Phenotypical characteristics of nontuberculous mycobacterial infection in patients with bronchiectasis.

BACKGROUND: The global mortality and morbidity rates of bronchiectasis patients due to nontuberculous mycobacteria (NTM) pulmonary infection are on a concerning upward trend. The aims of this study to identify the phenotype of NTM-positive individuals with bronchiectasis. METHODS: A retrospective single-center observational study was conducted in adult patients with bronchiectasis who underwent bronchoscopy in 2007-2020. Clinical, laboratory, pulmonary function, and radiological data were compared between patients with a positive or negative NTM culture. RESULTS: Compared to the NTM-negative group (n=677), the NTM-positive group (n=94) was characterized (P ≤0.05 for all) by older age, greater proportion of females, and higher rates of gastroesophageal reflux disease and muco-active medication use; lower body mass index, serum albumin level, and lymphocyte and eosinophil counts; lower values of forced expiratory volume in one second, forced vital capacity, and their ratio, and lower diffusing lung capacity for carbon monoxide; higher rates of bronchiectasis in both lungs and upper lobes and higher number of involved lobes; and more exacerbations in the year prior bronchoscopy. On multivariate analysis, older age (OR 1.05, 95% CI 1.02-1.07, P=0.001), lower body mass index (OR 1.16, 95% CI 1.16-1.07, P <0.001), and increased number of involved lobes (OR 1.26, 95% CI 1.01-1.44, P=0.04) were associated with NTM infection. CONCLUSIONS: Patients with bronchiectasis and NTM pulmonary infection are more likely to be older and female with more severe clinical, laboratory, pulmonary function, and radiological parameters than those without NTM infection. This phenotype can be used for screening patients with suspected NTM disease.

The impact of the COVID-19 pandemic on adult bronchiectasis patients and the relationship between clinical parameters and bronchiectasis severity.

OBJECTIVE: Viral infections are an important cause of exacerbation in bronchiectasis patients. We aimed to determine the influence of the COVID-19 pandemic on adult bronchiectasis patients and whether there was a relationship between the clinical parameters and the COVID-19 infection. PATIENTS AND METHODS: In this retrospective observational study, 547 bronchiectasis patients were included. Demographic characteristics, vaccination status, Bronchiectasis Severity Index (BSI), FACED and Reiff scores, and clinical and laboratory parameters during COVID-19 infection were evaluated. RESULTS: The median age was 56, and 49.2% of the patients were male. The COVID-19 infection rate was 27.6%. 431 (78.8%) patients had at least one dose of the COVID-19 vaccine. The patients were divided into two groups according to their COVID-19 infection status. Emergency admission was significantly higher in the COVID-19-infected group. There was no statistical difference with other clinical factors. The COVID-19-infected patients were divided into home treatment and hospital/intensive care unit (ICU) treatment groups. There was a statistically significant difference between the two groups regarding advanced age, male gender, presence of asthma, long-term oxygen therapy (LTOT) and non-invasive mechanic ventilator (NIMV) usage, sputum culture positivity, BSI and FACED scores, and multiple laboratory parameters (ferritin, C-reactive protein, eosinophil). In logistic regression analysis, BSI was found as a risk factor [OR 1.252 (1.077-1.456), p=0.004] and eosinophilia as a protective factor [OR 0.986 (0.973-0.999), p=0.030] for hospital/ICU admission. CONCLUSIONS: Frequent emergency visits might increase the risk of COVID-19 infection in bronchiectasis patients. BSI was found to be an independent risk factor, and blood eosinophilia could play a protective role in hospital/ICU admission for COVID-19 infection.

Growing from common ground: nontuberculous mycobacteria and bronchiectasis.

Bronchiectasis and nontuberculous mycobacteria (NTM) are intricately intertwined, with NTM capable of being both a cause and consequence of bronchiectatic disease. This narrative review focuses on the common ground of bronchiectasis and NTM pulmonary disease (NTM-PD) in terms of diagnostic approach, underlying risk factors and treatment strategies. NTM-PD diagnosis relies on a combination of clinical, radiological and microbiological criteria. Although their epidemiology is complicated by detection and reporting biases, the prevalence and pathogenicity of NTM species vary geographically, with Mycobacterium avium complex and Mycobacterium abscessus subspecies most frequently isolated in bronchiectasis-associated NTM-PD. Diagnosis of nodular bronchiectatic NTM-PD should prompt investigation of host factors, including disorders of mucociliary clearance, connective tissue diseases and immunodeficiencies, either genetic or acquired. Treatment of NTM-PD in bronchiectasis involves a multidisciplinary approach and considers the (sub)species involved, disease severity and comorbidities. Current guideline-based antimicrobial treatment of NTM-PD is considered long, cumbersome and unsatisfying in terms of outcomes. Novel treatment regimens and strategies are being explored, including rifampicin-free regimens and inclusion of clofazimine and inhaled antibiotics. Host-directed therapies, such as immunomodulators and cytokine-based therapies, might enhance antimycobacterial immune responses. Optimising supportive care, as well as pathogen- and host-directed strategies, is crucial, highlighting the need for personalised approaches tailored to individual patient needs. Further research is warranted to elucidate the complex interplay between host and mycobacterial factors, informing more effective management strategies.

Exacerbations of bronchiectasis.

Bronchiectasis presents a significant challenge due to its rising prevalence, associated economic burden and clinical heterogeneity. This review synthesises contemporary understanding and literature of bronchiectasis exacerbations, addressing the transition from stable state to exacerbations, underlining the importance of early and precise recognition, rigorous severity assessment, prompt treatment, and prevention measures, as well as emphasising the need for strategies to assess and improve early and long-term patient outcomes. The review highlights the interplay between stable state phases and exacerbations in bronchiectasis, introducing the concept of "exogenous and endogenous changes in airways homeostasis" and the "adapted island model" with a particular focus on "frequent exacerbators", a group of patients associated with specific clinical characteristics and worse outcomes. The pathophysiology of exacerbations is explored through the lens of microbial and nonmicrobial triggers and the presence and the activity of comorbidities, elaborating on the impact of both exogenous insults, such as infections and pollution, and endogenous factors such as inflammatory endotypes. Finally, the review proposes a multidisciplinary approach to care, integrating advancements in precision medicine and biomarker research, paving the way for tailored treatments that challenge the traditional antibiotic paradigm.

Type-2 severe asthma comorbidities in the era of biologics: time to rethink clinical response?

INTRODUCTION: The use of monoclonal antibodies in patients with severe asthma has led clinicians to explore new levels of clinical improvement, as testified by the growing interest on clinical remission achievement. In this context, a major role is played by asthma-related comorbidities, which can influence asthma pathophysiology and treatment response. AREAS COVERED: In this special report, we highlighted how asthma-related comorbidities could deeply affect monoclonal antibody response as well as clinical remission achievement. As examples, we provided data from clinical trials and real-life experiences involving patients with severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), eosinophilic granulomatosis with polyangiitis (EGPA) or bronchiectasis. EXPERT OPINION: Comorbidities associated with severe asthma development should be carefully assessed in everyday clinical practice, even with the help of new diagnostic technologies, artificial intelligence and multidisciplinary teams. Future studies should address the role of comorbidities in remission achievement, describing how these diseases could generate new trajectories of clinical and functional response in patient treated with monoclonal antibodies.

The impact of smoking on bronchiectasis and its comorbidities.

INTRODUCTION: Bronchiectasis, characterized by irreversible bronchial dilatation, is a growing global health concern with significant morbidity. This review delves into the intricate relationship between smoking and bronchiectasis, examining its epidemiology, pathophysiology, clinical manifestations, and therapeutic approaches. Our comprehensive literature search on PubMed utilized MESH terms including 'smoking,' 'smoking cessation,' 'bronchiectasis,' and 'comorbidities' to gather relevant studies. AREAS COVERED: This review emphasizes the role of smoking in bronchiectasis development and exacerbation by compromising airways and immune function. Interconnected comorbidities, including chronic obstructive pulmonary disease, asthma, and gastroesophageal reflux disease, create a detrimental cycle affecting patient outcomes. Despite limited studies on smoking cessation in bronchiectasis, the review stresses its importance. Advocating for tailored cessation programs, interventions like drainage, bronchodilators, and targeted antibiotics are crucial to disrupting the inflammatory-infection-widening cycle. EXPERT OPINION: The importance of smoking cessation in bronchiectasis management is paramount due to its extensive negative impact on related conditions. Proactive cessation programs utilizing technology and targeted education for high-risk groups aim to reduce smoking's impact on disease progression and related comorbidities. In conclusion, a personalized approach centered on smoking cessation is deemed vital for bronchiectasis, aiming to improve outcomes and enhance patients' quality of life in the face of this complex respiratory condition.

Bronchiectasis After Solid-Organ Transplant: A Retrospective Single Center Study.

OBJECTIVES: Bronchiectasis is characterized by abnormal, persistent, and irreversible enlargement of the bronchi. Many etiological factors have been described, but there are limited data on the development of bronchiectasis after organ transplantation. Our study is the first to study evaluate the frequency of bronchiectasis in heart and liver transplants as well as kidney transplants. Our aim is to analyze the frequency of bronchiectasis development after solid-organ transplant and the characteristics of the cases and to evaluate potential relationships. MATERIALS AND METHODS: We retrospectively analyzed data of patients who underwent solid-organ transplant at the Baskent University Faculty of Medicine Hospital through the hospital electronic information system. Demographic, clinical, and laboratory data and thoracic computed tomography scans were evaluated. RESULTS: The study included 468 patients (151 females/317 males). Kidney transplant was performed in 61.5% (n = 207), heart transplant in 20.3% (n = 95), and liver transplant in 18.2% (n = 85) of patients. Development of bronchiectasis was detected in only 13 patients (2.7%). We determined a 13.64-fold risk of developing bronchiectasis in patients with chronic obstructive pulmonary disease and 10.08-fold risk in patients with pneumonia by multivariate regression analyzes, in which all possible risk factors for the development of bronchiectasis after transplant were evaluated. CONCLUSIONS: The pathophysiology of transplantassociated bronchiectasis has not yet been clarified. Underlying diseases, recurrent pulmonary infections, and potential effects from immunosuppressive drugs may contribute to the pathogenesis of bronchiectasis. Further prospective studies are needed to include long-term health outcomes in transplant patients with and without bronchiectasis.

Bronchiectasis in Türkiye: Data from a Multicenter Registry (Turkish Adult Bronchiectasis Database).

Background: Bronchiectasis is a chronic lung disease characterized by permanent bronchial wall dilatation. Although it has been known as an orphan disease, it has recently gained attention because of registry-based studies and drug research. Aims: We aimed to use a multicenter database to analyze and compare data regarding the etiology, associated comorbidities, microbiological characteristics, and preventive strategies of bronchiectasis in Türkiye to those of other countries. Study Design: A multicenter prospective cohort study. Methods: The multicenter, prospective cohort study was conducted between March 2019 and January 2022 using the Turkish Adult Bronchiectasis Database, in which 25 centers in Türkiye participated. Patients aged > 18 years who presented with respiratory symptoms such as cough, sputum, and dyspnea and were diagnosed with non-cystic fibrosis bronchiectasis using computed tomography were included in the study. Demographic information, etiologies, comorbidities, pulmonary functions, and microbiological, radiological, and clinical data were collected from the patients. Results: Of the 1,035 study participants, 518 (50%) were females. The mean age of the patients was 56.1 ± 16.1 years. The underlying etiology was detected in 565 (54.6%) patients. While postinfectious origin was the most common cause of bronchiectasis (39.5%), tuberculosis was identified in 11.3% of the patients. An additional comorbidity was detected in 688 (66.5%) patients. The most common comorbidity was cardiovascular disease, and chronic obstructive pulmonary disease (COPD) and bronchiectasis was identified in 19.5% of the patients. The most commonly detected microbiological agent was Pseudomonas aeruginosa (29.4%). Inhaled corticosteroids (ICS) were used in 70.1% of the patients, and the frequency of exacerbations in the last year was significantly higher in patients using ICS than in nonusers (p < 0.0001). Age [odds ratio (OR): 1.028; 95% confidence interval (CI): 1.005-1.051], cachexia (OR: 4.774; 95% CI: 2,054-11,097), high modified medical research council dyspnea scale score (OR: 1,952; 95% CI: 1,459-2,611), presence of chronic renal failure (OR: 4,172; 95% CI: 1,249-13,938) and use of inhaled steroids (OR: 2,587; 95% CI: 1,098-6,098) were significant risk factors for mortality. Mortality rates were higher in patients with COPD than in those with no COPD (21.7-9.1%, p = 0.016). Patients with bronchiectasis and COPD exhibited more frequent exacerbations, exacerbation-related hospitalizations, and hospitalization in the intensive care unit in the previous year than patients without COPD. Conclusion: This is the first multicenter study of bronchiectasis in Türkiye. The study results will provide important data that can guide the development of health policies in Türkiye on issues such as infection control, vaccination, and the unnecessary use of antibiotics and steroids.

Causal relationship between rheumatoid arthritis and bronchiectasis: a bidirectional mendelian randomization study.

BACKGROUND: Epidemiological observational studies have elucidated a correlation between rheumatoid arthritis (RA) and bronchiectasis. However, the causal nature of this association remains ambiguous. To clarify this potential causal linkage, we conducted a two-sample Mendelian randomization (MR) analysis to explore the bidirectional causality between RA and bronchiectasis. METHODS: Summary statistics for RA and bronchiectasis were obtained from the IEU OpenGWAS database We employed various methods, including inverse variance weighting (IVW), MR-Egger, weighted median, weighted mode, and simple mode, to explore potential causal links between RA and bronchiectasis. Additionally, a series of sensitivity studies, such as Cochran's Q test, MR Egger intercept test, and leave-one-out analysis, were conducted to assess the MR analysis's accuracy further. RESULTS: In the forward MR analysis, the primary analysis indicated that a genetic predisposition to RA correlated with an increased risk of bronchiectasis in European populations (IVW odds ratio (OR): 1.28, 95% confidence interval (CI): 1.20-1.37, p = 1.18E-13). Comparable results were noted in the East Asian subjects (IVW OR: 1.55, 95% CI: 1.30-1.34, p = 8.33E-07). The OR estimates from the other four methods were consistent with those obtained from the IVW method. Sensitivity analysis detected no evidence of horizontal pleiotropy or heterogeneity. Conversely, in the reverse MR analysis, we found no evidence to support a genetic causality between bronchiectasis and RA in either European or East Asian populations. CONCLUSION: This study indicates that genetic predisposition to RA correlates with a heightened risk of bronchiectasis in both European and East Asian populations. These results imply that routine screening for bronchiectasis in RA patients could be beneficial, and effective management of RA may contribute to a reduced risk of bronchiectasis. Future research should aim to clarify the underlying mechanisms linking these two conditions.

Bronchiectasis-associated infections and outcomes in a large, geographically diverse electronic health record cohort in the United States.

BACKGROUND: Bronchiectasis is a pulmonary disease characterized by irreversible dilation of the bronchi and recurring respiratory infections. Few studies have described the microbiology and prevalence of infections in large patient populations outside of specialized tertiary care centers. METHODS: We used the Cerner HealthFacts Electronic Health Record database to characterize the nature, burden, and frequency of pulmonary infections among persons with bronchiectasis. Chronic infections were defined based on organism-specific guidelines. RESULTS: We identified 7,749 patients who met our incident bronchiectasis case definition. In this study population, the organisms with the highest rates of isolate prevalence were Pseudomonas aeruginosa with 937 (12%) individuals, Staphylococcus aureus with 502 (6%), Mycobacterium avium complex (MAC) with 336 (4%), and Aspergillus sp. with 288 (4%). Among persons with at least one isolate of each respective pathogen, 219 (23%) met criteria for chronic P. aeruginosa colonization, 74 (15%) met criteria for S. aureus chronic colonization, 101 (30%) met criteria for MAC chronic infection, and 50 (17%) met criteria for Aspergillus sp. chronic infection. Of 5,795 persons with at least two years of observation, 1,860 (32%) had a bronchiectasis exacerbation and 3,462 (60%) were hospitalized within two years of bronchiectasis diagnoses. Among patients with chronic respiratory infections, the two-year occurrence of exacerbations was 53% and for hospitalizations was 82%. CONCLUSIONS: Patients with bronchiectasis experiencing chronic respiratory infections have high rates of hospitalization.

Evaluating the causal association between bronchiectasis and different types of inflammatory bowel disease: a two-sample Mendelian randomization study.

Background and objectives: Previous observational studies have established a connection between bronchiectasis and inflammatory bowel disease (IBD), but none of these studies have provided a clear explanation for the underlying cause of this relationship. The present study thus implemented Mendelian randomization (MR) design to explore possible bidirectional relationships between IBD and bronchiectasis risk, with an additional focus on Crohn's disease (CD) and ulcerative colitis (UC) as IBD subtypes. Materials and methods: A large genome-wide association study (GWAS)-derived data pool was leveraged to examine the relationships between bronchiectasis and IBD, CD, and UC. Two-sample MR analyses were performed with an inverse variance weighted (IVW) approach supplemented with the MR-Egger and weighted median methods. Sensitivity analyses were used to further assess the reliability of the main MR study findings. The possibility of reverse causation was also evaluated using a reverse MR approach. Results: The IVW MR analytical approach revealed that IBD (p = 0.074), UC (p = 0.094), and CD (p = 0.644) had no significant impact on the incidence of bronchiectasis, with the converse also being true (p = 0.471, p = 0.700, and p = 0.099, respectively). Conclusion: This MR analysis demonstrated that the higher occurrence of bronchiectasis in patients with IBD is not caused by genetic predisposition.

Cardiovascular outcomes following hospitalisation for exacerbation of bronchiectasis: a territory-wide study.

BACKGROUND: Although bronchiectasis is reported to be associated with cardiovascular disease, evidence for an association with cardiovascular events (CVEs) is lacking. METHODS: A territory-wide retrospective cohort study was conducted in Hong Kong involving all patients who had bronchiectasis diagnosed in public hospitals and clinics between 1 January 1993 and 31 December 2017 were included. Patients were allocated to be exacerbator or non-exacerbator group based on hospitalzied bronchiecsis history and CVEs over the next 5 years determined. Propensity score matching was used to balance baseline characteristics. RESULTS: 10 714 bronchiectasis patients (mean age 69.6±14.4 years, 38.9% men), including 1230 in exacerbator group and 9484 in non-exacerbator group, were analysed. At 5 years, 113 (9.2%) subjects in the exacerbator group and 87 (7.1%) in the non-exacerbator group developed composite CVEs. After adjustment for age, sex, smoking and risk factors for cardiovascular disease, bronchiectasis exacerbation was associated with increased risks for acute myocardial infarction (AMI), congestive heart failure (CHF) and CVE compared with those in the non-exacerbator group with adjusted HR of 1.602 (95% CI 1.006-2.552, p value=0.047), 1.371 (95% CI 1.016-1.851, p value=0.039) and 1.238 (95% CI 1.001-1.532, p=0.049) in the whole cohort. Findings were similar for the propensity score-matched cohort for AMI and CVE. CONCLUSION: Patients who were hospitalised for exacerbation of bronchiectasis were at significantly increased risk of AMI, CHF and CVE over a 5-year follow-up period.

Five-Year Outcomes among U.S. Bronchiectasis and NTM Research Registry Patients.

Rationale: Nontuberculous mycobacteria (NTM) are prevalent among patients with bronchiectasis. However, the long-term natural history of patients with NTM and bronchiectasis is not well described. Objectives: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. Methods: Patients in the Bronchiectasis and NTM Research Registry with ⩾5 years of follow-up were eligible. Data were collected for all-cause mortality, lung function, exacerbations, hospitalizations, and disease severity. Outcomes were compared between patients with and without NTM at baseline. Mortality was assessed using Cox proportional hazards models and the log-rank test. Measurements and Main Results: In total, 2,634 patients were included: 1,549 (58.8%) with and 1,085 (41.2%) without NTM at baseline. All-cause mortality (95% confidence interval) at Year 5 was 12.1% (10.5%, 13.7%) overall, 12.6% (10.5%, 14.8%) in patients with NTM, and 11.5% (9.0%, 13.9%) in patients without NTM. Independent predictors of 5-year mortality were baseline FEV1 percent predicted, age, hospitalization within 2 years before baseline, body mass index, and sex (all P < 0.01). The probabilities of acquiring NTM or Pseudomonas aeruginosa were approximately 4% and 3% per year, respectively. Spirometry, exacerbations, and hospitalizations were similar, regardless of NTM status, except that annual exacerbations were lower in patients with NTM (P < 0.05). Conclusions: Outcomes, including exacerbations, hospitalizations, rate of loss of lung function, and mortality rate, were similar across 5 years in patients with bronchiectasis with or without NTM.