Introduction: COPD-OSA overlap syndrome (OVS) is defined by the coexistence of chronic obstructive pulmonary disease and obstructive sleep apnea syndrome in the same patient; it affects 28.3% of patients evaluated for either condition and is associated with significantly higher mortality compared to either pathology in isolation. Current therapeutic approaches, involving PAP therapy and bronchodilation, treat this syndrome as a homogeneous entity and ignore the biological heterogeneity of this patient population. Objectives: This review proposes a systematic framework for the endotypic classification of biological interactions between COPD and OSA, integrating current literature on the pathophysiological mechanisms underlying the OVS, clinically accessible biomarkers, and emerging therapies. Methods: A narrative review based on available literature, focusing on studies published between 2010 and 2026 identified via searches in PubMed, PMC, and Dove Medical Press using the terms: COPD-OSA overlap syndrome, endotype, precision medicine, phenotype, biomarker, dupilumab, and incretin-based therapies. Results: Four clinical phenotypes (obese-metabolic, emphysematous, bronchitic-hypoxemic, and hypercapnic) and three molecular endotypes (Th2/eosinophilic, neutrophilic/oxidative, and metabolic-adipokine) are proposed, each with distinct pathophysiological mechanisms and specific therapeutic implications. The interaction between the two conditions generates a unique, pronounced hypoxemic profile. We propose the “double-hit hypoxemia” model as a conceptual framework characterized by amplified systemic inflammation and increased cardiovascular risk compared to either pathology in isolation. This proposed model has not yet been prospectively validated. Dupilumab (approved for an inflammatory phenotype in COPD patients characterized by eosinophil counts ≥ 300 cells/μL) represents a promising option, though currently unsupported in the OVS population, that could nonetheless be relevant to the Th2/eosinophilic endotype of this syndrome and tirzepatide (which reduced the AHI by up to 23.8 events/hour versus placebo in the SURMOUNT-OSA trial, conducted in patients with obesity and moderate-to-severe OSA, rather than in patients with confirmed OVS) could represent a promising therapy for the metabolic-adipokine endotype of obese patients with OVS. A minimal biomarker panel, comprising blood eosinophils, FeNO, daytime PaCO2, BMI, and T90, allows for a practical approach to identifying the dominant endotype. Conclusions: Endotyping of OVS may provide a framework for moving beyond a uniform therapeutic approach toward more individualized management based on the dominant underlying biological mechanism. Randomized clinical trials focusing on endotypic stratification and OVS cohorts remain research priorities.
Purpose: Pulmonary hypertension (PH) is a serious complication of COPD associated with worse outcomes. Reliable circulating biomarkers of pulmonary vascular involvement are lacking. Angiopoietin-1 (ANGP-1) and angiopoietin-2 (ANGP-2) regulate endothelial homeostasis, but their relationship with echocardiographically estimated pulmonary pressure in COPD remains uncertain. Methods: This prospective cross-sectional study included 70 consecutively recruited adults with COPD, stratified using a study-specific echocardiographic threshold into the COPD PH group (mPAP > 20 mmHg; n = 46) and the COPD without PH (mPAP < 20 mmHg; n = 24), together with 20 additional controls. This non-invasive stratification was not considered equivalent to PH confirmed by right heart catheterization. Serum ANGP-1 and ANGP-2 were measured using ELISA. Group differences and associations with e-mPAP and right atrial pressure (RAP) were assessed. Results: Median ANGP-1 was higher in the elevated e-mPAP group [8780.06 (IQR 7955.29-9902.88) pg/mL] than in the lower e-mPAP group [3065.14 (1170.69-6200.41)] and controls [2997.19 (1292.13-3278.18); p < 0.001]. ANGP-2 showed a similar pattern [6152.92 (5380.27-8652.50), 2669.77 (1802.18-4744.00), and 2405.54 (1779.73-3751.76) pg/mL; p < 0.001]. Among COPD participants, ANGP-1 and ANGP-2 correlated with e-mPAP (r = 0.64 and r = 0.54) and RAP (r = 0.54 and r = 0.52; all Holm-adjusted p < 0.001). In multivariable models, e-mPAP and RAP were independently associated with ANGP-1, whereas RAP was independently associated with ANGP-2. Conclusions: Higher circulating ANGP-1 and ANGP-2 were associated with an elevated echo-estimated pulmonary-pressure phenotype in COPD. These findings are exploratory and require validation in larger cohorts using direct hemodynamic assessment.
Background: Bronchial asthma is a chronic inflammatory airway disease characterized by acute bronchoconstriction and type 2-driven inflammation. This study investigated whether inhaled amitriptyline, a functional inhibitor of acid sphingomyelinase, exerts both bronchodilatory and immunomodulatory effects in experimental murine models of allergic airway inflammation (AAI) and human cellular systems. Methods: Acute AAI was induced in mice using ovalbumin (OVA) and house dust mite (HDM) protocols, respectively. Inhaled amitriptyline (3.3 mg/mL) was administered for either 20 days (short-term) or 36 days (long-term). Lung function was assessed using FlexiVent®, and inflammatory markers including IgE, eosinophils, and type 2 cytokines were measured in bronchoalveolar lavage fluid and lung tissue. Complementary experiments were included using passively sensitized PCLSs and human type 2-differentiated CD4+ T cells. Results: Inhaled amitriptyline improved lung mechanics in both the OVA and HDM models, reducing total respiratory resistance and elastance. In the OVA model, eosinophil and T cell counts in BALF were decreased, whereas immunomodulatory effects were less pronounced in the short-term HDM model. In human TH2 cells, no significant changes in cytokine production or gene expression were observed. Ex vivo, amitriptyline dose-dependently inhibited allergen-induced bronchoconstriction in PCLSs. Conclusions: Inhaled amitriptyline improves lung function across murine models of AAI, supporting its potential in exhibiting model-dependent immunomodulatory effects, and directly attenuates allergen-induced bronchoconstriction, supporting its potential as a bronchodilator with context-dependent immunomodulatory properties.
Introduction: Allergic rhinitis (AR) imposes a substantial burden on individuals worldwide. Local allergic rhinitis (LAR) patients exhibit symptoms similar to those of AR without a positive skin prick test (SPT) or the presence of sIgE specific to one or more allergens. Our study evaluated specific and total grass pollen IgE in the nasal secretions of patients with suspected LAR, examining the effects of natural pollen exposure and nasal provocation testing (NPT). Methods: Twenty-nine subjects (18 with suspected LAR and 11 with AR) were included in this study. The total nasal symptom score (TNSS) and visual analog scale (VAS) were used for subjective assessment. NPT was performed using grass pollen allergen. Nasal lavage was used to obtain nasal secretions, and the levels of sIgE and total IgE were measured. Results: During the exposure vs. the off-exposure period, the TNSS and VAS were significantly higher in LAR (p < 0.0001 and p = 0.0061, respectively). sIgE and total IgE were significantly higher in the AR group than in the LAR group during the exposure period (p = 0.0008 and p = 0.0491, respectively). LAR diagnosis was confirmed in seven subjects. TNSS and VAS scores were higher after a positive NPT. The median level of sIgE was lower in the negative and positive NPT. A higher median total IgE level was observed post-provocation in both groups. A significantly higher median relative sIgE level was noted after positive and negative provocation (p = 0.0156 and p = 0.0143, respectively). Conclusions: The assessment of local sIgE levels in nasal secretions can be used as a method for the diagnostic workup of patients with suspected LAR. Achieving a well-defined and standardized protocol for the assessment of sIgE concentrations in nasal secretions of LAR is a goal of future larger studies.
Background: Acute exacerbation of obstructive airway disease (AEOAD) is a major cause of hospitalization, morbidity, and premature mortality in India. Hospitalized patients for the same are predominantly treated with short-acting bronchodilators, which require frequent administration and are associated with systemic adverse effects. Despite the availability of nebulized long-acting muscarinic antagonists (LAMAs) with quick onset of action, such as glycopyrronium, their role in acute care remains unclear in India. Methods: A pan-India expert opinion-building initiative was conducted among 220 pulmonologists across Tier I-II cities through 13 structured advisory meetings between April 2025 and July 2025. The final expert perspectives were then categorized into recurrent insights, raised in 75% or more meetings, and variable insights, raised in <75% of all meetings. Results: Experts reported that AEOAD management commonly involved initial stabilization with SABA/SAMA followed by transition to triple therapy with nebulized glycopyrronium, formoterol, and budesonide. Nebulized glycopyrronium was perceived to provide rapid and sustained bronchodilation with fewer cardiovascular side effects compared to short-acting agents. Benefits were reported in patients with frequent exacerbations, high sputum burden, and bronchiectasis. Operational advantages included reduced dosing frequency and nursing workload. Experts also noted potential improvements in hospital stay and readmissions; however, these observations were based on clinical experience rather than controlled data. Conclusions: Indian pulmonologists agreed that early initiation of nebulized glycopyrronium (with formoterol and budesonide) in hospitalized AEOAD may improve symptom control, lower exacerbation burden, reduce reliance on short-acting bronchodilators and corticosteroids, and shorten hospital stays.
This article presents recommendations aimed at reducing the risk of bleeding during bronchoscopy. The document was developed by a working group convened by the Polish Respiratory Society, which included pulmonologists experienced in bronchoscopic procedures, an anesthesiologist, a thoracic surgeon, a cardiologist, a hematologist, a nurse, and methodologists. Clinical questions were formulated according to the PICO (Population, Intervention, Comparison, Outcome) framework, followed by a systematic literature search and critical appraisal of the selected studies. Based on these data, 13 recommendations/good clinical practice points were developed addressing bronchoscopy in patients with thrombocytopenia, abnormal activated partial thromboplastin time or international normalized ratio results, and in those receiving antiplatelet agents, oral anticoagulants, or low-molecular-weight heparin.
Artificial intelligence (AI) is progressively reshaping interventional pulmonology (IP), yet its potential to erode procedural and cognitive competencies through AI-induced deskilling remains poorly characterized in this specialty. An international, observational, cross-sectional survey was conducted in May 2026 among 118 expert interventional pulmonologists from 10 different countries across 5 continents. Participants completed a structured questionnaire comprising five demographic items and 12 Likert-scale statements addressing deskilling risk perception and mitigation attitudes; percentage agreement was calculated for each item (scores 4-5). High perceived clinical value of AI was reported (87%), alongside substantial concern for procedural deskilling (73%) and upskilling inhibition (83%). Familiarity with automation bias was limited (38%), yet its clinical relevance was widely recognized after definition provision (81%)-a gap of 43 percentage points. Strong support emerged for AI-free training (84%), simulation-based training (86%), and longitudinal performance monitoring (78%). Concern for institutional fragility in the absence of AI was expressed by 74%, and governance frameworks, including minimum non-AI-assisted procedural volume requirements, were endorsed by 70%. Deskilling was identified as a high research priority by 89%. These findings indicate that AI-induced deskilling is perceived as a relevant and emerging risk by expert interventional pulmonologists internationally, even before the widespread clinical deployment of AI technologies. Although the extent to which these concerns will translate into measurable effects on procedural competence is currently uncertain, the results underscore the need for prospective research, educational initiatives, and appropriate governance frameworks to ensure the preservation of core procedural skills.
BACKGROUND/OBJECTIVES:Pulmonary hypertension (PH) is an increasingly recognized complication in patients with end-stage renal disease (ESRD) undergoing hemodialysis, particularly those utilizing arteriovenous fistulas (AVF) or grafts (AVG) for vascular access. The prevalence and clinical impact of PH in this population remain unclear due to methodological heterogeneity and variable diagnostic criteria. This systematic review and meta-analysis aimed to quantify the association between AVF/AVG use and PH prevalence in ESRD patients and to explore sources of heterogeneity. METHODS:A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted for studies published through 31 December 2024, without language or date restrictions. Eligible studies included adults (≥18 years) with ESRD on dialysis, comparing those with AVF/AVG access to non-AVF/AVG controls (e.g., tunneled dialysis catheters or peritoneal dialysis), and reporting PH prevalence or mean pulmonary artery pressures. Study quality was assessed using the Newcastle-Ottawa Scale, and risk of bias was evaluated. A random-effects meta-analysis calculated pooled odds ratios (OR) for PH prevalence, with heterogeneity assessed by I2 and Cochran's Q. Sensitivity analyses and tests for publication bias (Egger's and Begg's) were performed. Secondary analysis compared pooled mean pulmonary artery pressures between groups. RESULTS:Eleven observational studies (1299 dialysis patients) met the inclusion criteria; ten studies (1224 patients) contributed to the quantitative meta-analysis after exclusion of one study with a zero-event control arm. Most studies were small, predominantly cross-sectional, and of moderate methodological quality. The pooled analysis showed a statistically significant association between AVF/AVG use and PH (OR 2.06, 95% CI: 1.69-2.52), with low statistical heterogeneity (I2 = 0%). This estimate was sensitive to individual studies: in leave-one-out analysis the association lost statistical significance when the single most influential study was removed indicating that the pooled result is driven in part by a small number of studies rather than being uniformly robust. No statistical evidence of publication bias was detected. Five studies reported continuous pulmonary artery pressures, which were directionally higher in AVF/AVG patients but were not pooled because of extreme heterogeneity (I2 = 99.4%). CONCLUSIONS:In this synthesis of observational data, AVF/AVG use was associated with higher odds of pulmonary hypertension than non-AVF/AVG access. Because all included studies were observational and the pooled estimate is sensitive to individual influential studies, these findings indicate a possible association rather than a causal effect and should be interpreted with caution. They support the rationale for prospective hemodynamic studies and for evaluating-rather than presuming the benefit of-PH monitoring and individualized access strategies in higher-risk dialysis patients.
Background: Respiratory syncytial virus (RSV) infection is a cause of respiratory morbidity in high-risk patients, including those with chronic lung disease (CLD) and those undergoing hemodialysis (HD). In HD patients, evidence on the clinical impact of RSV vaccination on respiratory complications remains limited. We aimed to assess the clinical impact of RSV vaccination in HD patients by comparing vaccinated and unvaccinated patients with a focus on CLD. Methods: We retrospectively evaluated 56 adult HD patients: 28 received the RSV vaccine in autumn 2024 and 28 did not. Clinical data were collected from electronic medical records. Outcomes included influenza-like illness (ILI), pneumonia, and respiratory infection requiring hospitalization between September 2024 and September 2025. Results: Patients had a mean age of 74.4 years and a median Charlson Comorbidity Index (CCI) of 10. The RSV-vaccinated group had a greater comorbidity burden than the unvaccinated group (CCI 11 IQR 10-12 vs. 9 IQR 8-11, p = 0.02) and a higher prevalence of CLD (46.4% vs. 25.0%, p = 0.09). During follow-up, 28 patients (50.0%) had at least one ILI episode, 23 (41.1%) developed pneumonia, and 15 (26.8%) were hospitalized for respiratory infection. The incidence of ILI was 46.4% in vaccinated patients and 53.6% in unvaccinated patients (p = 0.28), while the incidence of pneumonia was 39.3% and 42.9%, respectively (p = 0.78). Respiratory infection requiring hospitalization occurred in 14.3% of vaccinated patients and 39.3% of unvaccinated patients (p = 0.035). CLD was significantly associated with pneumonia (p = 0.001) and showed trends toward higher rates of ILI (p = 0.09) and hospitalization for respiratory infection (p = 0.1). Conclusions: In our exploratory study, RSV vaccination in HD patients was associated with fewer hospitalizations for respiratory infection, despite greater comorbidity in vaccinated patients. CLD was associated with a higher incidence of respiratory complications, particularly pneumonia. The retrospective design and small sample size do not allow definitive conclusions; future prospective studies with an adequate sample size are needed to confirm our results.
Cystic fibrosis (CF) is an autosomal recessive disorder caused by mutations in the CFTR gene. The sequential approval of CFTR modulators ivacaftor (2012), lumacaftor/ivacaftor (2015), tezacaftor/ivacaftor (2018), and elexacaftor/tezacaftor/ivacaftor (2019) has transformed CF care, but population-level mortality trends across therapeutic periods have not been comprehensively assessed. We conducted a retrospective analysis of CF mortality in the United States from 1999 to 2024 using CDC WONDER Underlying Cause of Death data (ICD-10 codes E84.0-E84.9). Age-adjusted mortality rates (AAMR) per 100,000 were calculated using the 2000 U.S. standard population. The study period was divided into three periods: pre-modulator (1999-2011), early modulator (2012-2018), and elexacaftor/tezacaftor/ivacaftor (2019-2024). Annual mortality trends were evaluated using segmented log-linear Poisson regression, with annual death counts as the outcome and the corresponding U.S. population as an offset. Candidate models with multiple change points were compared to identify distinct temporal segments. Annual percent changes (APCs) and 95% confidence intervals (CIs) were estimated for each segment. Prespecified therapeutic periods, including pre-modulator (1999-2011), early modulator (2012-2018), and ETI period (2019-2024), were retained for descriptive analyses. Trends were stratified by sex and U.S. Census Region. A total of 10,959 CF deaths were recorded over 26 years. In the pre-modulator period, mortality was stable at a mean of 478 deaths/year (AAMR 0.14-0.17). The early modulator period showed a modest 5.4% reduction in mean annual deaths (452/year). The period following ETI availability was associated with a decline to 263/year, a 47% reduction from the pre-modulator period (AAPC -8.6%/year). The AAMR declined from 0.17 (1999) to 0.07 (2024). The female-to-male death count ratio shifted from 1.05 to 0.97 across periods, though age-adjusted rates were identical between sexes within each period, and this finding should be interpreted cautiously. Regionally, the South's share of CF deaths grew from 37.2% to 41.6% despite absolute declines in all regions, suggesting potential geographic disparities that warrant further investigation with individual-level data. Segmented regression identified change points in 2005 and 2015. Mortality declined significantly from 1999 through 2005 (APC, -2.70%; 95% CI, -4.01% to -1.37%), remained stable from 2006 through 2015 (APC, +0.21%; 95% CI, -0.47% to +0.90%), and declined sharply from 2016 through 2024 (APC, -9.76%; 95% CI, -10.66% to -8.84%). CF mortality in the United States has declined by more than half since the introduction of CFTR modulators. The shift in the sex-based death count ratio and the concentration of remaining deaths in the South are hypothesis-generating observations that require confirmation with individual-level data. These ecological findings cannot establish causation, as concurrent changes in supportive care, lung transplantation practices, and COVID-19 pandemic effects may have contributed to the observed trends.
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.
Drug delivery systems (DDS) may improve the therapeutic performance of chemotherapy in lung cancer, but their preclinical efficacy has not been quantitatively synthesized. We conducted a systematic review and meta-analysis of controlled in vivo mouse studies evaluating DDS-based chemotherapeutic formulations for lung cancer. Databases were searched from inception to 15 February 2025, and methodological quality was assessed using the SYRCLE risk-of-bias tool. Thirty studies comprising 47 experiments were included. Compared with corresponding free-drug treatments, DDS-based chemotherapy significantly reduced tumor volume (WMD -310.67 mm3; 95% CI: -375.51 to -245.83; p < 0.001), although substantial heterogeneity was observed. Both targeted and non-targeted DDS were associated with tumor growth inhibition, and targeted formulations showed a larger average reduction; however, this finding should be interpreted in light of differences in formulation properties, tumor models, and treatment protocols. Nanoparticle, liposomal, and micellar platforms all demonstrated significant antitumor effects, while combination DDS and docetaxel- or cisplatin-based systems showed large effects in subgroup analyses with variable sample sizes. These findings support the continued development of DDS-based chemotherapy for lung cancer, but standardized reporting of nanocarrier characterization, pharmacokinetics, biodistribution, toxicity, and rigorous animal-study design is required to improve reproducibility and translational relevance.
Introduction: Patients with rheumatoid arthritis (RA) have higher risk for pneumonia, interstitial lung disease (ILD) and pulmonary fibrosis (PF). However, the association between an ICD-10-coded pneumonia event (CPE) and the incidence of ILD or PF in the RA population remains unclear. Methods: We conducted a retrospective cohort study using the TriNetX database. Patients with ICD-10 for RA aged 50 or older who had a CPE within one year of RA diagnosis (CPE cohort, n = 4553) were matched 1:1 by propensity score for key factors, including demographics, comorbidities (i.e., COPD), and medication use (DMARDs, corticosteroids) to RA patients without a CPE (Control cohort, n = 4553). Cox proportional hazard models assessed the incidence of a composite ILD outcome, PF, and secondary complications over a 4-year follow-up after the index event defined as 1-year after RA diagnosis for both cohorts. Results: The CPE cohort showed an increased risk for all outcomes. Patients with CPE had a 2.48-fold increased risk for PF (HR = 2.48; 95% CI, 1.78-3.45; p < 0.01) and a 2.87-fold increased risk for the composite ILD outcome (HR = 2.87; 95% CI, 2.18-3.80; p < 0.01). The risk of rheumatoid lung disease was 4.15 times higher (HR = 4.15; 95% CI, 2.30-7.50; p < 0.01). Furthermore, the CPE group had a higher risk for all-cause mortality (HR = 1.82; 95% CI, 1.58-2.09; p < 0.01). Conclusions: The CPE within one year of RA diagnosis is associated with an increase in subsequent ILD-coded outcomes. While this retrospective design cannot establish causality, an unspecified pneumonia code in early RA may represent an early clinical manifestation of unrecognized ILD, serving as a high-risk marker that warrants pulmonary surveillance.
(1) Background: Innate lymphoid cells (ILCs) are potent cytokine producers that regulate local immune responses in tissues. Natural killer (NK) cells belong to group 1 ILCs and play an important role in tumor clearance and defense against intracellular pathogens. ILC2 and 3 have been implied in allergic responses and other chronic inflammatory diseases. The role of these cells in the pathogenesis of chronic rhinosinusitis (CRS) is not completely understood. There are changes in the cellular infiltrate in the mucosa of patients with CRS with and without polyps. The aim of this study was to characterize the number and phenotype of NK cells, ILC2s and ILC3s in patients with CRS. (2) Methods: Tissue samples were collected from patients with CRS with and without nasal polyps who were undergoing nasal sinus surgery as well as control patients who were undergoing surgery due to non-inflammatory reasons. Lymphocytes were isolated from the tissues using mechanical and enzymatic dissociation. Peripheral blood lymphocytes were obtained from the same patients. All cells were examined by multicolor flow cytometry. NK cells were analyzed for the distribution of CD56dimCD16+ and CD56brightCD16- subsets and the expression of IL18Rα, CD16, CD57, GATA3, TCF1 and NKp44. In ILC2s, GATA3 and IL18Rα expression was determined, and ILC3s as well as NKp44+ and NKp44-ILC3 subsets were analyzed for the expression of IL18Rα. (3) Results: There were significantly fewer NK cells in the nasal polyps compared to the peripheral blood of patients with CRSwNP and tissues from CRSsNP patients, which both showed higher levels of TCF1 expression. Irrespective of the disease condition, NK cells in tissues showed lower CD16 expression and a lower frequency of the CD56dimCD16+ subset compared to the peripheral blood mononuclear cells. Additionally, a smaller percentage of NK cells were terminally matured, as measured by CD16+ and CD57+ expression, in all examined nasal mucosa tissues. In the tissue ILC3s, we predominantly found cells from the NKp44- subset in all groups. ILC3s from CRSsNP patients showed the highest frequencies of IL18Rα+ cells of all examined tissues. ILC2s from the polyps ofCRSwNP patients showed higher levels of GATA3 expression than their peripheral blood counterparts. (4) Conclusions: We found that tissue-resident NK cells in mucosa from the nose and sinuses are a more heterogenous and less mature population than those in peripheral blood. Expression of the examined markers in NK cells was similar among groups. NK cell frequency, both in blood and tissue from CRSsNP patients, was higher than in the other groups, indicating that these cells might play an important role in this phenotype. Changes in the IL18Rα expression of ILC3s suggest a potential role of IL18 signaling in CRS pathogenesis.
Chronic obstructive pulmonary disease (COPD) is a respiratory disease that progressively impairs airway function. Its aetiology and clinical presentation are very complex, resulting in an unpredictable course of the disease. The most important causes include smoking and environmental pollutants. However, upper airway microbiome dysbiosis has been linked with COPD severity. Through this review, we aim to compare the microbiome of the respiratory tract between its sites, and to see if there are any significant differences in the composition of the microbial flora of patients with COPD when compared to healthy individuals. While preparing this review, the PubMed database was searched using keywords such as bacteriome, COPD, exacerbation, and microbiome. Analysis of the airway microbiome shows that the three most abundant phyla are Firmicutes, Proteobacteria, and Bacteroidetes. The severity of the disease and the selected therapeutic methods influence the ratio of Proteobacteria and Firmicutes. It has been observed that a decrease in microbial diversity resulted in lower values of FEV1 in patients and could be related with COPD’s progress and exacerbation events. While exacerbation cases need quick treatment, COPD’s complex background makes it difficult to find a singular, microbial cause.
Objectives: To provide an evidence-based reference for preventing and managing pediatric acute asthma exacerbations by examining epidemiology and long-term trends of hospitalized cases in a tertiary hospital in Beijing over 30 years. Methods: Retrospective analysis of clinical data from children hospitalized for acute asthma exacerbation at Peking University Third Hospital from 1994 to 2023. Data collected included demographics, onset timing, and hospital stay duration, with distribution patterns analyzed across ages, years, seasons, and months. Results: The study included 1106 patients (65.73% male, 34.27% female) with a median age of 4 years. Hospitalizations peaked in 1999 (8.40%) and declined, reaching the lowest point in 2020 (1.45%) coinciding with the COVID-19 pandemic. Most admissions occurred in autumn (34.27%), especially in October (13.29%). The average hospital stay was 5.35 ± 2.65 days, longest for toddlers. Conclusions: Over 30 years, pediatric hospitalizations for acute asthma exacerbations in this tertiary center have shown a declining trend, suggesting improved asthma management. However, the persistent autumn peak and male predominance highlight the need for targeted prevention strategies—particularly for male and preschool-aged children before the autumn school term—to further reduce acute exacerbations and hospitalizations.
Background: Highly effective CFTR modulation with Elexacaftor/Tezacaftor/Ivacaftor (ETI) markedly improves clinical outcomes in people with cystic fibrosis (CF). Data on its effects on physical activity, sleep, sinonasal symptoms, and parent-perceived outcomes in preschool-aged children are limited. Methods: In this prospective, observational, single-center cohort study, ten children with cystic fibrosis (aged 2-6 years) and at least one CFTR variant eligible for ETI were included. Data were collected using wrist-worn Garmin vívofit Junior 2 activity trackers and standardized questionnaires one month before ETI initiation and at 1, 3, 6, and 12 months after start of ETI. Outcomes included step count, minutes of moderate-to-vigorous physical activity, sleep parameters, sinonasal symptoms, and parental perceptions. Results: ETI was well tolerated. Sweat chloride levels decreased significantly. Physical activity improved at 3 and 6 months (step count and active minutes/day; p < 0.05) but declined to near-baseline levels at 12 months. Parental assessments of physical and sporting performance showed sustained improvement. Sleep duration remained stable, with no changes in deep or light sleep phases or nighttime awakenings. Sinonasal symptoms remained low. Discussion & Conclusions: Preliminary findings of this exploratory pilot study show that improvement in physical activity after three and six months of ETI therapy might be attributable to seasonality, as therapy was started in winter months. No changes in sleep duration or sleep patterns are reassuring in this small cohort of young children with CF. ETI therapy was safe and well tolerated. Parental appraisal of their children's physical performance improved after start of ETI. Longitudinal, controlled studies involving larger cohorts are required to validate these findings and to account for potential confounding factors, such as age-dependent changes and individual and environmental factors such as seasonal variation.
Background: This study was conducted to identify genetic risk variants associated with nicotine addiction in the CHRNA5, HTR2A, DRD4, and CYP2A6 genes among electronic cigarette users who also smoke combustible cigarettes (dual users), and to assess potential genotoxic and cytotoxic damage in the oral mucosal cells of the study population. Methods: We included dual e-cig users (ECIG, n = 70), combustible cigarette smokers (CCU, n = 24), and non-smokers and non-e-cig users (NS, n = 110). Genetic variants in CHRNA5, HTR2A, DRD4, and CYP2A6 were genotyped. Micronucleus analysis was performed on oral mucosal cells to detect cellular abnormalities. Results: The ECIG group demonstrated greater nicotine addiction on the Fagerström Test for Nicotine Dependence (FTND, 5.5 vs. 1, p = 0.023). Salivary cotinine levels were significantly higher in the ECIG group compared to the CCU group (39 vs. 12 ng/mL, p < 0.001). The carriers of the A allele (rs16969968/CHRNA5) had higher FTND scores, carriers of the C allele (rs1800955/DRD4) used electronic cigarettes more frequently each day, and carriers of the T allele (rs4105144/CYP2A6) started using nicotine products at a younger age. The number of micronuclei and cellular abnormalities in the oral mucosa was higher in the ECIG and CCU groups compared to the NS group. Conclusions: Salivary cotinine levels and FTND are higher in dual e-cigarette users than in combustible cigarette users. Dual users exhibit risk alleles in the CHRNA5, DRD4, and CYP2A6 genes, which are associated with traits linked to increased nicotine addiction. Dual e-cigarette use poses comparable genotoxic risks to combustible smoking.
Asthma is characterized by persistent airway epithelial dysfunction and remodelling of the reticular basement membrane (RBM). In healthy airways, the RBM is primarily composed of the extracellular matrix (ECM) proteins laminin and collagen-IV, but in remodelled asthmatic airways, the RBM has increased deposition of collagen-I, -III and fibronectin. Here, we systematically compared the effects of collagen-I, -III, -IV, fibronectin, laminin, and bovine serum albumin (BSA) control on bronchial epithelial cells (BECs) from six healthy controls and seven individuals with asthma. Epithelial attachment, spreading and barrier function were assessed in real time over 72 h using electrical cell-substrate impedance sensing. Cell culture supernatants were analyzed for release of epithelial cytokines, thymic stromal lymphopoietin (TSLP), interleukin (IL)-6, IL-8, and IL-11 using ELISA. BECs from both control and asthma donors had faster cell attachment, spreading, and barrier formation on collagen-I, -III, -IV, and fibronectin compared to laminin and BSA. BECs from both control and asthma donors cultured on collagen -I and -III produced more TSLP, but had no effect on IL-6, IL-8, and IL-11 expression. In summary, remodelling of the RBM in asthma may promote epithelial barrier formation whilst simultaneously enhancing epithelial-derived Th2 inflammation through increased TSLP release.
Objective: Rapid assessment of early treatment-related physiological improvement in emergency department (ED) patients with respiratory failure (RF) remains challenging. Blood gas analysis is informative but invasive and not ideal for repeated use. The vertical displacement index (VDI), an ultrasound-derived parameter based on pleural motion, may provide dynamic bedside information on early physiological change. This study evaluated whether changes in VDI are associated with early physiological improvement in ED patients with RF. Methods: This prospective observational study was conducted in the EDs of two tertiary care hospitals. Adult patients presenting with dyspnea and clinical evidence of RF were included. VDI was measured by lung ultrasound at baseline and 30 min after initial treatment. The primary endpoint was the change in VDI 30 min after the initial treatment, calculated as the difference between pre-treatment and post-treatment VDI. The expected direction was a post-treatment decrease in VDI, with greater VDI reduction expected to be associated with greater early physiological improvement. Secondary analyses included comparisons of VDI changes across oxygen saturation and diagnostic groups, as well as correlations between ΔVDI and physiological changes. Patients were grouped by admission oxygen saturation (<80%, 80-90%, and ≥90%). Results: Seventy-nine patients were included. Pre-treatment VDI differed significantly between oxygen saturation groups, with the highest values in the most hypoxemic patients (p = 0.028). VDI decreased significantly after treatment in all groups (p < 0.001 for all), with the greatest reduction in the <80% group. By diagnosis, VDI decreased significantly in pulmonary edema, COPD/asthma, and pneumonia, but not in pulmonary embolism (p = 0.138). VDI reduction correlated positively with improvements in oxygen saturation (r = 0.27, p = 0.016) and pH (r = 0.24, p = 0.037), but not with CO2. Conclusions: VDI may be explored as a practical ultrasound-derived bedside parameter associated with early physiological improvement in ED patients with RF.
