Airflow Obstruction Research Articles

Transforming Care in SEA: Evidence and Considerations for Evolution of the Current Treatment Paradigm

This article reviews an industry symposium held on 8 September 2024 as part of the European Respiratory Society (ERS) Congress 2024 in Vienna, Austria, which brought together four experts to discuss the current treatment paradigm for severe eosinophilic asthma (SEA), including the role of biologics and background medication tapering. Katrin Milger-Kneidinger, Professor of Respiratory Medicine at the University Hospital of the Ludwig Maximilian University Munich (LMU), in Germany, and the MedUni Graz, in Austria, explored the critical role eosinophils play in SEA pathology and how biologic therapies targeting eosinophils can address key disease features, including airway remodelling, airway hyperresponsiveness (AHR), and mucus production. Felix Herth, Professor of Pulmonary and Critical Care Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, discussed persistent airflow obstruction (PAO) in patients with SEA, focusing on a typical patient profile to understand the clinical manifestation and opportunities for management. Stephanie Korn, Professor of Pulmonary and Respiratory Medicine at Thoraxklinik Heidelberg, Heidelberg University Hospital, in Germany, and Head of the Clinical Research Centre, Institute für Klinische Forschung (IKP) Pneumologie in Mainz, Germany, presented on remission as a clinical target in SEA, focusing on how biologics can help achieve remission in some patients. Lastly, in a discussion led by symposium chair Stefano Del Giacco, Professor of Medicine, Allergy, and Clinical Immunology, at the University of Cagliari, Sardinia, in Italy, the experts agreed that a positive practice change would be to get more patients with relevant clinical manifestations on biologics, and that background medication tapering, when appropriate, could lead to improved patient outcomes and quality of life (QoL) in SEA.

CRP Levels and Vitamin D as Predictors of Asthma Control: A Data-Driven Approach

Background: Asthma is a chronic inflammatory disease of the airways characterized by episodic exacerbations and airflow obstruction. Elevated C-reactive protein (CRP) levels indicate systemic inflammation and are associated with increased disease severity in asthma. Additionally, vitamin D is thought to modulate immune responses and inflammation, potentially influencing asthma control. This study explores the relationships between CRP levels, vitamin D levels, and asthma control, as measured by the Asthma Control Test (ACT). Objectives: The primary objective of this study was to assess the correlation between CRP levels, vitamin D levels, and asthma control in adult patients with asthma. The study aimed to determine whether CRP and vitamin D could serve as predictive markers for asthma control. Methods: This single-center, prospective observational study enrolled 40 adult patients with confirmed asthma from the outpatient pulmonary clinic of ESIC Government Hospital, Guwahati, Assam, India. Asthma control was evaluated using the ACT, with scores categorized as well-controlled (ACT ≥ 20) or poorly controlled (ACT < 20). Serum CRP and vitamin D levels were measured using the ELISA method. Pearson’s correlation coefficient and ANOVA were employed to analyze the relationships between these variables. Results: The study found a moderate negative correlation between CRP levels and ACT scores (r = -0.58), indicating that higher CRP levels were associated with poorer asthma control. Patients with CRP levels greater than 10 mg/dL had significantly lower mean ACT scores compared to those with lower CRP levels. In contrast, a strong positive correlation was observed between vitamin D levels and ACT scores (r = 0.879), with higher vitamin D levels associated with better asthma control. The ANOVA test revealed significant differences in ACT scores across different vitamin D and CRP categories (p < 0.05). Conclusions: The study suggests that elevated CRP levels are indicative of poorer asthma control, while higher vitamin D levels are associated with better control of asthma. CRP and vitamin D levels may serve as valuable biomarkers for assessing asthma severity and guiding treatment strategies. However, the variability in response to vitamin D supplementation highlighted the need for personalized approaches to asthma management. Further research is required to confirm these findings and explore the underlying mechanisms.

CHF6523 data suggest that the phosphoinositide 3-kinase delta isoform is not a suitable target for the management of COPD

BackgroundChronic obstructive pulmonary disease (COPD) is a chronic inflammatory condition. Given patients with COPD continue to experience exacerbations despite the availability of effective therapies, anti-inflammatory treatments targeting novel pathways are needed. Kinases, notably the phosphoinositide 3-kinases (PI3K), are thought to be involved in chronic airway inflammation, with this pathway proposed as a critical regulator of inflammation and oxidative stress response in COPD. CHF6523 is an inhaled PI3Kδ inhibitor that has shown positive preclinical results. This manuscript reports the results of a study of CHF6523 in patients with stable COPD (chronic bronchitis phenotype), and who had evidence of type-2 inflammation.MethodsThis randomised, double-blind, placebo-controlled, two-way crossover study comprised two 28-day treatment periods separated by a 28-day washout. Patients (N = 44) inhaled CHF6523 in one period, and placebo in the other, both twice daily. The primary objective was to assess the safety and tolerability of CHF6523; the secondary objective was to assess CHF6523 pharmacokinetics. Exploratory endpoints included target engagement (the relative reduction in phosphatidylinositol (3,4,5)-trisphosphate [PIP3]), pharmacodynamic evaluations such as airflow obstruction, and hyperinflation, and to identify biomarker(s) of drug response using proteomics and transcriptomics.ResultsCHF6523 plasma pharmacokinetics were characterised by an early maximum concentration (Cmax), reached 15 and 10 min after dosing on Days 1 and 28, respectively, followed by a rapid decline. Systemic exposure on Day 28 showed limited accumulation, with ratios < 1.6 for Cmax and area under the curve from 0 to 12 h post-dose, and with steady state achieved on Day 20. Target engagement was confirmed by a significant 29.7% reduction from baseline in induced sputum PIP3 (29.5% reduction vs. placebo; adjusted ratio 0.705 [0.580, 0.856]; p = 0.001), but this did not translate into an anti-inflammatory pharmacodynamic effect, as assessed through measures including biomarkers and multi-omics. Additionally, although CHF6523 was generally well-tolerated, 95.2% of patients reported cough as an adverse event, most mild to moderate and resolving within one-hour post-dose.ConclusionsThese data, together with those from other PI3K inhibitors, suggest that PI3Kδ is not a suitable pathway for the management of COPD, as the achieved target engagement did not translate into any pharmacodynamic anti-inflammatory effect.Trial registrationClinicalTrials.gov (NCT04032535); posted 23rd July 2019.

Reference formulas for chest CT-derived lobar volumes in the lung-healthy general population.

Lung hyperinflation, a key contributor to dyspnea in chronic obstructive pulmonary disease (COPD), can be quantified via chest computed tomography (CT). Establishing reference equations for lobar volumes and total lung volume (TLV) can aid in evaluating lobar hyperinflation, especially for targeted lung volume reduction therapies. The Imaging in Lifelines study (ImaLife) comprises 11,729 participants aged 45 and above with analyzed inspiratory low-dose thoracic CT scans. Lung and lobar volumes were measured using an automatic AI-based segmentation algorithm (LungSeg). For the main analysis, participants were excluded if they had self-reported COPD/asthma, lung disease on CT, airflow obstruction on lung function testing, were currently smoking, aged over 80 years, or had height outside the 99% confidence interval. Reference equations for TLV and lobar volumes were determined using linear regression considering age and height, stratified by sex. For the subanalysis, participants who were currently smoking or experiencing airflow obstruction were compared to the group of the main analysis. The study included 7306 lung-healthy participants, 97.5% Caucasian, 43.6% men, with mean age of 60.3 ± 9.5 years. Lung and lobar volumes generally increased with age and height. Men consistently had higher volumes than women when adjusted for height. R2 values ranged from 7.8 to 19.9%. In smokers and those with airway obstruction, volumes were larger than in lung-healthy groups, with the largest increases measured in the upper lobes. The established reference equations for CT-derived TLV and lobar volumes provide a standardized interpretation for individuals aged 45 to 80 of Northern European descent. Question Lobar lung volumes can be derived from inspiratory CT scans, but healthy-lung reference values are lacking. Findings Lung and lobar volumes generally increased with age and height. Reference equations for lung/lobar volumes were derived from a sizeable lung-healthy population. Clinical relevance This study provides reference equations for inspiratory CT-derived lung and lobar volumes in a lung-healthy population, potentially useful for assessing candidates for lung volume reduction therapies, for lobe removal in lung cancer patients, and in case of restrictive pulmonary diseases.

CT Radiomics Features Predict Change in Lung Density and Rate of Emphysema Progression.

Rationale Emphysema progression is heterogeneous. Predicting temporal changes in lung density and detecting rapid progressors may facilitate selection of individuals for targeted therapies. Objective To test whether computed tomography (CT) radiomics can be used to predict changes in lung density and detect rapid progressors. Methods We extracted radiomics features from inspiratory chest CT in 4,575 subjects with and without airflow obstruction at enrollment, who completed a follow-up visit at approximately 5 years. We quantified emphysema using adjusted lung density (ALD) and estimated emphysema progression as the annualized change in ALD (∆ALD/year) between visits. We categorized participants into rapid progressors (>1% ∆ALD/year) and stable disease (≤1% ∆ALD/year). A gradient boosting model was used (1) to predict ALD at 5-years and (2) to identify rapid progressors. Four models using demographics (base clinical model); CT density; radiomics; and combined features (clinical, radiomics, and CT density) were evaluated and tested. Results There were 1,773 (38.8%) rapid progressors. For predicting ALD at 5-years in the 20% held-out data, the base model explained 31% of the variance (adjusted R2 = 0.31) whereas R2 was 0.74 for the CT density model, 0.66 for the radiomics-only model, and 0.77 for the combined features model. For detecting rapid progressors, the base model (AUC = 0.57, 95%CI 0.53-0.61) was outperformed by the radiomics-only model (AUC = 0.73, 95%CI 0.69-0.76, ∆ =0.0003, p < 0.001) and the combined model (AUC = 0.74, 95%CI 0.71-0.77, ∆ = 0.0003, p < 0.001). Conclusions Parenchymal and airway radiomics features derived from inspiratory scans can be used to predict temporal changes in lung density and help identify rapid progressors.

Dedicated low-cost electronic ocarina for people with COPD: Rationale and prototype development

ABSTRACT Introduction Chronic obstructive pulmonary disease (COPD) is a condition characterized by airflow obstruction which can lead to physical and psychosocial challenges, with a higher prevalence in developing countries. Non-pharmacological interventions for this group of people include pulmonary rehabilitation as well as music interventions. Although music technology was recommended to adjust to the user’s breathing capacity for music-making and to gather information about their performance, music therapy trials used acoustic wind instruments for their rehabilitation. This interdisciplinary project aims to develop a dedicated electronic wind instrument for people with COPD. Method This project follows a systematic prototype methodology that includes product research, instrument development, and user validation. Based in Brazil, our team has decided on an electronic ocarina based on its cultural features, its popularity as a digital application, and its potential for respiratory training. Unlike existing technologies, the prototype intends to be dedicated and a low-cost solution. Results The development process includes decision making about the appropriate mouthpiece, sensors, Arduino, pushbuttons, 3-D printing projects, building a MIDI interface and a dedicated software. This is an ongoing project, and our team is in the MIDI interface development stage. We aim to run the first hardware trial with users so that we can integrate their feedback into the functional prototype and the dedicated software for the following trials. Discussion This project’s strengths rely on the innovation of building viable electronic wind instruments that can facilitate self-management of people with COPD in developing countries, where access to healthcare can be challenging.

Chronic obstructive pulmonary disease and its treatment in the Russian Federation: Results of a cross-sectional assessment from the CORSAIR observational study

Abstract Up-to-date data on patients with chronic obstructive pulmonary disease (COPD) in the Russian Federation are necessary to improve medical care effectiveness.This article presents the results of the retrospective part and the cross-sectional assessment of the CORSAIR study, which aimed to assess the distribution of COPD patients in the Russian population by symptom severity and exacerbation risk as per GOLD (2020) classification groups A, B, C, D.Methods. The observational multicenter study CORSAIR included a cross-sectional assessment with data collection during the previous 12 months (retrospective part) and subsequent follow-up for 12 months (prospective part). Data from 704 patients obtained at 18 study sites from August 2021 to November 2022 are presented. At the first visit, the physician recorded medical history, clinical data on the disease course, and COPD therapy, assessed compliance of treatment with national guidelines, and determined whether treatment change was needed considering the predominant treatable trait (dyspnea or exacerbation).Results. Upon inclusion, most patients had severe COPD symptoms (mMRC score ≥ 2; САТ score ≥ 10) and severe and very severe airflow obstruction (GOLD III and GOLD IV; FEV1 &lt; 50% оf predicted). More than half of the patients had at least one moderate or severe COPD exacerbation within the previous 12 months. As per the GOLD (2020) classification, 57.2% of patients belonged to Group B (severe symptoms and low risk of exacerbations) and 30.3% to Group D (severe symptoms and high risk of exacerbations). 58.8% of patients received treatment that was not compliant with national clinical guidelines in force at the study initiation. 31.7% of patients had not COPD control. Blood eosinophil count was above 300 cells/μL in 15.1% of patients.Conclusion. In most cases, patients had severe COPD symptoms with frequent exacerbations, and the prescribed treatment did not comply with national clinical guidelines. These data will be analyzed alongside the prospective study results.

Degree of Airway Obstruction and Contributing Factors, Exploring Potential Mismatches and Pitfalls

BACKGROUND: The study investigates asthma, a chronic inflammatory respiratory condition that poses diagnostic challenges due to its variable symptoms, highlighting the importance of accurate documentation and interpretation. It aims to explore the demographic and clinical profiles of asthma patients, particularly focusing on the relationships among airway obstruction severity, spirometric measurements, atopic history, and family history to reveal the complex factors influencing asthma. AIMS: Employing a retrospective descriptive-analytic design, the research analyzes medical records of 107 patients treated at the Outpatient Installation of the Lung Polyclinic at Wlingi General Hospital in Blitar Regency from 2021 to 2022. The analysis incorporates descriptive statistics for demographic and clinical variables alongside Spearman correlation tests. METHOD: Results indicate a significant prevalence of smoking history among asthma patients, with 22.4% being active smokers and 52.3% passive smokers; however, no significant correlation with asthma control was found. Environmental risk factors such as dust and cold air were common but did not consistently correlate with asthma exacerbations. Spirometric analysis revealed a significant relationship between airway obstruction severity and parameters like FEV1, FVC, FEV1/FVC, PEF, FEF 25, FEF 50, and FEF 75, emphasizing the link between airflow obstruction and reduced lung function. Furthermore, no significant correlation was observed between stable asthma diagnosis and atopic or family history, suggesting that asthma control is influenced by various complex factors. CONCLUSION: Our research reveals critical pitfalls in the current understanding of asthma, advocating for a comprehensive evaluation of all contributing factors to enhance diagnostic accuracy and treatment efficacy. Recognizing these complexities is essential for improving asthma management and ensuring better health outcomes for patients.

Expiratory flow limitation development index (ELDI): a novel method of assessing respiratory mechanics in COPD

BackgroundExpiratory flow limitation (EFL) can be detected using oscillometric reactance and is associated with a worse clinical presentation in chronic obstructive pulmonary disease (COPD). Reactance can show negative swings upon exhalation, which may develop at different rates between patients. We propose a new method to quantify the rate of EFL development; the EFL Development Index (ELDI).MethodsA retrospective analysis of data from 124 COPD patients was performed. Data included lung function tests, Impulse Oscillometry (IOS), St Georges Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT) score. Fifty four patients had repeat data after 6 months. Twenty two patients had data recorded after 5 days of treatment with long acting bronchodilator therapy. EDLI was calculated as the mean expiratory reactance divided by the minimum expiratory reactance.ResultsThe mean ELDI was used to categorise patients with rapid onset of EFL (> 0.63; n = 29) or gradual onset (≤ 0.63; n = 34). Those with rapid development had worse airflow obstruction, lower quality of life scores, and greater resting hyperinflation, compared to those with gradual development. In patients with EFL, ELDI correlated with symptoms scores, airflow obstruction, lung volumes and gas diffusion. Both EFL and ELDI were stable over 6 months. EFL and EDLI improved with bronchodilator treatment.ConclusionsCOPD patients with rapid EFL development (determined by ELDI) had worse clinical characteristics than those with gradual EFL development. The rate of EFL development appears to be associated with clinical and physiological characteristics.

Debunking the GAMLSS Myth: Simplicity Reigns in Pulmonary Function Diagnostics

RationaleCurrent technical standards advocate using Generalized, Additive Models of Location, Scale, and Shape (GAMLSS) for lung function reference equations. These equations are complicated and require supplementary spline tables. Objective(1) To demonstrate that segmented (piecewise) linear regression (SLR) yields similar prediction accuracies as GAMLSS in pulmonary function diagnostics. (2) To determine the agreement between both SLR and GAMLSS. MethodsThe NHANES 2007-2012 database was utilized to construct spirometric reference equations for FEV1, FVC, and FEV1/FVC using both SLR and GAMLSS modeling techniques. K-fold cross-validation was used to provide the 95% confidence interval (CI) of the root-mean-square error (RMSE) as indicators of prediction accuracy. Additionally, agreement was assessed between the two modeling techniques in classifying spirometric patterns (standard, airflow obstruction, restrictive, or mixed disorder) using an unweighted kappa statistic. ResultsThe RMSE values for FEV1, FVC, and FEV1/FVC and correlation coefficients between predicted values and test data were similar between the two techniques. Agreement in classifying spirometric patterns between the two techniques ranged from 0.78 to 0.80 (95% CI). ConclusionsThe findings suggest that simple linear regression for FEV1/FVC and SLR for FEV1 and FVC offer prediction accuracies on par with GAMLSS while being more straightforward, parsimonious, and accessible to a broader audience in the field of pulmonary function diagnostics.

New classifications of COPD severity based on Impulse Oscillometry: a SAIO grade base on ECOPD cohort in China

Background: Recently, the severity of chronic obstructive pulmonary disease (COPD) can also be assessed by Impulse Oscillometry (IOS). This study aimed to explore a new classification of severity of COPD based on IOS and associations with acute exacerbations (AE) in patients with COPD.Methods: The data of our study were based on the baseline and 2-year follow-up data of a prospective cohort in China. COPD was defined as post-bronchodilation FEV1/FVC < 0.70. A new severity classification (Staging of airflow obstruction by IOS, SAIO) was evaluated based on IOS parameters (R5, R5-R20, and X5 Z-scores). We used quantified using the weighted Bangdiwala B for agreement of severities of COPD between IOS parameters and FEV1%pred. The differences among SAIO stages were performed in symptom scores and imaging using analysis of covariance, in the AE using Negative Binomial Regression.Results: Overall, 833 patients with COPD were included in this study. The weighted Bangdiwala B of R5, R5-R20, X5 Z-scores, and FEV1%pred for evaluating agreement of the severity of COPD was 0.68, 0.70 and 0.83, respectively. The SAIO classifications system identified a greater number of adults with Stage III-IV disease. SAIO provided significant discrimination between the Stage I and Stage Ⅲ, Ⅳ for symptom scores, emphysema, and air trapping. SAIO provided significant discrimination between the Stage I and other Stages for AE.Conclusions: The SAIO classifications provide discrimination between the Stage I and Stage Ⅲ, Ⅳ for symptom scores, emphysema, air trapping, and AE, similar to the GOLD classifications.Trial registration: Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.

Fixed Airflow Obstruction in Asthma Can Be Identified Early by Low FEF25-75% and is Associated with Environmental Exposure.

This study aimed to identify environmental risk factors associated with asthmatic fixed airflow obstruction (FAO) and assess the relationship between small airway abnormalities defined by forced expiratory flow at 25-75% (FEF25-75%) and FAO. We analyzed data from 312han Chinese patients with stable asthma on standard treatment. Low FEF25-75% was defined as post-bronchodilator FEF25-75% z-score <-0.8435, and FAO as post-bronchodilator FEV1/FVC z-score <-1.645. Exposure levels were retrospectively analyzed in relation to FAO risk in asthmatics. Asthmatics were grouped by low FEF25-75% and FAO, and lung function, environmental exposure, daily symptoms, and exacerbations in the previous year were compared cross-sectionally across groups. In retrospective analyses, pack-years of smoking in male patients (adjusted odd ratio [95% confidence interval] 1.05 [1.03-1.07], P<0.001), biomass exposure for >20 years (2.65 [1.13-6.43], P=0.027), occupational exposure for >10 years (2.01 [1.06-3.86], P=0.035) and occupational exposure for >20 years (2.67 [1.24-5.91], P=0.013) were associated with asthmatic FAO. In cross-sectional analyses, compared with the normal FEF25-75%/ asthmatics without FAO (NON-FAO) group, the low FEF25-75%/ asthmatics with FAO (FAO) group had lower FEV1 z-scores and FEV1/FVC z-scores, more pack-years and years of biomass and occupational exposure, higher Asthma Control Questionnaire-5 and Chronic Obstructive Pulmonary Disease Assessment Test scores, and more frequent exacerbations. The low FEF25-75%/NON-FAO group showed the same trend, but to a lesser extent. Chronic airway inflammation is not the only driver of asthmatic FAO, and management and treatment targeting environmental risk factors (smoking and biomass and occupational exposures) may slow FAO progression in asthmatics. The FEF25-75% determined by the z-score is a reliable marker of small airway abnormalities, and patients with low FEF25-75% are at greater risk for FAO, requiring more frequent follow-up.

Rapid Access Diagnostics for Asthma (RADicA): protocol for a prospective cohort study to determine the optimum series of investigations to diagnose asthma using conventional and novel tests

IntroductionThe diagnosis of asthma is often based on characteristic patterns of symptoms in the absence of an alternative explanation, resulting in over and under diagnosis. Therefore, diagnostic guidelines usually recommend...

Pulmonary Vascular Structure and Function Are Related to Exercise Capacity in Health and COPD

Although it is generally accepted that aerobic exercise training does not change lung structure or function, some work suggests that greater pulmonary vascular structure and function is associated with higher exercise capacity (VO2peak). Is there a cross-sectional association between the pulmonary vasculature and VO2peak? We hypothesized that those with higher computed tomography (CT) blood vessel volumes, and pulmonary diffusing capacity for carbon monoxide (DLCO) would have higher VO2peak, independent of airflow limitation. Participants from the CanCOLD study were categorized as: never-smokers with normal spirometry (n=263); ever-smokers with normal spirometry (n=407); and chronic obstructive pulmonary disease (COPD): individuals with spirometric airflow obstruction (n=334). Total vessel volume (TVV), the volume for all vessels with a cross-sectional area ≤5 mm2 (BV5), and between 5-10 mm2 (BV5-10) were generated from CT scans and used as indices of pulmonary vascular structure. DLCO was used as an index of pulmonary microvascular function. VO2peak was evaluated via incremental cardiopulmonary exercise testing. General linear regression models revealed that even after controlling for FEV1, emphysema severity and body morphology, DLCO, TVV, BV5 and BV5-10, were independently associated with VO2peak. Interaction effects were observed between COPD and TVV, BV5, and BV5-10 indicating a weaker association between pulmonary vascular volumes and VO2peak in COPD. Our results suggest that pulmonary vascular structure and DLCO is independently associated with VO2peak, regardless of severity of airflow limitation and emphysema, suggesting that these associations are not limited to COPD.

A Comparison of GOLD and STAR Severity Stages in Individuals with Chronic Obstructive Pulmonary Disease Undergoing Pulmonary Rehabilitation.

BackgroundAlongside the recognized Global Initiative for Obstructive Lung Disease (GOLD) classification, the STaging of Airflow obstruction by Ratio (STAR) severity scheme has been proposed for categorizing chronic obstructive pulmonary disease (COPD). Study QuestionWhat is the agreement and utility of the GOLD and STAR classifications in severe COPD patients entering the rehabilitation setting? Study Design and MethodsMedical records were reviewed in this multicenter retrospective study, examining key functional variables and their changes in a large cohort of COPD patients undergoing pulmonary rehabilitation (PR). ResultsA total of 1,516 participants (33.7% females, median age 72.0 years) were included in the analysis. Compared to GOLD, the use of the STAR classification resulted in a different disease severity category for 53.4% of patients. An unweighted Cohen’s κ of 0.25 and a Bangdiwala B value of 0.24 revealed a fair agreement between the two classifications. Higher weighted agreement measures (0.47 and 0.78, respectively) suggested that discrepancies between the classifications mainly occurred for contiguous stages. GOLD demonstrated superior discrimination between stages for chronic respiratory failure, while STAR exhibited better performance in detecting hyperinflation. In terms of their application within PR settings, GOLD exhibited superior performance compared to STAR in identifying the minimal clinically important difference (MCID) in 6-minute walking distance and modified Medical Research Council (mMRC) score. Accordingly, GOLD but not STAR acted as an independent predictor for achieving a MCID in mMRC (OR: 1.48; 95% CI: 1.12-1.94; P=0.005) and also independently predicted changes in Braden score (β=0.154; P=0.004). Interpretation.STAR shows a more uniform gradation of disease severity and enhanced performance in detecting hyperinflation but our preliminary findings do not endorse its utilization in the rehabilitation setting.

The bacterial serine protease inhibitor ecotin inhibits neutrophil elastase enzymatic activity in cystic fibrosis sputa

Cystic Fibrosis (CF) airway disease is characterized by impaired mucociliary clearance, chronic, polymicrobial infections and robust, neutrophil-dominated inflammation. Pulmonary disease is the leading cause of morbidity and mortality in people with CF and is due to progressive airflow obstruction and ultimately respiratory failure. One of the earliest abnormalities in CF airway disease is the recruitment of neutrophils to the lungs. Neutrophil activation leads to the release of their intracellular content, including neutrophil elastase (NE), that damages lung tissues in CF. Our goal is to characterize a known bacterial NE inhibitor, ecotin, in the CF airway environment. Our results indicate that ecotins cloned from four Gram-negative bacterial species (Campylobacter rectus, Campylobacter showae, Escherichia coli and Pseudomonas aeruginosa) inhibit NE activity in CF sputum samples in a dose-dependent manner. Although we observed differences in the NE-inhibitory activity of the tested ecotins with the Campylobacter homologs being the most effective in NE inhibition in CF sputa, none of the ecotins impaired the ability of human neutrophils to kill major CF respiratory pathogens, P. aeruginosa or S. aureus, in vitro. Overall, we demonstrate that bacterial ecotins inhibit NE activity in CF sputa without compromising bacterial killing by neutrophils.

Covert airflow obstruction dominates the overt ones in interstitial lung disease: An appraisal.

Background & objectives The co-presence of non-emphysematous airflow obstruction in interstitial Lung disease (ILD) is not elaborated. The present study aims the job with spirometry. Methods ILD affected individuals with or without airflow obstruction (FEV1/FVC<0.7 or >0.7) on spirometry were compared in terms of FEV1 and FEF25-75 derived variables [FEF25-75 (%-predicted), FEV1-FEF25-75 distance, reversibility of FEV1 and FEF25-75 to salbutamol and change in FEV1 and FEF25-75 in %-predicted values]. Those showing significant difference (P=0.0001) suggesting obstruction were selected to draw respective receiver operating curve (ROC) curves to identify the best cut-off value for individual parameters. The efficacy of each surrogate was tested to identify airflow obstruction in both the initial 'overlap' as well as the 'unmixed' ILD affected individual for the presence of airflow obstruction. Results FEV1/FVC identified 30 overlap from 235 ILDs. The FEF25-75 (%-predicted), FEV1-FEF25-75 distance, FEF25-75 reversibility (in ml) and FEV1 (%-predicted) were significantly (P<0.0001) different between the two groups. Of these, the FEF25-75 (%-predicted) had high specificity and sensitivity (93.33 and 79.47%) to identify airflow limitation in the initial unmixed ILD-group. The surrogates with their cut off values identified 92 extra individuals making it 122/235 (51.91%) of ILD having airflow obstruction. The 'unmixed' group showed higher frequency and degree of FEV1 reversibility. Interpretation & conclusions The findings of this study suggest that the airflow obstruction in ILD involves both the intrathoracic large and small airways. Although seemingly parallel, their relative status (qualitative and quantitative) needs research especially in light of the a etio pathology and the extent of involvement of ILD.

Sensitization to Staphylococcus Enterotoxin: Relationship with Aspects of Disease Severity

Background/Objective: Sensitization to specific IgE Staphylococcus aureus enterotoxins (SEs) is associated with an increased risk for severe asthma development. Limited data exist regarding the association of seropositivity for specific IgE SEs and the different aspects of severe asthma. We aimed to determine whether the presence of SEs is associated with asthma-related parameters such as inflammatory cells in the airways, features of airway remodeling, and other variables relating to asthma assessment and severity. Methods: Fifty patients with severe asthma were recruited in the study. Demographics, comorbidities, asthma duration, and asthma medication were recorded by treating physicians. Specific IgE SE measurement, lung function, atopic status, asthma control test (ACT), sputum induction, bronchoscopy with BAL, and indices of airway remodeling were also assessed. Results: Twelve patients were positive to enterotoxin sensitization. Patients seropositive to specific IgE SEs significantly differed in regard to FEV1% pred and FEV1/FVC ratio compared to seronegative ones. Analyzing the inflammatory variables obtained from induced sputum, BAL, and endobronchial biopsies, the only significant difference was that of smooth muscle area (SMA), which was greater in specific IgE SE seropositive patients. The multivariate linear regression analysis showed two significant associations of specific IgE SE seropositivity. We found a negative with FEV1% pred with beta standardized coefficient 95%CI −0.054 (−0.083, −0.031), p &lt; 0.001, and a positive with SMA with beta standardized coefficient 95%CI 0.054 (0.081, 0.037), p &lt; 0.001. Conclusions: Seropositivity to specific IgE SEs in severe asthma is associated with more severe airflow limitation, obstruction, and upregulation in SMA, indicating a possible role in the remodeling process.

Optimal spirometry thresholds for the prediction of chronic airflow obstruction: a multinational longitudinal study

IntroductionChronic airflow obstruction is key for COPD diagnosis but strategies for its early detection are limited. We aimed to define the optimal z-score thresholds for spirometry parameters to discriminate chronic airflow obstruction incidence.MethodsThe Burden of Obstructive Lung Disease study is a multinational cohort study. Information on respiratory symptoms was collected and pre- and post-bronchodilator spirometry was performed at baseline. Eighteen study sites were followed up with repeat measurements after a median of 8.4 years. We converted lung function measurements into z-scores using the Third National Health and Nutrition Survey reference equations. We used the Youden index to calculate the optimal z-score thresholds for discriminating chronic airflow obstruction incidence. We further examined differences by smoking status.ResultsWe analysed data from 3057 adults (57% females, mean age: 51 years at baseline). Spirometry parameters were good at discriminating chronic airflow obstruction incidence (AUC 0.80–0.84), while respiratory symptoms performed poorly. The optimal z-score threshold was identified for pre-bronchodilator FEV1/FVC &lt;-1.336, equivalent to the 9th percentile (sensitivity: 78%, specificity: 72%). All z-score thresholds associated with a lower post-bronchodilator FEV1/FVC and greater odds of chronic airflow obstruction at follow-up. The risk of chronic airflow obstruction was slightly greater for current smokers and, to some extent, never smokers with a pre-bronchodilator FEV1/FVC less than the 9th/10th percentiles at baseline, particularly among males.ConclusionsSpirometry is better than respiratory symptoms at predicting chronic airflow obstruction incidence. A pre-bronchodilator FEV1/FVC &lt;9th/10th percentiles, particularly among current smokers, could suggest early airflow obstruction or pre-COPD.

Alternative Therapy for Acute Exacerbation of Chronic Obstructive Pulmonary Disease: Moving Cupping along Meridians.

Chronic obstructive pulmonary disease (COPD) is a prevalent respiratory condition characterized by persistent and progressive airflow obstruction, resulting in chronic respiratory symptoms like dyspnea, cough, and sputum production, accompanied by wheezing, chest tightness, fatigue, and reduced physical activity. Under the influence of various factors, patients with COPD often experience acute exacerbations, which have a significant negative impact on the prognosis, quality of life, and life span of patients. As a branch of cupping therapy, moving cupping along meridians is an essential complementary therapy of the traditional Chinese medicine system. Cupping plays a unique role in treating and preventing many diseases by stimulating the local skin with negative pressure. This article elaborately describes the procedure of moving cupping along meridians therapy in the treatment of AECOPD. The effectiveness and feasibility of moving cupping along meridians therapy in relieving symptoms and enhancing the quality of life is demonstrated by comparing the changes in the 36-item Short-Form (SF-36) health survey questionnaire, the modified Medical Research Council dyspnea scale (mMRC), and the COPD Assessment Test (CAT) score before and after the treatment. As a cost-effective complementary treatment, the protocol for the moving cupping along meridians treatment described in this article is expected to provide a reference for non-pharmacological treatment options for AECOPD.