James D Chalmers

• MBChB, PhD
• Lecturer at University of Dundee

Dipeptidyl peptidase (DPP)-1 (also known as cathepsin C) inhibitors are the first disease-specific therapy shown to be effective in bronchiectasis. The mechanism of action of DPP-1 inhibitors is suppression of activity of neutrophil serine proteases (NSPs) by preventing them from being activated during neutrophil maturation in the bone marrow. NSPs...

Community-acquired pneumonia (CAP) remains a major global contributor of human morbidity and mortality, with Streptococcus pneumoniae as the leading bacterial cause across all ages. While pneumococcal vaccines reduce the impact of pneumococcal disease, the burden remains high, both invasive and non-invasive, partly due to infection with pneumococca...

Background The EMBARC registry shows considerable variation in culturable microbes in sputum between different European countries. The additive role of next generation metagenomic sequencing remains unexplored and association with antimicrobial resistomes unknown. Methods We prospectively assessed sputum from N=349 individuals recruited into the E...

Background: In bronchiectasis, neutrophilic inflammation is associated with an increased risk of exacerbations and disease progression. Brensocatib, an oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP-1), targets neutrophil serine proteases, key mediators of neutrophilic inflammation. Methods: In a phase 3, double-blind trial, we random...

Background Respiratory viral infections (RVIs) are a significant cause of morbidity and hospital admission worldwide. However, the management of most viral infection-associated diseases remains primarily supportive. The recent COVID-19 pandemic has underscored the urgent need for a deeper understanding of RVIs to improve patient outcomes and develo...

ARISE was a global clinical trial designed to generate evidence demonstrating the utility of the patient-reported outcome instruments Quality of Life–Bronchiectasis (QOL-B) [Respiratory Domain (RD) only] and Patient-Reported Outcomes Measurement Information System Short Form v1.0-Fatigue 7a (PROMIS F SF-7a) in patients with newly diagnosed or recur...

Noncystic fibrosis bronchiectasis, hereafter referred to as bronchiectasis, is a chronic, progressive lung disease that can affect people of all ages. Patients with clinically significant bronchiectasis have chronic cough and sputum production, as well as recurrent respiratory infections, fatigue and impaired health-related quality of life. The pat...

Introduction Current bronchiectasis guidelines advise against the use of inhaled corticosteroids (ICS) except in patients with associated asthma, allergic bronchopulmonary aspergillosis (ABPA) and/or chronic obstructive pulmonary disease (COPD). This study aimed to describe the use of ICS in patients with bronchiectasis across Europe. Methods Pati...

Background Ramadan, observed by nearly two billion Muslims worldwide, involves fasting from dawn to sunset, which can present challenges for individuals with chronic respiratory diseases due to altered medication regimens and oral intake restrictions. This study aimed to synthesise current evidence and develop consensus recommendations for managing...

Objective Post-COVID syndrome involves prolonged symptoms with multi-system and functional impairment lasting at least 12 weeks after acute COVID-19. We aimed to determine the efficacy of exercise-based rehabilitation interventions, either face-to-face or remote, compared to usual care in individuals experiencing Post-COVID syndrome following a hos...

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Rationale: In the WILLOW trial, the Dipeptidyl peptidase-1 inhibitor brensocatib reduced neutrophil serine protease (NSP) activity and prolonged time to first exacerbation in patients with bronchiectasis. Objectives: We hypothesized that, by reducing NSPs, brensocatib would affect antimicrobial peptides, mucins, and cytokines throughout the infl...

Bronchiectasis is a chronic respiratory condition characterised by irreversible dilation of the bronchi, leading to recurrent respiratory infections and chronic inflammation. Bacterial infections have been well-recognised as contributors to disease progression as well as potent inducers of exacerbations for decades. However, recent studies have ind...

Background People with diabetes are at increased risk of hospitalisation, morbidity, and mortality following SARS-CoV-2 infection. Long-term outcomes for people with diabetes previously hospitalised with COVID-19 are, however, unknown. This study aimed to determine the longer-term physical and mental health effects of COVID-19 in people with and wi...

Background: There is increasing interest in the use of home-based monitoring in people with chronic lung diseases to improve access to care, support patient self-management, and facilitate the collection of information for clinical care and research. However, integration of home-based monitoring into clinical and research settings requires careful...

Background People hospitalised for coronavirus disease 2019 (COVID‐19) have elevated incidence of diabetes. However, it is unclear whether this is due to shared risk factors, confounding or stress hyperglycaemia in response to acute illness. Methods We analysed a multicentre prospective cohort study (PHOSP‐COVID) of people ≥18 years discharged fro...

Background Dipeptidyl peptidase-1 (DPP1) activates neutrophil serine proteases (NSPs), which are implicated in chronic lung diseases. DPP1 inhibitors have shown positive results in bronchiectasis clinical trials, including one in Phase 3. We investigated the mechanism of action of a DPP1 inhibitor by exploring its impact on neutrophil proteins and...

Background Ramadan, observed by nearly two billion Muslims worldwide, involves fasting from dawn to sunset, presenting challenges for individuals with chronic respiratory diseases due to potential risks from altered medication regimens and oral intake restrictions. This study aimed to synthesise the current evidence to develop consensus recommendat...

Pseudomonas aeruginosa infections in bronchiectasis (BE) are common and associated with increased exacerbation frequency, risk of hospitalisation and death. These infections are poorly characterised, including the contribution of bacterial characteristics to disease severity. We hypothesise that genetic variants in P. aeruginosa will be associated...

Introduction Pleural infections are dominated by migration of neutrophils to the pleural space. Other severe acute infections such as COVID-19 can be associated with altered neutrophil phenotypes, and excessive neutrophil extracellular traps (NETs) contribute towards the pathophysiology of disease. However, there is little research into neutrophili...

Introduction: Prior exacerbations are the main risk factor for exacerbations in bronchiectasis. Guidelines recommend macrolide only in frequent exacerbators. Other studies suggest that symptoms are related to increased exacerbation risk. We aimed to investigate if symptoms could independently predict future exacerbations and identify responders to...

Persistent neutrophilic inflammation is a central feature in both the pathogenesis and progression of bronchiectasis (BE). Neutrophils release neutrophil serine proteases (NSPs), such as neutrophil elastase, cathepsin G and proteinase 3. When chronically high levels of free NSP activity exceed those of protective antiproteases, structural lung dest...

Objectives Allergic bronchopulmonary aspergillosis (ABPA) is a complex lung disease associated with significant morbidity. The ABPA Working Group (AWG) of the International Society for Human and Animal Mycology (ISHAM) revised their management guidelines in 2024, but there is currently no standardised tool to assess adherence to these recommendatio...

Background: Serum anti-glycopeptidolipid (GPL) core immunoglobuin A (IgA) antibody test has been proposed as a diagnostic tool for Mycobacterium avium complex pulmonary diseases. Cross-reactivity with other non-tuberculous mycobacteria (NTM), including M. abscessus, indicates that it may have a role as a broader screening test for NTM pulmonary dis...

Background Chronic airway disease (CAD) is characterized by chronic airway inflammation and colonization of the lungs by pro-inflammatory pathogens. However, while various other bacterial species are present in the lower airways, it is not fully understood how they influence inflammation. We aimed to identify novel anti-inflammatory species present...

Background Bronchiectasis is associated with psychological comorbidity and poor quality of life (QoL), yet guidelines lack focus on psychological morbidity. Using data obtained from the BronchUK database (1341 patients), we examined the link between anxiety/depression and physical disease severity, QoL and long-term outcomes in bronchiectasis. Met...

Introduction: Aspergillus sp. cause diverse clinical manifestations in bronchiectasis including Allergic bronchopulmonary aspergillosis (ABPA), Aspergillus sensitization (AS) and raised IgG indicating exposure or infection with Aspergillus. Research question: What is the prevalence and clinical significance of Aspergillus-associated conditions in...

Plain language summary A review on the safety aspects of drugs currently being used in bronchiectasis This review aims to detail the safety aspects of drugs that are currently prescribed to patients with bronchiectasis. These drugs are used in bronchiectasis without some of the high quality trials seen for other lung conditions. The drugs used have...

Recent bronchiectasis studies from large-scale multinational, multicentre registries have demonstrated that the characteristics of the disease vary according to geographic region. However, most perspectives on bronchiectasis are dominated by data from Western countries. This review intends to provide an Asian perspective on the disease, focusing on...

Chronic airway inflammation is a central feature in the pathogenesis of bronchiectasis (BE), which can be caused by cystic fibrosis (CFBE; hereafter referred to as CF lung disease) and non-CF-related conditions (NCFBE). Inflammation in both CF lung disease and NCFBE is predominantly driven by neutrophils, which release proinflammatory cytokines and...

Bronchiectasis is characterised by uncontrolled neutrophil serine protease (NSP) activity. Cathepsin C (CatC; dipeptidyl peptidase 1) activates NSPs during neutrophil maturation. CatC inhibitors can potentially reduce neutrophil-mediated lung damage. This Phase II, randomised, double-blind, placebo-controlled trial (AIRLEAF®; NCT05238675 ) evaluate...

Background The overall burden of bronchiectasis on patients and healthcare systems has not been comprehensively described. Here, we present the findings of a systematic literature review that assessed the clinical and socioeconomic burden of bronchiectasis with subanalyses by aetiology (PROSPERO registration: CRD42023404162). Methods Embase, MEDLI...

Bronchiectasis has an increasing prevalence and substantial clinical and economic burden. Therefore, physicians should identify patients with bronchiectasis at high risk of disease progression to ensure optimal management in advance. The heterogeneity of bronchiectasis means it is unlikely that any single parameter could identify high-risk patients...

Introduction Pulmonary embolism (PE) is a well-recognised complication of COVID-19 infection, and chronic thromboembolic pulmonary disease with and without pulmonary hypertension (CTEPD/CTEPH) are potential life-limiting consequences. At present the burden of CTEPD/CTEPH is unclear and optimal and cost-effective screening strategies yet to be estab...

Continued improvements in the treatment of pulmonary infections have paradoxically resulted in a growing challenge of individuals with postinfectious pulmonary complications (PIPCs). PIPCs have been long recognized after tuberculosis, but recent experiences such as the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic have under...

Respiratory viruses are a major trigger of exacerbations in chronic obstructive pulmonary disease (COPD). Airway neutrophilia is a hallmark feature of stable and exacerbated COPD but roles played by neutrophil extracellular traps (NETS) in driving disease pathogenesis are unclear. Here, using human studies of experimentally-induced and naturally-oc...