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In this randomized trial involving patients with noncystic fibrosis bronchiectasis, the rate of pulmonary exacerbations over a 52-week period was lower with brensocatib (10 mg or 25 mg per day) than with placebo.

Abstract Rationale There are no risk stratification tools for morbidity and mortality in bronchiectasis. Identifying patients at risk of exacerbations, hospital admissions, and mortality is vital for future research. Objectives This study describes the derivation and validation of the Bronchiectasis Severity Index (BSI). Methods Derivation of the BSI used data from a prospective cohort study (Edinburgh, UK, 2008–2012) enrolling 608 patients. Cox proportional hazard regression was used to identify independent predictors of mortality and hospitalization over 4-year follow-up. The score was validated in independent cohorts from Dundee, UK (n = 218); Leuven, Belgium (n = 253); Monza, Italy (n = 105); and Newcastle, UK (n = 126). Measurements and Main Results Independent predictors of future hospitalization were prior hospital admissions, Medical Research Council dyspnea score greater than or equal to 4, FEV1 < 30% predicted, Pseudomonas aeruginosa colonization, colonization with other pathogenic organisms, and three or more lobes involved on high-resolution computed tomography. Independent predictors of mortality were older age, low FEV1, lower body mass index, prior hospitalization, and three or more exacerbations in the year before the study. The derived BSI predicted mortality and hospitalization: area under the receiver operator characteristic curve (AUC) 0.80 (95% confidence interval, 0.74–0.86) for mortality and AUC 0.88 (95% confidence interval, 0.84–0.91) for hospitalization, respectively. There was a clear difference in exacerbation frequency and quality of life using the St. George’s Respiratory Questionnaire between patients classified as low, intermediate, and high risk by the score (P < 0.0001 for all comparisons). In the validation cohorts, the AUC for mortality ranged from 0.81 to 0.84 and for hospitalization from 0.80 to 0.88. Conclusions The BSI is a useful clinical predictive tool that identifies patients at risk of future mortality, hospitalization, and exacerbations across healthcare systems.

Background Brensocatib is an oral, selective, reversible inhibitor of dipeptidyl peptidase-1 (DPP-1), responsible for activating neutrophil serine proteases (NSPs) including neutrophil elastase (NE), proteinase 3 (PR3), and cathepsin G (CatG). In chronic inflammatory lung diseases such as non-cystic fibrosis bronchiectasis (NCFBE), neutrophils accumulate in the airways resulting in excess active NSPs that cause damaging inflammation and lung destruction. Methods The 24-week WILLOW trial (NCT03218917) was a randomized, double-blind, placebo-controlled, parallel-group trial in patients with NCFBE conducted at 116 sites across 14 countries. In this trial, treatment with brensocatib was associated with improvements in clinical outcomes including time to first exacerbation, reduction in exacerbation frequency and a reduction in NE activity in sputum. An exploratory analysis of NE activity in white blood cell (WBC) extracts and NE, PR3 and CatG activity in sputum was conducted to further characterize brensocatib’s effect and identify potential correlated effects. Results NE, PR3 and CatG activities were reduced in sputum and NE activity was reduced in WBC extracts in a dose-dependent manner after four weeks of brensocatib treatment, with a return to baseline four weeks after the end of treatment. Brensocatib produced the greatest reduction in the sputum activity of CatG, followed by NE and then PR3. Positive correlations among the sputum NSPs were observed both at baseline and in response to treatment, with the strongest correlation among the sputum NSPs for NE and CatG. Conclusions These results suggest a broad anti-inflammatory effect of brensocatib underlying its clinical efficacy observed in NCFBE patients. Trial registration: The study was approved by the corresponding ethical review boards of all participating centers. The trial was approved by the Food and Drug Administration and registered at clinicaltrials.gov (NCT03218917) on July 17, 2017 and approved by the European Medicines Agency and registered at the European Union Clinical trials Register (EudraCT No. 2017-002533-32). An independent, external data and safety monitoring committee (comprising physicians with pulmonary expertise, a statistician experienced in the evaluation of clinical safety, and experts in periodontal disease and dermatology) reviewed all adverse events.

Background Exercise training is recommended for non-cystic fibrosis (CF) bronchiectasis, but the long-term effects are unclear. This randomised controlled trial aimed to determine the effects of exercise training and review of airway clearance therapy (ACT) on exercise capacity, health related quality of life (HRQOL) and the incidence of acute exacerbations in people with non-CF bronchiectasis. Methods Participants were randomly allocated to 8 weeks of supervised exercise training and review of ACT, or control. Primary outcomes of exercise capacity and HRQOL (Chronic respiratory disease questionnaire) and secondary outcomes of cough-related QOL (Leicester cough questionnaire) and psychological symptoms (Hospital anxiety and depression scale) were measured at baseline, following completion of the intervention period and at 6 and 12 months follow up. Secondary outcomes of the exacerbation rate and time to first exacerbation were analysed over 12 months. Results Eighty-five participants (mean FEV 1 74% predicted; median Modified Medical Research Council Dyspnoea grade of 1 (IQR [1–3]) were included. Exercise training increased the incremental shuttle walk distance (mean difference to control 62 m, 95% CI 24 to 101 m) and the 6-minute walking distance (mean difference to control 41 m, 95% CI 19 to 63 m), but these improvements were not sustained at 6 or 12 months. Exercise training reduced dyspnoea (p = 0.009) and fatigue (p = 0.01) but did not impact on cough-related QOL or mood. Exercise training reduced the frequency of acute exacerbations (median 1[IQR 1–3]) compared to the control group (2[1–3]) over 12 months follow up (p = 0.012), with a longer time to first exacerbation with exercise training of 8 months (95% CI 7 to 9 months) compared to the control group (6 months [95% CI 5 to 7 months], p = 0.047). Conclusions Exercise training in bronchiectasis is associated with short term improvement in exercise capacity, dyspnoea and fatigue and fewer exacerbations over 12 months. Trial registry ClinicalTrials.gov ( NCT00885521 ).

Objectives To compare and evaluate the usefulness of magnetic resonance imaging (MRI) with computed tomography (CT) in bronchiectasis; to compare MRI and CT scores with pulmonary function tests (PFT) and to evaluate the role of Diffusion-weighted imaging (DWI) in bronchiectasis. Methods In this prospective study, 25 patients between 7–21 y of age with a clinical/radiological diagnosis of bronchiectasis underwent MDCT and MRI chest. MRI and CT scoring was performed using modified Bhalla-Helbich’s score by two independent radiologists for all parameters. A final consensus score was recorded. The overall image quality of different MRI sequences to identify pathologies was also assessed. Appropriate statistical tests were used for inter-observer agreements, and correlation amongst CT and MRI; as well as CT, MRI and PFT. Results Strong agreement (ICC 0.80–0.95) between CT and MRI was seen for extent and severity of bronchiectasis, number of bullae, sacculation/abscess, emphysema, collapse/ consolidation, mucus plugging, and mosaic perfusion. Overall CT and MRI scores had perfect concordance (ICC 0.978). Statistically significant ( p -value <0.01) intra-observer and inter-observer agreement for all CT and MRI score parameters were seen. A strong negative correlation was seen between total CT and MRI severity scores and forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), forced expiratory flow (FEF) 25–75%. DWI MR, with an apparent diffusion coefficient (ADC) cut-off of 1.62 × 10 –3 mm 3 /s had a sensitivity of 70% and specificity of 75% in detecting true mucus plugs. Conclusions MRI with DWI can be considered as a radiation-free alternative in the diagnostic algorithm for assessment of lung changes in bronchiectasis, especially in follow-up.

Background: The levels of exhaled and nasal nitric oxide (eNO and nNO) in groups of patients with inflammatory lung diseases are well documented but the diagnostic use of these measurements in an individual is unknown. Methods: The levels of nNO and eNO were compared in 31 children with primary ciliary dyskinesia (PCD), 21 with non-CF bronchiectasis (Bx), 17 with cystic fibrosis (CF), 35 with asthma (A), and 53 healthy controls (C) using a chemiluminescence NO analyser. A diagnostic receiver-operator characteristic (ROC) curve for PCD using NO was constructed. Results: The median (range) levels of nNO in parts per billion (ppb) in PCD, Bx, CF, and C were 60.3 (3.3–920), 533.6 (80–2053), 491.3 (31–1140), and 716 (398–1437), respectively; nNO levels were significantly lower in PCD than in all other groups (p<0.05). The median (range) levels of eNO in ppb in PCD, Bx, CF, A, and C were 2.0 (0.2–5.2), 5.4 (1.0–22.1), 2.6 (0.8–12.9), 10.7 (1.6–46.7), and 4.85 (2.5–18.3), respectively. The difference in eNO levels in PCD reached significance (p<0.05) when compared with those in Bx, A and C but not when compared with CF. Using the ROC curve, nNO of 250 ppb showed a sensitivity of 97% and a specificity of 90% for the diagnosis of PCD. Conclusions: eNO and nNO cannot be used diagnostically to distinguish between most respiratory diseases. However, nNO in particular is a quick and useful diagnostic marker which may be used to screen patients with a clinical suspicion of PCD.

Bronchiectasis is a chronic, complex, and heterogeneous respiratory disease characterized by irreversible bronchial dilation, persistent airway inflammation, and recurrent infections. Traditionally viewed from a lung-centered perspective, its pathophysiology has been explained by the “vicious cycle” hypothesis, later refined into the more dynamic concept of the “vicious vortex.” However, emerging evidence highlights the pivotal role of comorbidities in influencing disease progression, symptom burden, and prognosis. This review explores the evolving understanding of bronchiectasis by integrating comorbidities into current pathophysiological frameworks. We illustrate how coexisting conditions interact with components of the vicious vortex, amplifying airway inflammation, impairing host defenses, and disrupting clearance mechanisms. We summarize evidence on the prevalence, clinical impact, and prognostic significance of key comorbidities and discuss their implications for patient management. Finally, we emphasize the importance of an integrated, multidisciplinary approach and the emerging role of the treatable traits framework, which focuses on identifying clinically relevant, biologically measurable, and modifiable traits—regardless of whether they are etiological or nonetiological. In this sense, we propose a conceptual “Copernican Revolution” in bronchiectasis care: recognizing comorbidities not as secondary features, but as potential drivers of disease trajectory. By adopting this pragmatic strategy, clinicians can optimize quality of life, achieve patient-centered care, and improve outcomes in this condition. Plain language summary Looking beyond the lungs: how other health problems shape bronchiectasis Bronchiectasis is a chronic lung condition characterized by persistent cough, mucus accumulation, and recurrent chest infections. Historically considered a disease confined to the lungs, emerging research highlights the significant role of comorbidities in influencing its development, progression, and severity. In this review, we examine how conditions such as asthma, chronic obstructive pulmonary disease (COPD), upper airway disorders, gastroesophageal reflux disease (GERD), and inflammatory bowel disease (IBD) not only coexist with bronchiectasis but may also exacerbate its clinical course. Other important comorbidities—including cardiovascular disease, osteoporosis, malnutrition, periodontal disease, anxiety, diabetes and depression—are associated with increased exacerbation frequency, more frequent hospitalizations, and reduced quality of life. We also explore the role of immune system dysfunction, particularly primary immunodeficiencies, as potential underlying causes of bronchiectasis that warrant targeted diagnostic evaluation. Clinical tools such as the Bronchiectasis Aetiology Comorbidity Index (BACI) can assist clinicians in assessing the burden and prognostic impact of comorbidities. This review advocates for a paradigm shift: moving beyond a lung-centric model toward a holistic approach that recognizes bronchiectasis as a multisystem condition. This perspective emphasizes the early identification of comorbidities, implementation of practical screening strategies, and collaboration with specialists such as dieticians, psychologists, and immunologists. Addressing comorbid conditions alongside the management of bronchiectasis may alleviate symptoms, reduce infection rates, and improve overall well-being. We propose that this integrated, patient-centered approach will lead to more effective and individualized care for individuals living with bronchiectasis.

Background: The chronic respiratory disease questionnaire (CRDQ) is designed to assess health-related quality of life (HRQOL) in chronic respiratory conditions, but its reliability, validity and responsiveness in individuals with mild to moderate non-cystic fibrosis (CF) bronchiectasis are unclear. Objectives: This study aimed to determine measurement properties of the CRDQ in non-CF bronchiectasis. Methods: Participants with non-CF bronchiectasis involved in a randomised controlled trial of exercise training were recruited. Internal consistency was assessed using Cronbach's α. Over 8 weeks, reliability was evaluated using intra-class correlation coefficients and Bland-Altman analysis for measures of agreement. Convergent and divergent validity was assessed by correlations with the other HRQOL questionnaires and the Hospital Anxiety and Depression Scale (HADS). The responsiveness to exercise training was assessed using effect sizes and standardised response means. Results: Eighty-five participants were included (mean age ± SD, 64 ± 13 years). Internal consistency was adequate (>0.7) for all CRDQ domains and the total score. Test-retest reliability ranged from 0.69 to 0.85 for each CRDQ domain and was 0.82 for the total score. Dyspnoea (CRDQ) was related to St George's respiratory questionnaire (SGRQ) symptoms only (r = 0.38), with no relationship to the Leicester cough questionnaire (LCQ) or HADS. Moderate correlations were found between the total score of the CRDQ, the SGRQ (r s = -0.49) and the LCQ score (r s = 0.51). Lower CRDQ scores were associated with higher anxiety and depression (r s = -0.46 to -0.56). The responsiveness of the CRDQ was small (effect size 0.1-0.24). Conclusions: The CRDQ is a valid and reliable measure of HRQOL in mild to moderate non-CF bronchiectasis, but responsiveness was limited.

Background: Bronchiectasis exacerbations are a significant contributor to morbidity and mortality. While environmental factors, such as viral infections, are well-established triggers for exacerbations, the role of intrinsic factors, particularly chronic bacterial infections, remains incompletely understood. Objectives: In this context, we sought to investigate the impact of chronic bacterial infections using the COVID-19 pandemic as a natural experiment, providing a unique opportunity to assess the effects of reduced external infections. Design: A retrospective observational cohort study was conducted involving patients with non-cystic fibrosis bronchiectasis. Methods: Data were collected via telephone interviews and medical record reviews, comparing exacerbation rates before (2019) and during (2020) the pandemic. The difference in exacerbation rates between 2020 and 2019 (delta exacerbations) served as the dependent variable in a multiple regression model. Results: Sixty-three patients were included in the analysis. Those without chronic bacterial infections showed a significant reduction in exacerbations during the pandemic: mean (SD) was 1.06 (1.3) versus 1.61 (1.3), respectively (p-value = 0.006). In contrast, no such reduction was observed in patients with chronic bacterial infections. Notably, chronic infection with Pseudomonas aeruginosa emerged as an independent predictor of sustained or increased exacerbations in 2020 (positive delta exacerbations), despite the implementation of social distancing measures. Conclusion: While social distancing effectively reduced bronchiectasis exacerbations in patients without chronic bacterial infections, those with Pseudomonas aeruginosa infections remained vulnerable to exacerbations, underscoring the importance of intrinsic disease/host factors. These findings highlight the need for targeted management strategies addressing chronic infections in patients with bronchiectasis. Plain language summary How chronic infections affect bronchiectasis flare-ups. This study looked at how ongoing lung infections affect people with bronchiectasis, a lung condition that causes coughing and breathing problems. The researchers found that in people without long-term infections, the number of flare-ups (times when symptoms get worse) decreased when they wore protective devices like masks or avoided exposure to infections from others. But for those who had a long-lasting infection with a germ called Pseudomonas aeruginosa, flare-ups didn’t improve. This means that having a chronic infection makes the lung condition harder to manage. The findings show that people with these ongoing infections may need special treatments to keep their lungs healthier and reduce flare-ups.