Medication non-adherence remains a substantial obstacle in asthma care, prompting the exploration of novel therapeutic modalities that prioritize rapid symptom relief, anti-inflammatory activity and facilitate patients’ compliance. This task is well served by a new form of therapy - inhaled triple-combination medications ICS/LABA/LAMA (inhaled glucocorticosteroid/long-acting beta2-agonist/long-acting muscarinic antagonist). The integration of three medications within a singular inhalation device culminates in the reduction of the effective dose of the principal therapeutic agent for asthma management, namely, ICS. This consolidation yields a dual benefit of minimizing the likelihood of adverse effects typically linked with ICS while concurrently optimizing bronchodilator efficacy. The accumulated evidence suggests that adding LAMA to a medium- or high-dose ICS/LABA results in a decrease of asthma exacerbations compared to medium- or high-dose ICS/LABA alone, accompanied by sustained enhancements in lung function parameters. We propose in adult patients experiencing suboptimal asthma control despite medium/high-dose ICS/LABA treatment - regardless of adherence to GINA-recommended strategies, such as MART therapy as a first-line approach or alternative second-line strategies - the preferred course for intensifying asthma therapy involves the addition of a LAMA, ideally in the form of SITT.

Background: In susceptible hosts, SARS-CoV2 induced hyperinflammation accounts for an increased mortality. The search of adjuvant immunomodulatory therapies has been ongoing ever since the pandemic outbreak. Aim: Our purpose was to evaluate the efficacy of cyclosporin A (CsA) as add-on therapy to standard of care in patients with severe COVID-19 pneumonia. Methods: We conducted a randomized clinical trial in patients admitted to 8 Spanish Tertiary Hospitals. Patients were stratified into two severity categories and randomized 1:1 to receive a high dose corticosteroid-based standard therapy with or without CsA. The primary endpoint was FiO2 recovery by day 12 without relapses. Results: 109 patients were included and 98 randomized: 51 of them were assigned to CsA+SoC group and 47 to Standard of Care (SoC). 96/98 of them were included in the Intention to Treat population. 35 (68.6%) patients from CsA+SoC group and 32 (71,1%) patients from SoC group reached the primary endpoint in the ITT analysis. No differences were found after stratification into age groups, severity level at admission or the combination of both. Overall, time to FiO2 normalization was 7.4 days vs 7.9 days in the experimental and control groups, respectively. Global mortality was 8.2%. Severe adverse events were uncommon and equally distributed between arms. Conclusion: Addition of CsA did not show differences over a high-dose corticosteroids-based treatment in the clinical course of included patients. A better identification of candidates who will benefit from receiving immunomodulatory drugs is necessary in future studies.

Management of resistant Tuberculosis (TB) can be extremely difficult, especially in case of novel unpredicted complications. In this report, we present a case of a 48-year-old patient with pre-extensive-drug-resistant-(XDR)-TB who received a treatment regimen including Pretomanid, Bedaquiline, Linezolid, Cycloserine and Amikacin and died due to myocarditis. Acquired resistance to first- and second-line drugs developed due to previous poor adherence to medication. The clinical presentation of the patient, along with her initial ultrasonographical, electrocardiogram (ECG) and laboratory examinations, were typical for acute myocarditis, however, the patient was considered unstable and further investigation with Magnetic Resonance Imaging (MRI), pericardiocentesis and endomyocardial biopsy were not performed. To our knowledge, this is the first case of myocarditis in such a patient, the clinical features of which set a high suspicion of drug-induction that could be attributed to the treatment regimen that was administered. Clinicians who manage cases of drug-resistant TB should be aware of this, newly reported, potentially lethal, adverse event.

Idiopathic pulmonary fibrosis remains a relevant problem in the field of healthcare with an unfavorable prognosis for patients due to progressive fibrous remodeling of the pulmonary parenchyma. Starting with the reactions damaging the epithelial lining of alveoli, pulmonary fibrosis is implemented through a cascade of complex mechanisms, the crucial of which is the TGF-β/SMAD mediated pathway, involving various cell populations. Considering that a number of the available drugs (pirfenidone and Nintedanib) have only limited effectiveness in slowing the progression of fibrosis, the search and justification of application of other approaches aimed at regulating the immune response, cellular aging processes, programmed cell death and transdifferentiation of cell populations remains relevant. This literature review presents the key modern concepts concerning molecular genetics and cellular mechanisms of lung fibrosis development, based mainly on in vitro and in vivo studies in experimental models of bleomycin-induced pulmonary fibrosis, as well as the latest data on metabolic features, potential application points and effects of vitamin D and its metabolites.

Idiopathic pulmonary fibrosis [IPF] is a chronic progressive disease characterised by the accumulation of scar tissue in the lung parenchyma. It primarily occurs in middle-aged and elderly adults and results in significant morbidity and mortality worldwide. The disease occurs due to repetitive lung epithelial injury, subsequent fibroblast activation and myofibroblast differentiation, resulting in excessive extracellular matrix deposition. This leads to scar formation and subsequent loss of lung function. Current treatment options for patients with IPF include the two anti-fibrotic drugs, pirfenidone and nintedanib, which can slow disease progression; however, there are currently no known cures for the disease. As such, novel methods and drug targets are warranted. In this review, we provide an up-to-date account of the importance of specific cytokines and the potential role of regulatory immune cells. We discuss their role in the pathogenesis of IPF and address some of the key gaps in knowledge.

Background and objective: Analysis of inflammatory biomarkers, along with the neutrophil/lymphocyte ratio (NLR) or platelets/lymphocyte ratio (PLR), supports the connection between inflammation and carcinogenesis. Methods: We conducted a retrospective observational study at the Clinical County Hospital Mureș, including patients with lung cancer. The parameters analyzed included: histopathological type (NSCLC - squamous cell carcinoma or adenocarcinoma; SCLC), molecular mutations (EGFR, ALK, PD-L1), parameters from the complete blood count, inflammatory parameters and associated comorbidities. Results: 380 patients were included: 115 patients in the cancer group and 265 patients in the control group. Among patients in the lung cancer group, 88 were diagnosed with NSCLC (44 adenocarcinomas, 44 squamous cell carcinomas) and 27 with SCLC. Both NLR and PLR were significantly higher in cancer patients than in the control group (5,30 versus 2,60, p<0,001; 217 versus 136, p< 0.001, respectively). NLR and PLR differs between men and women (p = 0.005, respectively p=0.056). C-reactive protein was not correlated with either NLR (p-value: 0.0669) or PLR (p-value: 0.6733) in lung cancer patients. Conclusion: The NLR and PLR values ​​may serve as new predictive biomarkers for the diagnostic of disease in patients with lung cancer, especially those with NSCLC.

Background: The objective of this study was to evaluate, the clinical benefit of benralizumab in patients with uncontrolled severe asthma associated with chronic rhinosinusitis with nasal polyposis (CRSwNP). Methods: The study included patients with uncontrolled severe asthma associated with CRSwNP who started therapy with benralizumab. Pulmonary function, eosinophilia, IgE, comorbidity, changes in the Asthma Control Test (ACT), Asthma Control Questionnaire (ACQ), Visual Analogue Scale (VAS), Quality of Life (AQLQ), VAS (obstruction, drip, anosmia, facial pressure), SNOT-22, decrease or withdrawal of steroids and other medication, hospital admissions and emergency visits were analysed. The FEOS scale and EXACTO were employed in the assessment of response. Results: We analyzed 58 patients who completed minimal treatment at 12 months. After treatment with benralizumab, exacerbations were reduced by 82% (p

Pulmonary artery stenosis represents a group of disorders involving main, branch or peripheral pulmonary arteries resulting either in pain, dyspnea, hemoptysis or even no symptoms. Early diagnosis and timely intervention are crucial for reducing mortality, while timely diagnosis is challenging due to the nonspecific symptoms. Computed tomography pulmonary angiography (CTPA) is useful in the diagnosis because it can provide more details about the abnormal changes in the lumen, vessel wall and adjacent mediastinal structures. Congenital and acquired pulmonary artery anomalies have some characteristics on CTPA, which can be useful for differential diagnosis. Awareness of these conditions and is important for the radiologists. This pictorial review provides an overview of CTPA imaging features of pulmonary artery stenosis.

Recent years have been abundant in research concerning human microbiome and its impact on the host’s health. Studies have shown, that not only the commensal bacteria itself, but also postbiotics, understood as unalived microorganisms, possibly with the presence of their components, may have themselves effect on various elements of human physiology. In this article we take a closer look on the specific ways in which postbiotics can alter immune response in allergic asthma, which is one of the most prevalent allergic diseases in today’s world being a serious subject of concern. Through altering patients’ immune response, not only to allergens but also to pathogens, postbiotics could have a significant role in lowering the number of asthma exacerbations. We suggest that more profound research should be undertaken in order to launch postbiotics into clinical standards of asthma treatment, given greatly promising findings in the field of their immunomodulating potential.

Current epidemiological data about interstitial lung disease (ILD) are still poor. The principal cause of the discordant data is associated with a heterogeneous group of respiratory diseases that includes a large number, about 200 families, with low frequency, distinct and sometimes unknown etiology, and different progression. Furthermore, epidemiological data are limited. Scope of the narrative review is to report ILD incidence and prevalence in Registries from different Countries in the second millennium. We identified 16 ILD Registries (14 prospective and 2 retrospective) from major Countries in Europe (n = 10), Asia (n = 7), North America (n =2) and Oceania (n = 1). Significant discrepancies in ILD and ILD subtypes prevalence and incidence among countries are reported in Registries. These discrepancies could be determined by different ethnicities and socio-economic conditions as well as by updates in disease diagnosis and classification. ILD epidemiological Registries are progressively ameliorating through a better adherence to updated Guidelines and Classification codes. An accurate and definite compilation of ILD epidemiological Registries will be useful for a more precise monitoring of disease progression and treatment.

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: Prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini-Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8-12), 39 participants (32.50%) had normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear logistic models showed that the MNA score was associated with dyspnea and respiratory symptoms severity assessed by the Modified British Medical Research Council (mMRC) and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1 and with poorer QoL as assessed by the EQ-5D-3 questionnaire. Cox regression analysis according to nutritional status based on the MNA score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with a hazard ratio (HR) of 3.54 (p=0.002) and 8.20 (p=0.0001), respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value.

Smoking a cigarette before bed or first thing in the morning is a common habit. In this review the relationship between smoking and sleep is investigated, based on the existing literature. Tobacco smoking disrupts sleep architecture by reducing slow wave and rapid eye movement (REM) sleep and undermining sleep quality. Furthermore, smoking affects sleep-related co-morbidities, such as obstructive sleep apnoea-hypopnea syndrome (OSAHS), insomnia, parasomnias, arousals, bruxism, restless legs but also non-sleep-related conditions such as cardiovascular, metabolic, respiratory, neurologic, psychiatric, inflammatory, gynecologic and pediatric. This review aims to consolidate all the existing knowledge about the relationship between smoking and sleep.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p<0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p<0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p<0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

Fatigue and dyspnea are the most commonly presented long-term complaints in individuals previously infected with SARS-CoV-2. The purpose of the study was to comprehensively evaluate diaphragm muscle function in COVID-19 survivors, as well as investigate whether potential diaphragm dysfunction will contribute to physical functioning impairment. 46 patients qualified to pulmonary rehabilitation were examined. Diaphragm muscle function parameters were evaluated using ultrasonography, while severity of dyspnea, aerobic capacity and amount of energy used by the body during physical activity were assessed by 6-minute walk test, mMRC scale and Metabolic Equivalent Task (MET), respectively. We identified 69.5% patients with diaphragm atrophy and 6.5% with diaphragm paralysis. Percentage of atrophy was not related to age, gender, BMI index, oxygen therapy use during COVID-19 infection course and severity of disease. Patients with presence of cough, fever and without loss of smell during COVID-19 course had a significantly greater values of diaphragm inspiratory thickness, while patients with cough and no smell disorders had a significantly lower percentage of diaphragm atrophy. Diaphragm functional parameters were strongly associated with selected variables of person's exercise tolerance, such as distance in 6-minute walk test, saturation level, fatigue and exertion in Borg scale. In conclusion, diaphragm muscle dysfunction is a serious long-term post-COVID aftermath and can be viewed as a major contributing factor of prolonged functional impairments.

Primary Ciliary Dyskinesia (PCD) is a rare genetic disorder characterized by alterations in motile cilia func-tion. The diagnosis of PCD is challenging due to the lack of standardized methods in clinical practice. High-speed video microscopy analysis (HSVA) directly evaluates ciliary beat frequency (CBF) in PCD. Recently, open-source ciliary analysis software applications have shown promise in measuring CBF accurately. How-ever, there is limited knowledge about the performance of different software applications, creating a gap in understanding their comparative effectiveness in measuring CBF in PCD. We compared two open-source software applications, CiliarMove and Cilialyzer, against the manual count method. We used videos rec-orded at high-speed of nasal ciliary brush samples from PCD patients and healthy controls. All three meth-ods showed lower median CBF values in PCD patients than healthy controls. CiliarMove and Cilialyzer identified lower CBF in PCD patients, similar to the manual count. Cilialyzer, CiliarMove and manual count demonstrated statistical significance (p-value < 0.0001) in the difference of median CBF values be-tween PCD and healthy controls. These findings support the utility of open-source software-based analysis tools. Further studies are needed to validate these findings with other genetic variants and identify the op-timal software for accurate CBF measurement in PCD.

Background: The clinical spectrum of fibrotic interstitial lung diseases (ILD) is highly heterogeneous. We aimed to evaluate the prognostic value of widely available baseline biomarkers for improvement of lung function in patients with fibrotic ILD. Methods: This registry-based study included 142 patients with fibrotic ILD as defined by presence of reticulation, traction bronchiectasis or honeycombing on initial high-resolution computed tomography (HRCT). Functional improvement at 1 year was defined as relative increase of 5% in forced vital capacity (FVC) or of 10% in diffusion capacity for carbon monoxide (DLCO). The prognostic value of baseline biomarkers was evaluated for all patients and the subgroup with anti-inflammatory treatment. Results: At one year, 44 patients showed improvement while 73 progressed. Multivariate analyses found prognostic significance for age &lt;60 years (OR 5.4; 95%CI 1.9-15.4; p=0.002), lactate dehydrogenase (LDH) &gt;250U/L (OR 2.5; 95%CI 1.1-5.8; p=0.043) and blood monocyte count &lt;0.8G/L (OR 3.5; 95%CI 1.1-11.3; p=0.034). In 84 patients undergoing anti-inflammatory treatment, multivariate analysis revealed age &lt;60 years (OR 8.5 (95%CI 2.1-33.4; p=0.002) as the only significant variable. Conclusion: Younger age, higher LDH and lower blood monocyte count predicted functional improvement in fibrotic ILD patients, while in those treated with anti-inflammatory drugs, only age had significant implications.

Anxiety disorders, characterized by excessive fear and anxiety, are increasingly recognized as significant comorbidities in chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD). This study aimed to evaluate the prevalence of anxiety in COPD patients referred from primary care centers to pulmonology services and identify predictive factors for anxiety. Conducted as a multicentric, observational, and prospective study, 293 COPD patients were recruited, undergoing comprehensive respiratory and smoking histories, spirometry, and anxiety assessments using the Hospital Anxiety and Depression Scale (HADS). These results show: a diagnosis of suspected anxiety in in 85 patients (29.0%): 17 possible and 68 with a strong suspicion. The study found significant associations between anxiety and factors such as gender (women showed a risk 3.5 times higher than men), weight, and body mass index (BMI). Disease severity, smoking status, and clinical manifestations did not significantly influence anxiety prevalence. The findings underscore the need for systematic psychological evaluations in COPD management, advocating for the use of simple diagnostic tools like the HADS to facilitate referrals to mental health services. Addressing anxiety in COPD patients could potentially improve their quality of life and disease outcomes. The study highlights the importance of a multidisciplinary approach involving family medicine, pulmonology, and psychiatry to optimize COPD patient care and suggests future research should focus on the impact of anxiety treatment on COPD progression. These insights call for integrating psychological assessments into routine clinical practice for comprehensive COPD management.

Anxiety disorders, characterized by excessive fear and anxiety, are increasingly recognized as significant comorbidities in chronic diseases such as Chronic Obstructive Pulmonary Disease (COPD). This study aimed to evaluate the prevalence of anxiety in COPD patients referred from primary care centers to pulmonology services and identify predictive factors for anxiety. Conducted as a multicentric, observational, and prospective study, 293 COPD patients were recruited, undergoing comprehensive respiratory and smoking histories, spirometry, and anxiety assessments using the Hospital Anxiety and Depression Scale (HADS). These results show: a diagnosis of suspected anxiety in in 85 patients (29.0%): 17 possible and 68 with a strong suspicion. The study found significant associations between anxiety and factors such as gender (women showed a risk 3.5 times higher than men), weight, and body mass index (BMI). Disease severity, smoking status, and clinical manifestations did not significantly influence anxiety prevalence. The findings underscore the need for systematic psychological evaluations in COPD management, advocating for the use of simple diagnostic tools like the HADS to facilitate referrals to mental health services. Addressing anxiety in COPD patients could potentially improve their quality of life and disease outcomes. The study highlights the importance of a multidisciplinary approach involving family medicine, pulmonology, and psychiatry to optimize COPD patient care and suggests future research should focus on the impact of anxiety treatment on COPD progression. These insights call for integrating psychological assessments into routine clinical practice for comprehensive COPD management.

The emergence of acquired resistance to EGFR-TKIs is almost inevitable even after a remarkable clinical response. Secondary mutations such as T790M and C797S are responsible for the resistance to 1st/2nd generation (1/2G) TKIs and 3G TKIs, respectively. To overcome both the T790M and C797S mutations, novel 4G EGFR-TKIs are now under early clinical development. In this study, we evaluated the efficacy of a 4G EGFR-TKI in the treatment of lung cancer with EGFR mutation as well as explored resistance mechanisms to a 4G TKI. First, we compared the efficacies of seven TKIs including a 4G TKI, BI4020, against Ba/F3 cell models that simulate resistant tumors after frontline osimertinib treatment failure because of a secondary mutation. We also established acquired re-sistant cells to BI4020 by chronic drug exposure. Ba/F3 cells with an osimertinib-resistant secondary mutation were refractory to all 3G TKIs tested (alflutinib, lazertinib, rezivertinib, almonertinib, and befotertinib). BI4020 inhibited the growth of C797S-positive cells; however it was not effective against L718Q-positive cells. Erlotinib was active against all Ba/F3 cells tested. In the analysis of resistance mechanisms of BI4020 resistant (BIR) cells, none harbored secondary EGFR mutations. HCC827BIR cells had MET gene amplification and were sensitive to a combination of capmatinib (MET-TKI) and BI4020. HCC4006BIR and H1975BIR cells exhibited epithelial to mesenchymal transition. This study suggests that erlotinib may be more suitable than 4G TKIs to overcome sec-ondary mutations after front-line osimertinib. We found that off-target mechanisms that cause re-sistance to earlier generation TKIs will also cause resistance to 4G TKIs.

Pulmonary hypertension (PH) is a severe and chronic disease characterized by increased pulmonary vascular resistance and remodeling often precipitating right-sided heart dysfunction and death. Although the condition is progressive and incurable, current therapies for the disease focus on multiple different drugs and general supportive therapies to manage symptoms and prolong survival, ranging from medications more specific to pulmonary arterial hypertension (PAH) to exercise training. Moreover, there are multiple studies exploring novel experimental drugs and therapies including unique neurostimulation, to help better manage the disease. Here we provide a narrative review focusing on current PH treatments that target multiple underlying biochemical mechanisms, including but not limited to imbalances in vasoconstrictor-vasodilator and autonomic nervous system function, inflammation, and bone morphogenic protein (BMP) signaling. We also focus on the potential of novel therapies for managing PH, focusing on multiple types of neu-rostimulation including acupuncture. Lastly, we also touch upon the disease’s different subgroups, clinical presentations and prognosis, diagnostics, demographics, and cost.

Lymphangioleiomyomatosis (LAM) is a cystic pulmonary disorder that has been known to primarily affect women of childbearing age. The disorder can develop with mutations in the tuberous sclerosis (TSC) genes TSC1 & TSC2 but may arise by other irregular cases in the lack of these mutations. LAM can manifest in a wide variety of ways and generally compounded in symptoms of other lung disorders such as bronchitis, emphysema, & asthma. However, due to lack of effective diagnostic methods, biomarkers of LAM leading to a treatment for the disorder are currently unmet. Using integrative dating analytics and bioinformatics approaches; this study used publicly available microarray data to identify biomarkers in LAM. The results showed important differential expressed genes (DEGs) including: CDH2, CXCL6, ANXA10, MFAP5, RPS4Y1, DCBLD2, PAPPA, TFPI2, SERPINE1, LOX, MYH11, RGS1, SEPP1, TMOD1, ID1, SFTPB, CDH1, HTR2B, OGN, and IGLC1. Furthermore, gene – network and gene ontology (GO) analysis were conducted to show the importance of these genes from a molecular understanding. Taken together, the results revealed could serve as diagnostic and prognostic biomarkers with LAM patients.

Lung cancer remains one of the leading causes of cancer-related mortality worldwide. There is evidence of a complex interplay between lung cancer and interstitial lung disease (ILD), affecting disease progression, management strategies, and patient outcomes. Both conditions develop as the result of common risk factors such as smoking, environmental exposures, and genetic predispositions. The presence of ILD poses diagnostic and therapeutic challenges in lung cancer management, including difficulties in interpreting radiological findings, increased susceptibility to treatment-related toxicities, such as acute exacerbation of ILD after surgery and pneumonitis after radiation therapy and immunotherapy. Moreover, due to the lack of large, phase III randomized controlled trials in patients with lung cancer and ILDs, the evidence-based therapeutic options remain limited. The role of antifibrotic treatment in the prevention of lung-cancer-related treatment toxicities remains to be elucidated. Emerging diagnostic modalities and biomarkers, and optimizing personalized treatment strategies are essential to improve outcomes in this patient population.

Extracorporeal membrane oxygenation (ECMO) support for respiratory failure in the intensive care unit continues to have an expanded role in select patients. While acute respiratory distress syndrome remains the most common indication, ECMO may be used in other causes of refractory hypoxemia and/or hypercapnia. The most common configuration is veno-venous (V-V) ECMO, however in specific cases of refractory hypoxemia or right ventricular failure, some patients may benefit from veno-pulmonary (V-P) ECMO or veno-venoarterial (V-VA) ECMO. Patient selection and extracorporeal circuit management are essential to successful outcomes. This narrative review explores the physiology of ECMO, indications and contraindications, ventilator management, extracorporeal circuit management, troubleshooting hypoxemia, complications, and ECMO weaning in patients with respiratory failure. As the footprint of ECMO continues to expand it is essential that clinicians understand the underlying physiology and management of these complex patients.

Obstructive sleep apnea (OSA) is a common sleep disorder that is associated with a wide variety of health conditions, including cardiovascular, cerebrovascular, metabolic, neoplastic, and neurocognitive manifestations. OSA is mainly characterized by repeated upper airway obstructions during sleep that cause episodes of chronic intermittent hypoxia (IH), resulting in tissue hypoxia-reoxygenation. Decreased arterial oxygen pressure (PaO2) and hemoglobin saturation (SatO2) stimulate reflex responses to overcome the obstruction. The prevalence of OSA is significant worldwide, particularly in women during pregnancy, due to the physiological changes associated with this stage of life, especially in its later stages. It is associated with an increased risk of hypertension, pre-eclampsia and diabetes, among others. OSA during pregnancy can interfere with normal fetal development and is associated with growth retardation, preterm birth, or low term weight. Carotid body stimulation and hypoxia-reoxygenation episodes contribute to cardiovascular disease and oxidative stress, that can harm both, mother and the fetus, even into the adulthood. Because gestational intermittent hypoxia (GIH) is the hallmark of OSA in pregnancy, this review examines the impact of GIH on maternal, fetal, and offspring respiratory outcomes. Most adverse outcomes can be prevented by continuous positive airway pressure (CPAP) therapy and lifestyle changes if gestational OSA is detected early and treated appropriately.

Background/Objectives: The purpose of this study was to evaluate the relationship between 1-year mortality and health insurance benefit extension policy items in severe pneumonia pa-tients requiring mechanical ventilation using a South Korean nationwide cohort. Methods: A nationwide population-based retrospective study was conducted using the Korean National Health Insurance database. A total of 1,099 patients (542 patients in the health insurance benefit item group and 557 patients in the control group) were included. The primary outcome was 1-year mortality. Results: Among patients with health insurance benefit extension policy items, 203 patients (37.5%) were diagnosed with hemato-oncological disease, who were categorized as group A, and 339 patients (62.5%) were diagnosed with cerebrovascular, cardiovascular, or rare diseases, who were categorized as group B. Group B had lower 1-year mortality (50.7% vs. 62.5%, P

The COVID-19 pandemic remains a serious public health problem globally. During winter flu seasons, more aggressive SARS-CoV-2 infections with fatalities have been documented, indicating that influenza co-infections may significantly impact the disease outcome of COVID-19. Both influenza and SARS-CoV-2 viruses share many similarities in their transmission and cellular tropism for their replication in the human respiratory tract. However, it is still unclear how the two pathogens interplay to ensure their survival in the same lung microenvironment. In addition, clinical studies on influenza co-infections in COVID-19 patients do not provide conclusive evidence on how influenza co-infection mechanistically modifies the disease outcome in COVID-19. This mini-review discusses various viral as well as host factors that potentially influence the survival or synergism of these two respiratory pathogens in the infected lung microenvironment.

Mechanical ventilation (MV), used in patients with acute lung injury (ALI), induces diaphragmatic myofiber atrophy and contractile inactivity, termed ventilator-induced diaphragm dysfunction. Phosphoinositide 3-kinase- (PI3K-) is crucial in modulating fibrogenesis during the reparative phase of ALI; however, the mechanisms regulating the interactions among MV, myofiber fibrosis, and PI3K- remain unclear. We hypothesized MV with or without bleomycin treatment would increase diaphragm muscle fibrosis through the PI3K- pathway. Five days after receiving a single bolus of 0.075 units bleomycin intratracheally, C57BL/6 mice were exposed to 6 or 10 mL/kg MV for 8 h after receiving 5 mg/kg of AS605240 intraperitoneally. In wild-type mice, bleomycin exposure followed by MV 10 mL/kg prompted significant increases in disruptions of diaphragmatic myofibrillar organization, transforming growth factor-1, oxidative loads, Masson’s trichrome staining, extracellular collagen levels, positive staining of -smooth muscle actin, PI3K- expression, and myonuclear apoptosis (P &lt; 0.05). Decreased diaphragm contractility and peroxisome proliferator activated receptor- coactivator-1 levels were also observed (P &lt; 0.05). MV-augmented bleomycin-induced diaphragm fibrosis and myonuclear apoptosis were attenuated in PI3K-γ-deficient mice and through AS605240-induced inhibition of PI3K- activity (P &lt; 0.05). MV-augmented diaphragm fibrosis after bleomycin-induced ALI is partially mediated through PI3K-γ. Therapy targeting PI3K-γ may ameliorate MV-associated diaphragm fibrosis.

Acute and chronic respiratory diseases impose a significant economic and health burden. Distal small airway assessment requires invasive procedures such as a bronchoscopy and bronchoalveolar lavage. The Particles in Exhaled Air (PExA) device provides a non-invasive means of assessing small airways; it captures distal airway particles sized around 0.5-7m and contains particles of respiratory tract lining fluid (RTLF) that originate during airway closure and opening. The PExA device can measure particle count and mass according to particle size. Subsequent capture of particles in a thin membrane enables application of various analytical methods to assess a broad range of biomolecules including phospholipids, proteins, inflammatory profile, and other metabolites to characterise inflammation and diseases processes such as asthma, chronic obstructive pulmonary disease, acute respiratory distress syndrome, lung cancer, and more recently acute infections such as COVID-19. PExA analysis provides a promising alternative to traditional investigative methods in the assessment, diagnosis, and management of respiratory conditions. By evaluating specific biomarkers in the RTLF associated with airway inflammation, PExA may offer a more accurate and comprehensive understanding of the molecular-level changes in the small airways of patients with acute and chronic lung diseases.

Background: Over the past decades, efforts have been made to improve the nutritional well-being in people with cystic fibrosis (pwCF). Due to the correlation observed between nutritional indices and lung function, prevailing recommendations consistently advocate for BMI percentile goals at or above the 50th percentile in pwCF. Recent global trends show a notable increase in overweight and obese statuses among pwCF. This study aims to explore the nutritional status of Italian pwCF. Methods: Data from the Italian CF Patient’s Registry were analysed to assess the proportion of individuals categorized as underweight, target weight, overweight, and obese from 2010 to 2021. Patient-level comparison data from 2021 were also examined to identify potential determinants of overweight and obesity. Results: Analysis spanning 2010 to 2021 reveals a decrease of approximately 40% in underweight status among adults, while the proportion of malnourished patients 90, and lower prevalence of Pseudomonas aeruginosa colonization. Conclusions: Our study confirms the evolving nutritional status landscape among Italian adult pwCF, with a significant shift towards overweight and obesity over the past decade. These trends highlight the need for proactive measures within CF standards of care to adapt and address the changing needs of patients.

Chronic obstructive pulmonary disease (COPD) is a progressive lung disease that is commonly considered to be a potent driver of non-small cell lung cancer (NSCLC) development and related mortality. A growing body of evidence supports the role of the immune system, mainly played by alveolar macrophages (AMs), as key axes regulating the development of COPD or NSCLC phenotypes in response to harmful agents. MicroRNAs (miRNAs) are small non-coding RNAs that influence most biological processes and interfere with several regulatory pathways. The purpose of this study was to assess miRNA expression patterns in patients with COPD, NSCLC, and ever- or never-smoker controls to explore theirinvolvment in smoking-related diseases. Bronchoalveolar lavage (BAL) specimens were collected from a prospective cohort of 43 sex-matched subjects to determine expression of hsa-miR-223-5p, 16-5p, 20a-5p, -17-5p, 34a-5p and 106a-5p by RT-PCR. In addition, bioinformatic analysis of miRNA target genes linked to cancer was performed. Distinct and common miRNA expression levels were identified in each pathological group suggesting their possible role as an index of NSCLC or COPD microenvironment. Moreover, we identified miRNA targets linked to carcinogenesis using in silico analysis. In conclusion, this study identified miRNA signatures in AMs, allowing us to understand the molecular mechanisms underlying smoking-related conditions and potentially providing new insight for diagnosis or pharmacological treatment.

Obstructive sleep apnea (OSA) may be linked to various factors that narrow the upper airways, such as obesity, adenotonsillar hypertrophy and craniofacial abnormalities. Hypothyroidism has also been described as a risk factor for OSA. However, the implication of goiter independently of thyroid function in the occurrence of OSA remains unclear. We present the case of a 66-year-old patient, with a large compressive multinodular goiter for whom total thyroidectomy was indicated. During the preoperative assessment, the patient showed a body mass index (BMI) of 37.8 kg/m2 with symptoms of OSA. Respiratory polygraphy confirmed the diagnosis of severe OSA (apnea hypopnea index: AHI=32) and treatment with continuous positive airway pressure (CPAP) was initiated prior to thyroid surgery. Surprisingly, after total thyroidectomy, OSA symptoms disappeared and the patient abandoned CPAP therapy. Subsequent respiratory polygraphy after thyroidectomy showed a decrease in AHI to a normal value (AHI < 5). Interestingly, there was no change in BMI or other factors explaining the resolution of OSA, except for thyroidectomy. This case report suggests that goiter can be considered a risk factor for OSA. However, prospective studies are needed to accurately assess the effects of goiter on occurrence of OSA according to its dimensions and local extension.

Lung cancer is one of the leading causes of cancer-related mortality globally. Pulmonary nodules are one of the risk factors and their discovery rate has been increasing. Based on the nodule size and growth rate, their malignancy propensity is determined; however, it is very challenging to distinguish between benign and cancerous nodules. Many tumour-associated antigens (TAA) have been studied as blood biomarkers for lung cancer, most commonly the Cytokeratin 19 fragment (CYFRA 21-1), squamous cell carcinoma antigen (SCC Ag), carbohydrate antigen (CA19-9) and carcinoembryonic antigen (CEA). Due to their low sensitivity, TAAs are not recommended as tools for the early detection of lung cancer. However, cancer testis antigens (CTAs) are highly specific for carcinomas but their expression is more commonly associated with advanced stages of cancer and poor prognosis. Despite the fact that TAAs may provide useful insights for the diagnosis and prognosis of early lung cancer, their potential to do so has yet to be demonstrated.

Background: Previous neuroimaging studies have identified brain regions related to respiratory motor control and perception. However, little is known about the resting-state functional connectivity (FC) associated with respiratory impairment. We aimed to determine the FC involved in mild respiratory impairment without changing the saturation of percutaneous oxygen. Methods: We obtained resting-state functional magnetic resonance imaging data from 36 healthy volunteers during normal respiration and mild respiratory impairment induced by resistive load (effort breathing). ROI-to-ROI and seed-to-voxel analyses were performed using Statistical Parametric Mapping 12 and the CONN toolbox. Results: Compared to normal respiration, effort breathing activated FCs within and between the sensory perceptive area of respiration (the postcentral gyrus, anterior insular cortex (AInsula), and anterior cingulate cortex) and visual cortex (the visual occipital, occipital pole (OP), and occipital fusiform gyrus). Graph theoretical analysis showed strong centrality in the visual cortex. A significant positive correlation was observed between the dyspnoea score (modified Borg scale) and FC between the left AInsula and right OP. Conclusions: These results suggested that the FCs within the respiratory sensory area via the network hub may be neural mechanisms underlying effort breathing and modified Borg scale scores.

Background: The role of inhaled Nitric Oxide (iNO) in managing Acute Respiratory Distress Syndrome Covid-19 related (C-ARDS) is debatable. The study aimed to analyze the effect of iNO administration in patients with persistent severe hypoxia and Intensive Care Unit (ICU) mortality. Methods: This retrospective study included 98 consecutive critically ill patients with C-ARDS admitted to ICU from 1 October 2020 to 31 October 2021. Results: Of these patients, 28% had received iNO. Twelve (44.4%) were responders. Kaplan-Mayer plot shows mortality was higher in non-responders (86.6 vs 25.0%). Non-response to iNo was the most important predictive value (p. 0.01). The Receiver Operating Characteristic (ROC) curve for a percentage increase in PaO2 from baseline confirmed that it had a higher predictive value for in-hospital survival. A value of 19% can predict the death event with a sensitivity of 81.8% and a specificity of 81.2%. Conclusions: Therefore, we propose to use iNO as a vasoreactivity test for prognostic stratification in patients with persistent severe hypoxia.

Background: Features of post-traumatic stress disorder and anxiety may be present in Pulmonary Embolism (PE) patients along with impaired Quality of Life (QoL). We aim to evaluate health related QoL, anxiety and satisfaction with life, during the pandemic, in patients with a PE. Methods: Patients with PE were enrolled during their follow-up. All participants completed the Short Form 36 (SF-36) questionnaire, the State Trait Anxiety Inventory (STAI) X1 and X2 form, and the Satisfaction with Life Scale (SWLS). Results: 92 PE patients were included (mean age±SD=62.50±15.33 years, 56.5% males). Most of the mean values of the SF36 subscales were above the normative value except for “physical role functioning”) (45.92±42.41). “Emotional role functioning” (51.26±43.31) and “general health perceptions” (GH) (54.02±18.79) were slightly above the normative value of 50. Mean STAIX1 levels were 37.05±11.17 and mean STAIX2 levels were 39.80±10.47. Mean SWLS levels were 23.31±6.58. According to multiple linear regression analysis, mental healthscore (MH) and GH were predictive of SWLS(F (10,76) = 10.576, p

Study Objectives: The aim of this study is to explore the association between serum 25-hydroxyvitamin D [25(OH)D] levels, a marker of Vitamin D status, and excessive daytime sleepiness (EDS), expressed as increased scores of Epworth Sleepiness Scale (ESS), in a group of prospectively enrolled patients with obstructive sleep apnea (OSA). Methods: Newly diagnosed patients with OSA, divided into two groups, those with EDS (ESS>10) and those without EDS (ESS

Background: Severe eosinophilic asthma (SEA) represents a substantial global health burden. Benralizumab has been shown to restore good control of asthma. Robust data on benralizumab effectiveness over periods longer than 2 years are still scarce. Methods: This retrospective multicentric study was conducted on 108 Italian SEA patients treated with benralizumab for up to 36 months. Clinical outcomes were evaluated at 6, 12, 24 and 36 months. Partial and complete clinical remission (CR) were also assessed. Data were analysed either with descriptive statistics or using linear, logistic, and negative binomial mixed-effect regression models. Results: Benralizumab induced a persistent reduction in exacerbation rates (p

Growth environment greatly alters many facets of pathogen physiology, including pathogenesis and antimicrobial tolerance. The importance of host-mimicking environments for attaining an accurate picture of pathogen behaviour is widely recognised. Whilst this recognition has translated into the extensive development of artificial cystic fibrosis (CF) sputum medium, attempts to mimic the growth environment in other respiratory disease states have been completely neglected. The composition of the airway surface liquid (ASL) in different pulmonary diseases is far less well characterised than CF sputum, making it very difficult for researchers to model these infection environments. In this review we discuss the components of human ASL, how different lung pathologies affect ASL composition, and how different pathogens interact with these components. This will provide researchers interested in mimicking different respiratory environments with the information necessary to design a host-mimicking medium, allowing for better understanding of how to treat pathogens causing infection in these environments.

Primary ciliary dyskinesia (PCD) is an inherited disorder that impairs motile cilia, essential for respiratory health, with a reported prevalence of 1 in 16,309 within Hispanic populations. Despite having the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in 70% of Puerto Rican patients, the characterization of the ciliary dysfunction remains unidentified due to the unavailability of advanced diagnostic modalities like High-Speed Video Microscopy Analysis (HSVA). Our study implemented HSVA for the first time on the island as a tool to better diagnose and characterize the RSPH4A [c.921+3_921+6del (intronic)] founder mutation in Puerto Rican patients. By applying HSVA, we analyzed the ciliary beat frequency (CBF) and pattern (CBP) in native Puerto Rican patients with PCD. Our results showed decreased CBF and a rotational CBP linked to the RSPH4A founder mutation in Puerto Ricans, presenting a novel diagnostic marker that could be implemented as an axillary test into the PCD diagnosis algorithm in Puerto Rico. The integration of HSVA technology in Puerto Rico substantially enhances the framework for PCD evaluation and diagnosis, facilitating prompt detection and early intervention for improved disease management. This initiative, demonstrating the potential of HSVA as an adjunctive test within the PCD diagnostic algorithm, could serve as a blueprint for analogous developments throughout Latin America.

Introduction: Within primary ARDS, SARS-CoV-2-associated ARDS (C-ARDS) emerged in late 2019, reaching its peak during the subsequent two years. Recent efforts in ARDS research have concentrated on phenotyping this heterogeneous syndrome to enhance comprehension of its pathophysiology. Methods and Results: A retrospective study was conducted on C-ARDS patients from April 2020 to February 2021, encompassing 110 participants with a mean age of 63.2±11.92 (26-83 years). Of these, 61.2% (68) were male, and 25% (17) experienced severe ARDS, resulting in a mortality rate of 47.3% (52). Ventilation settings, arterial blood gases, and chest X-ray (CXR) were evaluated on the first day of invasive mechanical ventilation and between days two and three. CXR images were scrutinized using a convolutional neural network (CNN). A binary logistic regression model for predicting C-ARDS mortality was developed based on the most influential variables: age, PaO2/FiO2 ratio (P/F) on days one and three, CNN-extracted CXR features, and age. Initial performance assessment on test data (23 patients out of the 110) revealed an area under the receiver operating characteristic (ROC) curve of 0.862 CI (0.654-0.969). Conclusion: Integrating data available in all intensive care units enables the prediction of C-ARDS mortality by utilizing evolving P/F ratios and CXR. This approach can assist in tailoring treatment plans and initiating early discussions to escalate care and extracorporeal life support. Machine learning algorithms for imaging classification can uncover otherwise inaccessible patterns, potentially evolving into another form of ARDS phenotyping. The combined features of these algorithms and clinical variables demonstrate superior performance compared to either element alone.

Primary spontaneous pneumothorax (PSP) is a pleural disease that abruptly affects healthy adolescents and young adults, representing a common thoracic disorder in this age group. This study aimed to investigate the necessity of preoperative chest tube insertion in patients with PSP and to re-evaluate current clinical treatment approaches. A retrospective review of medical records was conducted for children and young adults aged 14–30 years, diagnosed with PSP and who underwent Video-assisted thoracoscopic surgery (VATS) between January 2016 and December 2022 at Wonju Severance Christian Hospital. Patients were retrospectively divided into two groups based on their initial treatment: chest tube insertion and non-chest tube insertion. Clinical data including demographics, treatment details, and outcomes were collected and compared. Total 128 cases of PSP were included in the study. The total length of hospital stay was significantly shorter in the non-chest tube group (p=0.000), which was attributed to the omission of pre-operative chest tube insertions. No significant differences were observed between the two groups in terms of postoperative complications or recurrence rates. In cases of young patients with PSP, omitting pre-operative chest tube insertion may be a viable option if the patient is scheduled for VATS.

This article aims to detect lung cavitations using lung ultrasound (LUS) in a cohort of patients with pulmonary tuberculosis (TB) and correlate the findings with chest computed tomography (CT) and chest x-ray (CXR) to obtain LUS diagnostic sensitivity. Patients with suspected TB were enrolled after being evaluated with CXR and chest CT. A blinded radiologist performed LUS within 3 days after the admission at the Infectious Diseases Department. Finally, 82 patients were enrolled in the study. BAL confirmed TB in 58/82 (71%). Chest CT showed pulmonary cavitations in 38/82 (43.6%; 32 TB patients and 6 non-TB ones), LUS in 15/82 (18.3%; 11 TB patients and 4 non-TB ones) and CXR in 27/82 (33%; 23 TB patients and 4 non-TB ones). Patients with multiple cavitations were 12 detected at CT and only 1 at LUS. LUS sensitivity was 39.5%, specificity 100%, PPV 100%, NPV 65.7%. CXR sensitivity was 68.4% and specificity 97.8%. No false positive cases were found. LUS sensitivity is rather low as many cavitated consolidations do not reach the pleural surface. Aerated cavitations could be detected with LUS with relative confidence, highlighting a thin air-crescent sign towards the pleural surface within a hypoechoic area of consolidation, easily distinguishable from dynamic or static air-bronchogram.

Background: In chronic obstructive pulmonary disease (COPD), there are two known classifications for assessing what is called disease severity. One is the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification, which is based on the post-bronchodilator value of FEV1 (% reference). The other is the STaging of Airflow obstruction by Ratio (STAR). Methods: We reanalyzed data from our outpatient cohort study, which included 141 participants with COPD from 2015 to 2023. We compared mortality and COPD-specific health status between the GOLD 1 to 4 groups and the STAR 1 to 4 groups. Results: By simple calculation, GOLD and STAR severity classes coincided in 75 participants (53.2%). The weighted Bangdiwala B value with linear weights was 0.775. The participants were observed for up to 95 months, with a median of 54 months. Death was confirmed in 29 participants (20.5%). In univariate Cox proportional hazards analyses, there was a significant difference in mortality between the GOLD 1 and GOLD 3+4 groups, with the GOLD 1 group used as the reference [Hazard Ratio 4.222 (95% CI 1.298 - 13.733), p=0.017]. However, there was no statistically significant predictive relationship between STAR 1 and STAR 2, or between STAR 1 and STAR 3+4. The St. George's Respiratory Questionnaire (SGRQ) Total and COPD Assessment Test (CAT) scores were significantly different between all GOLD groups, except for the CAT score between GOLD 1 and GOLD 2. The SGRQ Total and CAT scores were significantly different between STAR 1 and STAR 3+4, but not between STAR 1 and STAR 2. Conclusion: From the perspective of all-cause mortality and COPD-specific health status, the GOLD classification is more discriminative than STAR.

The COVID-19 pandemic and tuberculosis have epidemiological similarities, being transmitted airborne, favored by direct contact, crowded environments and vulnerable biological status. We performed a retrospective study of 45 cases of pulmonary tuberculosis associated with COVID-19 (TB+COV+) compared to 45 cases with tuberculous monoinfection (TB+COV-), hospitalized during 2021-2022. The demographic characteristics were similar in the two groups, predominating men, a median age of 51 years, living in rural areas, medium level of education and smoking. Common symptoms of the two groups were cough, weight loss, profuse sweating, loss of appetite and hemoptysis, while fever, headache, myo-arthralgias and digestive symptoms characterized the TB+COV+ forms. The scores of radiological lesions in the TB+COV+ compared to TB+COV- group were significantly higher and persistent, revealing more frequent bilateral extensive lung lesions. There were no significant differences in the biological parameters between the two groups. Mortality was 2.2%, regardless of the association of COVID-19. The frequency of infections with Clostridioides difficile was higher in TB+COV+ cases. In conclusion, the co-infection of COVID-19 had an impact on the clinical and biological expression of tuberculosis diagnosed in a pandemic context.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has been proven a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one's specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

Respiratory allergic diseases, affect over 500 million people globally and pose a substantial burden in terms of morbidity, mortality, and healthcare costs. Restrictive factors such as geographical disparities, infectious pandemics, limitations in resource, and shortage of allergy specialists in underserved areas, impede effective management. Moreover, the well-established suboptimal adherence in patients with respiratory allergies, contribute further to the accelerated loss of disease control. Telemedicine encompasses real-time visits, store-and-forward options triage, and computer-based technologies for establishing and efficient doctor-patient communication. Recent advances in digital technology, including designated applications, informative materials, digital examination devices, wearables, digital inhalers, and integrated platforms, facilitate personalized and evidence-based care delivery. The integration of telemonitoring in respiratory allergy care has shown beneficial effects in disease control, adherence, and quality of life. While the COVID-19 pandemic accelerated the adoption of telemedicine, certain concerns regarding technical requirements, platform quality, safety, reimbursement, and regulatory considerations remain unresolved. Challenges in telemonitoring implementation further include ensuring effective doctor-patient collaboration, addressing privacy concerns, and establishing cost-effective models. The integration of artificial intelligence (AI) in telemonitoring applications holds promise for data analysis, pattern recognition, and personalized treatment plans. Striking the balance between AI-enabled insights and human expertise is crucial for optimizing the benefits of telemonitoring. This overview reports the up- to- date telemedicine approaches in managing patients with respiratory allergies. While telemonitoring exhibits potential in enhancing patient care and healthcare delivery, critical considerations have to be addressed in order to ensure the successful integration of telemonitoring into the healthcare landscape.

Computational rhinology is a specialized branch of biomechanics leveraging engineering techniques for mathematical modelling and simulation to complement the medical field of rhinology. Computational rhinology has already contributed significantly to advancing our understanding of the nasal function, including airflow patterns, mucosal cooling, particle deposition, and drug delivery, and is foreseen as a crucial element in e.g. the development of virtual surgery as a clinical, patient-specific decision support tool. The current paper delves into the field of computational rhinology from a nasal airflow perspective, highlighting the use of computational fluid dynamics to enhance diagnostics and treatment of breathing disorders. The paper consists of three distinct parts – an introduction to and review of the field of computational rhinology, a review of published literature on in vitro and in silico studies of nasal airflow, and the presentation and analysis of previously unpublished high fidelity CFD simulation data of in silico rhinomanometry. While the two first parts of the paper summarize the current status and challenges in the application of computational tools in rhinology, the last part addresses the gross disagreement commonly observed when comparing in silico and in vivo rhinomanometry results. It is concluded that this discrepancy cannot readily be explained by CFD model deficiencies caused by poor choice of turbulence model, insufficient spatial or temporal resolution, or neglecting transient effects. Hence, alternative explanations such as nasal cavity compliance or drag effects due to nasal hair should be investigated.

A monolayer of endothelial cells (ECs) lines the lumen of blood vessels and as such provides a semi-selective barrier between the blood and the interstitial space. Compromise of the lung EC barrier due to inflammatory or toxic events may results in pulmonary edema, which is a cardinal feature of acute lung injury (ALI) and its more severe form, the acute respiratory distress syndrome (ARDS). The EC functions are controlled, at least in part, via epigenetic mechanisms mediated by histone deacetylases (HDACs). Zinc-dependent HDACs represent the largest group of HDACs and are activated by Zn2+. Members of this HDAC group are involved in the epigenetic regulation primarily via modifying the structure of chromatin upon removal of acetyl groups from histones. In addition, they can deacetylate many non-histone histone proteins, including those located in extra nuclear compartments. Recently, the therapeutic potential of inhibiting zinc-dependent HDACs for EC barrier preservation has gained momentum. However, the role of specific HDAC subtypes in EC barrier regulation remains largely unknown. This review aims to provide an update on the role of zinc-dependent HDACs in endothelial dysfunction and its related diseases. We will broadly focus on biological contributions, signaling pathways and transcriptional roles of HDACs in endothelial pathobiology associated mainly with lung diseases and we will discuss the potential of their inhibitors for lung injury prevention.

Distinguishing the level of pathology in the lungs through the sound of a cough is a complicated process that includes many factors. This paper explores the challenges of diagnosing lung pathology based solely on cough sounds. It emphasizes that while cough type can offer initial clues, it is just one piece of a complex diagnostic puzzle. For example, the differentiation of dry, productive, barking, hacking, and wheezing coughs provides initial insights into potential pathologies, which can range from respiratory infections to chronic diseases. The examination of cough characteristics, such as frequency, strength, and persistence, aids in identifying the severity of underlying conditions. Moreover, associated respiratory and systemic symptoms further contribute to the diagnostic landscape, with manifestations such as dyspnea, wheezing, chest pain, and hemoptysis offering valuable clinical information. Diagnostic tests, such as imaging studies and laboratory analyses, play a pivotal role in confirming diagnoses. However, challenges in diagnosis based solely on cough sounds require a more holistic approach, taking into consideration the complexity of lung pathologies. The paper concludes that accurately diagnosing lung pathologies based on cough sounds alone is difficult and requires careful consideration of multiple factors and stresses on contextualizing cough characteristics with other clinical features and diagnostic tests for an accurate assessment and comprehensive treatment planning.

Background: Oscillation and pulmonary expansion (OPE) therapy can decrease postoperative pulmonary complications in a general surgical population, but its effect after cardiac surgery has not been reported, to our knowledge. We hypothesized that using an OPE device after cardiac surgery before extubation would decrease pulmonary complications. Methods: This retrospective cohort study included adults undergoing elective open cardiac surgery at our institution from January 2018 through January 2019, who had an American Society of Anesthesiologists score of 3 or greater. For mechanically ventilated patients after cardiac surgery, a new OPE protocol was adopted July 1, 2019, comprising an initial 10-minute OPE treatment administered in-line with the ventilator circuit, then continued treatments for 48 hours after extubation. Severe postoperative respiratory complications (primary outcome measure) included need for antibiotics, increased supplemental oxygen use, and prolonged hospital length of stay (LOS). Demographic, clinical, and outcomes data were compared for patients before (usual care with postextubation hyperinflation) and after protocol implementation (OPE). Results: Of 104 patients, 54 patients received usual care, and 50 received OPE. Usual-care recipients had more men (74% vs 62%; P=.19) and were older (median, 70 vs 67 years; P=.009) than OPE recipients. The OPE group had a significantly shorter hospital LOS than the usual-care group (mean, 6.2 vs 7.4 days; P=.04). Other measures improved with OPE but did not reach significance: shorter ventilator duration (mean, 0.6 vs 1.1 days with usual care; P=.06) and shorter LOS in the intensive care unit (mean, 2.7 vs 3.4 days; P=.06). On multivariate analysis, intensive care unit LOS was significantly shorter for the OPE group (mean difference, 0.85 days; 95% CI, 1.65 to 0.06; P=.04). The OPE group had a lower percentage of postoperative complications (10% vs 20%). Conclusion: OPE therapy after cardiac surgery is associated with decreased ICU and hospital LOS.

Catheter-based revascularization procedures developed as an alternative of systemic thrombolysis for patients at intermediate-high and high-risk pulmonary embolism. USAT IH-PE is a retrospective and prospective multicenter registry of such patients treated with ultrasound-facilitated, catheter-directed thrombolysis, whose preliminary results are presented in this study. The primary endpoint was the incidence of pulmonary hypertension (PH) at follow up. Secondary endpoints were short- and mid-term changes in echocardiographic parameters of right ventricle (RV) function, in-hospital and all-cause mortality, and procedure-related bleeding events. Between March 2018 and July 2023, 102 patients were included. The majority were at intermediate-high risk PE (86%), mostly female (57%), median age 66.5 years (IQR 56-74), and 28.4% had active cancer. Echocardiographic follow-up was available for 70 patients, and in only one the diagnosis of PH was confirmed by right heart catheterization, resulting in an incidence of 1.43% (CI 95%, 0.036-7.7). RV echocardiographic parameters improved both at 24 hours and at follow up. In-hospital mortality was 3.9% (CI 95%, 1.08-9.74) while all-cause mortality was 11% (CI 95%, 5.4-19.2). Only 12% had bleeding complications, oh whom 4.9% were BARC 3. Preliminary results from USAT IH-PE registry showed low incidence of PH, improvement in RV function and a safe profile.

Delivery of drugs through the nasal route provides an alternative, yet highly efficacious modality for administering both large and small pharmaceutic molecules. This method proves particularly advantageous for drugs that are unstable during oral administration, as they undergo significant degradation in the gastrointestinal tract or metabolization through the first-pass effect in the liver. Nasal administration stands as a viable alternative to parenteral therapy and is also suitable for long-term medical management. The nasal mucosa, characterized by high vascularity and permeability, facilitates rapid pharmaceutical absorption, ensuring a swift onset of therapeutic action. Despite its noninvasive nature, the nasal delivery technique finds broad applicability for both local treatment and systemic therapy, as the drug directly enters systemic circulation. This article explores the feasibility of a novel spray delivery mechanism for intranasal drug deposition. The study aims to determine whether users can correctly follow the state-of-the-art application instructions for a nasal spray with an optimal nozzle placement angle (namely, 12-15°) at the nostril while maintaining sufficient safety and efficacy, and without engaging in preventable usage errors that could harm the user. Additionally, the study evaluates the effectiveness of device labeling, instructions for use, and a short video in supporting the correct application of the nasal spray at the optimal angle (12-15°) and assesses whether users can differentiate the product from others with similar appearances. We have also performed physical spray tests to experimentally evaluate drug penetration to the nasopharynx (a key target site for viral infections) for two different nozzle placements – one for current package instructions coming with over-the-counter spray products and the other for the optimal spray usage procedure to enhance targeted drug delivery. Human Factors (HF) validation studies were also conducted, instructing users to follow the application instructions of the nasal spray bottle with the nozzle placed at the optimal angle to target the nasopharynx. The experimental tests consistently confirmed improved penetration with the 12-15° nozzle placement, with visual cues proving effective when used in tandem with written instructions for guiding the study participants to adhere to the recommended usage procedures.

Pharmaceutical aerosols play a key role in the treatment of lung disorders, but also systemic diseases, due to their ability to target specific areas of the respiratory system (RS). This article focuses on identifying and clarifying the influence of various factors involved in the generation of aerosol micro- and nanoparticles on their regional distribution and deposition in the RS. Attention is given to the importance of process parameters during aerosolization of liquids or powders and the role of aerosol flow dynamics in RS. The interaction of deposited particles with the fluid environment of the lung is also pointed out as an important step in the mass transfer of the drug to the RS surface. The analysis presented highlights the technical aspects of preparing the precursors to ensure that the properties of the aerosol are suitable for a given therapeutic target. Analyzing existing technical limitations, several potential strategies for enhancing the efficiency of targeted therapeutic delivery to or through the respiratory system are identified and presented, including the use of smart inhaling devices incorporating AI algorithms.

Background: Current obstructive sleep apnea treatment relies on manual PAP titration, but it has limitations. Complex interactions during titration and variations in SpO2 data accuracy pose challenges. Patients with co-occurring chronic hypercapnia may require precise oxygen titration. To address these issues, we propose a Clinical Decision Support System using Markov Decision Processes. Methods: This study, compliant with data protection laws, focused on adults with OSA-induced hypoxemia utilizing supplemental oxygen and CPAP/BiPAP therapy. PAP titration, conducted over one night, involved vigilant monitoring of vital signs and physiological parameters. Adjustments to CPAP pressure, potential BiLevel transitions, and supplemental oxygen were precisely guided by patient metrics. Markov Decision Processes outlined three distinct phases for sleep disorder management, incorporating expert medical insights. Results: In our study involving 14 OSA patients (average age: 63 years, 27% females, BMI 41 kg m−2), significant improvements were observed in key health parameters. The initial AHI of 61.8 events per hour significantly decreased to an average of 18.0 events per hour after PAP and oxygen titration (p < 0.0001), indicating a substantial reduction in sleep-disordered breathing severity. Concurrently, SpO2 levels increased significantly from an average of 79.7% before titration to 89.1% after titration (p < 0.0003). Pearson correlation coefficients demonstrated aggravation of hypercapnia in 50% of patients (N=5) with initial hypercapnia during the increase of CPAP pressure. However, transitioning to BiPAP exhibited a reduction in pCO2 levels, showcasing its efficacy in addressing hypercapnia. Simultaneously, BiPAP therapy correlated with a substantial increase in SpO2, underscoring its positive impact on oxygenation in OSA patients. Markov dynamic process analysis demonstrated realistic patient behavior during stable night conditions, emphasizing minimal apnea and good toleration to high CPAP pressure. Conclusions: the development of a framework for Markov Decision Processes of PAP and oxygen titration algorithms holds promise for providing algorithms for deviation in pCO2 and SpO2 markers. While challenges remain, including the need for high-quality data, the potential benefits in terms of patient management and care optimization are substantial, and this approach represents an exciting frontier in the realm of telemedicine and respiratory healthcare. Obstructive sleep apnea, PAP titration, hypoxia, hypercapnia, Markov decision processes

(1) Background: During physical exercise, ventilation (VE) adapts to the intensity and characteris-tics of the effort. The breathing pattern is defined as the relationship between the tidal volume (VT) and breathing frequency (BF) for a given VE. The aim of this study was to evaluate whether inspiratory muscle training influenced the response of the breathing pattern during an incremen-tal effort in amateur cyclists. (2) Methods: 18 amateur cyclists completed an incremental test to exhaustion with gas analysis on a cycle ergometer and spirometry. Cyclists were randomly as-signed to two groups (IMTG=9; CON=9). The IMT group completed 6 weeks of inspiratory muscle training (IMT) using a PowerBreathe K3® device at 50% of the maximum inspiratory pressure (Pimax). The workload was adjusted weekly. After the 6-week intervention, the cyclists repeated the incremental exercise test with gas analysis and spirometry. The response of the breathing pat-tern was evaluated during the incremental exercise test. (3) Results: Pimax increased in the IMTG (p<0.05; +19.62%). Variables related to the breathing pattern response showed no differences be-tween groups after the intervention (EXPvsCON; p>0.05). Likewise, no differences were found in the IMTG after training (PREvsPOST; p>0.05). (4) Conclusions: IMT improved the strength of in-spiratory muscles and sports performance in amateur cyclists. These changes were not attributed to alterations in the response of the breathing pattern.

Haemolytic anaemia represents a risk factor for the development of pulmonary hypertension (PH), currently classified as World Health Organization group 5 PH and data regarding appropriate therapeutic strategy are limited. A total of 28 patients, 85.7% with thalassemia and 14,3% with sickle cell disease, with a diagnosis of PH confirmed by right heart catheterization, were included in the study. The patients were divided into three groups according to haemodynamics and overall diagnostic approach: 42,9% had precapillary PH (Pulmonary Arterial Hypertension -PAH group), 25% post-capillary PH and 32.1% Chronic Thromboembolic PH (CTEPH) (29% of b-thalassemia and 50% of SCD patients). The therapeutic approach in each group and its impact on the outcome and haemodynamics was recorded. PAH-specific drug therapy received 82.1% of patients and Balloon Pulmonary Angioplasty (BPA) was performed in 6 patients with CTEPH. There were statistically significant differences in baseline mPAP and PVR values between the CTEPH-haemolytic anaemia group and other groups. PAH-specific drug therapy resulted in haemodynamic improvement for PAH-group. Patients who underwent BPA improved Pulmonary Haemodynamics. Median survival time was 162 months and the survival rate was 1yr-100%, 2,3,4,5,6 years 96%, 9yrs 90% and 13yrs 78%. In patients with haemolytic anaemia, the wide spectrum of induced PH highlights the importance of a correct diagnosis. BPA in CTEPH patients and specific-PAH drug therapy for PAH patients represent potential therapeutic strategies, however the management should be offered in expert PH centers under patients’ individualized approach.

Fungal-bacterial co-colonization and co-infections are emerging among TB-suspected patients, yet the underlying mechanisms that enable and arise from their interactions are poorly understood. Understanding how environmental microbes such as fungi and bacteria co-evolve and develop traits to evade host immune responses and resist treatment is critical to controlling opportunistic co-infections. Our previous work has demonstrated that fungal-bacterial interactions can have dramatic impacts on fungal pathogenesis and drug resistance. Here, we, therefore, hypothesize that cross-kingdom synergistic interactions between environmental fungi and bacteria may influence both fungal and bacterial virulence, antimicrobial resistance patterns and aetiology. Through this, we aimed to establish the prevalence of fungal–bacterial microbial communities associated with chronic primary or opportunistic pulmonary infections. Concordantly, through surveilling 302 clinical samples from 151 patients, we established the prevalence of TB (0.7%) to be lower than that of fungi (1.3%) and non-TB bacterial (4.6%) mono-aetiologies Figure 2. However, our main observation was the unexpected taxonomic diversity with a striking twist of fungal-bacterial di-kingdom aetiological conformities. Interestingly, the majority of the patients presented with at least a di or mono-kingdom aetiological pairings. Importantly, fungi and non-TB bacteria formerly regarded as atypical opportunists are now frequently isolated as possible aetiology for chronic pulmonary infection. Hence, we revealed many di-kingdom aetiological pairings here but their significance remains a question of further examination. Among which Acremonium spp + K. pneumoniae (n=5), Acremonium spp +Streptococcus pneumoniae (n=4), Acremonium spp + C. albicans + K. pneumoniae (n=3) were among the most dominant aetiological pairings observed. Interestingly, Acremonium spp + K. pneumoniae pairings were also seen to be the most commonly associated with pulmonary TB both during and after treatment. Isolation from the same infection niche as seen here calls for further investigations into any interaction signatures that may exist between these organisms. Taken together, our data suggest that fungal-bacterial co-existence may influence their virulence attributes and antimicrobial resistance patterns, with relevance to patient outcomes. Therefore, our data reveals an array of fungal-bacterial pairings that may influence the prognosis of chronic pulmonary disease. Importantly, suggesting that the diversity of pulmonary infective fungi and bacteria, and their complex population structures may pose challenges to the analysis and interpretation of conventional data. Thus, there is a need to redirect our diagnostic approaches to encompass polymicrobial aetiology in order to enhance our suspicion index for better management of opportunistic fungal-bacterial co-infections.

Background: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns(ARP) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. Methods: Retrospective pre(2018) and post-intervention(2019-21) study in ICU patients. A rapid diagnostic algorithm was applied from 2019 in patients with lower respiratory tract infection. Incidence of nosocomial infection, ARP, and AC as DDD(defined daily dose) were monitored. Results: A total of 3635 patients were included, 987(pre-intervention) and 2648(post-intervention). A median age was 60 years, 64% male, with APACHE II of 19 points and SOFA of 3 points. Overall ICU mortality of 17.2% without differences between the periods. An increase in the number of infections was observed in the post-intervention period(44.5% vs 17.9%, p<0.01), especially due to an increase in ventilator-associated pneumonia(44.6% vs 25%,p<0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021(Rate Ratio=0.51). A recovery of P.aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. Conclusion: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed a significant reduction in AC and ARP without affecting the prognosis of critically ill patients.

Definitive surgical resection is the preferred treatment for early-stage non-small-cell lung cancer (NSCLC). Research into genetic alterations, including epidermal growth factor receptor (EGFR) mutation, in early stage NSCLC remains insufficient. Here, we investigated the prevalence of genetic alterations in early-stage NSCLC and the association between EGFR mutation and recurrence after complete resection. Between January 2019 and December 2021, 659 patients with NSCLC who underwent curative surgical resection at a single regional cancer center were recruited. We compared the clinical and pathological data between the recurrence and non-recurrence groups. Multivariate logistic regression was used to predict the risk factors for recurrence. Among the 659 enrolled cases, the most common histology was adenocarcinoma (74.5%), followed by squamous cell carcinoma (21.7%). The prevalence of EGFR mutation was 43% (194/451). Among them, L858R point mutation and exon 19 deletion was 52.3% and 42%, respectively. ALK rearrangement was found at 5.7% (26/453), and ROS1 fusion was found at 1.6% (7/441). The recurrence rate of the entire population was 19.7%. In multivariate analysis, the presence of EGFR mutation, stage II or III (vs. stage I), and pathologic subtype (presence of solid type) were associated with recurrence. Among the recurred group, 86.5% of the patients with EGFR mutation experienced distant recurrence compared to only 66.7% of wild-type (p = 0.016), with no significant difference in median disease-free survival (p = 0.983). In conclusion, the prevalence of EGFR mutation, ALK rearrangement, and ROS1 fusion was 43.0%, 5.7%, and 1.6%, respectively in patients with early-stage NSCLC who underwent curative resection. Along with stage II/III and solid pathologic subtype, EGFR mutation was an independent risk factor for recurrence. In the recurrence group, the rate of distant metastasis was higher in patients with EGFR mutation than in those with wild-type.

(1) Background: Ulcerative colitis (UC) is characterized by immune system dysregulation with frequent extraintestinal manifestations, including airways involvement. Reduction in CO diffusing capacity and functional alterations in small airways have been described. The extended analysis of Fractional Exhaled Nitric Oxide (FeNO), may distinguish the sites of production and the presence of small airways inflammation being a useful, non-invasive marker for these patient’s follow up. The aim of our study was to compare PFTs, FeNO and CANO values of UC patients with different clinical disease activity and healthy subjects to reveal lung function abnormalities and the presence of subclinical airway inflammation. (2) Methods: We enrolled 42 adult outpatients with different clinical activity stages of UC (mean age 39±13 years) and a healthy control group of 41 subjects (mean age 29±3 years). C-reactive protein (CRP) and FeNO values at different flows (50,100 and 200 ml/sec) were collected. All patients performed pulmonary function tests (PFT’s) with static volumes and diffusing capacity (DLCO). (3) Results: FENO, CANO and CRP values were significantly increased in UC patients when compared with controls (p=0.02 and p&lt;0.0001, respectively) and proportionally to the disease activity (FeNO class 3: 27.1 ppb vs class 1-2: 6.2 ppb; CANO values class 3: 8.1 ppb vs class 1-2: 2.0 ppb (p &lt; 0.0001). TLC and DLCO were significantly reduced in UC patients compared to controls (p=0.011 and p&lt;0.0001, respectively). (4) The results of this study show significant lung functional abnormalities in UC patients and suggest the presence of airway inflammation directly correlated with the disease activity suggesting an integrated approach in routine assessment.

Cytokine adsorption can resolve different complications characteristic of transplantation medicine, such cytokine storm activation, blood immuno- and AB0- incompatibilities but can also be performed for the treatment of various life-threatening conditions, such as sepsis, acute respiratory distress syndrome (ARDS), and cardiogenic shock, all of which can contribute to adverse clinical outcomes during transplantation. After surgery, dysmetabolism and stress response limit successful graft survival and can lead to primary (PGD) or secondary graft dysfunction. In this clinical context, and given that a major problem in transplant medicine is that the demand for organs far exceeds the supply, a technological innovation such as a hemoadsoption system could greatly contribute to increasing the number of usable organ donors. The objectives of this review are to describe the specific advantages and disadvantages of the application of cytokine adsorption in the context of transplantation and also to examine, before and/or after organ transplantation, the benefits of addition of a complementary cytokine adsorption therapy protocol.

Exudative-pleural-effusion (ePE) is a common presentation in pulmonology clinics. Pleural biopsy is indicated for identifying the aetiology in undiagnosed ePE especially the ones with low adenosine-deaminase levels. The access to rigid and semi-rigid medical thoracoscopy is scarce and heterogeneous in a resource limited country like India. In such circumstances, using flexible bronchoscope via intercostal-chest-tube for visualization of parietal pleura and pleural biopsy offers a way out. Here, in this retrospective study, we have presented our experience of such practice on 25 cases. Mean age was 52.4±1 years. Adhesions were present in 40% of the subjects. Most common finding was presence of nodules. On an average 6.8 passes were taken with maximum of 10. In 32% cases only tiny tissue was obtained, hence requiring multiple passes. Large tissue could be obtained in 44% of the subjects. Mean duration of the procedure was 35.6±9.0 minutes. Tissue diagnosis was established in 80% with most common being malignancy (48%) followed by tuberculosis (20%). In 3 cases, the final diagnosis was made by exclusion. No major complications were recorded. In conclusion, medical thoracoscopy using flexible video bronchoscope via intercostal-chest-tube was a feasible alternative for the diagnosis of ePE effusion in resource limited settings.

Few clinical factors can help predict spontaneous culture conversion (SCC) in patients with Mycobacterium avium complex-pulmonary disease (MAC-PD). We retrospectively classified 373 MPD patients who had undergone watchful waiting without antibiotics according to the so-called ‘body mass index (BMI), age, cavity, erythrocyte sedimentation rate (ESR), and sex (BACES)’ severity. We evaluated whether lower severity is associated with a higher rate of SCC. Of 373 patients, 153 (41%) achieved SCC without antibiotics during a median follow-up of 48.1 months. There was a trend toward a higher SCC rate in patients with lower BACES severity: 48% (87/183), 37% (58/157), and 24% (8/33) in the mild, moderate, and severe BACES groups, respectively. In addition, a favorable outcome, defined as maintaining SCC or having two consecutive negative sputum cultures until the last follow-up date, was also more common in patients with lower BACES severity with 53% (97/183), 34% (54/157), and 18% (6/33) in the mild, moderate, and severe BACES groups, respectively. In multivariate analysis, moderate (hazard ratio [HR]=0.63; 95% confidence interval [CI] 0.44 – 0.91; p = 0.013) and severe BACES (HR 0.37; 95% CI 0.16 – 0.90; p = 0.028) had a significantly negative impact on favorable outcomes compared to mild BACES. Lower BACES severity may be associated with SCC in MAC-PD patients.

Xpert MTB/RIF is rapid molecular diagnostic tool capable of simultaneously detecting Mycobacterium tuberculosis and rifampicin resistance. This study aimed to access the diagnostic precision of Xpert MTB/RIF assay to detect pulmonary and extra-pulmonary tuberculosis and to evaluate the performance for the detection of rifampicin resistance. Of 37695 samples, 7156(18.98%) were tuberculosis positive, 509(7.11%) were rifampicin-resistant. The sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay for PTB were 99.87% (95%CI:99.75-99.94), 99.92%(95%CI:99.88-99.95), 99.71%(95%CI:99.54-99.82),99.97%(95%CI:99.93-99.98),21.38% (95%CI:20.92-21.86),and 99.91%(95%CI:99.87-99.94), respectively. For EPTB, the sensitivity, specificity, PPV, NPV, Diseases prevalence and accuracy of Xpert MTB/RIF assay accounted for 99.45% (95%CI:98.73-99.82),99.84%(95%CI:99.73-99.92),98.70%(95%CI:97.73-99.25),99.93% (95%CI:99.84-99.97),10.64%(95%CI:9.99-11.31),and 99.80%(95%CI:99.68-99.88), respectively. Despite its high sensitivity for detecting tuberculosis and rifampicin resistance, Xpert MTB/RIF had contradictory results for 20.5% of cases among patients with negative smear results and 54.9% of cases among patients with a high risk of Multidrug-resistant tuberculosis. Of 47 fluoroquinolone-resistant, 16.56% (26/157) of Multidrug-resistant tuberculosis isolates and 4.02% (20/498) isoniazid-resistant are fluoroquinolone-resistant, a characteristic distribution leading to about 17.2% of fluoroquinolone resistance events and relevant marker gyr-A mutations in MDR tuberculosis isolates. Further, our study indicated that increased fluoroquinolone resistance among Rifampicin-resistant and isoniazid-resistant tuberculosis endangers the success of newly endorsed MDR-TB regimens.

Lung cancer, globally recognized as the leading cause of cancer-related mortality, presents a pressing need for innovative treatment strategies. Increasing evidence points towards the potential of monoamine oxidase (MAO) inhibitors in modulating cancer progression, primarily due to their role in regulating cellular metabolism and apoptotic pathways. This extraordinary study delves into the multifaceted therapeutic implications of MAO inhibitors in lung cancer management, elucidating their ability to pave the way for clinical advancement via novel targets and pathways. Capitalizing on recent advances in molecular biology, this research explores the molecular mechanisms underlying the anticancer actions of MAO inhibitors. By examining their impact on cell proliferation, migration, invasion, and apoptosis in lung cancer cell lines, we provide insight into the intricate signaling pathways and biochemical processes modulated by these compounds. The study also investigates the synergistic effects of MAO inhibitors in combination with established chemotherapeutic agents, elucidating their potential to enhance treatment efficacy and reduce cytotoxicity. Furthermore, we delve into the implications of MAO inhibitors on the tumor microenvironment, evaluating their influence on angiogenesis, immune regulation, and the epithelial-mesenchymal transition. This comprehensive analysis enables the identification of novel molecular targets, which hold promise for the development of advanced therapeutics tailored for specific lung cancer subtypes. To substantiate our findings, in this review, we thoroughly analyze the existing literature using state-of-the-art bioinformatics tools." in vivo orthotopic lung cancer models, and clinical patient cohorts. This robust and multidisciplinary approach permits the generation of clinical evidence supporting the integration of MAO inhibitors in lung cancer management. Conclusion: This ground-breaking study establishes the therapeutic potential of monoamine oxidase inhibitors in lung cancer management by unearthing novel pathways and targets for clinical advancement. The outcomes open doors for the development of innovative treatment strategies and inspire continued research efforts to combat the global burden of lung cancer.

Lung cancer, globally recognized as the leading cause of cancer-related mortality, presents a pressing need for innovative treatment strategies. Increasing evidence points towards the potential of monoamine oxidase (MAO) inhibitors in modulating cancer progression, primarily due to their role in regulating cellular metabolism and apoptotic pathways. This extraordinary study delves into the multifaceted therapeutic implications of MAO inhibitors in lung cancer management, elucidating their ability to pave the way for clinical advancement via novel targets and pathways. Capitalizing on recent advances in molecular biology, this research explores the molecular mechanisms underlying the anticancer actions of MAO inhibitors. By examining their impact on cell proliferation, migration, invasion, and apoptosis in lung cancer cell lines, we provide insight into the intricate signaling pathways and biochemical processes modulated by these compounds. The study also investigates the synergistic effects of MAO inhibitors in combination with established chemotherapeutic agents, elucidating their potential to enhance treatment efficacy and reduce cytotoxicity. Furthermore, we delve into the implications of MAO inhibitors on the tumor microenvironment, evaluating their influence on angiogenesis, immune regulation, and the epithelial-mesenchymal transition. This comprehensive analysis enables the identification of novel molecular targets, which hold promise for the development of advanced therapeutics tailored for specific lung cancer subtypes. To substantiate our findings, in this review, we thoroughly analyze the existing literature using state-of-the-art bioinformatics tools." in vivo orthotopic lung cancer models, and clinical patient cohorts. This robust and multidisciplinary approach permits the generation of clinical evidence supporting the integration of MAO inhibitors in lung cancer management. Conclusion: This ground-breaking study establishes the therapeutic potential of monoamine oxidase inhibitors in lung cancer management by unearthing novel pathways and targets for clinical advancement. The outcomes open doors for the development of innovative treatment strategies and inspire continued research efforts to combat the global burden of lung cancer.

Extracorporeal membrane oxygenation (ECMO) is used for the management of severe respiratory and cardiac failure, as well as bridge to definite treatment or transplantation. ECMO associated coagulopathy (EAC) is a frequent complication leading to high rates of thrombosis or severe haemorrhage, contributing to morbidity and mortality of patients. Understanding the pathophysiology of EAC is substantial for effectively managing patients on ECMO. We analyse the underlying mechanism of EAC and discuss the monitoring of coagulation profile, combining the viscoelastic point of care assays with the conventional coagulation laboratory tests.

Background: Patients with chronic obstructive pulmonary disease (COPD) often suffer from acute exacerbations. Our objective was to describe recurrent exacerbations in a GP based Swiss COPD cohort, and develop a statistical model for predicting exacerbation. Methods: In a questionnaire-based COPD cohort, demographic and medical data were recorded for 24 months. Data set was split into training (75%) and validation (25%) datasets. A negative binomial regression model was developed using the training dataset to predict the exacerbation rate within 1 year. An exacerbation prediction model was developed, and the overall performance was validated. A nomogram was created to facilitate the clinical use of the model. Results: Of the 229 COPD patients analyzed, 77% of patients had no exacerbation during the follow-up. The best subset in the training dataset found that lower forced expiratory volume, high scores on the MRC dyspnoea scale, exacerbation history, being on combination therapy of LABA+ICS or LAMA+LABA at baseline were associated with a higher rate of exacerbation. When validated, the area-under-curve (AUC) was 0.75 for one or more exacerbations. Calibration was accurate (predicted 0.34 exacerbations vs observed 0.28 exacerbations). Conclusion: Nomograms built from these models can assist clinicians in the decision-making process of their COPD care.

Sleep apnea is common in professional truck drivers. As undiagnosed and/or untreated sleep apnea is a risk factor for sleepiness-related traffic accidents, it should be recognized. We develop a new, simple tool to screen sleep apnea in this population. Altogether, 2066 professional truck drivers received a structured questionnaire. 175 drivers had a clinical examination and were invited to sleep laboratory studies, including cardiorespiratory polygraphy. We studied associations of different risk factors with the presence of sleep apnea. We established a new simple screening tool for sleep apnea that was compared to other existing screening tools. 1095 drivers filled in the questionnaire. 172 drivers had successful cardiorespiratory polygraphy. Full data was available for 160 male drivers, who were included in the analyses. The following five risk factors for sleep apnea formed the BAMSA-score (0 to 5): BMI>30 kgm-2, Age>50 years, Male gender, Snoring at least on one night per week and presence of Apneas at least sometimes. BAMSA showed a sensitivity of 85.7% and a specificity of 78.8% in detecting AHI≥15, when using a cut point of 4 and the ROC area was 0.823. BAMSA is a sensitive and easy-to-use tool in predicting sleep apnea in male professional drivers.

The emergence of M. tuberculosis strains resistant to Isoniazid (INH) and Rifampicin (RIF), the two most potent drugs of first-line anti-TB therapy is termed multidrug drug-resistant TB (MDR-TB). Multidrug-resistant tuberculosis has been a serious medical and epidemic problem all over the world. We present here a series of clinical cases consist of two patients diagnosed with isoniazid resistant tuberculosis. Histopathological examination supports the diagnosis of tuberculous granulomas. And the pathology molecular examination revealed the presence of Isoniazid-resistant Mycobacterium tuberculosis1,2 via the following mutation c.947G&gt;A; p.Gly316Asp. Isoniazid-resistance is associated with mutations in the furA-katG and fabG1-inhA operons, as well as mutations in the ahpC gene. 64% of the isoniazid-resistance phenotypes were associated with the katG315 mutation worldwide. The second most common mutation is inhA-15, and it has been reported in 19% of the Isoniazid-resistant isolates. The significant association between the two mutations, inhA c-15 and katG 315 respectively, and the high-level resistance is of interest in the interpretation of current and future molecular diagnostic testing, as an early prediction of the level of Isoniazid-resistance is essential to decide the benefit of high-dose Isoniazid use.

Background: Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic lung disease with a poor prognosis. Pirfenidone is approved and widely used for the treatment of IPF and reduces lung function decline. The aim of this study was to evaluate the efficacy of different doses of pirfenidone for the prevention of disease progression in patients with IPF. Methods: This was a prospective, observational, single-center cohort study conducted in Haeundae Paik Hospital, Republic of Korea, from April 2021 to March 2023. IPF patients were assigned to three groups according to the dose of pirfenidone (600mg, 1,200mg, 1,800mg). The primary endpoint was the efficacy of pirfenidone according to dose for the prevention of disease progression over 12 months. The secondary endpoint was the role of Krebs von den Lungen-6 (KL-6) in predicting disease progression. Results: A total of 44 patients were enrolled, of whom 39 completed the study, with 13 patients assigned to each of the three groups. The median age was 71.7 years, and 79.5% of patients were men. The baseline characteristics were similar across groups, except the 600mg group was older (75.9 vs. 69.2 vs. 68.2 years, p = 0.016). Fourteen patients (35.9%) suffered disease progression. The rate of disease progression did not differ according to the dose of pirfenidone (38.5 vs. 38.5 vs. 30.8%, p = 1.000). In multivariable logistic regression analysis, KL-6 was not a statistically significant predictor of disease progression. Conclusions: In our study, regardless of dose, consistent pirfenidone use for 12 months resulted in similar efficacy for the prevention of disease progression in patients with IPF. Large-scale, randomized, double-blind, placebo-controlled clinical trials are needed.

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.

It has been reported that prostaglandin I2, such as epoprostenol, develops Grave's disease. A 34-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension and started receiving continuous intravenous epoprostenol. Three years after starting epoprostenol, she started complaining of neck swelling and was diagnosed with Grave’s disease. Thyroid function was controlled by thiamazole and levothyroxine. Nevertheless, her thyroid gland enlargement worsened as epoprostenol dose was titrated. After 23 years of treatment with epoprostenol, she suddenly experienced respiratory failure with a giant goiter leading to airway stenosis and passed away. The autopsy confirmed a giant goiter associated with hyperthyroidism and airway stenosis. We experienced a case of idiopathic pulmonary hypertension with a giant goiter and airway stenosis after long-term intravenous epoprostenol therapy.

Interstitial lung disease (ILD) is one of the most serious extra-articular complications of rheu-matoid arthritis (RA), which increases the mortality of RA. Because the pathogenesis of RA-ILD remains poorly understood, appropriate therapeutic strategies and biomarkers have not yet been identified. Thus, the goal of this review was to summarize and analyze the reported data on the etiology and pathogenesis of RA-ILD. The incidence of RA-ILD increases with age, and is also generally higher in men than in women and in patients with specific genetic variations and eth-nicity. Lifestyle factors associated with an increased risk of RA-ILD include smoking and exposure to pollutants. The presence of an anti-cyclic citrullinated peptide antibody, high RA disease activity, and rheumatoid factor positivity also increase the risk of RA-ILD. We also explored the roles of biological processes (e.g., fibroblast–myofibroblast transition, epithelial–mesenchymal transition, and immunological processes), signaling pathways (e.g., JAK/STAT and PI3K/Akt), and the his-topathology of RA involved in RA-ILD pathogenesis based on published preclinical and clinical models of RA-ILD in animal and human studies.

Introduction: Asthma and bronchiectasis are often partners in a complex but uneven relationship with asthma receiving more attentions. The aim of this study is to describe how bronchiectasis are investigated in some Severe Asthma (SA) Centers scattered throughout the Italian territory. Materials and Methods: We enrolled 92 patients with SA and bronchiectasis from 8 Italian SA Centers and recorded diagnostic approaches to investigate SA and bronchiectasis at the time of enrollment (T0), at the 6-month (T1), and at the 12- month (T2) follow-up visits. Results: A statistically significant heterogeneous diagnostic approach emerged across the centers under study In fact, while, as expected, all involved centers made an in-depth investigation of SA, only few of them made a complete investigation of bronchiectasis in order to provide specific treatment. Discussion: This real-life multicenter study confirmed that patients with coexistent SA and bronchiectasis are mainly investigated for pheno-endotyping asthma but rarely for complete assessment of bronchiectasis. We believe that the diagnostic flowchart of SA patients with suspicion or confirmed bronchiectasis needs to be clarified and implemented as the association of these conditions strongly influences final outcomes and management of these patients.

The risk of lung exposure to silica nanoparticles (SiNPs) and related lung inflammatory injury is increasing with the wide application of SiNPs in a variety of industries. A growing body of research has revealed that cyclooxygenase (COX)-2/ prostaglandin E2 (PGE2) up-regulated by SiNPs toxicity has a role during pulmonary inflammation. The detailed mechanisms underlying SiNPs-induced COX-2 expression and PGE2 synthesis remain unknown. The present study aims to dissect the molecular components involved in COX-2/PGE2 up-regulated by SiNPs in human pulmonary alveolar epithelial cells (HPAEpiCs) which are one of the major targets while SiNPs are inhaled. In the present study, we demonstrated that SiNPs induced COX-2 expression and PGE2 release, which were inhibited by pretreatment with a reactive oxygen species (ROS) scavenger (edaravone) or the inhibitors of proline-rich tyrosine kinase 2 (Pyk2, PF-431396), epidermal growth factor receptor (EGFR, AG1478), phosphatidylinositol 3‑kinase (PI3K, LY294002), protein kinase B (Akt, Akt inhibitor VIII), p38 mitogen-activated protein kinase (MAPK) (p38 MAPK inhibitor VIII), c-Jun N-terminal kinases (JNK)1/2 (SP600125), Forkhead Box O1 (FoxO1, AS1842856), and activator protein 1 (AP-1, Tanshinone IIA). In addition, we also found that SiNPs induced ROS-dependent Pyk2, EGFR, Akt, p38 MAPK, and JNK1/2 activation in these cells. These signaling pathways induced by SiNPs could further cause c-Jun and FoxO1 activation and translocation from the cytosol to the nucleus. AP-1 and FoxO1 activation could increase COX-2 and PGE2 levels induced by SiNPs. Finally, the COX-2/PGE2 axis might promote the inflammatory responses in HPAEpiCs. In conclusion, we suggested that SiNPs induced COX-2 expression accompanied by PGE2 synthesis mediated via ROS/Pyk2/EGFR/PI3K/Akt/p38 MAPK- and JNK1/2-dependent FoxO1 and AP-1 activation in HPAEpiCs.

Background – Endobronchial squamous cell carcinoma is one of the most common types of tumors with such a location. Patients often present in advanced stages of the disease, which leads to a targeted therapeutic attitude of pneumonectomy, most of the time. Practicing a lung parenchyma-preserving surgery led us to do this review. Material and Methods - We used three search platforms SCIENCE, MEDLINE and PubMed, in order to identify studies presenting case reports, studies and reviews on endobronchial squamous cell carcinoma. We identified clinical and paraclinical features of endobronchial squamous cell carcinoma. All selected articles were in English and contained clinical criteria of endobronchial squamous cell carcinoma, autofluorescence bronchoscopy in endobronchial squamous cell carcinoma, imaging features of endobronchial squamous cell carcinoma, blood tumor markers specific for lung squamous cell carcinoma, histopathological features of endobronchial squamous cell carcinoma. Results - 73 articles were analyzed, from which 47 articles were selected as bibliographic references. We have presented the criteria found for endobronchial squamous cell carcinoma in order to highlight the main characteristics and high reliability technologies for the detection of this type of cancer. Conclusions – The current literature review highlights the clinical and paraclinical characteristics of endobronchial squamous cell carcinoma. It aims to open new horizons for research and early detection, frequent practice of lung parenchymal preservation surgery.

Context: Endobronchial tumors are relatively rare. Pathological types are varied, both benign and malignant. Establishing the diagnosis and sleeve resection criteria for such tumors remains a challenge for pulmonologists, bronchoscopists, radiologists, thoracic surgeons, and pathologists. The management of the preoperative assessment of these patients and the establishment of the indication for sleeve resection, represent a big problem. Lung parenchymal sparing surgery remains a challenge, especially in neoplastic patients. Material and methods: We carried out a monocentric retrospective study, during the period 2009-2017, on a number of 57 patients. In our center they benefited from clinical examination, radiography, tomography, respiratory function evaluations, autofluorescence bronchoscopy, cardiological evaluation and detection of blood tumor markers. All the patients benefited from the analysis of the tumorboard of our institute and the establishment of the surgical indication for scleev resection. Results: Sparing of the lung parenchyma was achieved in case of the 57 patients included in the study. The complex evaluations of laboratory parameters, functional tests, CT examination, bronchoscopy, cardiology, were analyzed by the tumor board, so that the indication for surgical intervention was sleeve resection with preservation of the lung parenchyma. Conclusions: We selected patients for sleeve resection, those who presented endobronchial tumors of 2 cm in diameter, with cartilages and bronchial mucosa intact at least 1 cm or 2 cartilages from the formation, on CT and bronchoscopic examination. Cardiological examination and functional tests showed values that do not contradict surgical intervention.

Background: The ever-growing emergence of antibiotic resistance associated with tuberculosis (TB) has become a global challenge. In 2012, USFDA has given expedited approval to bedaquiline (BDQ), as a new treatment for drug-resistant TB in adults when no other viable options are available. BDQ is a diarylquinoline derivative and exhibits targeted action on mycobacterium tuberculosis but due to poor solubility desired therapeutic action is not achieved. Objective: To develop a QbD-based self-nanoemulsifying drug delivery system of Bedaquiline using various oils, surfactants, and co-surfactants. Methods: The quality target product profile (QTPP) and critical quality attributes (CQAs) were identified with a patient-centric approach which facilitated the selection of critical material attributes (CMAs) during pre-formulation studies and initial risk assessment. Caprylic acid as a lipid, propylene glycol as a surfactant and Transcutol-P as a co-surfactant were selected as CMAs for the formulation of Bedaquiline fumarate SNEDDS. Pseudo-ternary phase diagrams were constructed to determine the optimal ratio of oil and Smix. To optimize the formulation, a Box-Benkhen design (BBD) was used. The optimized formulation (BDQ-F-SNEDSS) was further evaluated for parameters such as droplet size, polydispersity index (PDI), percentage transmittance, dilution studies, stability studies, and cell toxicity through the A549 cell. Results: Optimized BDQ-F-SNEDDS showed well-formed droplets of 98.88±2.1 nm with a zeta potential of 21.16 mV. In vitro, studies showed enhanced drug release with a high degree of stability at 25 ± 2 ºC & 60 ± 5 % and 40 ± 2 ºC & 75± 5 %. Furthermore, BDQ-F-SNEDDS showed promising cell viability in A549 cells indicating BDQ-F-SNEDDS as a safer formulation for oral delivery. Conclusion: Finally, it was concluded that the utilization of a QbD approach in the development of BDQ-F-loaded SNEDDS offers a promising strategy to improve the biopharmaceutical properties of the drug, resulting in potential cost and time savings.

Low nasal nitric oxide (nNO) is a typical feature in Primary Ciliary Dyskinesia (PCD). nNO is part of the PCD diagnostic algorithm due to its discriminative power against other lung diseases such cystic fibrosis (CF). However, the underlying pathomechanisms are elusive. To better understand NO dysregulation in PCD, the L-arginine/NO (Arg/NO) pathway in patients with PCD (pwPCD) and CF (pwCF) and in healthy control (HC) subjects was investigated. In a prospective, controlled study, we measured in 24 pwPCD, 25 age-matched pwCF, and 14 HC the concentrations of the NO precursors Arg and homoarginine (hArg), the arginase metabolite ornithine (Orn), the NO inhibitor asymmetric dimethylarginine (ADMA), and the major NO metabolites (nitrate, nitrite) in sputum, plasma and urine by validated methods. In comparison to HC, the sputum contents (in µmol/mg) of L-Arg (PCD 18.43 vs. CF 329.46 vs. HC 9.86, p &lt; 0.001) and of ADMA (PCD 0.055 vs. CF 0.015 vs. HC 0.010, p &lt; 0.001) were higher. In contrast, the sputum contents (in µmol/mg) of nitrate and nitrite were lower in PCD compared to HC (nitrite 4.54 vs. 9.26, p = 0.023; nitrate 12.86 vs. 40.33, p = 0.008), but higher in CF (nitrite 16.28, p &lt;0.001; nitrate 56.83, p = 0.002). The metabolite concentrations in urine and plasma were similar in all groups. The results of our study indicate that PCD, unlike CF, is associated with impaired NO synthesis in the lung, presumably due to mechano-chemical uncoupling.

Background: To our knowledge, the sudden onset of symptomatic pulmonary hypertension after COVID-19 vaccination has not been described. Both cases presented here resulted in functional limitations and likely permanent organ damage. Case Summary: We report two cases of acute onset pulmonary hypertension in previously healthy adult males within three weeks of receiving the second dose of the Pfizer (BNT162b2) mRNA COVID-19 vaccine from different lots. Both patients experienced the sudden onset of severe fatigue and dyspnea on exertion with negative COVID-19 PCR testing. The diagnosis was made by serial transthoracic echocardiography in the first case and by both transthoracic echocardiography and right heart catheterization in the second. Discussion: Pulmonary hypertension is a serious disease characterized by damage to lung vasculature and restricted blood flow through narrowed arteries from the right to left heart. The onset of symptoms is typically insidious, progressive and incurable, leading to right heart failure and premature death. The World Health Organization (WHO) classifies pulmonary hypertension into 5 categories and recently re-defined as a resting mean pulmonary artery pressure greater than 20 mmHg. Sudden onset pulmonary hypertension would only be expected in the settings of surgical pneumonectomy or massive pulmonary emboli with compromise of at least 50% of the lung vasculature.

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.

There is an increasing interest in biomarkers of nitric oxide dysregulation and oxidative stress to guide management and identify new therapeutic targets in patients with chronic obstructive pulmonary disease (COPD). We conducted a systematic review and meta-analysis of the association between circulating metabolites within the arginine (arginine, citrulline, ornithine, asymmetric, ADMA, and symmetric, SDMA dimethylarginine), transsulfuration (methionine, homocysteine, and cysteine) and folic acid (folic acid, vitamin B6, and vitamin B12) metabolic pathways and COPD. We searched electronic databases from inception to 30 June 2023 and assessed the risk of bias and the certainty of evidence. In 21 eligible studies, compared to healthy controls, patients with stable COPD had significantly lower methionine (standardized mean difference, SMD=-0.50, 95% CI -0.95 to -0.05, p=0.029) and folic acid (SMD=-0.37, 95% CI -0.65 to -0.09, p=0.009), and higher homocysteine (SMD=0.78, 95% CI 0.48 to 1.07, p˂0.001) and cysteine concentrations (SMD=0.34, 95% CI 0.02 to 0.66, p=0.038). Additionally, COPD was associated with significantly higher ADMA (SMD=1.27, 95% CI 0.08 to 2.46, p=0.037), SDMA (SMD=3.94, 95% CI 0.79 to 7.08, p=0.014), and ornithine concentrations (SMD=0.67, 95% CI 0.13 to 1.22, p=0.015). In subgroup analysis, the SMD of homocysteine was significantly associated with the biological matrix assessed and the forced expiratory volume in the first second to forced vital capacity ratio, but not with age, study location, or analytical method used. Our study suggests the presence of significant alterations in metabolites within the arginine, transsulfuration, and folic acid pathways which can be useful for assessing nitric oxide dysregulation and oxidative stress and identifying novel treatment targets in COPD. (PROSPERO registration number: CRD42023448036)

Background: COVID-19 pneumonia caused by SARS-Cov-2 virus induces alveolar collapse and hypoxia that may become severe. The aim of the study is to analyze the effects of chest physiotherapy using a threshold valve in patients with acute respiratory failure due to COVID-19 pneumonia. Methods; Retrospective observational study, in hospitalized patients from March to May 2020. Breathing exercises were performed with a threshold valve of 10 cmH2O. Fraction of inspired oxygen, oxygen saturation, heart rate, respiratory rate and dyspnea were collected before and after the first session and at the end of the 5th day of chest physiotherapy treatment. Results: The final sample included 125 patients. Significant differences (p&lt;0.01) were found in the pre-post intervention SpO2/FiO2 ratio (250±88.4 vs 275.6±97.5, p&lt;0.001), reaching 354.4±110.2 after 5 days of therapy (p&lt;0.001 with respect to baseline). Mean baseline respiratory, heart rate and level of dyspnea measure by the Borg scale did not change during the technique performance. In patient maneuvers with FiO2&gt;0.4, the SaO2/FiO2 ratio increase was higher than in patients with milder severity (46.85 ± 77.69, p&lt;0.01). Conclusions: Chest physiotherapy with a 10 cmH2O threshold valve is a safe and tolerated intervention with short-term improvement in oxygenation in patients with COVID-19 pneumonia.

Exposure to particulate matter (PM) causes considerable breathing-related health risks. We assessed the inhibitory effect of Siraitia grosvenorii extract (SGE) on airway inflammation in mice exposed to a fine dust mixture of PM10 (PM diameter &lt; 10 mm) and diesel exhaust particles (DEPs) known as PM10D. SGE attenuated neutrophil infiltration and the number of immune B and T cells in lung tissue and bronchoalveolar lavage fluid (BALF) of PM10D-exposed mice. SGE reduced the secretion of cytokines and chemokines, including interleukin (IL)-1a, tumor necrosis factor (TNF)- a, IL-17, chemokine (C-X-C motif) ligand (CXCL)-1, and macrophage inflammatory protein (MIP)-2 in BALF. Airway inflammation, accumulation of inflammatory cells, and collagen fibrosis in the lung after PM10D exposure were investigated by histopathological analysis, and SGE treatment ameliorated these symptoms. SGE decreased the mRNA expression of mucin 5AC (MUC5AC), CXCL-1, TNF-a, MIP-2, and transient receptor potential vanilloid and ankyrin 1 ion channels in the lung tissues of mice. Furthermore, SGE ameliorated mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling activated by PM10D in mice. We conclude that SGE attenuated PM10D-induced neutrophilic airway inflammation via inhibiting MAPK/NF-κB activation. These results show that SGE may be a candidate for the treatment of inflammatory respiratory diseases.

Asthma is a prevalent disease that around 300 million worldwide, resulting in substantial morbidity, mortality, and economic burden on a global scale. New clinical and laboratory research has shed light on the immunology causing asthma. Asthma is now recognized as a heterogeneous disease. A personalized medicine is based on the classification of asthma by endotype by linking observable characteristics to immunological mechanisms. Identifying endotype mechanisms is essential for better characterizing patients and personalizing therapeutic approaches with novel biological agents that target specific immune pathways. This article provides a summary of the major immunological mechanisms involved in the pathogenesis and emergence of the disease's phenotypic features, as well as the individualized treatment for severe asthma subtypes

Idiopathic pulmonary fibrosis (IPF) is one of the most common forms of interstitial lung disease characterized by progressive parenchymal fibrosis and respiratory failure. In a model of bleomycin-induced pulmonary fibrosis, the antifibrotic and anti-inflammatory activity of Longidaza (bovhyaluronidase azoxymer), which contains a conjugate of the hyaluronidase enzyme with a high molecular weight synthetic carrier azoxymer bromide, was investigated. Experiments were conducted in male C57BL/6 mice. Longidaza was administered at different doses by intranasal and intramuscular routes. Histology, hematology and enzyme-linked immunosorbent assay were used in the study. The use of Longidaza reduced pulmonary fibrosis as evidenced by an improvement in histopathologic damage to the lungs, a decrease in the area of connective tissue and the levels of profibrotic factors (TGF-β1, hydroxyproline, collagen I) in lung tissue. In addition, Longidaza inhibited the inflammatory response in pulmonary fibrosis, decreased the levels of IL-6, TNF-α, hyaluronic acid in lung tissue and the recruitment of inflammatory cells into lung tissue. The highest therapeutic efficacy was observed with the use of Longidaza at doses of 120 and 1200 U/kg intramuscularly, which was superior to that of the reference drug pirfenidone axunio. The data presented in this study suggest that Longidaza is a new and promising drug for the treatment of IPF that warrants further investigation in patients with fibrotic interstitial lung disease.

(1) Background: This retrospective study aimed to compare the efficacy and safety of one-stage computed tomography (OSCT)- to that of two-stage computed tomography (TSCT)-guided localization for the surgical removal of small lung nodules. (2) Methods: We collected data from patients with ipsilateral pulmonary nodules who underwent localization before surgical removal at Veteran General Hospital Kaohsiung between October 2017 and January 2022. The patients were divided into the OSCT and TSCT groups. (3) Results: We found that OSCT significantly reduced the localization time and risky time compared to TSCT, and the success rate of localization and incidence of pneumothorax were similar in both groups. However, the time spent under general anesthesia was longer in the OSCT group than in the TSCT group. (4) Conclusions: The OSCT-guided approach to localize pulmonary nodules in hybrid operation room is a safe and effective technique for the surgical removal of small lung nodules.

Background: Congenital Pulmonary Malformations (CPMs) are rare benign lesions potentially causing infective complications and/or malignant transformation requiring surgery even when asymptomatic. CPMs are infrequent in adult but potentially detected at any age. There is not a consensus indicating the correct extent of resection in both adults and paediatrics. This retrospective multicentric study aims to identify the appropriate surgical resection to prevent the recurrence of related respiratory symptoms. Methods: Between 2010 and 2020, a total of 96 patients (adult and pediatric) underwent surgery for CPMs in 4 centers. A 2:1 propensity score matching (considering sex and lesion side) was performed, identifying 2 groups: 50 patients underwent lobectomy (group A) and 25 sub-lobar resections (group B). Clinical and histopathological characteristics, early and late complications and symptom’s recurrence were retrospectively analyzed and compared between the two groups by univariate and multivariate analyses. Results: Patients who underwent lobectomy had a statistically significant lower rate of recurrence (4% vs 24% of group B, p = 0.014) and a lower rate of intraoperative complications (p = 0.014). Logistic regression identified sub-lobar resection (p=0.040), intra- and post-operative complications (p=0.105 and 0.022) and associated developed neoplasm (p=0.062) as possible risk factors for symptoms recurrence after surgery. Conclusions: Pulmonary lobectomy seems to be the most effective surgical treatment for CPMs, guaranteeing stable remission of symptoms and a lower rate of intra- and postoperative complications. To our knowledge this is one of the largest studies comparing lobectomy and sub-lobar resections in patients affected by CPMs, considering the low incidence worldwide.

MAD is the gold standard therapy for mild/moderate OSA and is a second-choice treatment in patients with severe OSA not responding to CPAP. The aim of this study was to analyze the upper airway characteristics of OSA patients and the morphological changes in the upper airway, inducted by four different types of mandibular advancement devices, using CBCT 3D imaging. Twenty-two patients were recruited after OSA diagnosis with polysomnography. Four different customized and titratable MAD were used and an initial CBCT scan was obtained for each patient. After 6 months to the end of the MAD titration phase, all the subjects showed an AHI of &lt; 5 or a decrease of 50% in AHI with MAD when compared with initial AHI and a second CBCT scan with MAD in situ was performed. An important improvement of the airway was observed (+33.76%) and a significant difference in the enlargement ratio between the posterior soft palate (+32.41%) and the posterior tongue (+36.96%) region was also found. The greatest increase in airway volume was achieved in patients treated with the MAD Forward and TAP (respectively +42.77% and + 41.63%). MAD therapy is effective to treat mild/severe OSA with increased upper airway volume. The design of the MAD can influence the effectiveness of the treatment.

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.

Individual susceptibility to pulmonary oxygen toxicity (PO2tox) is highly variable and currently lacks a reliable biomarker for predicting pulmonary hyperoxic stress. As nitric oxide (NO) is involved in many respiratory system processes and functions, we aimed to determine if expired nitric oxide (FENO) levels can provide an indication of PO2tox susceptibility in humans. Eight U.S. Navy trained divers volunteered as subjects. The hyperoxic exposures consisted of six- and eight-hour hyperbaric chamber dives conducted on consecutive days in which subjects breathed 100% oxygen at 202.65 kPa. Subjects’ individual variability in pulmonary function and FENO was measured twice daily over five days and compared with their post-dive values to assess susceptibility to PO2tox. Only subjects who showed no decrements in pulmonary function following the six-hour exposure conducted the eight-hour dive. FENO decreased by 55% immediately following the six-hour oxygen exposure (n=8, p<0.0001) and by 63% following the eight-hour exposure (n=4, p<0.0001). Four subjects showed significant decreases in pulmonary function immediately following the six-hour exposure. These subjects had the lowest baseline FENO and the lowest post-dive FENO and had clinical symptoms of PO2tox. Individuals with low FENO were the first to develop PO2tox symptoms and deficits in pulmonary function from the hyperoxic exposures. These data suggest that endogenous levels of NO in the lung may protect against the development of PO2tox.

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.

Background: A growing number of studies have reported Coronavirus disease (COVID-19)-related to both respiratory and central nervous system dysfunctions. This study evaluates the neuromodulatory effects of spinal cord transcutaneous stimulation (scTS) on the respiratory functional state in healthy controls and patients with post-COVID-19 respiratory deficits as a step toward the development of a rehabilitation strategy for these patients.; Methods: In this before-after, interventional, case-controlled clinical study, ten individuals with post-acute COVID-19 respiratory deficits and eight healthy controls received a single twenty-minute-long session of modulated monophasic scTS delivered over the T5 and T10 spinal cord segments. Forced Vital Capacity (FVC), Peak Forced Inspiratory Flow (PIF), Peak Expiratory Flow (PEF), Time-To-Peak of Inspiratory Flow (tPIF), and Time-To-Peak of Expiratory Flow (tPEF) were assessed before and after the intervention; Results: In COVID-19 group, the scTS intervention led to significantly increased PIF (p= .040) and PEF (p= .049) in association with significantly decreased tPIF (p= .035) and tPEF (p= .013). In the Control Group, the exposure to scTS also resulted in significantly increased PIF (p= .010) and significantly decreased tPIF (p= .031). Unlike the results in COVID-19 group, there was significantly decreased PEF (p= .028) in association with significantly increased tPEF (p= .036). There were no changes for FVC after scTS in both groups (p= .67 and p= .503); Conclusions: In post-COVID-19 patients scTS facilitates excitation of both inspiratory and expiratory spinal neural networks leading to an immediate improvement of respiratory functional performance. This neuromodulation approach could be utilized in rehabilitation programs for patients with COVID-19 respiratory deficits.

Despite recent advances in optimizing reliever, controller and maintenance therapy in asthma, a large subgroup of asthmatic patients continues to suffer from severe asthma, affecting their psychosociological status, their quality of life and even their life expectancy. Identifying and recognizing the specific phenotypic and endotypic characteristics in asthma has provided the medical community to drive the development of targeted therapies that are proved to benefit patients in terms of symptom control, exacerbation rate, quality of life and lung function. Adopting a more tailored and targeted approach is proving to be the key factor in reforming severe asthma treatment, minimizing the patients’ burden, as well as the socioeconomical impact worldwide. In this review, we are going to describe the different phenotypes and endotypes of asthma, the currently approved targeted therapies in severe asthma as imprinted in Global Initiative for Asthma (GINA) 2023, as well as other potential pharmacological agents and strategies investigated or currently under investigation for the treatment of severe asthma.

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.

Chronic pulmonary diseases such as asthma, COPD, and Idiopathic pulmonary fibrosis are significant causes of mortality and morbidity worldwide. Currently, there is no radical treatment for many chronic pulmonary diseases, and the treatment options focus on relieving the symptoms and improving lung function. Therefore, efficient therapeutic agents are highly needed. Bronchial epithelial cells and airway smooth muscle cells and their crosstalk play a significant role in the pathogenesis of these diseases. Thus, targeting the interactions of these two cell types could open the door to a new generation of effective therapeutic options. However, the studies on how these two cell types interact and how their crosstalk adds up to respiratory diseases are not well established. With the rise of modern research tools and technology, such as lab-on-chip, organoids, co-culture techniques, and advanced immunofluorescence imaging, a substantial degree of evidence about these cell interactions emerged. Hence, this contribution aims to summarize the growing evidence of bronchial epithelial cells and airway smooth muscle cells crosstalk under normal and pathophysiological conditions. The review first deliberates the effects of both healthy and stressed epithelial cells on airway smooth muscle cells, taking into account three themes; contraction, migration, and proliferation. Then, it discusses the impact of airway smooth muscle cells on the epithelium in inflammatory settings. Later, it examines the role of airway smooth muscle cells in the early development of bronchial epithelial cells and their recovery after injury.

Background: Arm elevation plays an important role in simple and complex daily tasks. Muscles that stabilize the shoulder girdle also function as respiratory accessory muscles. Dual demand on these muscles, particularly in patients with chronic respiratory conditions, leads to dyspnea and fatigue of the upper limb, making simple daily activities difficult. Various tests, including Grocery Shelving Task (GST), are designed to assess functional performance during upper limb activities. The aim of the study is to derive reference values for GST among the population of the United Arab Emirates Methods: This cross-sectional study was conducted with 220 healthy individuals of both genders between the ages of 20 and 69. Duration required to complete GST was recorded. The correlation between duration and age, height, body mass and body mass index (BMI) were also assessed. Results: Reference values for duration (in seconds) in females for age groups 20-29, 30-39, 40-49, 50-59 and 60-69 are 43.5±5.5, 43.1±8.08, 48.1±6.7, 44.9±7.1, 46.7±6.5 respectively. Values for males of age groups 20-29, 30-39, 40-49, 50-59 and 60-69 are 45.7±6.7, 44.8±8.9, 42.5±10.01, 53.4±4.2, and 53.9±5.4 respectively. Conclusion: Reference values for GST duration were obtained. Weak correlations were found between duration and age, height, body mass, BMI of the participants.

Pulmonary hypertension (PH) has a high mortality, and few treatment options. Adaptive immune mediators of PH in mice challenged with antigen/particulate matter (antigen/PM) has been the focus of our prior work. We identified key roles of type 2 and type 17 responses in C57BL/6 mice. Here, we focused on type 2 response related cytokines, specifically Resistin-like-molecule (RELM)α, a critical mediator of hypoxia-induced PH. Because of strain differences in the immune responses to type 2 stimuli, we compared C57BL/6J and BALB/c mice. A model of intraperitoneal antigen sensitization with subsequent, intranasal challenges with antigen/PM (ovalbumin and urban ambient PM2.5) or saline was used in C57BL/6 and BALB/c wild type or RELMα-/- mice. Vascular remodeling was assessed by histology, right ventricular (RV) pressure, RV weights and cytokines were quantified. Upon challenge with antigen/PM2.5, both C57BL/6 and BALB/c mice developed pulmonary vascular remodeling; these changes were more prominent in the C57BL/6 strain. Compared to wild type mice, RELMα-/- had significantly reduced pulmonary vascular remodeling in BALB/c, but not in C57BL/6 mice. RV weights, RV IL-33 and RV ST2-IL-33-receptor were significantly increased in BALB/c wild type mice, but not in BALB/c-RELMα-/- or in C57BL/6-wild type or C57BL/6-RELMα-/- mice. RV systolic pressures (RVSP) were higher in BALB/c compared to C57BL/6J mice, and RELMα-/- were not different from their respective wild type controls. In BALB/c mice, RELMα was a key contributor to antigen/PM2.5 induced pulmonary vascular remodeling, RV thickening and RV cytokine responses, highlighting the significance of the genetic background. The RELMα-/- animals demonstrated significantly decreased expression of RELMβ and RELM which makes these mice comparable to a situation where human RELMα levels would be significantly modified, as humans only have one RELM molecule.

Background: Arm elevation plays an important role in simple and complex daily tasks. Muscles that stabilize the shoulder girdle also function as respiratory accessory muscles. Dual demand on these muscles, particularly in patients with chronic respiratory conditions, leads to dyspnea and fatigue of the upper limb, making simple daily activities difficult. Various tests, including Grocery Shelving Task (GST), are designed to assess functional performance during upper limb activities. The aim of the study is to derive reference values for GST among the population of the United Arab Emirates Methods: This cross-sectional study was conducted with 220 healthy individuals of both genders between the ages of 20 and 69. Duration required to complete GST was recorded. The correlation between duration and age, height, body mass and body mass index (BMI) were also assessed. Results: Reference values for duration (in seconds) in females for age groups 20-29, 30-39, 40-49, 50-59 and 60-69 are 43.5±5.5, 43.1±8.08, 48.1±6.7, 44.9±7.1, 46.7±6.5 respectively. Values for males of age groups 20-29, 30-39, 40-49, 50-59 and 60-69 are 45.7±6.7, 44.8±8.9, 42.5±10.01, 53.4±4.2, and 53.9±5.4 respectively. Conclusion: Reference values for GST duration were obtained. Weak correlations were found between duration and age, height, body mass, BMI of the participants.