BackgroundAsthma is a heterogeneous disease, making uniform diagnosis challenging, resulting in both under- and overdiagnosis. We conducted a systematic review and meta-analysis to summarise the data on diagnostic accuracy of a cold air bronchial challenge test (CACh) in exercise-induced bronchoconstriction and asthma.MethodsDatabases (PubMed, Embase, Web of Science core collection, Cochrane Library and the Cumulative Index to Nursing and Allied Health Literature via EBSCO) were systematically screened for articles evaluating the use of CACh as a diagnostic tool in exercise-induced bronchoconstriction and asthma. A random-effects model was used to calculate the effect on the reduction in forced expiratory volume in 1 s (FEV1) by CACh in healthy controls compared to patients with asthma. Risk of bias was evaluated using the Quality Assessment of Diagnostic Accuracy Studies-Comparative. This study is registered with PROSPERO (www.crd.york.ac.uk/PROSPERO/ identifier number CRD42021290350).ResultsAfter screening and removal of duplicates, 39 studies were included. Aggregate sensitivity and specificity of a FEV1 decrease ≥10% after CACh were 0.808 and 0.959, respectively. The weighted mean difference in percentage FEV1 decrease after CACh for patients with asthma compared to healthy controls was −17.58. High heterogeneity (I2=99) was mainly explained by differences in reference tests to diagnose asthma. Application of the trim-and-fill method to account for publication bias imputed eight studies, resulting in a notable reduction in heterogeneity. The overall effect (a significant decrease in FEV1 in patients with asthma) remained statistically significant (−8.18, p<0.001).ConclusionOur study shows the high sensitivity and specificity and possible clinical implications of a CACh in the diagnosis of asthma. Further research is needed to confirm this.

Shareable abstractSustainable development of neonatal and paediatric lung organoid research requires effective regulatory and collaborative frameworks. Ethically compliant tissue sources should be prioritised; robust ethical governance on sensitive sources is essential.https://bit.ly/4b9qeLf

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive scarring primarily of the distal regions of the lung in a distinctive histological pattern. Consequently, drug discovery has focused on the activity of scar-forming fibroblasts, with some success shown by the pharmaceutical agents nintedanib and pirfenidone, and more recently nerandomilast. Yet an unmet medical need remains, pointing toward pathobiology not addressed by standard-of-care therapies. In recent years, single-cell sequencing of patient lung tissue has revealed several novel disease-associated epithelial populations. In addition, we are now beginning to understand, through functional co-culture studies, the importance of cellular crosstalk in both lung homeostasis and disease. Here, we review the advances made in “omic” technologies, the approaching spatial profiling revolution, current and future functional cell systems, novel in vivo models, how we assign disease-relevance to test systems via computational gene set enrichment analysis, and link all these elements to clinically relevant biomarkers. We show how epithelial populations, identified and validated through cutting-edge technologies, may provide targets for the next wave of therapeutics for patients with IPF.

<title>Extract</title> The <italic>European Respiratory Review</italic> is voluntarily reviewed. We are most grateful for the hard work and dedication of all those who reviewed articles for the <italic>ERR</italic> in 2025.

IntroductionLung cancer screening (LCS) is an evolving field with variations in its implementation worldwide. National LCS programmes are limited and preliminary data from national implementation are scarce.AimAn up-to-date overview of the available literature about 12 LCS-related topics that were identified as priorities by a multidisciplinary task force (TF) panel and patient representatives as well as synthesis of published evidence to inform clinical practice and health decision-making about LCS implementation. In specific areas where the scientific evidence is limited or mixed, the limitations are discussed and best practices based on available evidence are concluded.Materials and methodsA multidisciplinary TF expert panel collaborated with patient representatives, identified 12 areas of interest and incorporated patient priorities. A systematic literature search was conducted, followed by screening, review and synthesis of available evidence.ResultsThere is a lack of national LCS programmes in most countries worldwide. LCS benefits and potential risks are well established. Low-dose computed tomography (LDCT) combined with smoking cessation should be offered as part of a LCS strategy to ensure optimal clinical outcomes. Age and smoking status cut-offs as well as other inclusion criteria vary and should be based on national epidemiological data. Available LCS risk predictor models and biomarkers require further clinical validation prior to implementation across the entire spectrum of LCS candidates. LCS frequency remains controversial with biennial LDCT being supported by current evidence. Technical standards, quality assurance and LCS management protocols are essential in LCS implementation.ConclusionsLCS benefits override potential risks. There is slim evidence for specific cut-off values for inclusion criteria, the optimal duration of LCS programmes and the application of LCS biomarkers in clinical practice. Smoking cessation should be integrated within LCS programmes. Ongoing scientific activity in the area is expected to provide answers in the near future.

Shareable abstractAI can identify sex-related profiles among respiratory disease patients, which can refine risk stratification. Datasets must have a balanced male/female ratio and mechanisms underlying these associations require rigorous, disease-specific validation.https://bit.ly/4n8a33D

IntroductionDiaphragm dysfunction is prevalent across various patient populations, requiring precise structural and functional assessment. Ultrasound, being bedside-accessible and radiation-free, has gained relevance for evaluating the diaphragm and other respiratory muscle. Recent advancements have introduced novel techniques that have expanding its assessment scope. This review aims to identify emerging ultrasound methods for quantitative diaphragm assessment in adults, emphasising reliability and clinical relevance.MethodsA systematic literature search was conducted using keywords related to the diaphragm, ultrasound techniques and innovation. We included original studies on adult participants using innovative ultrasound methods extending beyond conventional assessments. Studies lacking original data, case reports, animal studies and studies on automated analysis techniques were excluded. Screening and data extraction followed a structured process, with one researcher extracting data and a second verifying accuracy. Results were categorised by reliability and by physiological and clinical outcomes.ResultsOf 1411 records screened, 288 full-text articles were reviewed, and 36 studies met inclusion criteria, with four additional studies identified via reference analysis. These studies, published between 2013 and 2024, explored seven innovative techniques: the area method, contrast-enhanced ultrasound, echogenicity/echodensity, excursion of the zone of apposition, shear wave/strain elastography, speckle tracking and pulsed-wave tissue Doppler imaging. Studies focused on both healthy subjects and critically ill, surgical and COPD patients.ConclusionsRecent ultrasound advancements enhance diaphragm assessment by evaluating muscle quality, functional mechanical properties and blood flow. These innovative methods also provide alternatives when conventional approaches are limited. Further research is essential to refine protocols, validate clinical applications and standardise assessments for broader implementation.

BackgroundBreathlessness is a debilitating symptom affecting many adults, yet its prevalence and correlates are not well summarised. This review synthesised evidence on breathlessness prevalence, correlates and assessment methods across general and clinical populations.MethodsWe undertook an umbrella review and updated systematic review using a comprehensive search of three databases up to January 2025. The umbrella review incorporated existing systematic reviews and meta-analyses, while the updated systematic review and meta-analysis included original studies published after the most recent eligible review.ResultsThe umbrella review encompassed 10 reviews conducted between 2010 and 2025, incorporating 315 studies. The primary tool for assessing self-reported breathlessness was the Medical Research Council questionnaire and its modified version (mMRC). The prevalence of breathlessness ranged from 0.9% to 61.6% in general populations and from 20.4% to 87% in clinical populations. Six categories of breathlessness correlates were identified: sociodemographic, physiological, clinical, psychological, environmental and radiological/pathological factors. An updated systematic review and meta-analysis found 15 studies published between 2021 and 2024 reporting prevalence of breathlessness. Using the most common criterion of an mMRC score ≥2, the pooled prevalence was 12.5% (range 3.7–29.5%) in general populations and 37.5% (range 27.5–48.6%) in clinical populations. These studies reported diverse correlates of breathlessness, including psychological and clinical factors.DiscussionSubstantial variability exists in the prevalence and correlates of breathlessness, emphasising its complexity and multifaceted nature. This review highlights the need for standardised assessment of breathlessness to assess prevalence and comprehensive approaches to address its diverse factors.

Currently, the only known clinically relevant hereditary risk factor for emphysema is limited to mutations within the SERPINA1 gene, encoding alpha-1 antitrypsin. Although several additional rare high-impact variants have been proposed, their role in emphysema pathophysiology is unclear. This review discusses recent cases investigating novel candidate genes that may be Mendelian causes for emphysema development. We also explore potential methods to confirm the causal relation to COPD. Identifying potential new rare high-impact genetic variants may lead to novel therapeutic targets, thus improving the personalised treatment of COPD. Several gene mutations have been implicated in emphysema development, including SERPINA1, SERPINA3, PTPN6, TERT, TR, NAF1, BICD1, ELN, FBLN, FLNA and SFTPC. Mutations of the SERPINA1 and PTPN6 genes are considered definitive causes of emphysema. Studies have ascertained rare variants in cutis laxa genes (ELN, FBLN and FLNA), which cause early-onset emphysema in infants and children via defective elastin synthesis. Telomerase pathway genes (TERT, TR, NAF1 and BICD1) have also been implicated in increased COPD risk along with another member of the serpin family (SERPINA3) and SFTPC. These probable mutations for emphysema tend to present later in life. Due to being unconfirmed, they may involve a more complex gene interaction that requires further interrogation with next-generation sequencing and molecular methods, including CRISPR (clustered regularly interspaced short palindromic repeats) screening libraries, whole-exome sequencing or whole-genome sequencing. Although multiple novel mutations have been reported to cause emphysema, further validation is needed. Next-generation sequencing offers a promising method to understand early-onset emphysema and COPD pathogenesis.

Shareable abstractSimplified and extended lung ultrasound scores are complementary tools. Their respective indications are supported by strong evidence, broad clinical adoption and international guidelineshttps://bit.ly/45HQ5pS