Airflow Limitation Research Articles

Glycaemic Status of COPD Patients on Long-term Steroid Therapy

Background: Chronic obstructive pulmonary disease (COPD) is a preventable and treatable disease characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Among the pharmacological therapy, inhaled beta-2 agonist and anticholinergics are the mainstay therapy of COPD along with corticosteroid. Steroid therapy is associated with various potential adverse effects like steroid induced deranged glycemic status. Objective: This study was aimed to assess the glycaemic status of COPD patients on long term steroid therapy. Methods: This cross-sectional observational study was conducted in the department of Medicine, Rangpur Medical College and Hospital, Rangpur, Bangladesh from January 2022 to June 2022. A total of 55 COPD patients were included in the study based on inclusion and exclusion criteria. Detailed information was obtained in each case according to protocol. Complete history was taken either from patient or accompanying attendants. A thorough clinical examination was done. Relevant investigation reports were collected. All the information was recorded according to fixed protocol. Collected data were classified, edited, coded and entered the computer for statistical analysis by using SPSS version 23. Results: Out of 55 COPD patients, the majority (41.8%) patients belonged to age 51-60 years with mean age 55.5±8.3 years. Male patients were predominant 47(85.5%) and male to female ratio was 5.88:1. Most (72.7%) of the patients received inhaled and 15(27.3%) received systemic with or without inhaled corticosteroid. Only 1 (2.5%) patient was found FBS _7.0 mmol/L in inhaled group and 2(13.3%) in systemic with or without inhaled corticosteroid group. One (2.5%) patient was found plasma glucose 2 hours after a 75-gm glucose _11.1 mmol/L in inhaled group and 2(13.3%) in systemic with or without inhaled corticosteroid group. One (2.5%) patient was found HbA1C > 6.5% in inhaled group and 2(13.3%) in systemic with or without inhaled group. The differences were not statistically significant (p>0.05) between two groups. Conclusion: Majority of the patients had normal HbA1c who were taking inhaled corticosteroid than systemic with or without inhaled corticosteroids. J Rang Med Col. September 2024; Vol. 9, No. 2: 27-32

Baicalin Targeting ALOX15 Inhibits Ferroptosis of Lung Epithelial Cells and Alleviates Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a progressive lung disorder characterized by chronic inflammation and irreversible airflow limitation. Ferroptosis has been implicated in the pathogenesis of COPD. In this study, we investigated the potential of baicalin, a natural compound with anti-inflammatory properties, to target ALOX15 and inhibit ferroptosis in lung epithelial cells, thereby alleviating COPD. Overexpression ALOX15 of BEAS-2B cells was induced by RSL-3, an activator of ferroptosis, to mimic the inflammatory environment in COPD. The effects of baicalin on ferroptosis were assessed by measuring cell viability, lipid peroxidation, lipid ROS, and ferrous ion (Fe2+). The expression of OH-1, ALOX15, and GPX4 was evaluated using Western blotting. Baicalin treatment significantly increased cell viability in RSL-3 induced epithelial cells. Our findings also demonstrate that baicalin significantly increases cell viability and reduces lipid ROS and Fe2+ levels, thereby inhibiting ferroptosis and improving cell viability, irrespective of ALOX15 expression Furthermore, baicalin upregulated the expression of GPX4, a key regulator of ferroptosis. Importantly, baicalin treatment inhibited ALOX15 expression, a critical enzyme involved in lipid peroxidation. Our study demonstrates that baicalin targeting ALOX15 inhibits ferroptosis of lung epithelial cells and alleviates COPD. These findings provide a basis for further research and development of baicalin-based therapies for COPD patients, with the potential to improve their clinical outcomes and quality of life.

The characteristics and prognosis of bronchiectasis patients with airflow limitation: a prospective longitudinal study

BackgroundAs bronchiectasis progresses, increasing degrees of airflow limitation can occur.ObjectivesThis study aimed to investigate whether concomitant airflow limitation was associated with poor prognosis in patients with bronchiectasis and to identify the characteristics of patients with airflow limitation in bronchiectasis.DesignA prospective longitudinal study was conducted to determine the characteristics and prognosis of bronchiectasis patients with airflow limitation.MethodsWe conducted a prospective longitudinal study. Patients who failed to complete the follow-up were withdrawn from the trial. High-resolution computed tomography (HRCT) was used for diagnosing bronchiectasis, whereas postbronchodilator forced expiratory volume in one second of the predicted value (post-FEV1%) was employed for grading airflow limitation. The main variables included questionnaires, anthropometric measurements, pulmonary function tests, laboratory tests, and CT findings. The primary outcome was frequent exacerbations. Differences among the groups were evaluated via two-tailed Student’s t test or ANOVA for continuous variables if the data were normally distributed. In the case of a nonnormal distribution, the Mann–Whitney U test and Kruskal–Wallis test were used. The chi-square test or Fisher’s exact test was used for categorical variables. Binary logistic regression analyses were used to identify factors and calculate the odds ratio (OR) for frequent exacerbations.ResultsA total of 189 subjects with bronchiectasis were enrolled in the study, including 97 patients with airflow limitation and 92 patients without airway obstruction. Patients with airflow limitation had greater numbers of exacerbations (1.46 ± 0.83 vs. 1.76 ± 1.10 times, P = 0.013) at 12 months after enrolment and greater numbers of hospitalizations (1.10 ± 0.30 vs. 1.36 ± 0.67 times, P = 0.0016) at 24 months after enrolment. In addition, acute exacerbations lasted longer (8.69 ± 3.78 vs. 13.11 ± 14.03 days, P = 0.0171), and the total number of hospitalizations was greater (1.34 ± 0.77 vs. 1.80 ± 1.67 times, P = 0.0421) for patients with a mean follow-up duration of 32 months (Table 3). Bronchiectasis patients with airflow limitation exhibit more severe manifestations of bronchiectasis both clinically and functionally. Furthermore, the cohort of bronchiectasis patients with airflow limitation had a significantly greater infection rate than did the BE group (P = 0.0244), with a notable disparity observed in the incidence of P. aeruginosa infection (P < 0.0001).ConclusionThe results of our study suggest that patients with airflow limitation are more likely to experience acute exacerbations and hospitalizations than are those without airflow limitation. Patients with bronchiectasis concomitant with airflow limitation should be identified as early as possible, and individualized treatment methods should be formulated.

Long-Term Outcome of Childhood Asthma: Characterizing COPD-A and COPD-C Subtypes in Adulthood.

Asthma in early life has been linked to subsequent development of COPD and according to GOLD 2023 COPD may be divided into distinct subtypes. We aimed to investigate factors associated with the GOLD classification COPD-A (asthma in childhood) and COPD-C (tobacco exposure) in a cohort of adults with a history of severe childhood asthma. In a cohort of Danish adults with a history of severe childhood asthma and a previous 4-month stay during childhood at the asthma care facility in Kongsberg, Norway, we divided participants in a long-term follow-up examination into COPD-A and COPD-C, defined as post-bronchodilator FEV1/FVC < 0.7, and never-smoker or ever-smoker, respectively, and no airflow limitation. Characteristics between groups were analysed. The study cohort comprised 232 adults with a history of severe childhood asthma, of whom 30 (13%) and 23 (10%), respectively, were classified as COPD-A and COPD-C. Compared to those with no airflow limitation, individuals with COPD-A and COPD-C more often had had at least one exacerbation (filled prescription of oral corticosteroid) in the past 12 months (risk ratio [RR] 1.83 and 2.65, respectively). The COPD-C group had a significantly higher Medical Research Council dyspnoea score (p<0.01) and significantly higher blood eosinophil count (p<0.01) than those with no airflow limitation. Compared to the COPD-C group, the COPD-A group had higher fractional exhaled nitric oxide (mean 29 [SD 28]) and FEV1%pred (mean 75 [SD 20]). Finally, when comparing participants with COPD-A to both COPD-C and participants without airflow limitation, the proportion of participants with osteoporosis (17%) and depression (10%) was more than twice as high. Our study revealed a high prevalence and unique features of the two COPD subtypes COPD-A and COPD-C in a cohort of adults with a history of severe childhood asthma.

Distinct physiological, transcriptomic, and imaging characteristics of asthma-COPD overlap compared to asthma and COPD in smokers

The clinical and pathological features of asthma and chronic obstructive pulmonary disease (COPD) can converge in smokers and elderly individuals as asthma-COPD overlap (ACO). This overlap challenges the diagnosis and treatment of the distinct aetiologies underlying these conditions. We analysed 2453 smokers (≥10 pack-years), aged 45-80 years, from the Genetic Epidemiology of COPD (COPDGene) Study, stratified as Control, Asthma, COPD, and ACO based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria. A comprehensive assessment was performed, encompassing symptomatology, pulmonary function tests (PFTs), complete blood counts (CBCs), bulk RNA sequencing (RNA-seq), and high-resolution quantitative computed tomography (QCT) imaging to evaluate clinical impact, lung function, systemic inflammation, and structural alterations contributing to disease progression across respiratory phenotypes. Differential expression (DE) analysis was performed using whole blood RNA-seq (BH-corrected FDR < 0.01), followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. Group differences were assessed using the Mann-Whitney U-test (MWU) or Chi-squared test (χ2), with Bonferroni correction applied for multiple comparisons. Multivariate linear regression models were used to adjust the associations between disease status and specific clinical outcomes for confounders, with one-way ANOVA and Tukey's Honest Significant Difference (HSD) post-hoc test applied for pairwise comparisons. Our analysis aimed to delineate the extent and variability of clinical features among disease phenotypes to guide targeted therapeutic strategies. Our study highlights distinct yet overlapping profiles across ACO, asthma, and COPD. We effectively isolated disease-specific mechanisms by comparing each phenotype to smoking controls (GOLD 0) while accounting for baseline smoking-related inflammation. ACO exhibited the most severe symptom burden, with significantly higher COPD Assessment Test (CAT) score (18.32, 95% CI: [17.02, 19.63], P<0.0001) and Modified Medical Research Council (mMRC) Dyspnea score (2.14, 95% CI: [1.92, 2.35], P<0.0001) compared to COPD and asthma. ACO also displayed reduced lung capacity (forced expiratory volume in 1s [FEV1]: 52.5%, 95% CI: [50.08, 54.93], P<0.0001) and airflow limitation (FEV1/forced vital capacity [FVC]: 0.55, 95% CI: [0.5471, 0.5546], P<0.0001), closely resembling COPD but significantly worse than asthma. The inflammatory profile of ACO exhibited a mixed response, featuring elevated neutrophil counts (4.57K/μL, 95% CI: [4.28, 4.86], P<0.0001) and eosinophil levels (0.22K/μL, 95% CI: [0.20, 0.25], P<0.01), contrasting with the predominantly neutrophilic inflammation in COPD and the absence of systemic inflammation in asthma. Structurally, ACO demonstrated significant airway remodelling (Pi10: 2.87, 95% CI: [2.83, 2.91], P<0.0001), intermediate emphysema (5.66%, 95% CI: [4.72, 6.60], P<0.0001), and moderate small airway disease (parametric response mapping for functional small airway disease [PRMfSAD]: 22.94%, 95% CI: [21.53, 24.34], P<0.0001), reflecting features of both asthma and COPD. COPD was characterised by more extensive emphysema (8.9%, 95% CI: [8.34, 9.45], P<0.0001), small airway disease (PRMfSAD: 27.09%, 95% CI: [26.51, 27.66], P<0.0001), and gas trapping (37.34%, 95% CI: [36.33, 38.35], P<0.0001), alongside moderate airway remodelling. At a molecular level, DE analysis revealed enrichment of the Hypoxia-Inducible Factor 1 (HIF-1) pathway in ACO, highlighting unique hypoxia-driven metabolic adaptations, while COPD was associated with neutrophil extracellular trap (NET) formation and necroptosis. In contrast, asthma exhibited significant airway remodelling (Pi10: 2.09, 95% CI: [2.05, 2.13], P<0.0001), minimal parenchymal damage, and no systemic gene expression changes. Collectively, our findings underscore the lung function impairments, systemic inflammation, molecular mechanisms, and structural correlates distinguishing ACO from COPD and asthma, emphasising the need for precise clinical management and the potential for novel therapeutic interventions. This work was supported by National Heart, Lung, and Blood Institute (NHLBI) grants U01 HL089897 and U01 HL089856, as well as by National Institutes of Health (NIH) contract 75N92023D00011. Additional support was provided by grants R01 HL166231 (C.P.H.) and K01 HL157613 (A.S.).

Imbalanced and Unchecked: The Role of Metal Dyshomeostasis in Driving COPD Progression.

Chronic obstructive pulmonary disease (COPD) is a chronic respiratory condition characterized by persistent inflammation and oxidative stress, which ultimately leads to progressive restriction of airflow. Extensive research findings have cogently suggested that the dysregulation of essential transition metal ions, notably iron, copper, and zinc, stands as a critical nexus in the perpetuation of inflammatory processes and oxidative damage within the lungs of COPD patients. Unraveling the intricate interplay between metal homeostasis, oxidative stress, and inflammatory signaling is of paramount importance in unraveling the intricacies of COPD pathogenesis. This comprehensive review aims to examine the current literature on the sources, regulation, and mechanisms by which metal dyshomeostasis contributes to COPD progression. We specifically focus on iron, copper, and zinc, given their well-characterized roles in orchestrating cytokine production, immune cell function, antioxidant depletion, and matrix remodeling. Despite the limited number of clinical trials investigating metal modulation in COPD, the advent of emerging methodologies tailored to monitor metal fluxes and gauge responses to chelation and supplementation hold great promise in unlocking the potential of metal-based interventions. We conclude that targeted restoration of metal homeostasis represents a promising frontier for ameliorating pathological processes driving COPD progression.

Chest CT assess the impact of omalizumab treatment on airway remodeling in refractory asthma.

BackgroundTo evaluate the benefits of omalizumab treatment in patients through real-world follow-up and assess the impact of omalizumab treatment on airway remodeling using chest CT. MethodsThis is a single-center prospective, observational study included Chinese patients with refractory asthma who received omalizumab treatment from May 2021 to December 2022. We collected real-world clinical data, including their hospitalization information, pulmonary function, FENO, laboratory assessment, ACT scores, chest CT at baseline and every follow-up month. A comparison was made between the pre-treatment and post-treatment laboratory indicators, pulmonary function, airway parameters, and mucous plug scores under chest CT. ResultsThis study included a total of 61 patients with refractory asthma treated with omalizumab. The study found that: ①regardless of whether the treatment lasted for a full four months or not, it significantly improved patient asthma control scores and reduced hospitalization costs and length of stay (p<0.05). ②After four months of treatment, pulmonary ventilation function examination revealed significant improvements (p<0.05) in MEF75, MEF50, MEF75/25, PEF, and FEV1/FVC. ③After four months of omalizumab treatment, the ratio of wall thickness and outer radius (T/D) and wall area percentage (WA%) of the bronchial wall decreased significantly (p<0.05). ④After medication, the expression of airway mucous plugs decreased. ConclusionsOmalizumab treatment can reduce airway wall thickness, decrease the percentage of airway wall area, and the expression of airway mucous plugs, thereby improving airflow limitation. Utilizing chest CT provides a novel and intuitive assessment of the efficacy of omalizumab treatment. Trial registrationThis study was registered in Chinese Clinical Trial Registry, the number is ChiCTR2100046343.

Prevalence and clinical significance of pre- and post-bronchodilator airflow obstruction in COPD patients.

Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by persistent airflow limitation. This study investigates the prevalence and clinical significance of pre-bronchodilator (PREO) and post-bronchodilator (POSTO) airflow obstruction in COPD. This retrospective cohort study analyzed data from 3252 COPD patients aged ≥40 years, registered from January 2012 to December 2019at 54 medical centers in South Korea. Patients were categorized into three groups: PREO & post-bronchodilator non-obstruction (POSTN), pre-bronchodilator non-obstruction (PREN) & POSTO, and PREO & POSTO. The primary outcome was moderate-to-severe exacerbation over 3 years. Secondary outcomes included GOLD group progression and rapid FEV₁ decline. The majority of patients (96.2%) were in the PREO & POSTO group, with smaller proportions in the PREO & POSTN (2.8%) and PREN & POSTO (1.0%) groups. During the 3-year observation, 21.6% of patients experienced moderate-to-severe exacerbations, 6.2% exhibited GOLD group progression, and 20.0% showed rapid FEV₁ decline. The PREO & POSTO group had a higher risk of exacerbations compared to the PREO & POSTN group (odds ratio=8.33 [95% CI=1.53-45.4], P-value=0.014), but this was not statistically significant in multivariable analysis. Post-bronchodilator spirometry patterns did not significantly impact GOLD group progression or FEV₁ decline. PREO & POSTO was common among COPD patients, while isolated PREO & POSTN was rare, supportingpre-bronchodilator spirometry as a screening tool. Although patients with PREO & POSTO showed higher exacerbation risks in univariable analysis, statistical significance disappeared after adjustment. GOLD group progression or FEV₁ decline did not significantly differ by post-bronchodilator spirometry patterns.

Efficacy and safety of tezepelumab versus placebo in adults with moderate to very severe chronic obstructive pulmonary disease (COURSE): a randomised, placebo-controlled, phase 2a trial.

Tezepelumab is a human monoclonal antibody that blocks thymic stromal lymphopoietin, which has shown increased expression in patients with chronic obstructive pulmonary disease (COPD) compared with healthy individuals. We aimed to assess the efficacy and safety of tezepelumab in patients with moderate to very severe COPD despite receiving triple inhaled therapy. COURSE was a double-blind, randomised, placebo-controlled, phase 2a trial across 90 sites in ten countries in Asia, Europe, and North America. Eligible participants were aged 40-80 years, had moderate to very severe airflow limitation, were receiving triple inhaled maintenance therapy, and had at least two moderate to severe COPD exacerbations in the 12 months before enrolment. Patients were randomly assigned (1:1) to receive tezepelumab 420 mg or placebo subcutaneously every 4 weeks for up to 52 weeks. Randomisation was stratified by geographical region and by number of exacerbations in the 12 months before enrolment. Participants, investigators, site staff, and the study sponsor were masked to treatment assignment. The primary endpoint was the annualised rate of moderate or severe COPD exacerbations over 52 weeks. A prespecified subgroup analysis assessed the primary endpoint in patients grouped by baseline blood eosinophil counts (BECs). Efficacy and safety were assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04039113 (completed). Between July 30, 2019, and Oct 4, 2022, 333 patients (mean age 67·2 years [SD 7·0]; 145 [44%] female and 188 [56%] male; 293 [88%] White, 34 [10%] Asian, and four [1%] Black or African American) were randomly assigned and treated with tezepelumab (n=165) or placebo (n=168). The annualised rate of moderate or severe COPD exacerbations over 52 weeks was 1·75 for tezepelumab versus 2·11 for placebo (rate ratio 0·83 [90% CI 0·64-1·06]; p=0·10 [one-sided]; the primary endpoint was not met). In prespecified subgroup analyses, the annualised rate of moderate or severe COPD exacerbations over 52 weeks was 2·04 with tezepelumab versus 1·71 with placebo (rate ratio 1·19 [95% CI 0·75-1·90]) in patients with a baseline BEC of less than 150 cells per μL, 1·64 versus 2·47 (0·66 [0·42-1·04]) in patients with a baseline BEC of 150 cells per μL to less than 300 cells per μL, and 1·20 versus 2·24 (0·54 [0·25-1·15]) in patients with a baseline BEC of 300 cells per μL or higher. Adverse events occurred in 133 (81%) of 165 patients in the tezepelumab group and 126 (75%) of 168 patients in the placebo group. Serious adverse events occurred in 49 (30%) patients in the tezepelumab group and 50 (30%) patients in the placebo group. Five patients died while receiving study treatment: two in the tezepelumab group and three in the placebo group. No deaths were determined to be causally related to study treatment by investigator assessment. A significant reduction was not observed in the annualised rate of moderate or severe COPD exacerbations with tezepelumab versus placebo. Further studies are required to evaluate the efficacy of tezepelumab in patients with moderate to very severe COPD, particularly in patients with a baseline BEC of 150 cells per μL or higher. Tezepelumab was well tolerated, with no safety concerns identified. AstraZeneca and Amgen.

SIRT-2 inhibition by AK-7 orchestrates fibrotic cascades in airways through neuroimmune interaction via TRPA1, TRPM8 and TGF-β signalling

Chronic obstructive pulmonary diseases (COPD) is characterized by airflow limitation, chronic inflammation and airway remodeling (AR) in airways and lung parenchyma. AR, a lung response, involves mucus production, airflow issues, and structural changes. It is exacerbated by neurogenic inflammation from activated sensory nerves, highlighting the interplay between neuronal and immune regulation in COPD. Sirtuins play a crucial role in lung remodeling, with SIRT-2 being the least studied. Present study explores how SIRT-2 regulates neurogenic inflammation and fibrosis in experimental BALB/c mice with cigarette smoke-induced COPD. Mice from each group, except the control, were exposed to CS for 60 days and AK-7 (100ug/kg and 200ug/kg) was administered intranasally. The study evaluated lung injury and inflammation marked by increased Cortisol, ACTH, COX-2 and LDH in COPD group with its attenuation by SIRT-2 inhibition. Additionally, CS exposure exhibited neurogenic inflammation represented by activated TPRV1 and TRPM8, elevated neuromediators levels (dopamine, acetylcholine, substance P, serotonin) and their respective receptors which were mitigated by AK-7. CS exposure enhanced fibrosis by targeting the fibrotic cascade, enhancing MMP-9, total collagen, hydroxyproline, and upregulating αSMA, MUC5AC, TGF-β, PKA, GATA-3, FOXO3, and STAT-6. SIRT-2 inhibition effectively reversed all these factors suppressing fibrosis further supported by downregulated SIRT-2 expression and histopathological studies where collagen deposition and mucus production were also attenuated by AK-7. Molecular docking revealed strong binding affinity of certain protein such as COX-2, D5DR and 5HT with AK-7. Overall, targeting SIRT-2 to modulate neuro-immune interplay presents a promising therapeutic approach for addressing AR in COPD.

COPD Risk Phenotypes in Older Smokers: Evaluation in GLI- and GOLD-Defined Respiratory Impairment

PurposeIn aging populations, the Global Initiative for Obstructive Lung Disease (GOLD) spirometry threshold may misclassify normal spirometry as airflow limitation. The Global Lung Initiative (GLI) method provides age-adjusted criteria. We investigated how the use of GOLD or GLI thresholds in an algorithm affects the classification of elderly smokers into COPD risk phenotypes.MethodsUsing a modified COPDGene algorithm, including exposure, symptoms, and abnormal spirometry, 200 smokers aged 60 years and older were classified into 4 mutually exclusive phenotypes: Phenotype A (no symptoms, normal spirometry; reference), Phenotype B (symptoms, normal spirometry; possible COPD), Phenotype C (no symptoms, abnormal spirometry; possible COPD), and Phenotype D (symptoms, abnormal spirometry; probable COPD). Abnormal spirometry was defined according to the GOLD or GLI criteria. A comparison was made between the GOLD- and GLI-defined phenotypes.ResultsUsing GLI criteria/cut-offs, 18.5% (n = 37) had phenotype A (no COPD), 42% (n = 84) had phenotype B (possible COPD), 7.5% (n = 15) had phenotype C (possible COPD), and 32% (n = 64) had phenotype D (probable COPD). Using GOLD criteria cut-offs, 14.5% (n-29) had phenotype A (no COPD); 31% (n = 62) had phenotype B, 11.5% (n = 23) had phenotype C (probable COPD), and 43% (n = 86) had phenotype D (probable COPD). Eight smokers with GOLD phenotype C were reclassified as GLI phenotype A, while 22 with GOLD phenotype D were reclassified as GLI phenotype B. Smokers identified as ‟probable COPD” by GOLD alone (potential false positives) had better spirometry results than those identified as ‟probable COPD” by both GOLD and GLI.ConclusionThe use of the GOLD threshold in an algorithm resulted in older smokers being classified into more severe COPD risk phenotypes compared to the GLI threshold. This suggests that GOLD may misclassify smokers with less affected phenotypes as having respiratory impairment, potentially leading to unnecessary and harmful treatments.

Early benefit of mepolizumab on small airways in severe asthma: insights from IMPOSE study

BackgroundSevere eosinophilic asthma adversely affects small airway function, but effective therapeutic options are limited. The IMPOSE trial (NCT05147155) assessed the early and sustained effects of mepolizumab on small airways in patients with severe eosinophilic asthma using Impulse Oscillometry (IOS).MethodsThe study included 130 participants: 40 with uncontrolled severe asthma initiating mepolizumab, 40 with well-controlled severe asthma, and 50 healthy controls. Lung function was assessed with IOS, spirometry, and plethysmography at baseline, and at 1-, 3-, and 6-months post-treatment. Clinical outcomes included asthma control, quality of life, and medication adherence.ResultsSmall airway function significantly improved within one month of mepolizumab initiation, shown by reductions in Fres, indicating decreased small airway resistance undetectable by spirometry. By six months, sustained improvements in FEF25–75%, TLC%, Fres, AX, and R5–20 were evident, accompanied by better asthma control and quality of life scores. Negative correlations between ΔR5 and ΔR5–20 with ΔACT at six months suggested that decreased small airway resistance and heterogeneity correlated with improved asthma control. These benefits were particularly prominent in patients without fixed airway obstruction. Notably, even patients with irreversible airflow limitations saw improvements in small airway dysfunction (SAD), suggesting that mepolizumab may provide benefits despite irreversible airway changes.ConclusionsThis study is the first to demonstrate that mepolizumab has a rapid and sustained therapeutic effect on small airways in severe eosinophilic asthma, as shown by IOS. IOS proves to be a valuable tool for monitoring the effects of biologic treatments on small airway function, revealing insights beyond spirometry.

Request for Study Design Modification in Examining Nutritional Intake and Muscle Strength in Individuals with Airflow Limitation.

Request for Study Design Modification in Examining Nutritional Intake and Muscle Strength in Individuals with Airflow Limitation.

Omics techniques reveal the pathogenesis of microbial communities in asthma

Abstract. The presence of airway hyperresponsiveness in asthma provides the basis for constriction in bronchus response to a variety of stimuli, leading to limited airflow, dyspnea, wheezing, and chest tightness, threatening patients lives. Statistics have shown that asthma is more prevalent in the adolescents and children than in the adults, suggesting that early ecological dysregulation of the gut and airway microbiome contributes to the occurrence of asthma, especially in the preschool years children. With the development of high-throughput sequence technologies such as genomics, it has become possible to study the association of pathophysiological processes of allergic reactions and ecological dysregulation using the multi-omics techniques. In this review, the author first briefly introduces the classification of asthma, summarizes the pathogenesis of microorganisms in asthma, providing a new direction and ideas for the research of the pathogenesis, diagnosis, and treatment of asthma.

Distinct phenotype and risk factor analysis of persistent airflow limitation among asthmatic children: a case-control study

BackgroundPersistent airflow limitation (PAL) in childhood asthma is associated with a poor prognosis. The aim of this study was to categorize asthmatic children with PAL into distinct phenotypes and investigate the risk factors associated with each phenotype.MethodsWe conducted a case-control study with a total of 119 PAL patients and 120 non-PAL (NPAL) individuals. To classify the patients into appropriate clusters, unsupervised cluster analysis using K-means clustering was employed. The clusters were then compared to explore different PAL phenotypes. Univariate and multivariate logistic regression analyses were performed to identify risk factors for PAL and calculate odds ratios (ORs) with 95% confidence intervals (95%CIs).ResultsK-means clustering divided patients into three clusters: Cluster 0 included 120 NPAL patients, Cluster 1 characterized by elevated blood neutrophils included 66 PAL patients, and Cluster 2 exhibited elevated blood eosinophils and FeNO levels, containing 53 PAL patients. Independent risk factors for PAL included older age in both Cluster 1 (9∼\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document}11y: OR 12.67, 95%CI 3.30-55.74; ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document}11y: OR 5.42, 95%CI 1.26-25.69) and Cluster 2 (9∼\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\sim$$\\end{document}11y: OR 7.25, 95%CI 1.70-33.35; ≥\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$\\ge$$\\end{document}11y: OR 11.28, 95%CI 2.79-51.89), as well as pneumonia history, with an OR of 6.41(95%CI 1.34-33.41) in Cluster 1 and an OR of 7.92(95%CI 1.83-37.44) in Cluster 2. Furthermore, specific factors associated with Cluster 1 included BMI above 22 kg/m2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$m^2$$\\end{document}(OR 12.28, 95%CI 2.68-70.45), asthma duration exceeding three years (OR 4.77, 95%CI 1.60-15.94), and a blood neutrophil percentage between 0.4 and 0.5 (OR 4.13, 95%CI 1.17-16.6). In Cluster 2, independent risk factors included a blood eosinophil percentage greater than 0.07 (OR 4.36, 95%CI 1.16-19.73) and a high FeNO level (OR 3.94, 95%CI 1.35-11.97).ConclusionOur study identified two phenotypes of PAL in asthmatic children: non-eosinophilic and eosinophilic inflammation. Older age and a history of pneumonia were independent risk factors for both phenotypes. For non-eosinophilic inflammation PAL, specific contributing factors included higher BMI, long duration of asthma, and a blood neutrophil percentage between 0.4 and 0.5. Elevated FeNO levels and blood eosinophilic percentage were independently associated with eosinophilic inflammation PAL.

Investigating Biomarkers and Molecular Mechanisms in COPD: Perspectives from In-vivo Models

Purpose: This review examines COPD pathogenesis, biomarkers, and treatment. COPD, a progressive respiratory illness that blocks airflow, causes high morbidity and death. The complicated pathophysiology of COPD involves genetic predisposition, environmental variables (particularly tobacco smoke), and inflammatory pathways. COPD diagnosis, prognosis, and monitoring depend on biomarkers in clinical and preclinical investigations. COPD care should include pharmaceutical and non-pharmacological therapies to improve symptoms, lung function, and outcomes. Materials and Method: This review examines COPD pathogenesis, cytokines, and risk factors. This review article discusses how immune system signalling molecules called cytokines contribute to COPD's persistent inflammation. Smoking and environmental contaminants are also examined as COPD risk factors. The analysis also covers biomarkers needed to diagnose and track the condition. Results: The review paper on COPD highlights the critical role of cytokines in the disease's pathophysiology, emphasizing their contribution to chronic inflammation. Various cytokines, particularly interleukins, are implicated in driving the inflammatory processes within the airways and lungs, resulting in tissue damage and airflow limitation, which are hallmark features of COPD. The paper also identifies smoking and exposure to environmental pollutants as major risk factors for the development of COPD. Conclusion: This review illuminates COPD's complex pathogenesis, highlighting cytokines' involvement in chronic inflammation. To create targeted therapeutics, cytokine-mediated pathways must be understood. The review emphasizes biomarkers' use in preclinical and clinical investigations to diagnose and monitor COPD and provide disease progression insights.

Update of prognosis and characteristics of chronic obstructive pulmonary disease in a real-world setting: a 5-year follow-up analysis of a multi-institutional registry

BackgroundWe conducted a prospective observational study to elucidate the long-term prognosis and management of chronic obstructive pulmonary disease (COPD) in clinical practice in Japan in the mid-2010s.MethodsThis prospective cohort study included 29 facilities. Data from 427 patients clinically diagnosed with COPD, enrolled between September 2013 and April 2016, were analyzed. Interstitial pneumonia was excluded through a central multidisciplinary discussion. Follow-up data were collected for up to 5 years after patient registration.ResultsAt the time of registration, 53 patients clinically diagnosed with COPD did not have airflow limitation (AFL). In the cohort with AFL (n = 374), 232 patients completed a 5-year follow-up, while 49 patients died during the 1576.6 person-years of observation. The mean age was 71.7 years with an overall 5-year survival rate of 85.4%. Stratified by % forced expiratory volume in one second (FEV1), survival rates were 93.6% in the mild and moderate AFL group, 82.5% in the severe AFL group, and 66.1% in the very severe AFL group. The prognosis of the subpopulation without AFL was poor with a 5-year survival of 81.6%. This subpopulation exhibited respiratory symptoms, low vital capacity and total lung capacity, and emphysematous changes.ConclusionsOur study presents the 5-year survival and real-world clinical practice scenario of a prospective cohort of patients clinically diagnosed with COPD in Japan in the mid-2010s. The survival rates of our cohort were numerically better than the Japanese cohort in the 1990s, regardless of the high median age of this cohort. Overall, 12.4% of the patients in this cohort with no AFL at registration exhibited respiratory symptoms and distinct spirometric patterns, and had a poor prognosis.

Persistent Airflow Limitation Prediction and Risk Factor Analysis Among Asthmatic Children: A Retrospective Cohort Study.

A minority of asthmatic children develop persistent airflow limitation (PAL), associated with an increased risk of chronic airflow obstruction and poor prognosis. This study aimed to identify risk factors for PAL and develop a prediction model to identify high-risk asthmatic children. This retrospective study included 2072 children (5-16 years) with asthma. After a 2-year follow-up, patients were categorized into non-PAL, reversible PAL (RPAL), and irreversible PAL (IPAL) groups. Logistic regression (LR) was used to identify independent risk factors for RPAL and IPAL. A prediction model based on multivariate LR was developed and validated to identify asthmatic children at high risk of developing PAL. A nomogram was created for visualization. Among the 2072 asthmatic patients, 14.72% (n = 305) developed PAL. Asthma exacerbation history (OR 1.80, 95% CI 1.03-3.01) and poor adherence (OR 1.83, 95% CI 1.26-2.65) were independent risk factors of RPAL. Independent risk factors for IPAL were BMI over 19.0 kg/m2 (OR: 1.81, 95% CI: 1.03-3.21) and a history of pneumonia (OR: 2.40, 95% CI: 1.30-4.26). The prediction model incorporated nine variables and showed good discriminatory ability, with AUC values of 0.79 (95% CI: 0.76-0.81) for the training set, 0.76 (95% CI: 0.76-0.77) for internal validation, and 0.73 (95% CI: 0.64-0.81) for temporal validation. Asthma exacerbation history and poor adherence were independent risk factors for developing RPAL. BMI over 19.0 kg/m2 and a history of pneumonia were risk factors for IPAL. Our prediction model effectively identified asthmatic children at high risk of developing PAL.

Associations of pulmonary microvascular blood volume with per cent emphysema and CT emphysema subtypes in the community: the MESA Lung study

BackgroundPulmonary microvasculature alterations are implicated in emphysema pathogenesis, but the association between pulmonary microvascular blood volume (PMBV) and emphysema has not been directly assessed at scale, and prior studies have...

Identification of immune-related hub genes in chronic obstructive pulmonary disease

ObjectiveAs a prevalent persistent respiratory disease, chronic obstructive pulmonary disease (COPD) is featured by airflow limitation and chronic inflammation. This study focused on the identification of immune-related hub genes in COPD. MethodsWe employed the GSE38974 dataset to analyze differentially expressed genes (DEGs) of COPD. Then, we obtained COPD immune-related DEGs (COPD-IMDEGs) based on the intersection of DEGs and immune-related genes. Subsequently, we carried out Gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses on COPD-IMDEGs. We established a protein-protein interaction network based on COPD-IMDEGs. The hub genes were determined by utilizing the Maximal Clique Centrality method. We utilized receiver operating characteristic (ROC) curves to analyze the clinical significance of hub genes in COPD. In addition, potential drugs targeting hub genes were predicted based on interactions between hub gene-corresponding proteins and drugs. ResultsA total of 45 COPD-IMDEGs were obtained through differential analysis. Enrichment analyses showed that COPD-IMDEGs were associated with cytokines, growth factors, and receptor ligands. Ten COPD-IMDEGs were identified as hub genes. As shown by ROC curves, these genes had potential value in identifying COPD patients. Drug prediction results showed that simvastatin and other drugs targeted hub genes. ConclusionThis study analyzed the potential biological functions enriched by COPD-IMDEGs, identified ten genes as biological markers for diagnosing COPD, and predicted potential drugs for treating COPD.