In the ASPEN trial (NCT04594369), brensocatib 10mg and 25mg significantly reduced the burden of pulmonary exacerbations (annualized rate [primary endpoint], time to first, proportion exacerbation-free) over 52 weeks vs placebo in patients with bronchiectasis; brensocatib 25mg significantly reduced lung function decline and nominally significantly improved patient-reported symptoms. Here we report efficacy and safety for Japanese patients. Adults with bronchiectasis with ≥2 exacerbations in the 12 months before screening were randomized to once-daily brensocatib (10mg or 25mg) or placebo for 52 weeks. Endpoints included annualized exacerbation rate, time to first exacerbation, proportion remaining exacerbation-free, change from baseline in lung function, severe exacerbation rate, and change from baseline in patient-reported symptoms. Baseline characteristics of Japanese patients (n=87) were generally consistent across groups. Brensocatib 10mg and 25mg reduced the annualized exacerbation rate vs placebo (rate ratio, 0.37 [95% CI, 0.16-0.87]; 0.32 [0.14-0.75]), prolonged time to first exacerbation, and increased odds of remaining exacerbation-free. The annualized severe exacerbation rate was lower with brensocatib 10mg and 25mg vs placebo (rate ratio, 0.11 [0.01-1.04]; 0.30 [0.06-1.62]). Brensocatib, particularly at the 25mg dose, also reduced lung function decline vs placebo (LS mean difference: forced expiratory volume in 1s, 97mL [95% CI, 32-162]; forced vital capacity, 164mL [84-244]) and improved patient-reported symptoms. Adverse events were similar across groups. Consistent with overall ASPEN results, brensocatib 10mg and 25mg reduced exacerbation frequency vs placebo in Japanese patients with bronchiectasis. Lung function, patient-reported symptoms, and safety data were consistent with overall ASPEN trial results. NCT04594369.

We evaluated the long-term outcomes of children undergoing thoracotomy lung resection for congenital lung malformations in terms of lung function, complications, and health-related quality of life (HRQOL). We retrospectively reviewed 27 children who underwent thoracotomy at Osaka University Hospital (1992-2017) with at least five years of follow-up and postoperative lung function testing after six years of age. We compared the percent predicted vital capacity (%VC), percent predicted forced expiratory volume in 1s (%FEV1), and FEV1 to FVC ratio (FEV1/FVC) as indicators of the lung function. Longitudinal changes in the lung function, pulmonary and musculoskeletal morbidities, and HRQOL were assessed using the Pediatric Quality of Life Inventory. %VC and FEV1/FVC remained within the normal range but were significantly lower than the controls; %FEV1 was below the normal range. No significant longitudinal changes in the lung function were observed. Asthma‑like symptoms appeared in 37.0% of the patients and persisted beyond adolescence. Musculoskeletal morbidities occurred in 33.3% of the patients, with five pectus excavatum cases requiring correction. HRQOL did not differ from that of the healthy controls. In our study, children undergoing thoracotomy lung resection for congenital lung malformations exhibited a significantly lower lung function than the healthy controls, and these impairments persisted over an extended follow-up period. Long-term complications and a reduced lung function were not reflected in the subjective HRQOL.

Clinical stability under FF/UMEC/VI triple inhaled therapy: A 12-month real life retrospective observational study.

Asthma heterogeneity remains a major barrier in precision medicine. Although elevated total serum immunoglobulin E (IgE) is a hallmark of asthma, even in nonatopic patients, its causal role in asthma pathogenesis is debated. We hypothesized that genetic predisposition to increased IgE defines a distinct asthma endotype. A genome-wide association study of total serum IgE in 1,287 non-asthmatic Japanese adults was used to construct IgE polygenic risk scores (IgE_PRS). Applying IgE_PRS to 745 patients with asthma, we performed cluster analysis incorporating age at onset, total IgE levels, IgE_PRS, and percent predicted forced expiratory volume in 1s (pFEV1), identifying four distinct adult asthma phenotypes. Notably, one cluster had the highest IgE_PRS and adult-onset-predominant type 2 inflammation. Conversely, the second cluster displayed the highest IgE levels but average IgE_PRS. The remaining two clusters comprised patients with lower IgE_PRS. One cluster was characterized by eosinophilia and smoking-related airflow limitation, whereas the other exhibited a type 2 low phenotype. In a 10-year retrospective cohort, over 30% of newly diagnosed asthma cases fell into the genetically predisposed high-IgE_PRS cluster. These findings reveal a distinct adult-onset-predominant asthma phenotype driven by genetically determined IgE production, offering new avenues for endotype-driven diagnosis and personalized therapy.

Elexacaftor-tezacaftor-ivacaftor (ETI) improves clinical outcomes in people with Cystic Fibrosis (pwCF), with possible anti-inflammatory properties. However, the molecular mechanisms underlying these effects remain unclear. This study investigates ETI's anti-inflammatory and immunomodulatory activity, focusing on essential signaling pathways. Forty-nine pwCF were followed for 24 months. PwCF underwent clinical and pulmonary function assessment along with sweat test chloride measurement. Blood samples were analyzed for red and white blood cell counts and C-reactive protein (CRP). Plasma cytokines were quantified and phospho-kinase arrays and western blotting were used to assess protein phosphorylation in peripheral blood mononuclear cells (PBMC) from pwCF and healthy controls, pre- and post-ETI. Gene expression was evaluated in patient-derived PBMC and CF bronchial epithelial cells in vitro. ETI treatment significantly improved percent-predicted forced expiratory volume in 1s (ppFEV1) and reduced intravenous antibiotic use. Inflammatory markers (including CRP) and circulating leukocytes decreased, especially lymphocytes and monocytes. Six of 27 pro-inflammatory cytokines were significantly downregulated. ETI strongly inhibited Signal Transducer and Activator of Transcription 5 (STAT5) phosphorylation in PBMC and CF epithelial cells, both in vivo and in vitro. This correlated with reduced interleukin IL-6, IL-8, and TNF-α mRNA levels. Pharmacological inhibition of JAK/STAT mimicked ETI effects on cytokine expression, supporting STAT5 as an important player involved in CF chronic inflammation. Long-term ETI treatment confirms clinical benefits and exerts measurable immunomodulatory effects, partially via inhibition of JAK/STAT signaling. These findings support its broader impact beyond CFTR correction. Further studies are warranted to explore long-term immunological outcomes, especially in younger patients initiating early therapy.

Fatigue is a pervasive, debilitating symptom of chronic obstructive pulmonary disease (COPD) that significantly impacts patients' overall health and quality of life. However, its underlying mechanisms and associations with physical, psychological, behavioral, and other health factors remain unclear. This study investigated longitudinal associations between fatigue and these factors in COPD. A total of 247 COPD patients (mean age, 67.3 ± 8.1years; 60% male; mean forced expiratory volume in 1s (FEV1) 57 ± 21% predicted) from primary and secondary care were enrolled in a longitudinal observational study. Two-wave autoregressive cross-lagged panel models (ARCLM) examined relationships between fatigue and associated factors at baseline and 1year later. Severe fatigue was prevalent in 53% of participants at baseline, with no significant change at follow-up. ARCLM findings indicated that baseline physical activity was the only predictor of reduced fatigue after 1year. Moreover, higher baseline fatigue predicted poorer health-related quality of life, more severe dyspnea, and greater dyspnea-related emotional distress at follow-up. Although the initial focus was on fatigue, the analysis revealed a complex network of longitudinal relationships between multiple studied variables extending beyond fatigue. Physical activity was the only direct predictor of fatigue, while fatigue directly influenced dyspnea, dyspnea-related emotions, and health-related quality of life. This study highlights the important role of fatigue within a complex network of physical, psychological, health status, and behavioral factors. The complexity of the interrelatedness of these factors suggests that single-target interventions are unlikely to be effective. Rather, integrated interventions, such as pulmonary rehabilitation, are needed.

This study aims to assess the impact of two kinds of Liuzijue Qigong on respiratory and motor functions of hemiplegic stroke patients with impaired balance and respiratory function in early-phase recovery rehabilitation. 66 Stroke patients were randomly divided into three groups: Liuzijue Qigong group (LG), ancient Liuzijue Qigong group (AG), and the control group (CG). The primary outcomes Trunk Impairment Scale (TIS) and secondary outcomes Maximal Inspiratory Pressure (MIP), Maximal Expiratory Pressure (MEP), Forced Expiratory Volume in 1s (FEV1), Forced Vital Capacity (FVC), Fugl-Meyer Assessment Upper Extremity (FMA-UE) Scale and Berg Balance Scale (BBS) was measured at baseline (T0), after 2 weeks of treatment (T1), and after 4 weeks follow-up (T2). The within-group comparison results showed that compared to T0, all three groups of stroke patients had significant increases (P<0.05) in TIS, MIP, MEP, FEV1, FVC and BBS at T1 and T2. CG and LG had significant increases (P<0.05) in FMA-UE at T1 and T2, but AG had no statistically significant differences at T1 (P>0.05). The intergroup comparison results showed that at T1-T0 and T2-T0, LG had significantly higher TIS, MIP, MEP, FEV1, FVC and FMA-UE scores than AG and CG (P<0.017). There were no statistically significant differences in the intergroup comparison of BBS at T1-T0 and T2-T0 (P>0.017). Both forms of Liuzijue Qigong resulted in notable enhancements in the respiratory and motor functions of hemiplegic stroke patients with respiratory and balance dysfunction. ChiCTR2100051325, Registered on September 20, 2021.

Relationship of serum polycyclic aromatic hydrocarbon (PAHs) and lung function in adults: Evidence from a large community-based population in Guangzhou, China.

Preserved ratio impaired spirometry (PRISm), defined as a forced expiratory volume in 1s (FEV1) to forced vital capacity (FVC) ratio ≥0.70 and a predicted FEV1 <80%, is associated with increased morbidity and mortality. However, determinants of PRISm, particularly in younger populations, remain poorly characterised. We aimed to address this knowledge gap. We conducted a cross-sectional analysis of 12,350 participants from a Japanese community-based cohort using data from the Tohoku Medical Megabank Project. Participants underwent spirometry, blood pressure measurement, laboratory testing, and completed standardised questionnaires. Multivariate logistic regression was used to identify factors associated with PRISm across three age groups: 20-39, 40-59, and ≥60 years. Interactions between age groups and other explanatory variables were assessed. In the 20-39-year group, PRISm was independently associated with being men, diabetes mellitus, hypothyroidism, and low body mass index (BMI <18.5kg/m2), and inversely associated with age. Among participants aged ≥60 years, PRISm was significantly associated with increasing age, overweight status (BMI ≥25.0-<30.0kg/m2), being men, current smoking, hypertension, diabetes mellitus, bronchial asthma, elevated eosinophil counts (≥300cells/μL), and birth weight ≥2000-<2500g. Significant interactions were observed between age and BMI, bronchial asthma, and thyroid dysfunction. Our findings indicate that PRISm in younger adults is associated with hypothyroidism and underweight status, whereas in older adults, it is more closely related to constitutional and lifestyle-related factors. These results highlight the heterogeneity of PRISm and indicate that its pathophysiology and optimal management may vary by age group.

Effects of neuromuscular breathing exercise with yogic practices on cardiopulmonary variables among women asthmatic patients: A randomized controlled trial.

Occurrence of allergic bronchopulmonary aspergillosis in Chinese adults with asthma and COPD comorbidity.

Accumulating evidence has suggested that low birth weight (LBW) influences lung function deficit in adulthood. The aim of this study was to examine the relationship between LBW and adult lung function deficit and to explore the potential mediating effect of the gut microbiota in this relationship. Using summary data from genome-wide association studies, we applied 2-sample Mendelian randomization to investigate the association between birth weight and adult lung function deficit. Various MR analysis methods were used, including the inverse variance weighted, MR-Egger, weighted median, simple mode and weighted mode. Furthermore, a mediation analysis was performed to identify the potential mediating role of 412 known bacterial microbiota. This study identified significant genetic associations between birth weight and forced vital capacity, forced expiratory volume in 1-s (FEV1), FEV1/forced vital capacity ratio, and lung volume. In addition, a 2-step MR analysis indicated that the effect of LBW on lung function was mediated by specific gut microbiota, including g_Blautia, s_Subdoligranulum_unclassified, and s_Ruminococcus_obeum. LBW is associated with adult lung function deficit, with gut microbiota partially mediating this relationship. These findings provide important insights for the prevention of lung function impairment in individuals with LBW.

Association of serum amide herbicide levels and genetic susceptibility with lung function: A prospective cohort study in general Chinese adults.

Exacerbation risk in patients with bronchiectasis receiving DPP-1 inhibitors vs placebo: A meta-analysis of RCTs.

Limited evidence exists on the relationship between social isolation and lung function, with few studies exploring underlying mechanisms. This study examined the association between social isolation and lung function decline, and the mediating roles of smoking, income, physical activity, and BMI in U.S. and Chinese populations. This study utilized data from adults aged ≥ 45 years in NHANES (2007-2012, cross-sectional) and CHARLS (2011 and 2015, longitudinal). Lung function metrics from NHANES included Forced Vital Capacity (FVC), Forced Expiratory Volume in 1s (FEV1), and Peak Expiratory Flow (PEF), while CHARLS provided PEF data. Social isolation was assessed using marital status, living alone, and social participation in both studies, with NHANES including daily life difficulties and CHARLS incorporating infrequent child contact. Weighted linear regression models were used to assess associations. A parallel mediation model was constructed using structural equation modeling, and statistical analysis was performed using the "lavaan" package in R version 4.3.2. Standardized coefficients with p-values and mediation proportions are presented. A total of 3,575 individuals from NHANES (mean age 63.49 ± 8.27) and 3,752 from CHARLS (mean age 61.00 ± 9.23) were included. Social isolation was significantly associated with lower FVC, FEV1, and PEF in both datasets. In NHANES, mediation analysis revealed significant total indirect effects for: FVC (-0.0628, p < 0.001), 67.0% mediated by smoking, income, activity, and BMI; FEV1 (-0.0666, p < 0.001), 79.3% mediated by the same factors; and PEF (-0.0643, p < 0.001), 49.1% mediated by smoking, income, and activity. Across all three lung function metrics, income contributed the largest proportion of the mediated effect, accounting for 35.32% of FVC, 37.26% of FEV1, and 26.28% of PEF. In CHARLS, only BMI had a significant indirect effect on PEF (-0.0088, p = 0.004), mediating 6.37% of the association. Social isolation is associated with poorer lung function in both U.S. and Chinese populations aged ≥ 45 years, with distinct mediating pathways. In the U.S., income, smoking, and physical activity play significant roles, while in China, BMI is the primary mediator. Cultural and societal contexts are crucial when addressing the impact of social isolation on respiratory health.

The 70kDa major stress-inducible member of the heat shock protein 70 family Hsp70 plays an important pathogenic role in inflammatory and autoimmune diseases, including bronchial asthma, and therefore the detection of the levels of the circulating chaperone in serum or plasma could be employed as a diagnostic and prognostic marker. The prospective open single-center study enrolled 78 adult bronchial asthma patients and age-matched healthy volunteers (n = 78). Serum HSP70 levels were measured using the ELISA Kit. Serum concentrations of HSP70 as detected by the R&D Systems Hsp70 ELISA in asthmatics patients were significantly higher as compared to control subjects constituting 31.2 ng/ml (p < 0.001) and were negatively correlated with FEV1 (forced expiratory volume in 1s) and FEV1/FVC in all patients with bronchial asthma. When compared the chaperone levels in non-eosinophilic and eosinophilic (> 150 cells/µL) asthma patients, statistical significance was detected (p < 0.05). Analysis revealed a significant increase of cytokines (IL-4, IL-17, IL-25, IL-33) and TSLP in bronchial asthma patients. Strong correlation was observed between the Hsp70 level and smoking (p < 0.001), but not with age and gender: In conclusion, increased Hsp70 levels in serum of asthmatic patients may serve as a potential biomarker of the disease pending further validation.

Predictors of Progression in Pre-COPD: The 3P Study Rationale and Design

Association of the high-density lipoprotein cholesterol to C-reactive protein ratio with pulmonary function among U.S. adults: A cross-sectional study from NHANES 2007-2010.

Non-specific low back pain (NSLBP) is common and often resistant to conventional physiotherapy. The diaphragm, given its dual role in posture and respiration, may be a therapeutic target. To determine whether diaphragm manual therapy plus conventional physiotherapy improves thoracic expansion and pulmonary function in NSLBP. A single-blind randomized controlled trial included 46 adults with NSLBP (mean age 46.0±16.2 years; 43% female; BMI 27.2±5.4kg/m2). Participants were randomized to an experimental group (n=20) receiving diaphragm manual therapy plus physiotherapy or a control group (n=26) receiving physiotherapy alone. Outcomes were inspiratory thoracic expansion, forced vital capacity (FVC), and forced expiratory volume in 1s (FEV1), measured at baseline, post-treatment, and 10- and 30-day follow-ups. Repeated-measures ANOVA and Spearman correlation were used (α=0.05). The experimental group showed greater improvements in thoracic expansion (mean difference=3.31cm; 95% CI 2.69-3.93; p<0.001; η2=0.78), FVC (Δ=1.24L; 95% CI 1.11-1.37; p<0.001; η2=0.76), and FEV1 (mean difference=1.25L; 95% CI 1.12-1.38; p<0.001; η2=0.77) compared with controls. Thoracic expansion correlated with FVC (ρ=0.731) and FEV1 (ρ=0.751) at 30 days (both p<0.001). Diaphragm manual therapy improved thoracic expansion and pulmonary function in NSLBP, supporting its role as an adjunct to physiotherapy. The trial has been registered under the name of "DIAFRAGMA" and number NCT06069388.

Effects of Daikin air purifiers on asthma control and pulmonary function: A multicenter, single-arm, observational pilot study.