ERJ Open Research最新文献

Background: Severe asthma affects the working life of millions of people worldwide. Interleukin (IL)-5/anti-interleukin-5 receptor α (IL-5Rα) antibodies are highly effective in reducing symptoms in patients with severe eosinophilic asthma. We analysed effects of anti-IL-5/anti-IL-5Rα treatment on self-reported productivity and absenteeism at work in patients with severe eosinophilic asthma.

Methods: In this prospective single-centre study, patients with severe eosinophilic asthma received a questionnaire assessing their actual occupational status and the influence asthma has on their work life, productivity and missed days at work prior to initiation of antibody treatment and after 6 and 12 months of therapy. Among others, the Work Productivity and Activity Impairment Questionnaire: Specific Health Problem (WPAI:SHP) was used.

Results: Out of 54 patients with a median age of 60 years, 27 (50%) were employed. In addition to an increase in asthma control and lung function, self-reported productivity increased significantly with a decrease on the WPAI:SHP from 30% (interquartile range (IQR) 20-50%) to 10% (IQR 0-27.5%) under treatment (p=0.001). Furthermore, self-reported missed days at work were reduced from 2 days·month^-1 (IQR 1.75-6 days·month^-1) to 0 days·month^-1 (IQR 0-2 days·month^-1; p=0.067). At baseline 22 employed patients (81%) stated they were affected at work by their asthma. After 12 months of treatment, this number decreased to eight patients (30%; p=0.038).

Conclusions: This prospective analysis could prove the substantial impact severe asthma has on patients' working life. Anti-IL-5/anti-IL-5Rα treatment in patients with severe eosinophilic asthma leads to a significant increase in self-reported productivity at work, and after 12 months of treatment patients state substantially fewer negative effects on their working situation.

Background: Bronchiectasis is a complex, chronic disease with geographic and ethnic diversity. While the most substantial cohort studies have been conducted in Europe and the USA, Canada also faces considerable challenges. The comprehensive Canadian Bronchiectasis and Nontuberculous Mycobacterial (NTM) Registry aims to 1) outline the clinical characteristics and natural history of bronchiectasis in Canada, 2) identify risk factors contributing to disease progression within Canadians, 3) integrate comprehensive clinical information to better understand the phenotypes of bronchiectasis and 4) support the development of large-scale, randomised controlled trials in Canada.

Methods: The Canadian Bronchiectasis and NTM Registry is an ongoing prospective, longitudinal, multi-centre, observational cohort study. It aims to enrol at least 2000 participants to collect data such as medical history, aetiological assessments, lung function tests, microbiological profiles, radiographic evaluations, comorbidities and quality of life (QoL) metrics. Participants will undergo annual follow-ups to gather longitudinal information regarding outcomes, treatments and changes in QoL. The inclusion criteria are a diagnosis of bronchiectasis by clinical history and computed tomography and/or pulmonary NTM infection as defined by American Thoracic Society/Infectious Diseases Society of America guidelines. The study's protocol received ethical approval from the lead site, the University of Calgary, with future additional approval from local ethics committees at all participating centres.

Discussion: The outcomes of the registry will be instrumental in uncovering the clinical traits and natural history of bronchiectasis. This longitudinal study will be used for analysis to form evidence-based clinical practices and serve as a resource in Canada to inform future studies in NTM and bronchiectasis.

Introduction: COPD is characterised by airflow obstruction, expiratory airway collapse and closure causing expiratory flow limitation (EFL) and hyperinflation. Supine posture may worsen ventilatory function in COPD, which may cause hyperinflation to persist and contribute to symptoms of orthopnoea and sleep disturbance. Our aim was to determine the impact of supine posture on hyperinflation, dynamic elastance and EFL in COPD and healthy subjects. We hypothesised that changes in hyperinflation in supine posture are influenced by EFL and gas trapping in COPD.

Methods: Clinically stable COPD patients (compatible symptoms, smoking >10 pack-years, obstructed spirometry) and healthy controls underwent oscillometry in the seated and supine positions. Hyperinflation was measured by inspiratory capacity (IC) and the ratio of IC to total lung capacity (IC/TLC) while seated and supine EFL was measured as the difference in mean inspiratory and mean expiratory oscillatory reactance at 5 Hz (X _rs5). Relationships between IC, IC/TLC and X _rs5, were examined by Spearman correlation.

Results: 42 COPD patients demonstrated no change in IC/TLC from seated (0.31 L) to supine (0.32 L) position (p=0.079) compared to significant increases seen in 14 control subjects (0.37 L seated versus 0.44 L supine; p<0.001). In COPD, worse dynamic elastance (X _rs5 r_s 0.499; p=0.001) and EFL (ΔX _rs5 r_s -0.413; p=0.007), along with increased age and lower body-mass-index were predictors of supine hyperinflation.

Conclusion: Supine persistent hyperinflation occurs in COPD and is associated with increased dynamic elastance and EFL, likely the result of increased airway closure due to gravitational redistribution of lung mass.

Background: The COVID-19 pandemic has led to significant concern due to its impact on human health, particularly through pneumonia-induced lung damage. Surfactant proteins A and D (SP-A and SP-D) are implicated in COVID-19 lung damage, but the role of surfactant protein B (SP-B) remains unclear.

Methods: We conducted a single-centre, prospective observational study involving 73 hospitalised COVID-19 pneumonia patients. SP-B levels were measured within 48 h of admission, alongside SP-A and SP-D in a subset. Clinical data were collected, and follow-up visits were conducted after 6 months.

Results: At hospitalisation, circulating immature SP-B levels measured in 73 patients (median 26.31 arbitrary units (AU) (interquartile range 14.27-41.31)) correlated significantly with lung involvement (r=0.447, p<0.001) and oxygen support requirement (p=0.005). SP-B levels did not predict mechanical ventilation or intensive care unit admission. SP-B decreased significantly (p<0.001) from 25.53 AU (14.36-41.46) at the acute hospitalisation to 12.73 AU (9.12-20.23) at the 6-month follow-up, whereas SP-A and SP-D did not change significantly. Immature SP-B (but not SP-A and SP-D) was confirmed to be significantly associated with the need for oxygen support (n=26, 58%) during the hospitalisation (p<0.05).

Conclusion: Immature SP-B emerges as a potential biomarker for COVID-19 pneumonia severity and prognosis. Its dynamic changes suggest utility in monitoring disease progression and long-term outcomes, despite limitations in predicting hard end-points. Larger studies are needed to validate these findings and understand the underlying mechanisms of surfactant protein dysregulation in COVID-19 pathogenesis.

Background: Persistent airflow obstruction (PAO) in patients with asthma can be difficult to treat. Tezepelumab blocks thymic stromal lymphopoietin, an epithelial cytokine implicated in asthma pathogenesis. This analysis evaluated the efficacy of tezepelumab in patients with severe, uncontrolled asthma and PAO.

Methods: PATHWAY (phase 2b) and NAVIGATOR (phase 3) were multicentre, randomised, double-blind, placebo-controlled studies. This post hoc analysis included PATHWAY and NAVIGATOR patients who received tezepelumab 210 mg or placebo every 4 weeks for 52 weeks. Change from baseline to week 52 in pre-bronchodilator forced expiratory volume in 1 s (FEV₁) and the annualised asthma exacerbation rate (AAER) over 52 weeks were assessed in patients with and without PAO (post-bronchodilator FEV₁/forced vital capacity ratio <0.7) at baseline.

Results: Of the 1334 included patients, 782 (58.6%) had PAO at baseline. At week 52, greater improvements in pre-bronchodilator FEV₁ from baseline were observed in tezepelumab versus placebo recipients with PAO (least-squares (LS) mean 0.24 versus 0.07 L; difference 0.17 L, 95% confidence interval (CI): 0.11-0.23) and without PAO (LS mean 0.20 versus 0.12 L; difference 0.08 L, 95% CI: 0.01-0.15). Tezepelumab reduced the AAER versus placebo by 61% (95% CI: 51-69) and 56% (95% CI: 42-67) in patients with and without PAO, respectively. For patients with PAO at baseline, the proportion without PAO at week 52 was higher with tezepelumab (12.1%) than placebo (6.6%) (odds ratio 1.96, 95% CI: 1.30-2.94).

Conclusion: Tezepelumab improved lung function and reduced exacerbations versus placebo in patients with severe, uncontrolled asthma with and without PAO.

[This corrects the article DOI: 10.1183/23120541.00838-2023.].

A study in ERJ Open Research documents the effects of supine posture on lung mechanics in patients with COPD. Specifically, it finds that hyperinflation is related to expiratory flow limitation and increased dynamic elastance. https://bit.ly/4eQG7G7.

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing and progressive interstitial lung disease of unknown aetiology with a pathogenesis still partly unknown. Several microvascular and macrovascular abnormalities have been demonstrated in the pathogenesis of IPF and related pulmonary hypertension (PH), a complication of the disease.

Methods: We carried out a non-systematic, narrative literature review aimed at describing the role of the vasculature in the natural history of IPF.

Results: The main molecular pathogenetic mechanisms involving vasculature (i.e. endothelial-to-mesenchymal transition, vascular remodelling, endothelial permeability, occult alveolar haemorrhage, vasoconstriction and hypoxia) and the genetic basis of vascular remodelling are described. The prevalence and clinical relevance of associated PH are highlighted with focus on the vasculature as a prognostic marker. The vascular effects of current antifibrotic therapies, the role of pulmonary vasodilators in the treatment of disease, and new pharmacological options with vascular-targeted activity are described.

Conclusions: The vasculature plays a key role in the natural history of IPF from the early phases of disease until development of PH in a subgroup of patients, a complication related to a worse prognosis. Pulmonary vascular volume has emerged as a novel computed tomography finding and a predictor of mortality, independent of PH. New pharmacological options with concomitant vascular-directed activity might be promising in the treatment of IPF.

Objective: Inspiratory muscle training (IMT) is used to improve inspiratory muscle strength in patients with COPD. However, the effect of IMT on diaphragmatic function has not yet been thoroughly evaluated. This study aimed to evaluate the effect of IMT on maximum diaphragmatic excursion (DE_max) using ultrasonography in patients with COPD.

Methods: This was a single-centre, randomised, prospective, parallel-group, unblinded controlled trial involving 38 participants with stable COPD. Participants underwent a standardised 12-week pulmonary rehabilitation (PR) programme followed by a 12-week IMT programme, consisting of home-based IMT and low-frequency outpatient PR sessions supervised by physiotherapists (once every 2 weeks), versus low-frequency outpatient PR alone as a control. The DE_max and exercise tolerance were measured.

Results: Out of the 38 patients initially enrolled in the PR programme, 33 successfully completed it and were subsequently randomised to the IMT programme. Finally, 15 (94%) and 14 (88%) patients from the IMT and control groups, respectively, completed the study. Following the IMT programme, DE_max increased in the IMT group (mean±sd 50.1±7.6 mm to 60.6±8.0 mm, p<0.001), but not in the control group (47.4±7.9 mm to 46.9±8.3 mm, p=0.10). Changes in DE_max and exercise tolerance (peak oxygen uptake) were greater in the IMT group than in the control group (both p<0.01).

Conclusions: IMT following the PR programme improved DE_max and exercise tolerance. Therefore, DE_max may be an important outcome of IMT.

Wearable devices could offer valuable support for managing and preventing COPD exacerbations in the future https://bit.ly/4cPnHUK.