RESPIRATORY Medicine / Pulmonology Updates

[Articles] State-level burden of chronic respiratory diseases in the USA, 1990–2023, with forecasts to 2050: a systematic analysis for the Global Burden of Disease Study 2023 https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00218-3/fulltext?rss=yes State-level policy environments, including fiscal and preventive health measures, might contribute to shaping respiratory health outcomes beyond individual risk factors. Integrating tobacco control measures, equitable vaccination programmes, and targeted health-system investments could help to address the uneven burden of chronic respiratory diseases across US states and the growing mortality gap despite stable prevalence, although further research is needed to clarify which specific policy determinants underlie these associations.

[Comment] Understanding US state-level heterogeneity in chronic respiratory disease burden https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00226-2/fulltext?rss=yes Chronic respiratory diseases (CRDs) are a major contributor to global mortality. In 2023, they accounted for an estimated 4·2 million deaths and ranked fourth among the leading causes of death worldwide (fifth in the USA, with 221 000 deaths) according to the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023.1 Mortality alone, however, understates the total health loss attributable to these diseases. Disability-adjusted life-years (DALYs), a composite measure of premature deaths and years lived with disability, more fully captures the totality of disease burden.

[News] AI data centres could worsen US air pollution https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00293-6/fulltext?rss=yes Artificial intelligence (AI) firms are exploiting loopholes and lax air pollution enforcement in a race to build new on-site fossil-fuel power plants for data centres across the USA. Concerns over air pollution, water use, secrecy, and noise have fomented a growing backlash against the construction boom just ahead of November's mid-term elections.

[Comment] When spirometry is normal: can FeNO fill the gap in asthma diagnosis? https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00288-2/fulltext?rss=yes Asthma is one of the most prevalent chronic respiratory diseases, imposing a considerable individual and societal burden, yet objective diagnosis remains challenging. Diagnosis relies on several complementary tests, many of which are not routinely available in primary care. In their absence, the risk of both under-diagnosis and over-diagnosis is substantial, and treatment is sometimes initiated as a diagnostic trial—an approach rarely considered for other chronic diseases.

[Articles] Accuracy of type 2 inflammatory biomarkers to diagnose asthma in adults and children: a meta-analysis of 30 studies with prospective validation in an adult primary care cohort https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00228-6/fulltext?rss=yes In adults and children with suspected asthma, FeNO predicted airway hyper-responsiveness and enabled clinically applicable rule-in and rule-out thresholds. BEC performed poorly alone and added no value to FeNO. Findings and thresholds were replicated in a prospective adult primary care cohort; a similar study in children is ongoing. FeNO-guided diagnostic algorithms using context-specific rule-in and rule-out thresholds, while accounting for recent inhaled corticosteroid exposure, warrant consideration.

Is acetazolamide a 'REMedy for rapid eye movement-predominant obstructive sleep apnoea? http://thorax.bmj.com/cgi/content/short/81/10/933?rss=1 Pharmacotherapy for obstructive sleep apnoea (OSA) has entered a new phase in which the focus is shifting from broad, one-size-fits-all approaches to targeted treatments matched to specific physiological endotypes. While continuous positive airway pressure (CPAP) remains the standard of care, many individuals, particularly those with rapid eye movement (REM)-predominant OSA (REM-OSA), struggle with adherence.1 REM sleep is characterised by more frequent and prolonged obstructive events due to dips in ventilatory drive and greater upper-airway vulnerability,2 making this subgroup uniquely challenging to treat. Against this backdrop, interest has grown in the use of medications such as the carbonic anhydrase inhibitor acetazolamide, which modulates ventilatory drive and potentially offers targeted benefit where REM-related pathophysiology dominates. In this issue of Thorax, it is therefore with great interest that we read the recent study by Messineo et al3 which is the first trial to directly test the...

Increase in second primary lung cancers in a nation-wide cohort study from Sweden http://thorax.bmj.com/cgi/content/short/81/10/981?rss=1 Background We describe the occurrence of second primary lung cancers (SPLCs) and their determinant in Sweden. Methods Nation-wide cancer registry from years 1961 to 2021 identified a total of 853 SPLCs. Results The incidence of SPLCs increased almost linearly from 1980 onwards, equally for women and men and approximately equally after the four main histological types. SPLC included adenocarcinoma 63.9%, squamous cell carcinoma (SCC) 19.4%, small cell carcinoma 9.6% and large cell carcinoma 9.1%. The female cumulative probability (CumP) of SPLC after first adenocarcinoma in 10 years reached 0.019, after SCC 0.015 and after small and large cell carcinoma 0.008. The respective CumP for men was 0.013, 0.012, 0.002 and 0.005. While adenocarcinoma was often followed by second adenocarcinoma, after first non-adenocarcinoma SPLCs presented in diverse histologies. Relative risk of SPLC compared with first lung cancer was overall 3.59, higher for women (4.16) than for men (2.99) and approximately equally high after adenocarcinoma and SCC. In patients diagnosed before age 55 years, the relative risk was 6.68 for all, but after female adenocarcinoma it was 9.95 compared with 6.77 for males. The highest relative risks, up to 20-fold, were found after early onset female adenocarcinoma diagnosed after defined T stages. Conclusions Although SPLCs are still rare, their number is increasing rapidly and the relative risks compared with first lung cancer are substantial, qualifying selected groups of high-risk patients, such as patients with early onset adenocarcinoma for early detection by CT screening when/if such tests become available.

2024 BTS/NICE/SIGN asthma guidelines have the potential to improve UK asthma outcomes, but we must act now http://thorax.bmj.com/cgi/content/short/81/10/949?rss=1 WHAT IS ALREADY KNOWN ON THIS TOPICAsthma is a common lung disease and outcomes in the UK are among the worst in Europe. The overuse of short-acting beta agonist and underuse of anti-inflammatory, inhaled corticosteroid-containing inhalers are associated with risk of exacerbations and death. The new collaborative British Thoracic Society(BTS), National Institute for Health and Care Excellence (NICE), Scottish Intercollegiate Guideline Network (SIGN) Asthma Guideline endorses an anti-inflammatory reliever-based approach to asthma management and has potential to significantly improve asthma outcomes in the UK. WHAT THIS STUDY ADDS We discuss the role of guidelines to support delivery of evidence-based practice and highlight the knowledge-action gap that can prevent implementation of guidelines in practice. Based on the published literature and expert consensus, we describe some of the challenges/barriers that will be faced at both a system and individual level when implementing the BTS, NICE, SIGN...

Development and validation of the Hypersensitivity Pneumonitis South Asian Questionnaire for Exposure (HP-SAQE): a novel, qualitative and quantitative tool http://thorax.bmj.com/cgi/content/short/81/10/958?rss=1 Introduction There is an unmet need for a validated qualitative and quantitative tool to assess environmental exposures in patients with interstitial lung disease (ILD). This study aimed to develop and validate a comprehensive tool to systematically identify exposures in patients with ILD. Methods A systematic literature search was completed to identify exposures associated with more than five documented hypersensitivity pneumonitis (HP) cases. These exposures were evaluated through a two-round Delphi survey involving 39 pulmonologists from India, Sri Lanka, Pakistan and Nepal. The questionnaire was prospectively derived at one centre and validated across five centres in India and Sri Lanka. The HP South Asian Questionnaire for Exposure (HP-SAQE) was validated against the gold standard multidisciplinary discussion diagnosis, distinguishing HP from non-HP ILD. Results The literature search screened 5170 records and included 407 studies, identifying 24 exposures. A 50-item Delphi survey achieved expert consensus (>70%) on 17 qualitative and 4 quantitative items (six questions) by 39 pulmonologists. HP-SAQE score ranged from 0 to 14. After pilot testing, the questionnaire was translated into Hindi, Tamil and Sinhala. In the derivation cohort (n=40), the HP-SAQE score was significantly higher in patients with HP versus non-HP (mean: 10.2±1.6 vs 6.7±4.2; p=0.001). This finding was validated in a separate cohort (n=163; mean: 9.4±2.2 vs 4.13±4.28; p Conclusion The HP-SAQE is the first qualitative and quantitative exposure assessment tool for patients with ILD that has a good diagnostic performance.

Time to next pleural procedure: should we take it as RED? http://thorax.bmj.com/cgi/content/short/81/10/941?rss=1 Malignant pleural effusion (MPE) is a common problem in both respiratory and general medical practice, occurring in up to 15% of all patients with malignancy.1 Initial management is principally guided by the degree of symptoms experienced by the patient, especially breathlessness. For large volume symptomatic MPE, options include therapeutic aspiration, inpatient chest drainage with talc pleurodesis or indwelling pleural catheter insertion. The precise strategy employed should be based on individual patient choice, taking into consideration the relative risks and benefits of each modality.2 In practice, this is largely influenced by the ability to intervene safely (ie, whether there is sufficient fluid amenable to drainage) and the presence or absence of non-expandable lung. The size of effusion is readily assessed using bedside thoracic ultrasound; however, non-expandable lung is not always evident from prior imaging. Consequently, a trial of therapeutic aspiration is frequently employed ‘first-line’ to help...

Standardising terminology in routine electronic health records for respiratory endpoints: why we still can't agree http://thorax.bmj.com/cgi/content/short/81/10/943?rss=1 Introduction Clinical practice guidelines and healthcare policies increasingly leverage real-world data, often retrieved from electronic healthcare records (EHRs), to optimise disease prevention, diagnosis and management.1 Traditionally, randomised controlled trials (RCTs) have been regarded as the gold standard for establishing causal relationships between interventions and outcomes, primarily due to their control over confounding factors. However, RCTs face what has been called the clinical trial paradox wherein their strict inclusion criteria and tightly controlled conditions improve internal validity but reduce generalisability to routine care settings.2 3 It is well known that clinical trial populations exclude people with complex morbidity.4 5 Additionally, different research designs answer different research questions and RCTs are not always fit for purpose to answer many important clinical questions. While strict criteria and conduct of RCTs indeed ensure internal validity on drug efficacy, external validity on drug...

Non-invasive ventilation timing in ALS: one size does not fit all http://thorax.bmj.com/cgi/content/short/81/10/939?rss=1 Non-invasive ventilation (NIV) is a cornerstone of respiratory management in amyotrophic lateral sclerosis (ALS), extending survival and relieving symptoms of respiratory failure.1 2 However, ALS has highly heterogeneous patterns of onset and progression, and the optimal timing for NIV initiation remains debated.3 4 In this issue of Thorax, Tankéré et al5 used the French national health database (Système National Des Données De Santé; SNDS) to analyse health trajectories around NIV initiation in a large ALS cohort. Their study aimed to identify phenotypic subgroups and evaluate whether starting NIV earlier compared with later affects survival outcomes. The authors identified over 3400 people with ALS who received NIV between 2015 and 2019. Using time-sequence clustering, they described four distinct care trajectories. Two clusters had a longer interval between ALS diagnosis and NIV start (defined as ‘late’ NIV initiation), and two had...

Beyond age: comorbidity-informed stratification for RSV hospital outcomes http://thorax.bmj.com/cgi/content/short/81/10/937?rss=1 Tommaso Morelli and colleagues present a timely and methodologically robust study that sheds new light on how risk (for poor outcome) could be assessed in adults hospitalised with respiratory syncytial virus (RSV) infection in the UK.1 Using data from a multicentre cohort of 334 patients with PCR-confirmed RSV-related acute respiratory infection, the authors critically evaluate the relevance of existing age-based thresholds used by the Joint Committee on Vaccination and Immunization for guiding RSV vaccine eligibility. Their findings show that simple age-based cut-offs applied currently, such as ≥75 years (or even ≥60 years), offer only limited discriminatory power for predicting Intensive Care Units (ICU)/High Dependency Units (HDU) admission or 60-day mortality, with optimism-adjusted AUCs between 0.58 and 0.61. By contrast, a more clinically nuanced model incorporating age, chronic obstructive pulmonary disease (COPD), current or past cancer and dementia yielded a considerably higher area under the curve (AUC) of...

Rising burden of second primary lung cancers: from survivorship to secondary prevention http://thorax.bmj.com/cgi/content/short/81/10/935?rss=1 Improved survival in lung cancer represents one of the most significant achievements in contemporary thoracic oncology. Earlier diagnosis, stage migration and advances in systemic therapy—particularly for adenocarcinoma—have steadily increased the population of long-term lung cancer survivors. An inevitable consequence of this success is the emergence of second primary lung cancers (SPLCs) as a clinically meaningful and growing problem. In this issue of Thorax, Zitricky et al provide compelling population-based evidence that SPLCs are no longer a marginal phenomenon but an expanding challenge for clinicians and health systems alike.1 Using nationwide Swedish Cancer Registry data spanning six decades, the authors demonstrate a more than threefold increase in SPLC incidence over the past 30 years, with remarkably similar temporal trends across sex and histological subtypes.1 The overall relative risk of SPLC compared with first primary lung cancer was 3.6, rising to over fourfold in women and approaching...

Critical care research in low- and middle-income countries: a narrative review http://thorax.bmj.com/cgi/content/short/81/10/1022?rss=1 Critical illness poses a significant global health challenge, disproportionately affecting low- and middle-income countries (LMICs) and other low-resource settings, where healthcare resources and infrastructure are often limited. This narrative review explores the multifaceted dynamics of critical care research in low-resource settings, focusing on socioeconomic, demographic and structural barriers that impact the delivery of intensive care services and its consequences for clinical research. Research is a cornerstone in addressing these challenges. Locally relevant evidence is crucial for informing healthcare policies and clinical guidelines, particularly in adapting high-income country recommendations to resource-constrained contexts. This review describes research challenges and findings on several fields of critical care in LMICs. It underscores the pressing need for sustained investment in critical care research and infrastructure in LMICs to overcome health disparities and improve outcomes for critically ill patients.

Acetazolamide to prevent ventilatory drive withdrawal in REM sleep apnoea: a randomised controlled trial http://thorax.bmj.com/cgi/content/short/81/10/969?rss=1 Background Obstructive sleep apnoea (OSA) pathogenesis during rapid-eye movement (REM) sleep has been linked to dips in ventilatory drive and downstream genioglossus hypotonia. The carbonic anhydrase inhibitor acetazolamide is known to increase ventilatory drive and improve OSA severity. Therefore, we tested the effect of acetazolamide on REM-predominant OSA severity (apnoea hypopnoea index (AHI) and hypoxic burden, co-primary outcomes) and underlying physiological mechanisms (ventilatory drive, ventilation and pharyngeal muscle activity). Methods 11 participants with REM-predominant OSA per baseline polysomnography (REM AHI/non-REM AHI≥2) were allocated to receiving acetazolamide 500 mg for three nights (first night at half dose) or placebo according to a randomised, crossover, double-blind design. Detailed physiological polysomnography with recording of diaphragm and genioglossus electromyography was conducted after each intervention, with a 1-week washout in between. Results As hypothesised, acetazolamide reduced AHI by 35.5% (95% CI 23.1% to 46.3%) and hypoxic burden by 35.9% (95% CI 21.1% to 48.4%) vs placebo (pventilation/drive, p Conclusions Acetazolamide modestly improved REM OSA, with meaningful improvements in upper airway physiology, but failed to mitigate the dips in ventilatory drive responsible for REM OSA. Trial registration number NCT05589792 (http://thorax.bmj.com/cgi/content/short/81/10/NCT05589792).

Journal club http://thorax.bmj.com/cgi/content/short/81/10/1033?rss=1 Nnintedanib and pirfenidone are established therapies in idiopathic pulmonary fibrosis (IPF), but limitations with side effect and efficacy leave scope for novel therapies. Richeldi and colleagues report the phase 3 FIBRONEER-IPF trial of nerandomilast, an oral preferential phosphodiesterase-4B inhibitor (N Engl J Med 2025;392:2193-202. doi:10.1056/NEJMoa2414108). In this double-blind trial across 332 sites, 1177 patients were randomised 1:1:1 to nerandomilast 18 mg twice daily, 9 mg twice daily, or placebo, stratified by background antifibrotic use (77.7% were taking nintedanib or pirfenidone). The primary endpoint was absolute change in forced vital capacity (FVC) at week 52. Adjusted FVC decline was –114.7 mL (18 mg) vs –183.5 mL (placebo), a difference of 68.8 mL (95% CI 30.3 to 107.4; p

Think globally, act locally: inhalational exposure questionnaires in interstitial lung disease http://thorax.bmj.com/cgi/content/short/81/10/931?rss=1 Interstitial lung disease (ILD) is a worldwide clinical challenge with clearly increasing incidence throughout the world.1 Consequently, an increasing number of studies have found that ILD has differential clinical presentations outside of the paradigm seen in North America and Western Europe. A systematic review of the incidence and prevalence of ILD worldwide, for instance, found higher rates of hypersensitivity pneumonitis (HP) in Asia.2 Most notably, an analysis of a multicentre prospective registry in India with diagnosis made following multidisciplinary discussion (MDD) noted nearly half of all patients were diagnosed with HP, rates much higher than that in North America and Europe.3 While differences in registry methodology may explain some of this heterogeneity, differential exposures, such as air coolers, have been postulated as a partial explanation for these findings.4 Among ILD subtypes, HP remains one of the most diagnostically challenging. While findings...

[News] Unravelling of tuberculosis control in Ukraine https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00285-7/fulltext?rss=yes On July 13, 2026, Médecins Sans Frontières (MSF) released a new report accusing Russia of deliberately targeting medical personnel and health-care infrastructure in Ukraine. The report stated that MSF had “repeatedly witnessed the destruction or severe damage of functional hospitals, ambulances and ambulance bases, and primary health-care facilities.” From February, 2022 to November, 2025, according to the Ukrainian Ministry of Health, more than 2500 medical facilities in Ukraine were damaged, 327 of which were completely destroyed.

[Articles] Global hospital admission and case fatality risks among patients with influenza virus infection: a systematic review and meta-analysis https://www.thelancet.com/journals/lanres/article/PIIS2213-2600(26)00200-6/fulltext?rss=yes Our findings provide estimates of hospital admission and case fatality risks among laboratory-confirmed influenza cases identified in health-care or surveillance settings relevant for clinical and public health decision-making. Even when these risks are modest for seasonal or pandemic influenza, widespread transmission can still result in substantial absolute numbers of hospital admissions and deaths.