ERJ Open Research最新文献

Introduction: Idiopathic pulmonary fibrosis (IPF) has high morbidity and mortality with limited treatment options. Goal-oriented management approaches, such as the "treatable traits" concept, have yet to be implemented in IPF. This study aims to identify specific treatment goals in IPF for potential interventions by analysing outcomes from two national registries.

Methods: We used data from the INSIGHTS-IPF registry, comprising 1232 IPF patients, enrolled from 2014 to 2020 as derivation cohort. Baseline and 6-month follow-up data were examined to assess clinical progression and predict 1-year mortality. Variables included forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (D _LCO), 6-min walk distance (6MWD), body mass index (BMI) and comorbidities. For validation we used data from 490 IPF patients enrolled in the Canadian Registry for Pulmonary Fibrosis (CARE-PF) and the full 2576 fibrotic interstitial lung disease (ILD) cohort of the CARE-PF registry.

Results: Multivariable analysis identified FVC, D _LCO, 6MWD and BMI as independent predictors of 1-year survival. We established three risk groups based on these variables: low risk (<15% 1-year mortality), intermediate risk (15-30%) and high risk (>30%). Potential treatment goals were defined based on FVC, D _LCO, 6MWD and BMI, which are readily available and may be responsive to interventions. Our risk model showed equivalent accuracy in the validation cohort, both for IPF alone and the overall population.

Conclusion: This study provides a novel risk model for IPF patients, which may also apply to a broader spectrum of fibrotic ILD. It is based on potentially actionable variables which deserve further evaluation as measurable treatment goals in interventional clinical trials.

Background: The Global Initiative for Asthma recommends as-needed combination inhaled corticosteroid-formoterol reliever for mild asthma. Its cost-effectiveness is uncertain outside double-blind regulatory trials. The study objectives were to assess the cost-effectiveness of as-needed budesonide-formoterol versus maintenance budesonide plus as-needed salbutamol, and versus as-needed salbutamol, in averting exacerbations in adults with mild asthma during 12-month follow-up of the New Zealand participants (n=551) of the open-label Novel START multicountry clinical trial.

Methods: New Zealand health-system and societal perspectives were adopted using 2025 resource costs. Healthcare utilisation comprised electronically monitored inhaler use (with multiple imputation for missing data), asthma-related pharmaceuticals, primary-care visits, emergency-department visits and hospitalisations. Regression methods were used for cost-effectiveness analysis. Scenarios included generic substitution and prescription-charge exemption.

Results: As-needed budesonide-formoterol, compared with maintenance budesonide plus as-needed salbutamol, is more effective at reducing severe exacerbations and provides an annual health-system cost saving of NZD 12 (95% CI 0-28) per patient, increasing to NZD 22 (95% CI -15-58) if a societal perspective is adopted. Compared with as-needed salbutamol alone, as-needed budesonide-formoterol costs the health system NZD 38 and NZD 111, respectively, to prevent an exacerbation and a severe exacerbation. From a societal perspective it is cost-saving NZD 70 (95% CI 2-134). Findings were robust to scenario analyses.

Conclusion: For patients with mild asthma, as-needed budesonide-formoterol 200/6 μg is cost-saving from health-system, patient and societal perspectives, while improving outcomes, dominating maintenance budesonide plus as-needed salbutamol. Compared with as-needed salbutamol, as-needed budesonide-formoterol is cost-effective from a health-system perspective and dominates from a societal perspective.

Background: Obstructive sleep apnoea (OSA) is a prevalent disorder. No consistent mortality benefit from treating OSA has been reported in randomised controlled trials. This analysis of an age-and-sex-representative anonymised German public health insurance database from 2015-2020 investigated mortality and hospitalisation rates in positive airway pressure (PAP)-treated versus non-PAP-treated individuals with OSA, accounting for key confounders, including demographic factors, socioeconomic status, comorbidities and medication use.

Methods: Treatment-naïve individuals with OSA were selected and stratified by PAP prescription (PAP treated versus non-PAP-treated (controls)). All-cause mortality rates were compared between groups using Cox proportional hazard models, and all-cause hospitalisation rates were compared using 1:1 nearest neighbour matching based on estimated propensity score, age and sex. Group comparisons were made using Chi-squared tests.

Results: The mortality analysis included 12 297 PAP and 10 020 non-PAP-treated individuals. During a mean 4.0 years of follow-up, 1067 people (4.8%) died; the mortality rate was significantly lower in the PAP versus non-PAP group (hazard ratio 0.87, 95% confidence interval (CI) 0.77-0.98; p=0.026). The hospitalisation analysis included 8768 PAP-treated individuals and 8768 matched controls. 1926 people (11.0%) were hospitalised; the hospitalisation rate was significantly lower in the PAP versus non-PAP group (odds ratio 0.81, 95% CI 0.74-0.89; p<0.0001).

Conclusion: In this comprehensive analysis, PAP therapy was associated with lower mortality and fewer hospitalisations during the follow-up period compared with no PAP therapy, though residual confounding and the observational nature of the study should be considered when interpreting the results.

Rationale: Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia (DIPNECH) is characterised by diffuse bronchial hyperplasia of pulmonary neuroendocrine cells, which are situated within the walls of bronchi and bronchioles. Presenting symptoms are nonspecific and the clinical course varies, making diagnosis challenging. We sought to describe the clinical characteristics of patients with DIPNECH in a large multinational case series to guide and inform future care and research.

Methods: Data were collated from 18 international centres. Information collected included disease presentation, pulmonary function testing, histopathology, radiological patterns and outcomes. The relationship between clinical features, radiology and symptoms were explored in parametric and nonparametric group-wise analyses, univariate linear regressions, and multivariate binomial logistic regression.

Results: The mean±sd age of the 258 patients in this study was 63.3±10.6 years and 93.4% were female. Diffuse pulmonary nodules (98.8%) and mosaic attenuation (59.1%) were the most common radiological findings and 29.5% had obstructive spirometry with a mean±sdforced expiratory volume in 1 s (FEV₁) % pred of 69.0±23.7%. There was a significant association between the number of nodules and a reduction in FEV₁ % pred (p<0.001), while the presence of bronchial wall thickening on imaging was most closely associated with cough (OR 4.97, p=0.001) dyspnoea (OR 3.14, p=0.003) and bronchodilator responsiveness (OR 3.09, p=0.013). Approximately half of patients treated with inhaled beta agonist and corticosteroids (46.3%) or somatostatin analogue (54.1%) reported improvement in symptoms.

Conclusions: The presence of radiological bronchial wall thickening is associated with the presence of symptoms, while mosaic attenuation is correlated with airflow obstruction; hence, the presence of these radiological findings has the potential to guide possible treatment decisions.

Background: Pulmonary arterial hypertension (PAH) requires a complex and multidisciplinary care approach with regular follow-up visits to monitor disease progression and adaptation of treatment regimens. Current ESC/ERS Guidelines recommend initial double oral treatment (endothelin-receptor antagonist + phosphodiesterase type 5 inhibitor) in patients presenting at diagnosis with intermediate risk according to the three-strata risk score. Retrospective data analyses indicate a clinical benefit for upfront triple combination therapy including parenteral prostacyclins (PCA) in intermediate and high-risk patients. The multicentric TripleTRE trial aims to investigate the effect of initial triple combination therapy including parenteral PCA on risk status, compared to double oral in a prospective setting in patients at intermediate-high risk at diagnosis according to the four-strata risk score.

Methods: A phase IV, multicentre, prospective, randomised, two-arm, open-label trial will be conducted. The study will enrol a total of 110 patients with intermediate-high risk of death at PAH diagnosis. Patients are randomised (1:1) to receive either initial double-oral treatment or upfront triple combination treatment including parenteral treprostinil. The primary end-point is the achievement of a low-risk status between week 24 and 48 assessed with the simplified four-strata risk assessment tool.

Discussion: Despite retrospective evidence for greater benefit, prospective investigation of upfront triple therapy including a parenteral PCA is lacking. The TripleTRE trial aims to fill this gap and test the hypothesis of "hit hard and early" in patients with newly diagnosed PAH.

Introduction: Pulmonary exacerbations contribute to disease progression in chronic lung diseases. In a large prospective cohort study, we studied the incidence and predictors of pulmonary exacerbations among persons with primary ciliary dyskinesia (PCD), which can inform follow-up care. We also assessed healthcare use, changes in management and pathogens during exacerbations.

Methods: Participants in the Living with PCD study reported increased respiratory symptoms in the past 7 days, indicating a pulmonary exacerbation, from June 2020 through May 2022 via online questionnaires. We derived incidence rates and studied predictors of pulmonary exacerbation incidence by fitting multivariable negative binomial regression models.

Results: We obtained data from 660 persons (408 adults, 57 adolescents, 195 children) who completed 17 853 follow-up questionnaires (median 17, range 1-84). The 1026 reported exacerbations indicate an incidence rate of 3.1 pulmonary exacerbations per person per year, with minor variation across age groups, but changes over time. Incidence was higher among adult females (incidence rate ratio (IRR) 2.0, 95% confidence interval (CI) 1.4-2.7) and those in whom Pseudomonas aeruginosa was isolated (children IRR 1.9, 95% CI 1.1-3.6; adults/adolescents IRR 1.4, 95% CI 1.0-1.9). Participants saw a health professional during only 185 of 1404 exacerbation weeks (13%). P. aeruginosa was the pathogen most frequently observed during exacerbations in children (18 of 118 samples, 15%) and adults/adolescents (132 of 303 samples, 44%).

Conclusion: Pulmonary exacerbations are frequent in PCD and heighten the disease burden. Patients for whom targeted management is particularly important include adult females and those who carry P. aeruginosa.

Background: Community-acquired pneumonia (CAP) is a leading cause of morbidity and mortality. While tools predicting short-term prognosis exist, there is urgent need for the early identification of patients requiring close follow-up monitoring for post-acute mortality. We therefore conducted cluster analysis of baseline clinical data to investigate predictors of post-acute mortality in CAP.

Methods: We analysed 7840 participants from the German CAPNETZ cohort, using self-organising map (SOM)-clustering and survival analyses. Random survival forest (RSF) models were used to identify key predictors of mortality, which were then analysed using time-dependent area under the curve and Cox proportional hazard regression models.

Results: SOM-clustering based on 10 predictors identified 879 (12%, in four clusters) patients with high risk for post-acute (30-180 days) mortality. Across the cohort, age and urea were the most important predictors of post-acute mortality, while in the high-risk cohort, body mass index emerged as the strongest predictor, as identified by RSF modelling. In one high-risk cluster, there was an association with elevated platelet counts (HR: 1.13, 95% CI 1.03-1.21, p=0.01; increments of 40 platelets·nL^-1, c14, 35% of high-risk patients), in another (c15, 50% of high-risk patients) with elevated urea (HR: 1.06, 95% CI 1.01-1.11, p=0.02) and C-reactive protein (CRP) (HR: 1.27, 95% CI 1.01-1.58, p=0.04).

Conclusion: Using 10 clinical predictors for post-acute mortality in CAP, predictive SOM-clustering revealed several high-risk subgroups, with heterogeneous biomarkers, suggestive of differences in the underlying pathophysiology (thrombocytes, urea, CRP). Adapting medical therapy to these high-risk subgroups may reduce post-acute mortality following CAP.

Background: Most patients in real-world severe asthma populations would not be eligible for biologic randomised controlled trials (RCTs), although observational evidence has confirmed the effectiveness of biologics in real-world populations. We therefore investigated whether satisfying specific RCT inclusion/exclusion criteria affects biologic response in the real world.

Methods: Inclusion and exclusion criteria from 11 pivotal phase 3 asthma biologics RCTs were reviewed to identify criteria themes, and median stringency within each characterised. Patients within the UK Severe Asthma Registry (UKSAR) with at least one year of follow-up on biologics were assessed as to whether they would satisfy inclusion/exclusion for each theme. Regression models were undertaken to assess whether the proportion of patients achieving a composite biologic response, defined as a ≥50% reduction in exacerbations or maintenance oral corticosteroids, was noninferior in patients ineligible by each theme. Superiority analyses and domain-specific responses were also analysed.

Results: 1421 adult patients with severe asthma from 13 specialist centres were included in this analysis. Noninferiority of composite response was demonstrated for all eligibility criteria except medication adherence. In superiority analyses, patients ineligible by adherence theme had a significantly lower odds ratio (OR) for composite response of 0.37 (95% CI 0.20-0.68), whilst patients ineligible by (low) baseline asthma symptom score had a significantly higher OR for response of 2.09 (1.31-3.32).

Conclusions: Ineligibility by typical RCT inclusion/exclusion themes was generally not associated with inferior biologic composite response. Asthma biologics are effective in a broad range of patients, many of whom would not have met clinical trial eligibility criteria.

Repeat expansion of RFC1 (RE-RFC1) is associated with refractory chronic cough but no treatment has emerged as a therapeutic option on cough in patients with RE-RFC1. Here, we show that morphine has a beneficial effect on cough in patients with RE-RFC1. https://bit.ly/4g3iviQ.

Introduction: Social determinants of health (SDH) including age, sex, ethnicity, socioeconomic status, education, occupation and rural status impact the development and prognosis of COPD. Nevertheless, it is unclear whether SDH are reported or considered in clinical trials examining the efficacy of long-term oral antibiotics (LTOA) in people with COPD.

Methods: A search of three clinical trial registries (clinicaltrials.gov, ANZCTR, ISRCTN) and Cochrane CENTRAL was conducted for trials involving LTOA prescribed to people with COPD registered between 1 January 2000 and 7 May 2023. Data were extracted regarding trial location, recruitment strategies and eligibility criteria. Where available, reporting of SDH data and relevant subgroup analyses were extracted.

Results: From 781 trials identified, 17 trials were included in this review. Most (94.1%) were conducted in high-income countries alone. 94.1% of trials described age and gender, and 12.5% described ethnicity within recruitment strategies or eligibility criteria. No other SDH were reported in recruitment or eligibility criteria. Of seven completed trials with publicly available results (n=2888), all reported age and gender and 42.9% reported ethnicity; no other SDH were reported. Participants were predominantly male (66.3%) and white (72.6% to 99.0%).

Conclusion: There was limited reporting of SDH in clinical trials investigating the efficacy of LTOA in people with COPD, and those that did report this information demonstrated limited participant diversity. Consequently, the safety and effectiveness of LTOA in under-represented patient populations remain unclear. Proactive recruitment of diverse populations and greater transparency in trials' reporting of participant demographics is needed.