Extract Traditionally, COPD has been understood to be a self-inflicted disease caused by tobacco smoking, occurring in old, "susceptible" males and characterised by an accelerated decline of lung function with age [1, 2]. Yet, our understanding of the pathogenesis of COPD has changed very significantly over the past few years [3–6] and, as a result, it is now defined as a heterogeneous condition that

Extract We sincerely appreciate the correspondence from S.S. Sohal, whose recent discoveries in human pulmonary fibrosis [1, 2] are complementary to our report on an abnormal endothelial differentiation trajectory contributing myofibroblasts to pulmonary fibrosis in matrix Gla protein (MGP)-deficient mice [3]. S.S. Sohal and his collaborators have provided strong evidence for an essential role of endothelial

Extract In recent decades, the perception of the epithelium lining the airways has drastically changed from that of a physical barrier that mediates mucociliary transport to a multifunctional tissue that is actively involved in initiating and regulating tissue inflammation and remodelling [1, 2]. The airway epithelium produces a range of mediators, including chemokines, cytokines, growth factors and

Extract I read with great interest the recent original research article by Wu et al. [1] published in the prestigious European Respiratory Journal (ERJ), which reported on endothelial cell-like myofibroblasts and their role in pulmonary fibrosis using mouse models. I highly commend this work and the focus on endothelial cells in this decidedly fibrotic condition. To further enhance discussion, and

Extract COPD is defined as a heterogeneous lung condition characterised by chronic respiratory symptoms (dyspnoea, cough, expectoration and/or exacerbations) due to abnormalities of the airways (bronchitis, bronchiolitis) and/or alveoli (emphysema) that cause persistent, often progressive, airflow obstruction [1]. COPD has a long latency period and once the diagnosis is established, modifying disease

Extract People with interstitial lung disease (ILD) often have persistent breathlessness that worsens over months or years, despite optimal disease modifying therapies and non-pharmacological interventions [1]. Regular, low-dose, systemic morphine is recommended as treatment for persistent breathlessness [2, 3], but the majority of participants in studies of this therapy have COPD as the most prevalent

Extract The airway epithelium plays a central role in the initiation and development of chronic airway diseases [1]. It is the first line of defence against the external environment; therefore, numerous inflammatory and tissue remodelling pathways exist to protect against damage caused by constant exposure to inhaled stimuli (e.g. allergens, cigarette smoke or pathogens) [1, 2]. Dysregulation of these

Infectious diseases have played a major role in shaping our history—none more so than tuberculosis (TB), which accompanied the first humans out of Africa, and continues to cause the untimely death of more than 1.5 million people each year.1 The COVID-19 pandemic has provided a much-needed wake-up call to the global threat posed by infectious disease at a time of rising population density and mobility

Background Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease, predisposing to an increased risk of infection. A complete picture of these infections is lacking. Research question Describe the characteristics and clinical outcomes of patients diagnosed with aPAP, and to identify risk factors associated with opportunistic infections. Methods We conducted a retrospective cohort including

Introduction There is high heterogeneity of outcomes and measures reported in pulmonary rehabilitation (PR) trials of people with chronic obstructive pulmonary disease (COPD). This hinders study comparability and benchmarking of PR. We have developed a core outcome set (COS) to overcome these challenges. Methods This study was informed by a systematic review and two qualitative studies and had patient

Autoimmune pulmonary alveolar proteinosis (aPAP) is an ultra-rare lung disease characterised by myeloid cell dysfunction, abnormal pulmonary surfactant accumulation resulting in progressive dyspnoea of insidious onset and respiratory failure, innate immune deficiency and secondary infection.1 2 Autoantibodies that bind GM-CSF (granulocyte/macrophage colony-stimulating factor) drive the pathogenesis

Background Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset). Methods We used data from the population-based

Background Trajectories of bedside vital signs have been used to identify sepsis subphenotypes with distinct outcomes and treatment responses. The objective of this study is to validate the vitals trajectory model in a multicenter cohort of hospitalized COVID-19 patients and to evaluate the clinical characteristics and outcomes of the resulting subphenotypes. Research Question Can the trajectory of

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Introduction The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE)

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Background Although racial and ethnic differences in continuous positive airway pressure (CPAP) adherence for obstructive sleep apnea (OSA) are widely established, no studies have examined the influence of perceived racial discrimination on CPAP usage, to our knowledge. Research Questions: 1) Do Black adults with OSA report experiencing greater amounts of discrimination than non-Hispanic White adults

Despite many improvements in neonatal care, prematurity remains a significant cause of childhood mortality and morbidity, and the second largest cause of death in children worldwide.1 2 Chronic lung disease of prematurity, also known as bronchopulmonary dysplasia (BPD) is the most common respiratory complication, associated with poor long-term health and neurodisability.3 Early lung protective ventilation

Background Traditional electromagnetic navigation bronchoscopy (ENB) is a real-time image-guided system and used with thick bronchoscopes for the diagnosis of peripheral pulmonary nodules (PPNs). A novel ENB that could be used with thin bronchoscopes was developed. This study aimed to evaluate the diagnostic yield and the experience of using this ENB system in a real clinical scenario. Methods This

Background Cystic fibrosis (CF) lung disease is characterised by progressive airway wall thickening and widening. We aimed to validate an artificial intelligence-based algorithm to assess dimensions of all visible bronchus-artery (BA) pairs on chest CT scans from patients with CF. Methods The algorithm fully automatically segments the bronchial tree; identifies bronchial generations; matches bronchi

Background Programmed death-ligand 1 (PD-L1) expression on tumor cells, evaluated by immunohistochemistry, guides the use of immunotherapy in advanced non-small cell lung cancer (NSCLC). Research Question What is the sensitivity and specificity of PD-L1 testing performed in cytological vs. paired histological specimens, in patients with non-small cell lung cancer? Study Design and Methods The MEDLINE

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Extract Pulmonary arterial hypertension (PAH) is a severe progressive disease characterised by obliterative vascular remodelling and increased resistance in small and medium-sized pulmonary arteries (PAs). Contributing factors to PAH pathogenesis include genetic mutations such as those in bone morphogenetic protein receptor type 2 (BMPR2), perivascular inflammation, systemic immune dysregulation, and

Extract We commend Khor et al. [1] for their important article that proposes a framework for delivering comprehensive care in patients with interstitial lung disease (ILD) based on treatable traits.

Background In the phase 3 STELLAR trial, sotatercept, an investigational first-in-class activin signalling inhibitor, demonstrated beneficial effects on 6-min walk distance and additional efficacy endpoints in pre-treated participants with pulmonary arterial hypertension (PAH). Methods This post hoc analysis evaluated data from right heart catheterisation (RHC) and echocardiography (ECHO) obtained

Extract With increasing climate change, all sources of greenhouse gases must be considered. Hydrofluorocarbon (HFC) propellants are used in all pressurised metered dose inhalers (pMDIs) and, although they are not as ozone-depleting as the earlier chlorofluorocarbons (CFCs), they are potent greenhouse gases and there is a general ask for reduction in their use [1]. In this respect, respiratory doctors

Extract Efforts to curb the tuberculosis (TB) pandemic remain hindered by a lack of objective measures to quantify disease severity and track treatment success that are valid in both HIV-1-infected and -uninfected TB patients. Ralph et al. [1] developed a promising radiographic scoring system, with baseline scores being predictive of sputum smear conversion at 2 months, but it is reliant on skilled

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Background A clinically applicable mortality-risk prediction system for pulmonary tuberculosis may improve treatment outcomes, but no easy-to-calculate and accurate score has yet been reported. We aimed to construct a simple and objective disease-severity score for patients with pulmonary tuberculosis. Research Question Does a clinical score consisting of simple objective factors predict the mortality

Background We recently conducted a double-blinded randomised controlled trial showing that fish-oil supplementation during pregnancy reduced the risk of persistent wheeze or asthma in the child by 30%. Here, we explore the mechanisms of the intervention. Methods 736 pregnant women were given either placebo or n-3 long-chain polyunsaturated fatty acids (LCPUFAs) in the third trimester in a randomised

Background The effect of supplemental oxygen therapy in patients with intermediate-risk pulmonary embolism (PE) who do not have hypoxemia at baseline is uncertain. Research Question Does supplemental oxygen improve echocardiographic parameters in non-hypoxemic patients with intermediate-risk PE? Study Design and Methods This pilot trial randomly assigned non-hypoxemic patients with stable PE and echocardiographic

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Chronic obstructive pulmonary disease (COPD) affects between 15% and 25% of older people,1 2 who suffer also frequently from mental illnesses.3–5 As such, patients with COPD may require pharmacological treatments to manage psychiatric disorders. Guidelines for the treatment of depression in geriatric population recommend the use antidepressants (combined with interpersonal psychotherapy),6 and specifically

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Background COVID-19 vaccines with alternative strain compositions are needed to provide broad protection against newly emergent SARS-CoV-2 variants of concern. This study aimed to describe the clinical efficacy and safety of a bivalent SARS-CoV-2 recombinant protein vaccine as a two-injection primary series during a period of circulation of the omicron (B.1.1.529) variant. Methods We conducted a phase

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In this edition of Thorax , the new British Thoracic Society (BTS) guideline for diagnosing and monitoring paediatric sleep disordered breathing (SDB)1 is published. The primary aim of the guideline is to promote clinical networking and to equip paediatricians in secondary care, with an interest in sleep, with the skills and knowledge to run a local service. The tertiary referral centre would offer

The value of pulmonary rehabilitation (PR) for people with chronic respiratory disease has been firmly established. A large body of evidence supports its efficacy and cost-effectiveness, improving symptoms of breathlessness, exercise capacity and quality of life.1 Although clinical guidelines and quality frameworks support its delivery, access and adherence to PR remains a challenge2 3 (figure 1).

The prototypical study of diagnostic test accuracy compares the results of one or more index tests to an independent ‘reference-standard’ determination of true disease status: ‘disease positive’ (D+) or ‘disease negative’ (D−). If the index test is binary—either ‘test positive’ (T+) or ‘test negative’ (T−)—then sensitivity is the proportion of D+ individuals who have T+ on the index test and specificity

It is not a novel observation that the clinical trial enterprise has largely been unsuccessful in finding new and effective treatments for the acute respiratory distress syndrome (ARDS).1 2 While a significant contributor to the absence of success may be the testing of ineffective treatments, other likely contributors include selecting the wrong population and having unrealistic expectations about

Background Obesity is associated with more severe asthma, however, the mechanisms responsible are poorly understood. Obesity is also associated with low-grade systemic inflammation; it is possible that this inflammation extends to the airways of adults with asthma, contributing to worse asthma outcomes. Accordingly, the aim of this review was to examine whether obesity is associated with increased

Background Inhaled mannitol provokes bronchoconstriction via mediators released during osmotic degranulation of inflammatory cells, and, hence represents a useful diagnostic test for asthma and model for acute attacks. We hypothesised that the mannitol challenge would trigger changes in exhaled volatile organic compounds (VOCs), generating both candidate biomarkers and novel insights into their origin

Background Infections are considered as leading causes of acute exacerbations of chronic obstructive pulmonary disease (COPD). Non-infectious risk factors such as short-term air pollution exposure may play a clinically important role. We sought to estimate the relationship between short-term air pollutant exposure and exacerbations in Canadian adults living with mild to moderate COPD. Methods In this

Rationale Estimating the causal effect of an intervention at individual level, also called individual treatment effect (ITE), may help in identifying response prior to the intervention. Objectives We aimed to develop machine learning (ML) models which estimate ITE of an intervention using data from randomised controlled trials and illustrate this approach with prediction of ITE on annual chronic obstructive

Background Efficiency of randomised clinical trials of acute respiratory distress syndrome (ARDS) depends on the fraction of deaths attributable to ARDS (AFARDS) to which interventions are targeted. Estimates of AFARDS in subpopulations of ARDS could improve design of ARDS trials. Methods We performed a matched case-control study using the Large observational study to UNderstand the Global impact of

Background Metabolic alkalosis may lead to respiratory inhibition and increased need for ventilatory support or prolongation of weaning from ventilation for patients with chronic respiratory disease. Acetazolamide can reduce alkalaemia and may reduce respiratory depression. Methods We searched Medline, EMBASE and CENTRAL from inception to March 2022 for randomised controlled trials comparing acetazolamide

Introduction People with cystic fibrosis (CF) are often on multiple long-term treatments, including mucoactive nebulisers. In the UK, the most common mucoactive nebuliser is dornase alfa (DNase). A common therapeutic approach for people already on DNase is to add hypertonic saline (HS). The effects of DNase and HS used alone have been studied in randomised trials, but their effects in combination have

Background Tracheostomies in children are associated with significant morbidity, poor quality of life, excess healthcare costs and excess mortality. The underlying mechanisms facilitating adverse respiratory outcomes in tracheostomised children are poorly understood. We aimed to characterise airway host defence in tracheostomised children using serial molecular analyses. Methods Tracheal aspirates

Background Testing is critical for detecting SARS-CoV-2 infection, but the best sampling method remains unclear. Objectives To determine whether nasopharyngeal swab (NPS), oropharyngeal swab (OPS) or saliva specimen collection has the highest detection rate for SARS-CoV-2 molecular testing. Methods We conducted a randomised clinical trial at two COVID-19 outpatient test centres where NPS, OPS and saliva

Pulmonary rehabilitation programmes including aerobic training improve cardiorespiratory fitness in patients with COPD, but the optimal programme design is unclear. We used random effects additive component network meta-analysis to investigate the relative effectiveness of different programme components on fitness measured by V̇O2peak in COPD. The included 59 studies involving 2191 participants demonstrated

Home-based pulmonary telerehabilitation (PTR) has been proposed to be equivalent to supervised outpatient pulmonary rehabilitation (PR) but available randomised trials have failed to reach the minimal important changes (MIC). The purpose of this study was to analyse the proportion of MIC responders and non-responders on short-term (10 weeks from baseline) and long-term (62 weeks from baseline) in total

The following is a summary of the British Thoracic Society (BTS) Guideline for diagnosing and monitoring paediatric sleep-disordered breathing (SDB) and includes a summary of the recommendations and good practice points (GPPs). The full guideline is published as a separate Thorax Supplement1 and is available from the BTS website.52 Please refer to the full guideline for full information about each

Fibrosing mediastinitis (FM) is an uncommon cause of haemoptysis, characterised by sclerosis of the mediastinum that may occur as an inflammatory sequela of histoplasmosis, lymphoma, sarcoidosis or an idiopathic process. Bleeding is predominantly due to concomitant collateral vessels and engorgement. However, the endobronchial findings obtained via flexible bronchoscopy are not clearly defined in the

There is increasing interest in phenotypes of patients with COPD that may indicate different response to treatments. Patients with COPD and type 2 inflammation have been shown to have a different response to glucocorticoids and so may also respond to other anti-inflammatory medications. The BOREAS trial (NEJM 2023: DOI 10.1056/NEJMoa2303951) was a phase 3, international, multicentre, randomised, double-blind

Background The early-life origins of chronic pulmonary diseases are thought to arise in peripheral small airways. Predictors of ventilation inhomogeneity, a proxy of peripheral airway function, are understudied in schoolchildren. Research Question Is the double-tracer gas single-breath washout (DTG-SBW) measurement feasible in a pediatric field study setting? What are the predictors of the DTG-SBW

Background Evidence is low regarding the choice of calcineurin inhibitor for immunosuppression after lung transplantation. We aimed to compare the use of tacrolimus once per day with ciclosporin twice per day according to the current definition of chronic lung allograft dysfunction (CLAD) after lung transplantation. Methods ScanCLAD is an investigator-initiated, open-label, multicentre, randomised

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