Sanjay Haresh Chotirmall

The classic organ‐centric model of human physiology is rapidly giving way to a unified approach embracing the human body as an integrated network of bidirectional interorgan communication. The human microbiome serves as a fundamental mediator of this shift, regulating immune homeostasis, barrier integrity and metabolic signaling across organs. While the lung maintains a characteristic low‐biomass microbiome in dynamic equilibrium, any disruption primes local and systemic immune responses contributing to disease. Beyond the well‐described gut‐lung axis, crosstalk between the lung and other distal organ systems is lesser recognized; however, increasingly acknowledged as a key under‐appreciated contributor to respiratory disease including extrapulmonary complications. This review synthesizes current established evidence on axial connectivity of the lung microbiome across the gut, brain, skin, heart, kidney, and liver, and finds that such crosstalk is predominantly, though not exclusively gut‐mediated. Direct lung‐organ interactions are described for several axes; however, they remain preliminary. Across these lung‐axial systems, common pathophysiological mechanisms emerge, including dysbiosis‐induced depletion of microbial metabolites, immunomodulation, and barrier perturbations, all linking pulmonary disease with neuroinflammation, gastrointestinal deficits, and cardiac, renal, hepatic, and dermatological abnormalities. We assess how therapeutic modulation of interorgan systems offers promising avenues for improved risk stratification and novel therapeutics. Recognizing microbiome‐mediated pulmonary‐organ crosstalk represents an emerging conceptual framework in respiratory medicine, repositioning microbial communities as key modulators of extrapulmonary disease.

(2026). The design of AIRTIVITY – a research study of verducatib as a potential new type of treatment for bronchiectasis: a plain language summary. Future Rare Diseases: Vol. 6, No. 1, 2695583.

Over 400 million people have chronic obstructive pulmonary disease (COPD), with exacerbations representing a major health burden. Although the overall incidence of invasive pulmonary aspergillosis (IPA) in patients with COPD with hospitalised exacerbation is only 1 to 4%, certain factors substantially increase this frequency. Risk factors compromising defences against Aspergillus spp in COPD patients include systemic or high-dose inhaled corticosteroids, comorbidities including bronchiectasis, diabetes, and cardiovascular disease, and prolonged courses of antibiotics. An international group of experts met to develop criteria for diagnosing IPA based on existing literature and consensus in non-ventilated COPD patients. The preliminary diagnostic recommendations were further evaluated by additional experts using the Delphi methodology. A hospitalized exacerbation of COPD with two or more of the above clinical risk factors should prompt 1) a CT scan of the chest, 2) sending a respiratory sample (sputum, induced sputum or bronchoscopy sample) for direct microscopy for fungi, high volume fungal culture and preferably Aspergillus PCR, and if a bronchoscopy sample is obtained then also Aspergillus antigen (galactomannan), 3) a serum sample for galactomannan and Aspergillus IgG. The combination of a high-risk COPD patient, with compatible imaging abnormalities and any two positive tests (two samples or different tests on the same respiratory sample) for Aspergillus is sufficient to establish the diagnosis of IPA with enough confidence to initiate antifungal therapy and/or enroll the patient in a clinical or epidemiological study of IPA in COPD. Additional studies are required to augment performance data for most assays in COPD and validate the proposed diagnostic criteria.

Rationale: The frequent exacerbator phenotype was previously defined using a threshold of ≥3 exacerbations per year in bronchiectasis. However, the contribution of each prior exacerbation to future risk as well as the influence of severe exacerbations and different etiologies and regions remain poorly understood. Objectives: To quantify the risk associated with each prior exacerbation of bronchiectasis in predicting future exacerbations and severe exacerbations, and to determine whether this association varies across different etiologies and geographic regions. Methods: We analyzed data from the European Bronchiectasis Registry (EMBARC), including 30 countries across Europe and Asia. The association between baseline exacerbation history and future exacerbations was tested using negative binomial regression over up to 5 years of follow-up. Severe exacerbations were defined as those requiring hospitalization. Measurements and Main Results: A total of 19 324 patients with bronchiectasis were included. Each prior exacerbation was associated with an increased risk of exacerbations and severe exacerbations. Incidence rate ratio (IRR) for future exacerbations was 1.45 (95% CI 1.34-1.58, P < .001) for 1 exacerbation; 1.84 (95% CI 1.69-1.99, P < .001) for 2 exacerbations; 2.50 (95% CI 2.29-2.73, P < .001) for 3 exacerbations; and 3.56 (95% CI 3.32-3.82, P < .001) for patients with 4 or more prior exacerbations. Additionally, 1 prior severe exacerbation was associated with increased risk of exacerbation (IRR = 1.52, 95% CI 1.45-1.60, P < .001) and strongly associated with future severe exacerbations (IRR = 3.96, 95% CI 3.71-4.22, P < .001). The frequent exacerbator phenotype was consistent across different etiologies and geographic regions. Conclusions: The frequent exacerbator phenotype is highly consistent across patient subgroups and regions. Each prior exacerbation is associated with a progressively higher risk, with no definitive threshold-defining high risk.

Mucus plugs have been previously recognized as an important pathological feature in asthma and COPD, but their clinical role in these diseases has not been explored in-depth until recently. Mucus plug formation is driven by mucus hyperconcentration, changes in mucus viscoelastic properties, impaired clearance, and mucociliary collapse. Scoring systems, such as the bronchopulmonary segment mucus plug score, have been used to associate greater mucus plug burden with poor clinical outcomes. Additional scoring methods obtained through quantitative image processing are currently under development. Mucus plug burden has been associated with greater exacerbations and spirometric decline in both asthma and COPD, as well as greater mortality in COPD. Recently, mucus plug burden has been used as an endpoint in clinical trials to evaluate the effectiveness of biologic therapies in asthma; multiple biologic therapies demonstrated decreases in mucus plug burden and associated improvements in spirometry with treatment. Together, this data suggests mucus plugs may be a treatable trait in asthma and COPD. Mucus plug burden has current clinical, phenotypic, and predictive utility and shows promise as a future biomarker. Increased incorporation into clinical trials, expanded evidence of treatment effect, and standardization of methodology and imaging protocols will be needed. CT-detection of mucus plug burden is ready for greater incorporation into both research outcomes and clinical care.

Extract Cough and sputum production are the most frequent and troublesome symptoms for patients with bronchiectasis [1, 2]. Symptom severity is associated with worse outcomes, including risk of exacerbation, therefore reducing daily symptoms is a key objective of the recent European Respiratory Society (ERS) clinical practice guidelines for the management of adult bronchiectasis, which were published in December 2025 [3]. Shareable abstract A recent randomised trial showed that hypertonic saline and carbocisteine were not effective in the treatment of bronchiectasis. How does this impact the ERS bronchiectasis guideline recommendation to consider mucoactive drugs in refractory patients? https://bit.ly/467Sg6Q

There is an unmet need for therapies targeting chronic neutrophilic inflammation in bronchiectasis. In the Phase II, dose-finding AIRLEAF® study, the dipeptidyl peptidase 1 (cathepsin C) inhibitor verducatib (BI 1291583) reduced the pulmonary exacerbation risk in people with bronchiectasis and demonstrated a similar safety profile to placebo; these results support the investigation of verducatib in a Phase III study. Here, we describe the design of the Phase III, randomised, double-blind AIRTIVITY™ study (ClinicalTrials.gov identifier NCT06872892 ), assessing the efficacy, safety, and tolerability of verducatib in people with bronchiectasis. In AIRTIVITY™, approximately 1680 adults and 75 adolescents (aged 12–versus placebo. All pulmonary exacerbations are adjudicated. If the efficacy of verducatib is demonstrated and there is a favourable benefit–risk ratio, the AIRTIVITY™ results will provide confirmatory evidence for the use of verducatib 2.5 mg in a large and broad bronchiectasis population, independent of underlying aetiology.

This review provides an overview of the 2025 European Respiratory Society guidelines for adult bronchiectasis. We cover the initial assessment of patients with bronchiectasis to identify the underlying cause, pharmacotherapy including long-term oral and inhaled antibiotic treatment, anti-inflammatory treatments and mucoactive drugs, and non-pharmacological treatments including airway clearance and pulmonary rehabilitation. We provide examples of how to implement the guideline algorithms in practice including how to manage patients during an acute exacerbation and the deteriorating patient. An important component of the new guideline is assessing patients' future risk of exacerbation, which takes into account not just prior history of exacerbations, but also severity of baseline symptoms and additional risk factors such as the underlying cause of bronchiectasis and infection with pathogens like Pseudomonas aeruginosa . The guideline provides an evidence-based framework for identifying the appropriate treatments for individual patients taking into account the heterogeneity and complexity of bronchiectasis.

Respiratory medicine is one of the most varied medical specialties, with several subspecialties [1]. Furthermore, respiratory research involves a plethora of preclinical, fundamental and translational science within individual specialities but also spanning across several specialities. For medical professionals, each subspecialty has its own benefits and challenges, and they can be very different from each other: the working life of a thoracic oncologist with a specialist interest in interventional pulmonology is likely to be very different from that of a COPD specialist who primarily works in the community. Similarly, life as a scientist working in cellular/molecular biology may differ in day-to-day tasks when compared with a scientist interested in systems biology or epidemiology.