Medicine and Pharmacology

Abstract: Chronic obstructive pulmonary disease (COPD) is a chronic progressive respiratory disease, characterized by respiratory symptoms and airflow limitation, and is one of the leading causes of morbidity and mortality worldwide. The evolution of the disease is associated with episodes of acute exacerbations (AECOPD), characterized by worsening symptoms and accelerated deterioration of lung function. Acute exacerbations of COPD have different severity, being mild, moderate or severe depending on how aggravated the patients’ symptoms are, but also depending on the pulmonary functional and biological changes. Around 70% of AECOPD are infectious in nature, through upper or lower respiratory tract infections. Often, exacerbations associated with lower respiratory tract infections are more severe and have a higher risk of unfavorable outcome compared to AECOPD associated with upper respiratory tract infections. Severe exacerbations require hospital management, most of them being treated in the intensive care unit (ICU). In this narrative review, we evaluated the frequency of different bacterial pathogens involved in severe COPD exacerbations associated with lower respiratory tract infections and the need for treatment in the ICU. Identifying patients with exacerbated COPD at high risk of respiratory infections especially with gram-negative bacilli is extremely important to choose the optimal treatment, thus reducing the risk of death.

Abstract: Background: While non-specific pleural empyema in children can be successfully managed with minimally invasive drainage and pleural puncture in 85–90% of cases. Tuberculous pleural empyema (TB empyema) exhibits high clinical resistance and frequently requires extensive thoracic surgical interventions. The choice of surgical extent directly depends on the disease stage and the presence of complications. Methods: We conducted a retrospective analysis of diagnostic and surgical outcomes in 85 children and adolescents (aged 4 to 17 years) with tuberculous pleural empyema treated between 1984 and 2022. TB empyema staging was performed using the American Thoracic Society (ATS) classification was adapted for tuberculous etiology. Results: Stage I TB empyema was diagnosed in 3 patients, Stage II in 7 patients, and Stage III in 75 patients. Patients with Stage I and II disease underwent video-assisted thoracoscopic (VATS) debridement of the empyema cavity. In Stage III, 75 patients underwent 79 surgical interventions of varying extents. Postoperative complications occurred in 2 patients (2.5%). This occurred as delayed lung re-expansion, which was successfully managed with repeat thoracentesis in one patient and chest tube drainage in the other. The overall 30-day postoperative mortality rate was 0.0%. No recurrences were reported during the 3-year follow-up period.Conclusion: Comprehensive treatment combined with timely surgical intervention achieves clinical cure in all patients. Early minimally invasive VATS interventions during Stages I–II prevent the need for more traumatic procedures, such as pleurectomy and lung resection, which are often required in Stage III disease.

Abstract: Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality worldwide. Finding patients with early COPD is already difficult, but even those have already an advanced disease in the biological point of view with irreversible lung damage. A lot of effort is done to find the parameters for detection of patients with early pathophysiological changes before they develop airflow limitation. The importance of this stage is recently recognized and has different labels as “pre-COPD” and “early COPD”. Exhaled breath temperature (EBT) is a non-invasive method to detect and monitor inflammation in the respiratory system. Most studies on EBT have been performed in asthma and showed the utility of this approach to assess changes in airway inflammation. In the COPD patients, the number of airways and their vasculature is reduced and EBT decreases proportionally to the level of destruction, but is still increased during the COPD exacerbation. In recent studies, change in EBT after smoking a cigarette in patients without a diagnosis of COPD was significantly predictive for disease progression after 2 years. Early interventions based on these results should be tested for efficacy in prevention of the development of overt COPD.

Abstract: Asthma exacerbation, frequently triggered by viral infections, is a leading cause of hospitalization, respiratory failure, and death. COVID-19 and asthma share a bidirectional relationship, with each potentially worsening the other. We compared outcomes in hospitalized asthma exacerbation patients with and without COVID-19 using the National Inpatient Sample (2020–2022), adjusting for confounders via multivariable logistic regression. Among 603,219 hospitalizations for asthma exacerbation, 69,600 (11.5%) had concomitant COVID-19. The COVID-19 group had significantly higher in-hospital mortality (6.7% vs. 1.4%; aOR 6.16; 95% CI 5.61-6.76) and greater need for invasive mechanical ventilation (10.1% vs. 4.9%; aOR 2.30; 95% CI 2.15-2.45), despite lower non-invasive ventilation use. Mean length of stay (7.7 vs. 4.6 days) and total hospital charges ($97,133 vs. $58,547) were also higher. These patients were more critically ill, with higher rates of respiratory failure, ARDS, acute kidney injury, and pulmonary embolism, and greater use of ECMO, renal replacement therapy, tracheostomy, and vasopressors. COVID-19 was independently associated with worse clinical outcomes among hospitalized asthma exacerbation patients. Early recognition of COVID-19 in asthma exacerbation is warranted to guide risk stratification and timely management.

Abstract: Background:Telomeres are repetitive DNA sequences at chromosome ends that maintain genomic stability and shorten with age. Mutations in genes such as DKC1, TERC, TERT, NOP10, TINF2 and NHP2 cause Telomere Spectrum Disorders (TSD), leading to shortened telomeres. Acquired TSDs arise from environmental or occupational exposures and commonly affect veterans, truck drivers, and industrial workers (10). These exposures generate reactive oxygen species associated with cancer, liver disease, pulmonary disease, and bone marrow complications. Idiopathic Pulmonary Fibrosis (IPF) is most common pulmonary manifestation, followed by hepatic fibrosis / cirrhosis, hematologic disorders (e.g., aplastic anemia, MDS), and rarely gastrointestinal findings. This case describes a Gulf War veteran with suspected acquired short telomeres and multisystem involvement (idiopathic cirrhosis, pulmonary fibrosis, cytopenias) and uniquely found to have gastrointestinal (Gastric Antral Vascular Ectasia, GAVE)), a potential unsuspected manifestation of TSD. Methods/ Case: A 76-year-old male with atrial fibrillation (post-Watchman), cryptogenic cirrhosis, COPD, IPF, diabetes, and anemia presented with severe shortness of breath and hypoxia. Admitted for Sepsis and Acute Hypoxic Respiratory Failure. Treated with AVAPS, IV Zosyn, IV Lasix, steroids, bronchodilators, and diuretics. His condition improved, and he was discharged on baseline 3L O2. His Gl history included GAVE, an unsuspected bleeding complication causing chronic iron-deficiency anemia. Hematologic findings included chronic anemia, thrombocytopenia, and a hypocellular bone marrow with 12% atypical NK cells. Discussion/ Results: The patient's Gulf War exposure to oil fire pollutants (benzene, toluene, PAHs, lead, cadmium, and particulate matter) likely contributed to telomere shortening and TSD-related multisystem disease (10). Given his shortened telomeres, testing for TERC and TERT mutations is warranted. GAVE ("watermelon stomach") is a rare cause of GI bleeding characterized by dilated gastric vessels and chronic anemia and has been linked to TSD but no current reports have documented this association. Its occurrence in this patient suggests an unrecognized gastrointestinal manifestation of TSD as the patient does not have known history of portal hypertension. Conclusion: This represents an potentially underreported manifestation of acquired TSD presenting with combined hepatic, pulmonary, hematologic, and gastrointestinal (GAVE) involvement.

Abstract: Tuberculous meningitis (TBM) is a critically severe form of extrapulmonary tuberculosis in pediatric patients. Presents a significant diagnostic challenge during the early stages of clinical manifestation. Delayed recognition of meningeal tuberculous inflammation leads to the involvement of the brain parenchyma (encephalitis) and may result in irreversible neurological sequelae. Objective: To evaluate the clinical features, the spectrum of complications, and the outcomes of tuberculous meningitis in pediatric patients under current epidemiological conditions. Materials and Methods: A retrospective analysis of 21 medical records was conducted for pediatric patients aged 3 months to 17 years (mean age: 6.7 ± 5.8 years) with a confirmed TBM diagnosis. The study included pediatric patients treated in the tuberculosis department or evaluated through the telemedicine consultation system between January 2017 and May 2025. Results: A history of contact with a tuberculosis patient was established in 62% (13/21) of cases. At initial presentation, fever was recorded in 67% (14/21) of patients, headache and nausea/vomiting in 52% (11/21), and meningeal signs in 38% (8/21). The majority of patients (52%, 11/21) had not received BCG vaccination. Mycobacterium tuberculosis (MBT) was identified in 19 patients (90%). MTB DNA was detected in the cerebrospinal fluid (CSF) in 79% of patients (15/21). Drug resistance (DR) was confirmed in 57.9% of patients (11/19), including MDR/XDR strains in 81.8% (9/11) of the DR subgroup. Complications included motor deficits in 38% (8/21), hydrocephalus in 47.6% (10/21), and epileptic syndrome in 19% (4/21). Four patients (19%) with an unfavorable outcomes were transitioned to palliative care. Conclusion: In pediatric patients; TBM delayed diagnosis results in a more severe clinical course characterized by the development of profound neurological deficits. This study demonstrates that TBM has evolved from a predominantly meningeal disease into a severe form of meningoencephalitis; frequently accompanied by hydrocephalus; epilepsy; and motor deficits. Notably; seizure disorder serves as a critical predictor of an unfavorable outcome. These findings underscore the urgent need to optimize early diagnostic strategies within general healthcare networks.

Abstract: Hedera helix L. leaf extracts are regulated expectorants for productive cough, yet their evidence is dispersed across pharmaceutical quality, nonclinical pharmacology, disposition, toxicology, clinical pharmacology, efficacy, safety, and regulatory assessment. This review integrates those domains in a single study-level account and explicitly distinguishes isolated constituents, incompletely specified extracts, defined monograph preparations, proprietary extracts, and combination products. Hederacoside C is the pharmacopoeial marker, while α-hederin is the constituent most extensively examined in β2-adrenergic receptor models. Cell studies documented reduced agonist-induced receptor internalization, greater ligand binding and cAMP responsiveness, and altered GRK2/β-arrestin signaling. Isolated-tissue and animal studies reported antispasmodic, anti-inflammatory, antitussive, and tracheobronchial secretory effects. Rat studies showed low, matrix-dependent oral exposure to hederacoside C and α-hederin. Small exploratory human studies detected no or only trace α-hederin and did not permit conventional pharmacokinetic analysis. Clinical evidence includes placebo-controlled adult trials, active-comparator studies, pediatric investigations, postmarketing cohorts, systematic reviews, and pharmacovigilance reports. Controlled adult trials of EA 575 reported greater short-term improvement in cough or Bronchitis Severity Score than placebo; pediatric efficacy evidence is dominated by observational studies and small airway-function trials. Short-term tolerability was generally favorable, with gastrointestinal and hypersensitivity reactions as the principal recognized adverse effects. The European Union monograph recognizes specified extracts for productive cough, contraindicates use below two years, and does not recommend use during pregnancy or lactation. The distinctive contribution of this review is the complete quality-to-clinic evidence map, including dose, model, endpoint, study design, extract identity, and unresolved evidence domain for each major dataset.

Abstract: Background: Immunotherapy and targeted therapy have gained ground over conven-tional chemotherapy in treating various cancers. While pulmonary toxicity associated with these agents is rare, it represents a significant factor in both mortality and morbidity and may influence the overall success of cancer treatment. This case series report adds to the emerging evidence of cancer therapy-induced pneumonitis features and cortico-therapy outcomes. Patients and methods: This case series report consists of a retrospective analysis of 12 cases of patients undergoing immunotherapy (4 Nivolumab, 4 Pembrolizumab) or targeted therapy (3 Obinutuzumab, 1 Abemaciclib) for cancer (7 lung, 3 non-Hodgkin lymphoma, 1 breast, 1 renal) that developed pneumonitis during their follow-up. Results: The onset of pneumonitis ranged from 6 to 48 months (median = 18.5), and in 4 cases it occurred after discontinuation of oncologic treatment. The diagnosis was estab-lished with a high probability based only on clinical picture, radiologic features, and concomitant oncologic therapy. The cases with onset after discontinuation of oncologic treatment required a more thorough investigation (including bronchoscopy with BAL analysis). The main symptom was dyspnea (10/12 cases), and 3 of 12 patients had res-piratory failure (SpO2≤88%). The CTCAE severity grades were: 1 mild, 7 moderate, 3 severe, and 1 life-threatening. The CT scan showed different patterns (7 OP, 4 NSIP, and 1 HP). 11 patients received oral methylprednisolone (0.40 to 0.82 mg/kg) for 5 to 16 weeks. 2 patients continued oncologic treatment, and 6 discontinued. All patients showed fa-vorable outcomes. Conclusions: Immunotherapy and targeted therapy-induced pneumonitis can express various features and severities, and prompt recognition and diagnosis based on clinical, radiologic and contextual elements is mandatory. Corticotherapy regimens used, based on severity and treatment response, had a favorable outcome. The follow-up can consist only of clinical assessment and chest X-ray, and extensive tests are reserved for non-responsive cases.

Abstract: Background: Tuberculosis (TB) remains a leading cause of infectious morbidity worldwide, with increasing recognition of post-tuberculosis lung disease (PTLD). Structural lung damage begins early in the disease course, often preceding clinical or radiographic detection. Methods: The objective of this study was to review diagnostic approaches for detecting early structural lung damage in TB. A structured narrative review was conducted using PRISMA principles, including studies published between 2018 and 2025. Results: We found high-resolution computed tomography (HRCT) is the most sensitive modality for early structural abnormalities such as tree-in-bud nodules and ground-glass opacities. Pulmonary function tests, particularly DLCO, detect early impairment. Biomarkers such as matrix metalloproteinases (MMPs) and cytokines reflect ongoing tissue damage. Conclusion: We concluded that a multimodal diagnostic approach integrating imaging, functional assessment, and biomarkers enables early detection and may prevent progression to chronic lung disease.

Abstract: Background: Chronic cough is a major determinant of impaired quality of life and recurrent exacerbations in bronchiectasis. The BEAT-COUGH Study evaluated the effectiveness of adjunctive oral erdosteine plus nebulised amikacin during acute exacerbation and long-term maintenance in patients with non-cystic fibrosis bronchiectasis. Methods: The BEAT-COUGH Study was a prospective, two-centre observational study (VCC:37/2023) with 52-week follow-up. A total of 164 adults with HRCT-confirmed bronchiectasis, Modified Reiff Score >10, acute exacerbation, and positive sputum microbiology were enrolled. Eighty-two patients received standard care alone and 82 received standard care plus oral erdosteine and nebulised amikacin (250 mg twice daily during exacerbation, followed by once daily during maintenance). A total of 144 patients completed maintenance follow-up. Cough severity was assessed using a 100-mm Visual Analogue Scale (VAS), with VAS < 20 mm defining a satisfactory response. Secondary outcomes included exacerbation frequency, duration, time to first exacerbation, exacerbation-free days, sputum rheology, microbiology, hospitalization, antibiotic use, and healthcare costs. Results: Adjunctive therapy produced significantly higher satisfactory cough responses during both acute exacerbation and maintenance (both p< 0.001). Combination therapy reduced the duration of mild, moderate, and severe exacerbations by 39.97%, 37.30%, and 30.26%, respectively (all p< 0.0001), prolonged time to first exacerbation and exacerbation-free days (all p< 0.0001), and reduced moderate and severe exacerbations while increasing the proportion of exacerbation-free patients (p=0.00019). Significant improvements were observed in sputum viscosity and clearance (90.3% vs. 19.4%), sputum volume (94.4% vs. 13.9%), and sputum colour (91.7% vs. 13.9%) (all p< 0.0001). Conclusions: Adjunctive erdosteine plus nebulised amikacin significantly improved cough control, sputum rheology, exacerbation outcomes, and healthcare utilization, supporting its role as an effective adjunctive strategy for exacerbation-prone non-cystic fibrosis bronchiectasis.

Abstract: Background/Objectives: Human adenoviruses (HAdVs) are widely used as vectors for vaccines and gene therapy; however, pre-existing immunity can reduce their efficacy. Therefore, rapid and accessible serological methods are required to assess antibody levels against adenoviruses. Lateral flow immunochromatographic assay (LFIA) sensitivity depends on the label and antigen. In this study, we aimed to develop and evaluate LFIA systems based on gold nanoparticles (GNPs) and quantum dots (QDs) using a recombinant HAdV hexon protein. Methods: A recombinant HAdV hexon protein fragment (rhHAdV, 35 kDa; amino acids A120–R316) was expressed in Escherichia coli and purified using Ni²⁺ affinity chromatography. Protein identity was confirmed using sodium dodecyl sulfate-polyacrylamide gel electrophoresis, western blotting, and liquid chromatography–tandem mass spectrometry analyses. Two LFIA formats were developed using Protein G-conjugated GNPs (GNP-G) and QDs (QD-G). Analytical sensitivity was evaluated using serial dilutions of positive serum samples. Diagnostic performance was assessed using 90 human serum samples and compared with that of a commercial enzyme-linked immunosorbent assay (ELISA). Results: The rhHAdV antigen demonstrated high immunoreactivity in ELISA. Antibody detection was achieved at serum dilutions of up to 1:300 and 1:1000 for the GNP- and QD-based LFIA, respectively. Both LFIA formats showed high specificity (98.2%). Sensitivity was 96.9% and 100% for GNP-G and QD-G, respectively; ROC analysis demonstrated excellent diagnostic accuracy, with AUC values of 0.976 and 0.991, respectively. Conclusions: The findings of this study highlight the potential of QD-based LFIA as an advanced tool for rapid serodiagnostics and large-scale immunological monitoring.

Abstract: Interstitial lung diseases (ILDs) comprise a heterogeneous group of pulmonary disorders associated with substantial morbidity and mortality. We examined mortality attributed to selected J84-coded ILDs in the United States from 1999 to 2024 using CDC WONDER underlying-cause-of-death data. Age-adjusted mortality rates (AAMRs) per 100,000 population were standardized to the 2000 U.S. population and stratified by sex and race. Joinpoint regression was used to identify changes in temporal slope and estimate annual percent change (APC), average annual percent change (AAPC), 95% confidence intervals (CIs), and p-values. After the removal of overlapping years between the CDC WONDER database series, 444,573 unique deaths occurred. Annual deaths increased from 11,358 in 1999 to 22,849 in 2024, while AAMR increased from 4.2 to 5.1 per 100,000. Overall, AAMR increased during 1999–2004 (APC 2.32%, 95% CI 1.39–3.26; p<0.001) and more slowly during 2004–2024 (APC 0.36%, 95% CI 0.16–0.56; p=0.001), with an overall AAPC of 0.75% (95% CI 0.60–0.90; p<0.001). Male AAMRs remained higher than female AAMRs, while race-specific trends were heterogeneous. No temporal reduction in population mortality coincided with the introduction of antifibrotic therapies; however, this ecological analysis cannot evaluate treatment effectiveness or individual treatment exposure.

Abstract: Background: Sarcoidosis is a [chronic granulomatous disease of unknown etiology that predominantly affects the lungs but can involve virtually any organ, including the liver. Pulmonary involvement occurs in over 90% of patients, while hepatic involvement is reported in 5–25% of cases. Despite the expanding therapeutic armamentarium, evidence regarding both pulmonary efficacy and hepatic safety/efficacy of sarcoidosis therapies remains fragmented across heterogeneous studies. This systematic review synthesizes the available evidence on pharmacological therapies for sarcoidosis, with a dual focus on pulmonary outcomes (forced vital capacity, steroid-sparing, radiographic response) and hepatic outcomes (hepatotoxicity, efficacy in hepatic sarcoidosis).Methods: A comprehensive literature search was conducted across PubMed, MEDLINE, Cochrane Library, and ClinicalTrials.gov through May 2025. Studies evaluating pharmacological therapies for sarcoidosis reporting pulmonary and/or hepatic outcomes were included. Therapies were categorized as first-line (glucocorticoids, methotrexate), second-line (antimetabolites, hydroxychloroquine), third-line (anti-TNF biologics, rituximab, repository corticotropin injection), and investigational agents (JAK inhibitors, efzofitimod, antifibrotics). Data were extracted on study design, sample size, pulmonary function outcomes, hepatic efficacy, hepatotoxicity, and adverse events. Quality assessment was performed using the Cochrane Risk of Bias tool for RCTs and the Newcastle-Ottawa Scale for observational studies.Results: A total of 22 therapies across 4 treatment lines were identified with reportable pulmonary and/or hepatic outcome data. The evidence base comprised 8 randomized controlled trials, 8 single-arm trials, multiple retrospective cohort studies, and real-world database analyses. Key findings are summarized by treatment line below.Conclusions: Methotrexate has emerged as a noninferior first-line alternative to prednisone for pulmonary sarcoidosis. Anti-TNF agents, particularly infliximab, provide modest but consistent pulmonary benefit and demonstrate efficacy in hepatic sarcoidosis phenotypes. JAK inhibitors and efzofitimod represent promising investigational therapies. Hepatotoxicity remains a critical consideration across multiple drug classes, necessitating structured monitoring. Prospective studies specifically evaluating hepatic sarcoidosis outcomes are urgently needed.

Abstract: Background: Prognostic heterogeneity among patients with stage I-IIIA non-small cell lung cancer (NSCLC) following curative-intent resection limits the utility of anatomical staging alone. We evaluated the prognostic value of the C-reactive protein-albumin-lymphocyte-monocyte (CALM) index as an integrative biomarker for overall survival (OS) in this population. Methods: This retrospective study included 533 patients with stage I-IIIA NSCLC. We assessed the association between the CALM index and OS using multivariable Cox proportional hazards models, adjusted for established clinicopathological factors. To ensure model robustness, we utilized Least Absolute Shrinkage and Selection Operator (LASSO)-penalized Cox regression for variable selection. Predictive performance was comprehensively evaluated using Harrell's concordance index (C-index), integrated area under the curve (iAUC), integrated discrimination improvement (IDI), and decision-curve analysis (DCA). Results: The CALM index was identified as a stable, independent predictor of OS across both conventional and LASSO-penalized models. The final prognostic model included age, American Society of Anesthesiologists physical status, pleural invasion, pathological stage, the modified Shine-Lal index, and the CALM index. Incorporation of the CALM index significantly enhanced model discrimination and risk reclassification at 3 and 5 years, while consistently increasing net clinical benefit across a wide range of threshold probabilities. Conclusions: The CALM index is a biologically plausible, robust, and readily accessible prognostic biomarker that provides incremental prognostic information beyond established factors in patients with resected stage I-IIIA NSCLC. Its integration into postoperative assessment offers a framework for refined prognostic stratification and more individualized clinical decision-making.

Abstract: Background/Objectives: Investigation of whether visual and AI-based assessments of the severity of COVID-19 pneumonia using an established semi-quantitative chest CT scoring system (Pan score) correlate with laboratory parameters as well as pulmonary function, and of the score’s diagnostic value in predicting the patients’ clinical outcome. Methods: This retrospective analysis comprises patients with PCR-confirmed COVID-19, who received a chest CT scan (not more than three days prior to or after the positive PCR test) between March 21, 2020, and December 27, 2021. Each of the five lung lobes was assessed separately using a scoring system ranging from 0 (no pulmonary involvement) to 5 (> 75% pulmonary involvement) by a radiology specialist, an experienced resident physician, a medical student, and a dedicated AI-based chest CT software tool. In addition, pulmonary function and laboratory parameters, the duration of ICU stays and of any required mechanical ventilation, as well as the clinical outcome (discharge vs. death) were recorded, and their correlation with the obtained CT score was analysed. Statistical analyses comprised descriptive baseline comparisons using non-parametric tests, bivariate correlation matrices, and ROC curves to assess diagnostic accuracy. Furthermore, multivariable logistic, ordinal, and age-adjusted spline regression models were constructed to calculate odds ratios and estimate predicted probabilities for cumulative ICU and mechanical ventilation duration thresholds. Results: In total, 351 consecutive patients with confirmed COVID-19 (223 males [63.5%], 128 females [36.5%]; mean age 67.0 years) were included, all of whom underwent at least one chest CT scan. Compared with patients who were discharged, deceased patients had a significantly (p &lt; 0.05) higher mean Pan score (11.7 ± 6.0 vs. 8.8 ± 5.0), higher rates of mechanical ventilation (56.0 vs. 32.1 %), and both a higher incidence (42.7 vs. 25.4 %) and longer duration (10.5 [6.0–20.0] vs. 6.0 [3.0–10.0] days) of ICU stays. The Pan score showed a strong and consistent association with the requirement for mechanical ventilation (r = 0.54; p &lt; 0.01) and the duration of the ICU stay (r = 0.39; p &lt; 0.01). Conclusions: The investigated semi-quantitative CT score is a simple, reliable tool for assessing the extent of COVID-19 pneumonia and can be evaluated both by radiologists and fully automated AI software. While its predictive value for all-cause mortality was only moderate, it showed good performance in predicting the need for and duration of mechanical ventilation, as well as intensive care requirement.

Abstract: Increasing evidence suggests that acquired dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channel occurs as a result of cigarette smoke exposure in Chronic obstructive pulmonary disease (COPD). CFTR-targeted therapies were developed for the treatment of genetic CFTR defects in cystic fibrosis, but they have not demonstrated consistent clinical efficacy in small trials of patients with COPD. Here, we aimed to characterise CFTR activity, other ion channels, and differentiation to cilia in primary bronchial epithelial cells (pBECs) from COPD donors, compare to healthy controls, and to determine the extent to which CFTR dysfunction can be rescued by clinically relevant CFTR modulators. Conditionally reprogrammed (CR) air-liquid interface (ALI) cultures of pBECs from healthy controls (n = 7) and COPD donors (n = 7) were comprehensively assessed for transepithelial electrical resistance, immunofluorescence, cilia activity, ion channel function and expression of cell markers at transcript level. COPD cultures exhibited reduced active area of ciliated cells, accompanied by significantly decreased forskolin/IBMX stimulated CFTR-mediated Cl- transport and ATP induced calcium activated chloride currents compared to healthy controls cultures, despite preserved CFTR mRNA expression. Treatment with CFTR potentiators (VX-770, GLPG1837 and Icenticaftor) resulted in modest and highly variable functional responses, with no statistically significant improvement compared with vehicle-treated control. Notably, CFTR function did not correlate with cumulative smoking exposure (pack-years), indicating that smoking burden alone does not predict the extent of acquired CFTR dysfunction. Collectively, these findings demonstrate that COPD airway epithelium exhibits intrinsic defects in ion transport and mucociliary differentiation consistent with acquired CFTR dysfunction phenotype but this is not readily reversible with the tested CFTR modulators. These results highlight fundamental differences between genetic and acquired CFTR dysfunction and underscore the need for alternative or combinatorial therapeutic strategies targeting epithelial dysfunction in COPD.

Abstract: Although poverty and tuberculosis are insidiously linked, knowledge of the relationship between social determinants of health (SDH) and post-tuberculosis lung disease (PTLD) is limited. This study aimed to analyze the association between physical function, pulmonary function, and SDH in individuals with PTLD (iwPTLD), considering the impact of social inequalities on physical performance. This cross-sectional study collected social data from 69 iwPTLDs using a standardized assessment form. The patients underwent pulmonary function testing via spirometry and body plethysmography, as well as respiratory muscle strength and quadriceps muscle strength (QMS) testing. They also completed the six-minute step test (6MST). The median value of steps climbed by participants on the 6MST was 88 (57–117), corresponding to 50.1% (34.9–73.2) of the predicted value. The mean QMS was 28.7 ± 11.9 kgf, with 11 participants (17.4%) showing QMS below the cutoff point. Spirometry revealed normal, obstructive, restrictive, and mixed patterns in 19 (27.5%), 20 (29%), 18 (26.1%), and 12 (17.4%) of the participants, respectively. Performance on the 6MST showed no statistically significant association with SDH. QMS showed a statistically significant association with treated sewage (W=84, p=0.026). Forced expiratory volume in one second showed significant correlations with education level (ρ=0.248, p=0.040), social protection (W=207, p=0.050, r=0.238), and treated water (W=24.5, p=0.029, r=0.264). Maximum inspiratory pressure showed significant correlations with education level (ρ=0.246, p=0.042) and treated water (W=20, p=0.021, r=0.280). The regression model for 6MST and QMS performance showed that 12% and 45% of the variability was explained by the studied variables, respectively. In iwPTLD, impairments in physical function and damage to lung function lead to deterioration of SDH. While the relationship between impairments in bodily function and SDH is weak to moderate, it should not be overlooked, as it may operate through indirect pathways.

Abstract: Background: Chronic occupational lung diseases (COLD) remain a major medical and social problem, often associated with persistent respiratory impairment, reduced exercise tolerance, and cardiovascular comorbidities. Conventional rehabilitation improves symptoms but may not fully address the complex pathophysiological mechanisms involved. Intermittent hypoxic–hyperoxic exposure (IHHE) has recently been proposed as an adjunctive rehabilitation strategy that may enhance adaptive physiological responses. Objective: To evaluate the efficacy and safety of IHHE as an adjunctive intervention in the rehabilitation of patients with COLD. Methods: A single-centered pilot study was conducted in 60 patients with clinically stable COLD. Participants were randomly assigned to an IHHE group (n = 30) or a sham control group (n = 30). The IHHE group underwent 12 sessions over 3 weeks using a ReOxy device, consisting of alternating cycles of hypoxic gas (FiO₂ ≈ 12%) and hyperoxic gas (FiO₂ ≈ 35%) delivered through a facial mask under continuous monitoring of oxygen saturation and heart rate. The control group received identical procedures with room air (FiO₂ ≈ 21%). All patients continued standard pharmacological therapy and pulmonary rehabilitation. Clinical and functional assessments included hypoxic tolerance tests, spirometry (FEV₁), blood pressure, dyspnea severity, and the six-minute walk test (6MWT). Results: After 3 weeks, the IHHE group demonstrated significant improvements in hypoxic tolerance, pulmonary function (FEV₁), and exercise capacity compared with baseline and the control group. The distance covered during the 6MWT increased, while dyspnea severity and bronchial obstruction decreased. Additionally, systolic and diastolic blood pressure showed significant reductions in the IHHE group. Improvements observed in the control group were smaller and generally not statistically significant. No serious adverse events were reported. Conclusion: IHHE appears to be a safe and effective adjunct to standard rehabilitation in patients with COLD, improving hypoxic adaptation, pulmonary function, cardiovascular parameters, and exercise capacity. These effects may be related to enhanced adaptive responses to hypoxia and modulation of inflammatory and oxidative pathways. Further studies are required to evaluate long-term benefits and optimize individualized IHHE protocols.

Abstract: Background: Rheumatoid arthritis-associated interstitial lung disease (RA-ILD) is an important extra-articular manifestation of rheumatoid arthritis and is associated with impaired pulmonary function and poor clinical outcomes. Although interstitial abnormalities in RA-ILD have been widely studied, airway involvement, particularly small airway dysfunction, has received less attention. This study aimed to evaluate small airway function and impulse oscillometry parameters in patients with RA-ILD and to explore their associations with disease severity. Methods: This retrospective study included patients with RA-ILD who were treated at Beijing Jishuitan Hospital, Capital Medical University, between January 2021 and December 2025. Age- and sex-matched healthy individuals without pulmonary disease were included as controls. Clinical data, high-resolution computed tomography (HRCT) findings, pulmonary function parameters, and impulse oscillometry indices were collected. Small airway function was assessed using MEF25–75%, MEF50%, and MEF25%. Disease severity was evaluated using HRCT visual scores, the gender–age–physiology (GAP) score, and the composite physiologic index (CPI). Subgroup analyses were performed according to the presence of small airway dysfunction, HRCT subtype, and history of RA-related joint surgery. Correlations between airway function parameters and disease severity indices were analyzed. Results: A total of 255 patients with RA-ILD were included, including 85 men (33.3%), with a mean age of 67.53 years. Compared with controls, patients with RA-ILD had significantly lower BMI, FVC%, TLC%, and DLCO% (all P < 0.05). Small airway function parameters, including MEF25–75%, MEF50%, and MEF25%, were significantly reduced in the RA-ILD group. Impulse oscillometry showed significantly higher Z5, R5–R20, R5/R20, and Fres, and significantly lower X5 in patients with RA-ILD compared with controls. Patients with RA-ILD and small airway dysfunction had lower FVC% than those without small airway dysfunction (87.7% vs. 95.46%, P = 0.015), and their GAP scores tended to be higher, although the difference did not reach statistical significance (2.59 vs. 1.79, P = 0.055). Among different ILD subtypes, only MEF50% differed significantly among the UIP, NSIP, and other-pattern groups. No significant differences in airway function or disease severity were observed between patients with and without a history of RA-related joint surgery. Correlation analysis showed that MEF25–75%, MEF50%, and MEF25% were negatively correlated with GAP score and positively correlated with FVC%. MEF25–75% and MEF50% were also positively correlated with DLCO%. Conclusions: Patients with RA-ILD showed evidence of small airway dysfunction, increased airway resistance, and reduced airway compliance. Small airway function parameters were associated with FVC%, DLCO%, and GAP score, suggesting that small airway dysfunction may be related to disease severity in RA-ILD. Assessment of small airway function and impulse oscillometry may provide useful supplementary information for the clinical evaluation and monitoring of RA-ILD.

Abstract: INTRODUCTION: Delayed initiation of mepolizumab may influence long-term disease control and the achievement of clinical and functional outcomes in patients with uncontrolled severe asthma (SUA), but no definitive conclusions have yet been established regarding the optimal timing for biologic initiation. The aim of this study was to evaluate, in a real-world clinical setting, the effect of delayed mepolizumab initiation—from the moment patients first met EMA eligibility criteria— on the treatment response (using the EXACTO scale), clinical remission (according to SEPAR-REMAS criteria) and lung function at 12 months and 3 years after treatment initiation. MATERIAL AND METHODS: We conducted a retrospective observational cohort study including 148 patients with SUA treated with mepolizumab from January 2017 to November 2024 in our hospital. Patients were stratified into tertiles according to delay: ≤5 months, 6–19 months, and >19 months. Baseline demographic, clinical, and lung function characteristics were analyzed. RESULTS: Patients with shorter delay exhibited distinct significance baseline profiles, including higher eosinophil counts, lower IMB and current smoker, and better pre-treatment lung function (p< 0,05). Shorter delay was significantly associated with higher rates of good/complete response according to the EXACTO scale at both 12 months and 3 years (p< 0.05). Clinical remission rates were numerically higher in the early-treatment group, although differences did not reach statistical significance. No significant differences in lung function outcomes were observed between delay groups at either 12 months or 3 years. CONCLUSIONS: In conclusion, earlier initiation of mepolizumab after meeting EMA criteria is associated with improved clinical response, although it does not significantly influence remission rates or lung function recovery. These findings underscore the importance of timely treatment initiation and reinforce the relevance of accurate phenotypic and endotypic characterization to optimize biologic selection in SUA.