environmental Science Keywords: spatial heterogeneity; AOD-PM2.5; respiratory-cardiovascular; lag grids; urban-rural; season
Online: 28 March 2022 (13:52:49 CEST)
Optimal use of Hierarchical Bayesian Model (HBM) assembled aerosol optical depth (AOD)-PM2.5 fused surfaces in epidemiologic studies requires homogeneous temporal and spatial fused surfaces. No analytical method is available to evaluate spatial heterogeneity. The temporal case-crossover design was modified to assess the spatial association between four experimental AOD-PM2.5 fused surfaces and four respiratory-cardiovascular hospital events in 12 km2 grids. The maximum number of adjacent lag grids with significant odds ratios (ORs) identified homogeneous spatial areas (HOSAs). The largest HOSA included 5 grids (lag grids 04; 720 km2) and the smallest HOSA contained 2 grids (lag grids 01; 288 km2). Emergency department asthma and inpatient asthma, myocardial infarction, and heart failure ORs were significantly higher in rural grids without air monitors than in urban grids with air monitors at lag grids 0, 1, and 01. Rural grids had higher AOD-PM2.5 concentration levels, population density, and poverty percent than urban grids. Warm season ORs were significantly higher than cold season ORs for all health outcomes at lag grids 0, 1, 01, and 04. The possibility of elevated fine and ultrafine PM and other demographic and environmental risk factors synergistically contributing to elevated respiratory-cardiovascular chronic diseases in persons residing in rural areas was discussed
REVIEW | doi:10.20944/preprints202202.0313.v3
Subject: Medicine And Pharmacology, Pharmacology And Toxicology Keywords: seawater; seawater preparation; Aqua Maris; nasal irrigation; upper respiratory track; otorhinolaryngology
Online: 21 March 2022 (09:16:41 CET)
The history of saline nasal irrigation (SNI) is indeed a long one, beginning from the ancient Ayurvedic practices and starting to gain a foothold in the west at the beginning of 20th century. Today, there is a growing number of papers covering effects of SNI from in vitro studies to randomized clinical trials and literature overviews. Based on the recommendations of most of the European and American professional associations, seawater, alone or in combination with other preparations, has its place in treatment of numerous conditions of the upper respiratory tract (URT), primarily in chronic (rhino)sinusitis, allergic rhinitis, acute URT infections and postoperative recovery. Additionally, taking into account its multiple mechanisms of action and mounting evidence from recent studies, locally applied seawater preparations may have an important role in prevention of viral and bacterial infections of the URT. Therefore, in this review we discuss results published in the past years focused on the seawater preparations and their use in clinical and everyday conditions, since such products are superior to saline, have an excellent safety profile and are recommended by most professional associations in the field of otorhinolaryngology.
ARTICLE | doi:10.20944/preprints202108.0090.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: Airflow restriction, Physical exercise, Respiratory Muscle Training, Endurance performance, VEGF, EPO
Online: 3 August 2021 (15:04:27 CEST)
Introduction: The Elevation Training Mask 2.0 (ETM) has been introduced as a novel tool to allow for respiratory muscle training and altitude exposure during exercise that can improve performance and hematological markers in elite and well-trained athletes. Thus, the aim of the present study was to assess the effect of wearing ETM while training on erythropoietin (EPO), vascular endothelial growth factor (VEGF), peak oxygen consumption (VO2max), lactate, and 1000-m kayaking performance in elite Kayaking girls. Methods: Thirty elite Kayaking girls (14 to 18-year-old) were equally and randomly assigned into mask, no mask, and control groups. The mask and no-mask groups completed 8 weeks of repeated sprint training, while the control group performed their routine kayaking training programs. Pre- and post-training tests included EPO, VEGF, VO2max, lactate, and 1000-m kayaking performance. Results: 1000-m time trial significantly decreased for mask (p < 0.001) and control (p = 0.035) groups, and was significantly lower in mask group than control (p = 0.014) and no mask (p = 0.009) groups. EPO did not show any significant changes for all groups. VEGF was increased significantly for mask (p = 0.04) and no mask (p = 0.014) groups. Lactate was decreased significantly for mask group (p = 0.025). VO2max increased significantly for no mask group (p = 0.021). Conclusion: Wearing the ETM while participating in 8 weeks of repeated sprint training might improve specific blood markers and endurance performance, especially anaerobic pathways. Performing repeated sprint training while wearing ETM has the potential to enhance performance in Kayak racing.
REVIEW | doi:10.20944/preprints202008.0065.v1
Subject: Biology And Life Sciences, Immunology And Microbiology Keywords: SARS-CoV-2; SARS-CoV; influenza; pneumonia; respiratory tract infectious diseases
Online: 3 August 2020 (08:44:56 CEST)
The short study implicates few basic similarities of COVID-19 such as diseases origination, symptoms, diagnosis with other relatable viral diseases viz SARS-CoV, common Flu, pneumonia etc. In the present situation, other viral diseases are frequently chaotic and misled with COVID-19 disease because of few clinical features similarities in signs and symptoms and also due to lack of specific diagnostic test. To avoid unnecessary suspects, quarantines of false positive results and to prevent the spread of COVID-19 diseases, the scientific technical research field are highly encourage to implement an efficient, rapid and sophisticated superior test for early stages of infection detection. It will be significantly convenient for physician, laboratory technicians and most importantly the common population facing a psychological disturbance.
REVIEW | doi:10.20944/preprints202007.0568.v1
Subject: Medicine And Pharmacology, Anesthesiology And Pain Medicine Keywords: SARS-CoV-2; COVID-19; respiratory failure; ARDS; ventilation; MODS; ECMO
Online: 24 July 2020 (04:00:50 CEST)
The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in a significant surge of critically ill patients and an unprecedented demand on intensive care services. The rapidly evolving understanding of pathogenesis, limited disease specific evidence and demand-resource imbalances have posed significant challenges for intensive care clinicians. COVID-19 is a complex multisystem inflammatory vasculopathy with a significant mortality implication for those admitted to intensive care. Institutional strategic preparation and meticulous intensive care support are essential to maximising outcomes during the pandemic. The significant mortality variation observed between institutions and internationally, despite a single aetiology and uniform presentation, highlights the potential influence of management strategies on outcome. Given that optimal organ support and adjunctive therapies for COVID-19 have not yet been well defined by trial-based outcomes, strategies are predicated on existing literature and experiential learning. This review outlines the relevant pathophysiology and management strategies for critically ill patients with COVID-19, and shares some of the collective learning accumulated in a high volume Severe Respiratory Failure centre in London.
Subject: Medicine And Pharmacology, Epidemiology And Infectious Diseases Keywords: COVID-19; SARS-CoV-2; coronavirus; severe acute respiratory syndrome coronavirus
Online: 5 July 2020 (10:16:43 CEST)
Background: The information on the difference in clinical characteristics between severe and non-severe cases is limited in some countries including Iran. The objective of this case series is to compare the clinical characteristics, radiologic features, and laboratory findings between COVID-19 severe cases who received the intensive care unit (ICU) care with non-severe cases who did not receive ICU care. Methods: In this retrospective cohort study, 186 laboratory-confirmed patients with COVID-19 diagnosed from 1 March 2020 to 30 March 2020 were investigated. Results: This study population included 186 hospitalized patients with confirmed COVID-19. The median age was 47 years, and 88 (47.31%) were female. Of these patients, 48 were admitted and transferred to ICU. Of 186 patients, 44.62% had medical comorbidities including hypertension and diabetes. The most common clinical manifestation were shortness of breath 86.56%, myalgia 74.19%, and headache. Higher neutrophil counts, CRP, and LDH as well as the lower levels of lymphocytes were the most important laboratory finding among COVID-19 patients. As of April 15, 2020, 33 were still hospitalized. A total of 116 patients (62.70 %) had been discharged, and 36 patients (19.94 %) had died. Of the 48 patients admitted to the ICU, 33.33% have died. Conclusion: In the present study, shortness of breath was the most common clinical symptom, and the mortality rate in patients admitted to the ICU was about 33%, indicating that about one-third of patients with severe illness who admitted to the ICU section died.
REVIEW | doi:10.20944/preprints202004.0495.v1
Subject: Public Health And Healthcare, Health Policy And Services Keywords: COVID - 19; coronavirus; respiratory syndrome; SARS-CoV; preventive and control measures
Online: 28 April 2020 (10:04:07 CEST)
The most striking and dramatic catastrophe, as on April 2020, is - COVID - 19. Understanding of the COVID-19, the causing agent- the virus and the resultant causalities are still evolving. Till now, there is no specific treatment, no vaccine for the COVID-19. At this stage, what is utmost important now to face the disaster is to put emphasis on the preparedness and responses: research to discover vaccine, antivirals as soon as possible. Till then, it is necessary to put emphasis on infection preventive and control measures like to avoid close contact of infected people showing symptoms of respiratory diseases, hand hygiene and coughing etiquette. To make the infection preventive and control measures a success, the followings are to make success: ‘quarantine’ ‘isolation’, ‘travel bans’, ‘cordon sanitaire’ and ‘social distancing’ measures. The tools of modern information technology could help the authority to manage and monitor the preventive measures. Above all, preventive and control measures will not be successful if we fail to make aware the common people about the fatality of the COVID - 19. So, rapid preparedness and responses to COVID-19 are critically essential to face such disaster. Not a single moment is to waste!
ARTICLE | doi:10.20944/preprints201908.0069.v1
Subject: Biology And Life Sciences, Biochemistry And Molecular Biology Keywords: coenzyme Q deficiency; mitochondrial disease; respiratory chain; fatty acids; myopathy; ADCK2
Online: 6 August 2019 (07:52:35 CEST)
Fatty acids and glucose are the main bioenergetic substrates in mammals that are alternatively used during the transition between fasting and feeding. Impairment of mitochondrial fatty acid oxidation causes mitochondrial myopathy leading to decreased physical performance. Here, we report that haploinsufficiency of ADCK2, a member of the aarF domain-containing mitochondrial protein kinase family, in human is associated with liver dysfunction and severe mitochondrial myopathy with lipid droplets in skeletal muscle. In order to better understand the etiology of this rare disorder, we generated a heterozygous Adck2 knockout mouse model to perform in vivo and cellular studies using integrated analysis of physiological and omics data (transcriptomics-metabolomics). The data show that Aldh2+/- mice exhibits impaired fatty acid oxidation, liver dysfunction, and mitochondrial myopathy in skeletal muscle resulting in lower physical performance. Significant decrease in CoQ biosynthesis was observed and supplementation with CoQ partially rescued the phenotype both in the human subject and mouse model. These results indicate that ADCK2 is involved in organismal fatty acid metabolism and in CoQ biosynthesis in skeletal muscle. We propose that patients with isolated myopathies and myopathies involving lipid accumulation be tested for possible ADCK2 defect as they are likely to be responsive to CoQ supplementation.
ARTICLE | doi:10.20944/preprints201907.0155.v1
Subject: Medicine And Pharmacology, Pediatrics, Perinatology And Child Health Keywords: immune system; immunedeficiency; respiratory tract infections; children; impedance; serum; laboratory diagnostics
Online: 11 July 2019 (09:12:55 CEST)
Despite considerable progress in the diagnosis of various diseases, an ideal, simple tool for diagnosing patients with respiratory tract infections has not yet been invented. Many simple diagnostic tests are widely available to most doctors, provided they are aware of the prevalence of primary immunodeficiency. Other, more accurate studies are available only to immunologists. The aim of the study was to investigate the occurrence of dependence between selected physical parameters of serum such as: electrical conductivity, electrical permeability, dielectric loss factor, and selected parameters of the immune system. In addition, we have also included the ionogram (Na, K, Cl, Ca, Mg) and glucose concentration. As a result of research, the statistically significant, but very weak correlations between impedance magnitude |Z| and platelet counts (PLT), mean platelet volume (MPV) and chloride ions (Cl-) were found. The statistically significant differences according |Z| between children with and without deficiency in parameters of the immune system were noticed. Values of |Z| are higher in the case of children without deficiency in parameters of the immune system. The method of impedance measurements presented in our work is significantly easier then biosensors presented by other scientists. Taking into account our results, it can be stated that this method is promising for fast and easy detection of immunological disorders.
ARTICLE | doi:10.20944/preprints201711.0175.v1
Subject: Environmental And Earth Sciences, Environmental Science Keywords: carbon monoxide; COHb; air pollution; GIS interpolation; spatial analysis; respiratory diseases
Online: 27 November 2017 (09:13:06 CET)
This paper aims to investigate carbon monoxide (CO) concentrations on roadways of Karachi, potential blood levels carboxy-hemoglobin (COHb) in Karachi. Geographical information system (GIS) was used for spatial analysis of diseases potentiality while an interpolation technique has been applied for surface generation with town boundaries and later evaluates risk areas.The higher concentration of carbon monoxide in the ambient is mainly due to automobile emissions. The City center and CBD areas are more perilous.
ARTICLE | doi:10.20944/preprints202311.0133.v1
Subject: Public Health And Healthcare, Public, Environmental And Occupational Health Keywords: wildfires; smoke; air pollution; climate change; asthma; respiratory diseases; emergency medical services
Online: 2 November 2023 (07:58:23 CET)
Wildfires are a rising environmental threat which health impact remains poorly documented, in particular beyond the fire period. This ecological study investigates changes in health conditions before, during, and after two consecutive wildfires that occurred in France´s Gironde district in the summer 2022. Electronic records from the district´s emergency medical communication centre were used to identify calls with respiratory and cardiovascular diseases, and two specific subgroups of those, asthma (all ages and 0-5 years) and cardiac arrest, respectively. Compared to before the fires, respiratory disease cases were fewer during each fire (OR = 0.85, 95% CI: 0.79, 0.90 and OR = 0.62, 95% CI: 0.58, 0.67, respectively), cardiovascular disease cases, more common during the second fire, and asthma cases, higher following the fires (ORall ages= 1.85, 95% CI: 1.56, 2.21 and ORchildren= 3.52, 95% CI: 2.62, 4.80). Asthma cases also rose during the same calendar time in 2021, but to a lesser extent. In sum, except for asthma, emergency calls data in Gironde reveal few significant potentially smoke-related symptoms around fire periods, apart from post-fire asthma. Whether the effects are smoke- or season-related remains to be determined, preferably using additional data sources.