RARE DISEASE
Idiopathic bronchiectasis
Idiopathic bronchiectasis
Idiopathic bronchiectasis
Drug discovery
10
drugs
With orphan designations
Overview
Idiopathic Bronchiectasis Overview
Idiopathic bronchiectasis, accounting for 38-41% of cases globally, involves irreversible bronchial dilation without identifiable cause. Characterized by chronic cough, sputum production, and recurrent infections, it disproportionately affects older adults and women [4][12][20]. Management focuses on airway clearance, exacerbation reduction, and symptom control, using macrolides, inhaled antibiotics, and mucolytics. Economic burden is significant, driven by frequent hospitalizations and high treatment costs [1][2][5].
Burden
Economic: Annual respiratory-related costs exceed $4.1B (US); hospitalizations average $60,500 per episode [1][2].
Clinical: Exacerbations correlate with accelerated lung decline and 20-36% mortality rates (respiratory causes) [1][14].
Quality of life: Daily therapy requires 2+ hours, impacting mental health and productivity [1][13].
Categories: rare genetic diseases, rare respiratory diseases
Research Papers
125 drug discovery papers about Idiopathic bronchiectasis, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
125 drug discovery papers about Idiopathic bronchiectasis, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-05-01 | A58-11 Demographics and Clinical Characteristics of the Argentine Bronchiectasis Registry (ReBroAr): A Comparative Analysis With the European Registry (EMBARC)
Abstract Rationale Bronchiectasis exhibits significant geographic variations globally. While European registries like EMBARC have established comprehensive databases, Latin American data remain scarce. This study characterized the Argentine Bronchiectasis Registry (ReBroAr) and compared it with EMBARC to identify unique regional patterns. Methods This multicenter, prospective observational study enrolled 1,288 adult patients with bronchiectasis. Comprehensive data included demographics, etiology, pulmonary function, microbiological cultures, severity scores, and treatment patterns. Patients underwent thorough etiological investigation including immunologic, microbiological, and genetic testing when indicated. Results Mean age was 60.7 years with marked female predominance (69% vs 34% EMBARC, p < 0.001). Most patients (71.6%) were never-smokers. Microbiological analysis revealed 50.3% had no bacterial isolation. Among positive cultures, Pseudomonas aeruginosa predominated (21.7%), followed by other bacteria (12.6%), Haemophilus influenzae (11.3%), and Staphylococcus aureus (4.1%). Pseudomonas aeruginosa chronic infection affected only 16.4% of patients. Etiological distribution differed significantly from EMBARC. Post-infectious causes accounted for 28.5% (vs 21.2% EMBARC), with post-tuberculosis etiology notably elevated at 16.9% versus 4.9% (3.4-fold higher, p < 0.001). Idiopathic classification was 2.5-fold lower (15.5% vs 38.1%, p < 0.001). COPD-associated bronchiectasis represented 10.3% and asthma-associated 10.2%.Spirometric obstruction was present in 39.6%, intermediate between EMBARC (34%) and USA registries (51%). Disease severity revealed predominantly mild disease: FACED score showed 61.1% mild, 31.2% moderate, 7.7% severe; E-FACED demonstrated 71.8% mild, 23.7% moderate, 4.5% severe.Clinical presentation included cough (87%), sputum production (69%), and dyspnea (62%). Eosinophilia was present in 52.5%. Bronchodilator response was positive in only 17% despite high asthma association. There was a predominance of involvement of the lower lobes (51-55%).Treatment patterns revealed 67.8% used inhaled corticosteroids: 44.9% on ICS/LABA combinations, 20.4% on triple therapy, and 14.4% untreated. Conclusions ReBroAr reveals unique epidemiological patterns: female predominance, 3.4-fold higher post-tuberculous etiology versus EMBARC, and lower idiopathic classification reflecting comprehensive etiological investigation. The relatively low Pseudomonas aeruginosa chronic infection rate (16.4%) and 50.3% without bacterial isolation suggest distinct microbiological patterns. Predominantly mild-to-moderate severity despite significant symptoms and high inhaled corticosteroid use (67.8%) suggests opportunities for optimizing phenotype-specific therapy. These findings emphasize the importance of regional registries in understanding bronchiectasis heterogeneity and informing population-specific management approaches. This abstract is funded by: None
2026-01-01 | Phospholipids with Odd-chain Fatty Acids as Markers of Improved Inflammation in Chronic Lung Infections
Chronic inflammatory lung diseases, including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and non-CF bronchiectasis, are characterized by persistent polymicrobial infection, excessive neutrophilic inflammation, mucus accumulation, and progressive loss of lung function. Current therapies aimed at suppressing airway inflammation remain limited and often lack efficacy or produce substantial side effects, highlighting a critical need for novel immunomodulatory strategies. Our metabolomics studies of airway secretions from patients with chronic lung disease have identified a previously unrecognized class of phospholipids containing odd-chain fatty acids (PC-OCFAs) that strongly correlate with improved lung function. These lipids, containing C15:0 and C17:0 fatty acid chains, are unusual components of the human lipidome and are poorly understood in pulmonary biology. Emerging evidence from other inflammatory diseases suggests odd-chain fatty acids possess anti-inflammatory and immunometabolic properties, potentially mediated through PPAR-α and PPAR-δ signaling pathways; however, their role in airway inflammation and lung health is unknown. The overall objective of this exploratory R21 project is to define the biological origin, abundance, and anti-inflammatory activity of PC-OCFAs in chronic lung disease. Our central hypothesis is that PC-OCFAs are associated with improved lung function because they attenuate inflammatory signaling in airway epithelial cells. To test this hypothesis, we will pursue two aims. In Aim 1, we will use advanced LC-MS/MS lipidomics and molecular networking approaches to quantify PC-OCFAs and free odd-chain fatty acids in explanted human lung tissues, isolated primary lung cell populations, and airway bacterial isolates to determine their abundance, clinical associations, and cellular source. In Aim 2, we will expose primary human airway epithelial cells to PC-OCFAs and free odd-chain fatty acids under basal and inflammatory conditions and perform RNA sequencing and cytokine profiling to characterize their effects on inflammatory signaling pathways and epithelial immune responses. This project is highly innovative because it investigates a cryptic and poorly studied component of the human lipidome that emerged from unbiased metabolomic profiling as one of the strongest molecular correlates of improved lung function in CF. The proposed studies integrate state-of-the-art metabolomics, molecular networking, airway cell biology, and transcriptomics to investigate a fundamentally new area of pulmonary immunometabolism. Successful completion of this work will establish foundational knowledge regarding the role of odd-chain fatty acids in airway biology and may identify a novel class of endogenous anti-inflammatory molecules with therapeutic potential for chronic inflammatory lung diseases.
2026-01-01 | The European Respiratory Journal 2026: towards the golden age of respiratory science?
Welcome to our New Year editorial for 2026! What a time to be working in respiratory medicine and science! Your editors cannot remember a period of more rapid development in our field. Objectively, more new drugs have been approved by regulators for respiratory indications in 2025 that at any time in history, with a notable acceleration overall since 2020. New treatments in 2025 include those for diseases such as COPD (e.g. mepolizumab), idiopathic pulmonary fibrosis/progressive pulmonary fibrosis (e.g. nerandomilast), bronchiectasis (e.g. brensocatib), asthma (e.g. depemokimab) and respiratory syncytial virus (e.g. clesrovimab), as well as extraordinary developments for multiple approved therapies in areas such as pulmonary hypertension and pulmonary hypertension-associated interstitial lung disease (ILD) (e.g. inhaled treprostinil and sotatercept), cystic fibrosis (e.g. vanzacaftor/tezacaftor/deutivacaftor) and lung cancer (e.g. telisotuzumab, taletrectinib, datopotamab deruxtecan, sunvozertinib, zongertinib and sevabertinib) [1]. Respiratory translational science has never been healthier or more in the public eye. Practice is changing and respiratory guidelines are stronger, more impactful and greater in number than ever before. This is an exciting time for a respiratory-focused scientific journal.
2025-09-27 | Factors associated with Mycobacterium abscessus infection in bronchiectasis patients
There is limited knowledge on factors associated with Mycobacterium abscessus (M.abscessus) infection in bronchiectasis patients. We investigated the factors of M.abscessus infection over a 7-year period in Singapore. Objective: To investigate the factors associated with M.abscessus infection in bronchiectasis patients in a tertiary referral centre from 2016-2022. Method: Demographic and clinical profiles were analysed prospectively. M.abscessus pulmonary disease (MAPD) was diagnosed based on American Thoracic Society and Infectious Disease Society of America (ATS/IDSA) criteria. M. abscessus colonisation was defined by presence of 2 positive cultures at least 3-months apart over a 12-month period, without worsening clinico-radiological features. Patients with idiopathic bronchiectasis were categorised as control group. Results: 23 MAPD patients, 24 with colonisation and 68 with idiopathic bronchiectasis were studied. MAPD and M.abscessus colonised patients had lower BMI than control (p=0.009 and p=0.003 respectively). MAPD patients had greater decline in FEV1 than control (77ml/year vs. 22ml/year, p=0.04). Sputum cultured positive with Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) were more common in MAPD and M.abscessus colonised patients (p=0.01 and p=0.003 respectively), whilst Klebsiella pneumoniae was more common in MAPD patients (p=0.01). A third of the M.abscessus infection patients had a history of pulmonary tuberculosis (PTB). Conclusion: Low BMI (< 19), history of PTB, P.aeruginosa and S.aureus were associated with M. abscessus infection in bronchiectasis. Future large-scale multicenter prospective studies on risk modification will be crucial.
2025-09-27 | Subgroup analysis: AIRLEAF® Phase II study of a cathepsin C (CatC, or DPP1) inhibitor, BI 1291583, in adults with non–cystic fibrosis bronchiectasis
Background: AIRLEAF®, a Phase II study, evaluated the efficacy, safety and optimal dosing of the CatC inhibitor BI 1291583 in adults with bronchiectasis.1 BI 1291583 treatment reduced the risk of experiencing a pulmonary exacerbation (PEx), most notably with the 2.5 mg dose, the dose taken forward into the Phase III AIRTIVITY® study. Methods: This double-blind, placebo-controlled study randomised 322 participants to BI 1291583 (1/2.5/5 mg) or placebo for up to 48 weeks. The subgroups evaluated here are 1 PEx with SGRQ Symptoms score >40 vs ≥2 PExs in the year prior to screening, baseline P. aeruginosa status, maintenance use of macrolides at baseline and aetiology (idiopathic/post-infectious vs all others). Results: All subgroups in the 2.5 mg dose group had reductions in risk and rate of PExs consistent with the overall study population (Table 1). Hazard ratios ranged from 0.47 to 0.82, illustrating consistent prolongation of time to first PEx. Particularly, estimates of benefit for unique populations included in AIRLEAF®, such as 1 PEx plus high symptom score, were consistent with the overall population. Conclusion: These results support the use of the 2.5 mg dose across all subgroups in AIRTIVITY®. 1Chalmers JD et al. Eur Respir J 2025; 65:2401551 Table 1. Subgroup analyses of risk and rate of PExs up to 48 weeks in the 2.5 mg dose group vs placebo erj;66/suppl_69/PA4959/F1F1F1
cell therapies
2026-07-13 | Insights into extracellular vesicles in senescence-associated chronic lung diseases.
Chronic lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, obstructive sleep apnea, asthma, bronchiectasis, and lung cancer, are intricately linked to the aging process. These diseases are characterized by a high prevalence rate and a paucity of effective treatment options. Emerging evidence highlights the critical role of extracellular vesicles (EVs) in the pathogenesis and progression of these diseases. EVs, released by senescent cells, mediate intercellular communication and modulate immune responses through their cargo of microRNAs, proteins, and other molecules. These vesicles contribute to disease progression by promoting inflammation, fibrosis, tissue remodeling, and cellular senescence. Specifically, certain microRNAs, such as miR-21, miR-34a, and miR-570-3p, along with several proteins in EVs, have been identified as key factors influencing these processes. Additionally, EVs play significant roles in immune regulation and have potential anti-inflammatory effects, making them promising candidates for therapeutic applications. Recent advances in the use of EVs as therapeutic agents, including their application in nanotechnology for targeted drug delivery, have demonstrated potential in reducing inflammation, modulating immune responses, and enhancing tissue repair. Understanding the role of EVs in these diseases offers insights into potential therapeutic targets to mitigate disease progression and improve patient outcomes. Future research should focus on standardizing EV isolation and characterization methods, verifying the safety and efficacy of EV-based therapies in clinical trials, and elucidating the complex biological mechanisms of EVs in aging and disease.
2018-05-22 | Outcomes of lung transplantation in adults with bronchiectasis
Lung transplantation is a well-established treatment for end-stage non-cystic fibrosis bronchiectasis (BR), though information regarding outcomes of transplantation remains limited. Our results of lung transplantation for Br are reported here.A retrospective review of case notes and transplantation databases was conducted for patients that had underwent lung transplantation for bronchiectasis at the Freeman Hospital between 1990 and 2013.Fourty two BR patients underwent lung transplantation, the majority (39) having bilateral sequential lung transplantation. Mean age at transplantation was 47.1 years. Pre-transplantation osteoporosis was a significant non-pulmonary morbidity (48%). Polymicrobial infection was common, with Pseudomonas aeruginosa infection frequently but not universally observed (67%). Forced expiratory volume in 1 second (% predicted) improved from a pre-transplantation mean of 0.71 L (22% predicted) to 2.56 L (79 % predicted) at 1-year post-transplantation. Our survival results were 74% at 1 year, 64% at 3 years, 61% at 5 years and 48% at 10 years. Sepsis was a common cause of early post-transplantation deaths.Lung transplantation for end-stage BR is a useful therapeutic option, with good survival and lung function outcomes. Survival values were similar to other bilateral lung transplants at our centre. Pre-transplantation Pseudomonas infection is common.
2013-07-02 | Lung Transplantation for Cystic Fibrosis and Bronchiectasis
Lung transplantation has become an excellent treatment option for patients with cystic fibrosis (CF) and bronchiectasis with very advanced lung disease. Despite the challenges that the CF patients present, survival is more favorable than that seen in patients with chronic obstructive pulmonary disease and pulmonary fibrosis. Although those CF and bronchiectasis patients with severe respiratory disease are often infected with organisms that display in vitro resistance to the commonly used antibiotics, they usually have successful outcomes with transplantation, which are reported to be the same as in those patients with less resistant bacteria. Preoperative synergy testing has been demonstrated to reduce the presence of postoperative bacteremia and empyema in patients with CF. Newer challenges include the increasing presence of nontuberculous mycobacteria and in particular the rapid grower Mycobacterium abscessus, for which patient-to-patient spread has been recently recognized. The increased recognition of gastroesophageal reflux offers challenges regarding when and to whom one should offer fundoplication. Most potential CF recipients have metabolic bone disease warranting treatment, especially with the significant loss of bone density seen in the first year after transplantation. Diabetes mellitus, renal dysfunction, and hypertension and their consequences remain common and are of increasing importance as median survival increases in excess of 10 years. With increased experience, more programs are now transplanting patients who require membrane oxygenator support in addition to noninvasive ventilation pretransplantation and the use of a membrane device in the awake patient principally to remove excessive CO2 and reduce acidemia is worthy of note (Novalung; Novalung GmbH, Heilbronn, Federal Republic of Germany). Many centers now take the view that an awake and ambulant patient receiving such support represents a more favorable option than an intubated patient. The limiting factor in lung transplantation remains the number of organs available. Efforts to increase the donor pool, such as low tidal volume ventilation, are effective in allowing a greater percentage of offered organs to be accepted. Perhaps the most encouraging development, however, is that of ex vivo lung perfusion. This permits not only the ability to measure the function of the lungs, something of great value for lungs from donors with circulatory death (donation after cardiac death), but also the potential to introduce lung repair and convert a nonusable lung to one that can be safely used for transplantation.
2012-09-06 | First Report of Lung Transplantation in a Patient With Active Pulmonary Mycobacterium simiae Infection
Mycobacterium simiae is a slow-growing mycobacteria that in rare cases can cause chronic pulmonary infection. We report the first case of lung transplantation in a patient with active M simiae infection at the time of transplantation. A 56-year-old immunocompetent nonsmoking woman underwent bilateral lung transplantation for end-stage idiopathic bronchiectasis and chronic M simiae infection. The disease proved manageable on a regimen of clarithromycin, moxifloxacin, and cotrimoxazole with a successful outcome 1-year posttransplantation. There is increasing evidence that nontuberculous mycobacterium infection should no longer be an absolute contraindication for lung transplantation.
2005-05-10 | Lung Transplantation for Non-Cystic Fibrosis Bronchiectasis: Analysis of a 13-Year Experience
Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis.Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months.One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%-91%), and 5-year survival was 62% (95% CI, 41-83%). One-year survival after SLTX was 57% (95% CI, 20%-94%) vs 73% (95% CI, 51-96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%-97%), and mean forced vital capacity was 68% predicted (range, 53%-94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%-61%), and mean forced vital capacity was 53% predicted (range 46-63%) (n = 4).Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.
antibodies
2025-12-09 | IMMUNOLOGICAL MECHANISMS IN THE PATHOGENESIS AND MANAGEMENT OF BRONCHIECTASIS
Resume. Bronchiectasis is characterized by a constant and abnormal expansion of the airways of the lungs (bronchi) and/or a violation of the tone of the muscle layer of the bronchial wall due to inflammation, sclerosis, dystrophy, hypoplasia. Bronchiectasis is a very common disease that is the main cause of respiratory problems. A deficiency in the host's immune response to bacterial infection is considered to be the main condition for the development of bronchiectasis. In addition, many patients have no identifiable cause and are defined as having an idiopathic disease. This can lead to the development of a chronic respiratory tract infection and subsequent inflammation. Patients tend to have persistent disease despite aggressive use of antibiotics and optimal sputum clearance techniques. New therapies based on the manipulation of the immune response are becoming available and offer significant promise for the treatment of this condition. Keywords: bronchiectasis, respiratory infections, inflammation, immune response, immunological approaches
2025-09-27 | Expression of activation markers of circulating neutrophils and eosinophils in stable bronchiectasis
Background: Neutrophilic and, less frequently, eosinophilic inflammation is implicated in bronchiectasis, however the activation of circulating neutrophils and eosinophils has not been extensively determined in this disease. Aims and Objectives: The study aimed to investigate the potential expansion of actively reprogrammed circulating neutrophils and eosinophils in stable bronchiectasis and further compare them with other inflammatory markers. Methods: The expression of activation markers of neutrophils (CD14-CD15+CD16+ cells) and eosinophils (CD16-Siglec-8+ cells), i.e. CD62L, CD11b, and IL-3R, was quantified by flow cytometry in the peripheral blood of 9 post-infectious or idiopathic bronchiectasis patients and 9 healthy controls. Results: Low and high expression of CD62L and CD11b, as activation markers of neutrophils, respectively, was similar between patients and controls (mean±SD: 9.72%±0.06 vs. 10.46%±0.08, p=0.9090 and 95.32%±0.06 vs. 99.38±0.01, p=0.2850, respectively). Low and high expression of CD62L and IL-3R, as activation markers of eosinophils, respectively, was similar between patients with T2-high endotype and controls (20.71%±13.98 vs. 40.25%±27.31, p=0.3021 and 17.06%±28.07 vs. 31.31±25.59, p=0.4559, respectively). Neutrophilic expression of CD11b was correlated with fibrinogen levels (r=0.75, p=0.0255). Conclusions: Actively reprogrammed neutrophils and eosinophils do not expand in the systemic circulation in stable bronchiectasis, although their alterations locally in the airways or during exacerbations remain to be studied. Neutrophilic expression of CD11b is highlighted as a potential marker of disease activity in bronchiectasis. *AMM & NB contributed equally
2025-05-01 | Deciphering the Lung Microbiome During Pulmonary Exacerbations and Clinical Stability in Bronchiectasis
Abstract Background: Bronchiectasis is characterized by cycles of inflammation and chronic infection. Pulmonary exacerbations are defined by periods of worsening symptoms and dropping lung function. Traditional dogma suggests this is due to overgrowth of canonical bacterial pathogens; however recent studies have shown this to not fully represent all events. The cause(s) of exacerbations are currently unknown, representing a knowledge gap. The central hypothesis of this research project is different endotypes exist in bronchiectasis, are unique to the individual, and can be used for future applications to delineate appropriate clinical therapy. Methodology: Unique at the University of Calgary, we maintain a prospectively collected sputum from all patients, including those with bronchiectasis, who submitted samples from 1980 to present (>20,000 sputum samples and associated metadata). In this study, we sought to identify sputum samples at periods of clinical stability and acute exacerbation within our retrospective cohort. Long-read DNA sequencing was performed using the MinION (Oxford Nanopore). For alpha-diversity analyses, rarefaction curves and diversity indices of observed species richness Chao1, and Shannon were measured followed by Kruskal-Wallis test (p-value < = 0.05). For Beta-Diversity analysis and to visualize overall community structure PCoA plots based on Bray-Curtis dissimilarities are generated and PERMANOVA to measure differences between the microbial community profiles. Preliminary Findings: Our preliminary data evaluates 162 samples from 69 patients at different timepoints. Interim analysis demonstrates that the majority (13/16, 81%) had no clear etiology and was deemed idiopathic. Sequencing data demonstrated majority of microbes were classified as expected pathogens within bronchiectasis including Pseudomonas followed by Staphylococcus and Escherichia. Anaerobic genera were present including Prevotella, Gemella and Veillonella. Not surprisingly, we observed varying degree of inter and intra patient variability and heterogeneity with some patients demonstrating relative stability during altered clinical periods and others showing considerable temporal variation. The constrained coordination plot reveals dissimilarities between the community composition at species level and stronger effect of constraint (different time points) on the ordination. No significant changes in the alpha diversity were observed in any of the timepoints across all subjects and PERMANOVA analysis did not reveal any community-wide differences (p=0.20). Conclusions: Our preliminary data suggests cohorts of patients with bronchiectasis that experience temporal change during periods of exacerbations, whereas others do not. This suggests endotypes exist and may be used to personalize therapeutic approaches. Expansion into our cohort across more subjects will be required as next steps to validate our initial findings and delineate clinical associations.
2025-04-25 | Pulmonary rehabilitation utilization in patients with chronic respiratory diseases: 2014-2019.
Chronic respiratory diseases are associated with significant disability and death. Pulmonary rehabilitation (PR) is recommended in the management of chronic respiratory diseases. There is limited population level data comparing PR utilization and completion among patients with chronic respiratory diseases. A retrospective, cross sectional analysis concerning PR use in adults residing in the U.S. with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), pulmonary hypertension, and bronchiectasis was conducted using the Merative™ MarketScan® Research Databases. PR use was identified using current procedural terminology (CPT) and healthcare common procedure coding system (HCPCS) codes. Demographics, comorbidities, oxygen use, medications, initiation and participation of PR by disease state were collected. Analysis involved chi-square tests and generalized estimating equations. From 2014 to 2019, we identified 892,741 adults with chronic respiratory diseases and COPD was the most prevalent. PR initiation occurred in 2.3 % and annual participation ranged from 1.5 % to 1.7 %. The IPF group had the largest proportion of patients that initiated PR compared to other groups. Completion of ≥8 sessions was greatest for the group with IPF (60.8 %), followed by non IPF ILD (56.2 %), bronchiectasis (55.3 %), pulmonary hypertension (55.1 %) and COPD (53.9 %). Completion of ≥8 sessions was significantly greater for the IPF group compared to the COPD group, (p < 0.0001). PR was underutilized among individuals with chronic respiratory disease, however the group with IPF demonstrated the greatest proportion of PR initiation and completion compared with other groups.
2023-06-26 | Immunological Approaches to The Pathogenesis and Treatment of Bronchiectasis
Bronchiectasis is characterized by a constant and abnormal expansion of the airways of the lungs (bronchi) and/or a violation of the tone of the muscle layer of the bronchial wall due to inflammation, sclerosis, dystrophy, hypoplasia. Bronchiectasis is a very common disease that is the main cause of respiratory problems. A deficiency in the host's immune response to bacterial infection is considered to be the main condition for the development of bronchiectasis. In addition, many patients have no identifiable cause and are defined as having an idiopathic disease. This can lead to the development of a chronic respiratory tract infection and subsequent inflammation. Patients tend to have persistent disease despite aggressive use of antibiotics and optimal sputum clearance techniques. New therapies based on the manipulation of the immune response are becoming available and offer significant promise for the treatment of this condition
proteins
2025-05-01 | Investigating WFDC2 as an Etiology of Lifelong Bronchiectasis & Sinusitis: A Case Report
Abstract Introduction: Non-cystic fibrosis pediatric bronchiectasis is an orphan disease. Although chronic infections, inborn errors of immunity, aspiration, and genetic mucociliary clearance defects have all been identified as underlying causes of bronchiectasis, idiopathic cases still represent the largest diagnostic category. Like bronchiectasis, chronic rhinosinusitis is caused by a complex interaction of host factors, immune response, infections, and environmental exposures with a similar differential. When these conditions co-exist, systemic or genetic predispositions to epithelial dysfunction should be considered. Case Description: A teenager with respiratory problems since age 2 weeks experienced progression during childhood, with the development of diffuse bronchiectasis and pan-rhinosinusitis by age 6. Pulmonary function demonstrated progressive obstruction. Airways demonstrated abundant purulent secretions chronically infected with pseudomonas and other pathogens typically found in bronchiectasis. Diagnostic evaluation excluded inborn errors of immunity, cystic fibrosis (CF), primary ciliary dyskinesia (PCD), atopic/eosinophilic associated disorders, and aspiration. Repeat sweat chloride tests, cystic fibrosis transmembrane conductance regulator (CFTR) gene panel, whole exome sequencing (WES), and in-vitro epithelial cell CFTR assay were not consistent with the diagnosis of CF. PCD was considered due to low nasal nitric oxide, however the patient had a negative PCD gene panel and normal ciliary structure on electron microscopy with normal ciliary motility on light microscopy. WES revealed 35 candidate mutations. By focusing on autosomal recessive variants and genes associated with respiratory disease, the homozygous missense variant WFDC2 c.145T>C (p.Cys49Arg) was identified as the most likely causative pathogenic mutation. Discussion: WFDC2, also known as Human Epididymis Protein 4 (HE4), is a protease inhibitor of the Whey Acidic Protein (WAP). WFDC2 is expressed in respiratory epithelia, salivary glands, and reproductive organs. WFDC2 dysfunction has been associated with chronic sinusitis with nasal polyps. Soon after we identified this variant, an international multicenter group reported 11 individuals from 10 unrelated families with biallelic pathogenic variants in WFDC2 presenting with bronchiectasis and nasal polyposis. This group identified the same p.Cys49Arg seen in our patient as a likely founder variant. Our case identifies another individual with a WFDC2 variant, lending support to the prior work. WFDC2 mutation, and in particular pCys49Arg variant, should be considered as a monogenic cause for neonatal onset respiratory distress and for bronchiectasis and rhinosinusitis alongside PCD and CF. Longitudinal studies and functional assays are needed to clarify the phenotypic spectrum of WFDC2 mutations and guide the development of targeted therapies.
small molecules
2026-05-01 | A58-11 Demographics and Clinical Characteristics of the Argentine Bronchiectasis Registry (ReBroAr): A Comparative Analysis With the European Registry (EMBARC)
Abstract Rationale Bronchiectasis exhibits significant geographic variations globally. While European registries like EMBARC have established comprehensive databases, Latin American data remain scarce. This study characterized the Argentine Bronchiectasis Registry (ReBroAr) and compared it with EMBARC to identify unique regional patterns. Methods This multicenter, prospective observational study enrolled 1,288 adult patients with bronchiectasis. Comprehensive data included demographics, etiology, pulmonary function, microbiological cultures, severity scores, and treatment patterns. Patients underwent thorough etiological investigation including immunologic, microbiological, and genetic testing when indicated. Results Mean age was 60.7 years with marked female predominance (69% vs 34% EMBARC, p < 0.001). Most patients (71.6%) were never-smokers. Microbiological analysis revealed 50.3% had no bacterial isolation. Among positive cultures, Pseudomonas aeruginosa predominated (21.7%), followed by other bacteria (12.6%), Haemophilus influenzae (11.3%), and Staphylococcus aureus (4.1%). Pseudomonas aeruginosa chronic infection affected only 16.4% of patients. Etiological distribution differed significantly from EMBARC. Post-infectious causes accounted for 28.5% (vs 21.2% EMBARC), with post-tuberculosis etiology notably elevated at 16.9% versus 4.9% (3.4-fold higher, p < 0.001). Idiopathic classification was 2.5-fold lower (15.5% vs 38.1%, p < 0.001). COPD-associated bronchiectasis represented 10.3% and asthma-associated 10.2%.Spirometric obstruction was present in 39.6%, intermediate between EMBARC (34%) and USA registries (51%). Disease severity revealed predominantly mild disease: FACED score showed 61.1% mild, 31.2% moderate, 7.7% severe; E-FACED demonstrated 71.8% mild, 23.7% moderate, 4.5% severe.Clinical presentation included cough (87%), sputum production (69%), and dyspnea (62%). Eosinophilia was present in 52.5%. Bronchodilator response was positive in only 17% despite high asthma association. There was a predominance of involvement of the lower lobes (51-55%).Treatment patterns revealed 67.8% used inhaled corticosteroids: 44.9% on ICS/LABA combinations, 20.4% on triple therapy, and 14.4% untreated. Conclusions ReBroAr reveals unique epidemiological patterns: female predominance, 3.4-fold higher post-tuberculous etiology versus EMBARC, and lower idiopathic classification reflecting comprehensive etiological investigation. The relatively low Pseudomonas aeruginosa chronic infection rate (16.4%) and 50.3% without bacterial isolation suggest distinct microbiological patterns. Predominantly mild-to-moderate severity despite significant symptoms and high inhaled corticosteroid use (67.8%) suggests opportunities for optimizing phenotype-specific therapy. These findings emphasize the importance of regional registries in understanding bronchiectasis heterogeneity and informing population-specific management approaches. This abstract is funded by: None
2026-01-01 | Phospholipids with Odd-chain Fatty Acids as Markers of Improved Inflammation in Chronic Lung Infections
Chronic inflammatory lung diseases, including cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), idiopathic pulmonary fibrosis (IPF), and non-CF bronchiectasis, are characterized by persistent polymicrobial infection, excessive neutrophilic inflammation, mucus accumulation, and progressive loss of lung function. Current therapies aimed at suppressing airway inflammation remain limited and often lack efficacy or produce substantial side effects, highlighting a critical need for novel immunomodulatory strategies. Our metabolomics studies of airway secretions from patients with chronic lung disease have identified a previously unrecognized class of phospholipids containing odd-chain fatty acids (PC-OCFAs) that strongly correlate with improved lung function. These lipids, containing C15:0 and C17:0 fatty acid chains, are unusual components of the human lipidome and are poorly understood in pulmonary biology. Emerging evidence from other inflammatory diseases suggests odd-chain fatty acids possess anti-inflammatory and immunometabolic properties, potentially mediated through PPAR-α and PPAR-δ signaling pathways; however, their role in airway inflammation and lung health is unknown. The overall objective of this exploratory R21 project is to define the biological origin, abundance, and anti-inflammatory activity of PC-OCFAs in chronic lung disease. Our central hypothesis is that PC-OCFAs are associated with improved lung function because they attenuate inflammatory signaling in airway epithelial cells. To test this hypothesis, we will pursue two aims. In Aim 1, we will use advanced LC-MS/MS lipidomics and molecular networking approaches to quantify PC-OCFAs and free odd-chain fatty acids in explanted human lung tissues, isolated primary lung cell populations, and airway bacterial isolates to determine their abundance, clinical associations, and cellular source. In Aim 2, we will expose primary human airway epithelial cells to PC-OCFAs and free odd-chain fatty acids under basal and inflammatory conditions and perform RNA sequencing and cytokine profiling to characterize their effects on inflammatory signaling pathways and epithelial immune responses. This project is highly innovative because it investigates a cryptic and poorly studied component of the human lipidome that emerged from unbiased metabolomic profiling as one of the strongest molecular correlates of improved lung function in CF. The proposed studies integrate state-of-the-art metabolomics, molecular networking, airway cell biology, and transcriptomics to investigate a fundamentally new area of pulmonary immunometabolism. Successful completion of this work will establish foundational knowledge regarding the role of odd-chain fatty acids in airway biology and may identify a novel class of endogenous anti-inflammatory molecules with therapeutic potential for chronic inflammatory lung diseases.
2026-01-01 | The European Respiratory Journal 2026: towards the golden age of respiratory science?
Welcome to our New Year editorial for 2026! What a time to be working in respiratory medicine and science! Your editors cannot remember a period of more rapid development in our field. Objectively, more new drugs have been approved by regulators for respiratory indications in 2025 that at any time in history, with a notable acceleration overall since 2020. New treatments in 2025 include those for diseases such as COPD (e.g. mepolizumab), idiopathic pulmonary fibrosis/progressive pulmonary fibrosis (e.g. nerandomilast), bronchiectasis (e.g. brensocatib), asthma (e.g. depemokimab) and respiratory syncytial virus (e.g. clesrovimab), as well as extraordinary developments for multiple approved therapies in areas such as pulmonary hypertension and pulmonary hypertension-associated interstitial lung disease (ILD) (e.g. inhaled treprostinil and sotatercept), cystic fibrosis (e.g. vanzacaftor/tezacaftor/deutivacaftor) and lung cancer (e.g. telisotuzumab, taletrectinib, datopotamab deruxtecan, sunvozertinib, zongertinib and sevabertinib) [1]. Respiratory translational science has never been healthier or more in the public eye. Practice is changing and respiratory guidelines are stronger, more impactful and greater in number than ever before. This is an exciting time for a respiratory-focused scientific journal.
2025-09-27 | Factors associated with Mycobacterium abscessus infection in bronchiectasis patients
There is limited knowledge on factors associated with Mycobacterium abscessus (M.abscessus) infection in bronchiectasis patients. We investigated the factors of M.abscessus infection over a 7-year period in Singapore. Objective: To investigate the factors associated with M.abscessus infection in bronchiectasis patients in a tertiary referral centre from 2016-2022. Method: Demographic and clinical profiles were analysed prospectively. M.abscessus pulmonary disease (MAPD) was diagnosed based on American Thoracic Society and Infectious Disease Society of America (ATS/IDSA) criteria. M. abscessus colonisation was defined by presence of 2 positive cultures at least 3-months apart over a 12-month period, without worsening clinico-radiological features. Patients with idiopathic bronchiectasis were categorised as control group. Results: 23 MAPD patients, 24 with colonisation and 68 with idiopathic bronchiectasis were studied. MAPD and M.abscessus colonised patients had lower BMI than control (p=0.009 and p=0.003 respectively). MAPD patients had greater decline in FEV1 than control (77ml/year vs. 22ml/year, p=0.04). Sputum cultured positive with Pseudomonas aeruginosa (P. aeruginosa) and Staphylococcus aureus (S. aureus) were more common in MAPD and M.abscessus colonised patients (p=0.01 and p=0.003 respectively), whilst Klebsiella pneumoniae was more common in MAPD patients (p=0.01). A third of the M.abscessus infection patients had a history of pulmonary tuberculosis (PTB). Conclusion: Low BMI (< 19), history of PTB, P.aeruginosa and S.aureus were associated with M. abscessus infection in bronchiectasis. Future large-scale multicenter prospective studies on risk modification will be crucial.
2025-09-27 | Subgroup analysis: AIRLEAF® Phase II study of a cathepsin C (CatC, or DPP1) inhibitor, BI 1291583, in adults with non–cystic fibrosis bronchiectasis
Background: AIRLEAF®, a Phase II study, evaluated the efficacy, safety and optimal dosing of the CatC inhibitor BI 1291583 in adults with bronchiectasis.1 BI 1291583 treatment reduced the risk of experiencing a pulmonary exacerbation (PEx), most notably with the 2.5 mg dose, the dose taken forward into the Phase III AIRTIVITY® study. Methods: This double-blind, placebo-controlled study randomised 322 participants to BI 1291583 (1/2.5/5 mg) or placebo for up to 48 weeks. The subgroups evaluated here are 1 PEx with SGRQ Symptoms score >40 vs ≥2 PExs in the year prior to screening, baseline P. aeruginosa status, maintenance use of macrolides at baseline and aetiology (idiopathic/post-infectious vs all others). Results: All subgroups in the 2.5 mg dose group had reductions in risk and rate of PExs consistent with the overall study population (Table 1). Hazard ratios ranged from 0.47 to 0.82, illustrating consistent prolongation of time to first PEx. Particularly, estimates of benefit for unique populations included in AIRLEAF®, such as 1 PEx plus high symptom score, were consistent with the overall population. Conclusion: These results support the use of the 2.5 mg dose across all subgroups in AIRTIVITY®. 1Chalmers JD et al. Eur Respir J 2025; 65:2401551 Table 1. Subgroup analyses of risk and rate of PExs up to 48 weeks in the 2.5 mg dose group vs placebo erj;66/suppl_69/PA4959/F1F1F1
cell therapies
2026-07-13 | Insights into extracellular vesicles in senescence-associated chronic lung diseases.
Chronic lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, obstructive sleep apnea, asthma, bronchiectasis, and lung cancer, are intricately linked to the aging process. These diseases are characterized by a high prevalence rate and a paucity of effective treatment options. Emerging evidence highlights the critical role of extracellular vesicles (EVs) in the pathogenesis and progression of these diseases. EVs, released by senescent cells, mediate intercellular communication and modulate immune responses through their cargo of microRNAs, proteins, and other molecules. These vesicles contribute to disease progression by promoting inflammation, fibrosis, tissue remodeling, and cellular senescence. Specifically, certain microRNAs, such as miR-21, miR-34a, and miR-570-3p, along with several proteins in EVs, have been identified as key factors influencing these processes. Additionally, EVs play significant roles in immune regulation and have potential anti-inflammatory effects, making them promising candidates for therapeutic applications. Recent advances in the use of EVs as therapeutic agents, including their application in nanotechnology for targeted drug delivery, have demonstrated potential in reducing inflammation, modulating immune responses, and enhancing tissue repair. Understanding the role of EVs in these diseases offers insights into potential therapeutic targets to mitigate disease progression and improve patient outcomes. Future research should focus on standardizing EV isolation and characterization methods, verifying the safety and efficacy of EV-based therapies in clinical trials, and elucidating the complex biological mechanisms of EVs in aging and disease.
2018-05-22 | Outcomes of lung transplantation in adults with bronchiectasis
Lung transplantation is a well-established treatment for end-stage non-cystic fibrosis bronchiectasis (BR), though information regarding outcomes of transplantation remains limited. Our results of lung transplantation for Br are reported here.A retrospective review of case notes and transplantation databases was conducted for patients that had underwent lung transplantation for bronchiectasis at the Freeman Hospital between 1990 and 2013.Fourty two BR patients underwent lung transplantation, the majority (39) having bilateral sequential lung transplantation. Mean age at transplantation was 47.1 years. Pre-transplantation osteoporosis was a significant non-pulmonary morbidity (48%). Polymicrobial infection was common, with Pseudomonas aeruginosa infection frequently but not universally observed (67%). Forced expiratory volume in 1 second (% predicted) improved from a pre-transplantation mean of 0.71 L (22% predicted) to 2.56 L (79 % predicted) at 1-year post-transplantation. Our survival results were 74% at 1 year, 64% at 3 years, 61% at 5 years and 48% at 10 years. Sepsis was a common cause of early post-transplantation deaths.Lung transplantation for end-stage BR is a useful therapeutic option, with good survival and lung function outcomes. Survival values were similar to other bilateral lung transplants at our centre. Pre-transplantation Pseudomonas infection is common.
2013-07-02 | Lung Transplantation for Cystic Fibrosis and Bronchiectasis
Lung transplantation has become an excellent treatment option for patients with cystic fibrosis (CF) and bronchiectasis with very advanced lung disease. Despite the challenges that the CF patients present, survival is more favorable than that seen in patients with chronic obstructive pulmonary disease and pulmonary fibrosis. Although those CF and bronchiectasis patients with severe respiratory disease are often infected with organisms that display in vitro resistance to the commonly used antibiotics, they usually have successful outcomes with transplantation, which are reported to be the same as in those patients with less resistant bacteria. Preoperative synergy testing has been demonstrated to reduce the presence of postoperative bacteremia and empyema in patients with CF. Newer challenges include the increasing presence of nontuberculous mycobacteria and in particular the rapid grower Mycobacterium abscessus, for which patient-to-patient spread has been recently recognized. The increased recognition of gastroesophageal reflux offers challenges regarding when and to whom one should offer fundoplication. Most potential CF recipients have metabolic bone disease warranting treatment, especially with the significant loss of bone density seen in the first year after transplantation. Diabetes mellitus, renal dysfunction, and hypertension and their consequences remain common and are of increasing importance as median survival increases in excess of 10 years. With increased experience, more programs are now transplanting patients who require membrane oxygenator support in addition to noninvasive ventilation pretransplantation and the use of a membrane device in the awake patient principally to remove excessive CO2 and reduce acidemia is worthy of note (Novalung; Novalung GmbH, Heilbronn, Federal Republic of Germany). Many centers now take the view that an awake and ambulant patient receiving such support represents a more favorable option than an intubated patient. The limiting factor in lung transplantation remains the number of organs available. Efforts to increase the donor pool, such as low tidal volume ventilation, are effective in allowing a greater percentage of offered organs to be accepted. Perhaps the most encouraging development, however, is that of ex vivo lung perfusion. This permits not only the ability to measure the function of the lungs, something of great value for lungs from donors with circulatory death (donation after cardiac death), but also the potential to introduce lung repair and convert a nonusable lung to one that can be safely used for transplantation.
2012-09-06 | First Report of Lung Transplantation in a Patient With Active Pulmonary Mycobacterium simiae Infection
Mycobacterium simiae is a slow-growing mycobacteria that in rare cases can cause chronic pulmonary infection. We report the first case of lung transplantation in a patient with active M simiae infection at the time of transplantation. A 56-year-old immunocompetent nonsmoking woman underwent bilateral lung transplantation for end-stage idiopathic bronchiectasis and chronic M simiae infection. The disease proved manageable on a regimen of clarithromycin, moxifloxacin, and cotrimoxazole with a successful outcome 1-year posttransplantation. There is increasing evidence that nontuberculous mycobacterium infection should no longer be an absolute contraindication for lung transplantation.
2005-05-10 | Lung Transplantation for Non-Cystic Fibrosis Bronchiectasis: Analysis of a 13-Year Experience
Lung transplantation is a well-established treatment for end-stage cystic fibrosis, and there are considerable data on medium- and long-term results. However, less information exists about transplantation for non-cystic fibrosis bronchiectasis.Between December 1988 and June 2001, 22 patients (12 men, 10 women) underwent transplantation for bronchiectasis not due to cystic fibrosis. Procedures were bilateral sequential single-lung transplants (BSSLTX) in 4 patients, en bloc double lung transplants (DLTX) in 5, heart-lung transplants (HLTX) in 6, and single-lung transplants (SLTX) in 7. Lifelong outpatient follow-up was continued at a minimum of every 6 months.One-year Kaplan-Meier survival for all patients was 68% (95% confidence interval [CI], 54%-91%), and 5-year survival was 62% (95% CI, 41-83%). One-year survival after SLTX was 57% (95% CI, 20%-94%) vs 73% (95% CI, 51-96%) for those receiving 2 lungs. At 6 months, mean forced expiratory volume in 1 second was 73% predicted (range, 58%-97%), and mean forced vital capacity was 68% predicted (range, 53%-94%) after receiving 2 lungs (n = 10); in the SLTX group at 6 months, mean forced expiratory volume in 1 second was 50% predicted (range, 34%-61%), and mean forced vital capacity was 53% predicted (range 46-63%) (n = 4).Survival and lung function after transplantation for non-cystic fibrosis bronchiectasis was similar to that after transplantation for cystic fibrosis. A good outcome is possible after single lung transplantation in selected patients.
antibodies
2025-12-09 | IMMUNOLOGICAL MECHANISMS IN THE PATHOGENESIS AND MANAGEMENT OF BRONCHIECTASIS
Resume. Bronchiectasis is characterized by a constant and abnormal expansion of the airways of the lungs (bronchi) and/or a violation of the tone of the muscle layer of the bronchial wall due to inflammation, sclerosis, dystrophy, hypoplasia. Bronchiectasis is a very common disease that is the main cause of respiratory problems. A deficiency in the host's immune response to bacterial infection is considered to be the main condition for the development of bronchiectasis. In addition, many patients have no identifiable cause and are defined as having an idiopathic disease. This can lead to the development of a chronic respiratory tract infection and subsequent inflammation. Patients tend to have persistent disease despite aggressive use of antibiotics and optimal sputum clearance techniques. New therapies based on the manipulation of the immune response are becoming available and offer significant promise for the treatment of this condition. Keywords: bronchiectasis, respiratory infections, inflammation, immune response, immunological approaches
2025-09-27 | Expression of activation markers of circulating neutrophils and eosinophils in stable bronchiectasis
Background: Neutrophilic and, less frequently, eosinophilic inflammation is implicated in bronchiectasis, however the activation of circulating neutrophils and eosinophils has not been extensively determined in this disease. Aims and Objectives: The study aimed to investigate the potential expansion of actively reprogrammed circulating neutrophils and eosinophils in stable bronchiectasis and further compare them with other inflammatory markers. Methods: The expression of activation markers of neutrophils (CD14-CD15+CD16+ cells) and eosinophils (CD16-Siglec-8+ cells), i.e. CD62L, CD11b, and IL-3R, was quantified by flow cytometry in the peripheral blood of 9 post-infectious or idiopathic bronchiectasis patients and 9 healthy controls. Results: Low and high expression of CD62L and CD11b, as activation markers of neutrophils, respectively, was similar between patients and controls (mean±SD: 9.72%±0.06 vs. 10.46%±0.08, p=0.9090 and 95.32%±0.06 vs. 99.38±0.01, p=0.2850, respectively). Low and high expression of CD62L and IL-3R, as activation markers of eosinophils, respectively, was similar between patients with T2-high endotype and controls (20.71%±13.98 vs. 40.25%±27.31, p=0.3021 and 17.06%±28.07 vs. 31.31±25.59, p=0.4559, respectively). Neutrophilic expression of CD11b was correlated with fibrinogen levels (r=0.75, p=0.0255). Conclusions: Actively reprogrammed neutrophils and eosinophils do not expand in the systemic circulation in stable bronchiectasis, although their alterations locally in the airways or during exacerbations remain to be studied. Neutrophilic expression of CD11b is highlighted as a potential marker of disease activity in bronchiectasis. *AMM & NB contributed equally
2025-05-01 | Deciphering the Lung Microbiome During Pulmonary Exacerbations and Clinical Stability in Bronchiectasis
Abstract Background: Bronchiectasis is characterized by cycles of inflammation and chronic infection. Pulmonary exacerbations are defined by periods of worsening symptoms and dropping lung function. Traditional dogma suggests this is due to overgrowth of canonical bacterial pathogens; however recent studies have shown this to not fully represent all events. The cause(s) of exacerbations are currently unknown, representing a knowledge gap. The central hypothesis of this research project is different endotypes exist in bronchiectasis, are unique to the individual, and can be used for future applications to delineate appropriate clinical therapy. Methodology: Unique at the University of Calgary, we maintain a prospectively collected sputum from all patients, including those with bronchiectasis, who submitted samples from 1980 to present (>20,000 sputum samples and associated metadata). In this study, we sought to identify sputum samples at periods of clinical stability and acute exacerbation within our retrospective cohort. Long-read DNA sequencing was performed using the MinION (Oxford Nanopore). For alpha-diversity analyses, rarefaction curves and diversity indices of observed species richness Chao1, and Shannon were measured followed by Kruskal-Wallis test (p-value < = 0.05). For Beta-Diversity analysis and to visualize overall community structure PCoA plots based on Bray-Curtis dissimilarities are generated and PERMANOVA to measure differences between the microbial community profiles. Preliminary Findings: Our preliminary data evaluates 162 samples from 69 patients at different timepoints. Interim analysis demonstrates that the majority (13/16, 81%) had no clear etiology and was deemed idiopathic. Sequencing data demonstrated majority of microbes were classified as expected pathogens within bronchiectasis including Pseudomonas followed by Staphylococcus and Escherichia. Anaerobic genera were present including Prevotella, Gemella and Veillonella. Not surprisingly, we observed varying degree of inter and intra patient variability and heterogeneity with some patients demonstrating relative stability during altered clinical periods and others showing considerable temporal variation. The constrained coordination plot reveals dissimilarities between the community composition at species level and stronger effect of constraint (different time points) on the ordination. No significant changes in the alpha diversity were observed in any of the timepoints across all subjects and PERMANOVA analysis did not reveal any community-wide differences (p=0.20). Conclusions: Our preliminary data suggests cohorts of patients with bronchiectasis that experience temporal change during periods of exacerbations, whereas others do not. This suggests endotypes exist and may be used to personalize therapeutic approaches. Expansion into our cohort across more subjects will be required as next steps to validate our initial findings and delineate clinical associations.
2025-04-25 | Pulmonary rehabilitation utilization in patients with chronic respiratory diseases: 2014-2019.
Chronic respiratory diseases are associated with significant disability and death. Pulmonary rehabilitation (PR) is recommended in the management of chronic respiratory diseases. There is limited population level data comparing PR utilization and completion among patients with chronic respiratory diseases. A retrospective, cross sectional analysis concerning PR use in adults residing in the U.S. with chronic obstructive pulmonary disease (COPD), interstitial lung disease (ILD), idiopathic pulmonary fibrosis (IPF), pulmonary hypertension, and bronchiectasis was conducted using the Merative™ MarketScan® Research Databases. PR use was identified using current procedural terminology (CPT) and healthcare common procedure coding system (HCPCS) codes. Demographics, comorbidities, oxygen use, medications, initiation and participation of PR by disease state were collected. Analysis involved chi-square tests and generalized estimating equations. From 2014 to 2019, we identified 892,741 adults with chronic respiratory diseases and COPD was the most prevalent. PR initiation occurred in 2.3 % and annual participation ranged from 1.5 % to 1.7 %. The IPF group had the largest proportion of patients that initiated PR compared to other groups. Completion of ≥8 sessions was greatest for the group with IPF (60.8 %), followed by non IPF ILD (56.2 %), bronchiectasis (55.3 %), pulmonary hypertension (55.1 %) and COPD (53.9 %). Completion of ≥8 sessions was significantly greater for the IPF group compared to the COPD group, (p < 0.0001). PR was underutilized among individuals with chronic respiratory disease, however the group with IPF demonstrated the greatest proportion of PR initiation and completion compared with other groups.
2023-06-26 | Immunological Approaches to The Pathogenesis and Treatment of Bronchiectasis
Bronchiectasis is characterized by a constant and abnormal expansion of the airways of the lungs (bronchi) and/or a violation of the tone of the muscle layer of the bronchial wall due to inflammation, sclerosis, dystrophy, hypoplasia. Bronchiectasis is a very common disease that is the main cause of respiratory problems. A deficiency in the host's immune response to bacterial infection is considered to be the main condition for the development of bronchiectasis. In addition, many patients have no identifiable cause and are defined as having an idiopathic disease. This can lead to the development of a chronic respiratory tract infection and subsequent inflammation. Patients tend to have persistent disease despite aggressive use of antibiotics and optimal sputum clearance techniques. New therapies based on the manipulation of the immune response are becoming available and offer significant promise for the treatment of this condition
proteins
2025-05-01 | Investigating WFDC2 as an Etiology of Lifelong Bronchiectasis & Sinusitis: A Case Report
Abstract Introduction: Non-cystic fibrosis pediatric bronchiectasis is an orphan disease. Although chronic infections, inborn errors of immunity, aspiration, and genetic mucociliary clearance defects have all been identified as underlying causes of bronchiectasis, idiopathic cases still represent the largest diagnostic category. Like bronchiectasis, chronic rhinosinusitis is caused by a complex interaction of host factors, immune response, infections, and environmental exposures with a similar differential. When these conditions co-exist, systemic or genetic predispositions to epithelial dysfunction should be considered. Case Description: A teenager with respiratory problems since age 2 weeks experienced progression during childhood, with the development of diffuse bronchiectasis and pan-rhinosinusitis by age 6. Pulmonary function demonstrated progressive obstruction. Airways demonstrated abundant purulent secretions chronically infected with pseudomonas and other pathogens typically found in bronchiectasis. Diagnostic evaluation excluded inborn errors of immunity, cystic fibrosis (CF), primary ciliary dyskinesia (PCD), atopic/eosinophilic associated disorders, and aspiration. Repeat sweat chloride tests, cystic fibrosis transmembrane conductance regulator (CFTR) gene panel, whole exome sequencing (WES), and in-vitro epithelial cell CFTR assay were not consistent with the diagnosis of CF. PCD was considered due to low nasal nitric oxide, however the patient had a negative PCD gene panel and normal ciliary structure on electron microscopy with normal ciliary motility on light microscopy. WES revealed 35 candidate mutations. By focusing on autosomal recessive variants and genes associated with respiratory disease, the homozygous missense variant WFDC2 c.145T>C (p.Cys49Arg) was identified as the most likely causative pathogenic mutation. Discussion: WFDC2, also known as Human Epididymis Protein 4 (HE4), is a protease inhibitor of the Whey Acidic Protein (WAP). WFDC2 is expressed in respiratory epithelia, salivary glands, and reproductive organs. WFDC2 dysfunction has been associated with chronic sinusitis with nasal polyps. Soon after we identified this variant, an international multicenter group reported 11 individuals from 10 unrelated families with biallelic pathogenic variants in WFDC2 presenting with bronchiectasis and nasal polyposis. This group identified the same p.Cys49Arg seen in our patient as a likely founder variant. Our case identifies another individual with a WFDC2 variant, lending support to the prior work. WFDC2 mutation, and in particular pCys49Arg variant, should be considered as a monogenic cause for neonatal onset respiratory distress and for bronchiectasis and rhinosinusitis alongside PCD and CF. Longitudinal studies and functional assays are needed to clarify the phenotypic spectrum of WFDC2 mutations and guide the development of targeted therapies.
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Drug Discovery Landscape
10 orphan drug designations for Idiopathic bronchiectasis.
10 orphan drug designations for Idiopathic bronchiectasis.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
ciprofloxacin dry powder inhaler | small molecules | FDA | Bayer HealthCare Pharmaceuticals, Inc. | |
doxofylline | small molecules | FDA | — | Alitair Pharmaceuticals, Inc. |
erdosteine | small molecules | FDA | — | Edmond Pharma S.r.l. |
ciprofloxacin | small molecules | FDA | Savara Inc. | |
liposomal amikacin | small molecules | FDA | Insmed, Inc. | |
aztreonam | small molecules | FDA | Gilead Sciences, Inc. | |
Alpha1-antitrypsin(human) | proteins | FDA | — | Kamada Ltd. |
Liposomal ciprofloxacin for inhalation | small molecules | FDA | Savara Inc. | |
Tobramycin | small molecules | FDA | Novartis Pharmaceuticals Corp. | |
Recombinant human gelsolin | proteins | FDA | — | BioAgeis, Therapeutics, Inc. |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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