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.

Criteria and definitions for the radiological and clinical diagnosis of bronchiectasis in adults for use in clinical trials: international consensus recommendations.

Bronchiectasis refers to both a clinical disease and a radiological appearance that has multiple causes and can be associated with a range of conditions. Disease heterogeneity and the absence of standardised definitions have hampered clinical trials of treatments for bronchiectasis and are important challenges in clinical practice. In view of the need for new therapies for non-cystic fibrosis bronchiectasis to reduce the disease burden, we established an international taskforce of experts to develop recommendations and definitions for clinically significant bronchiectasis in adults to facilitate the standardisation of terminology for clinical trials. Systematic reviews were used to inform discussions, and Delphi processes were used to achieve expert consensus. We prioritised criteria for the radiological diagnosis of bronchiectasis and suggest recommendations on the use and central reading of chest CT scans to confirm the presence of bronchiectasis for clinical trials. Furthermore, we developed a set of consensus statements concerning the definitions of clinical bronchiectasis and its specific signs and symptoms, as well as definitions for chronic bacterial infection and sustained culture conversion. The diagnosis of clinically significant bronchiectasis requires both clinical and radiological criteria, and these expert recommendations and proposals should help to optimise patient recruitment into clinical trials and allow reliable comparisons of treatment effects among different interventions for bronchiectasis. Our consensus proposals should also provide a framework for future research to further refine definitions and establish definitive guidance on the diagnosis of bronchiectasis.

Association between Cardiorespiratory Fitness and Bronchiectasis at CT: A Long-term Population-based Study of Healthy Young Adults Aged 18-30 Years in the CARDIA Study.

Background Protective factors against the risk of bronchiectasis are unknown. A high level of cardiorespiratory fitness is associated with a lower risk of chronic obstructive pulmonary disease. But whether fitness relates to bronchiectasis remains, to the knowledge of the authors, unknown. Purpose To examine the association between cardiorespiratory fitness and bronchiectasis. Materials and Methods This was a secondary analysis of a prospective observational study: the Coronary Artery Risk Development in Young Adults cohort (from 1985-1986 [year 0] to 2015-2016 [year 30]). During a 30-year period, healthy participants (age at enrollment 18-30 years) underwent treadmill exercise testing at year 0 and year 20 visits. Cardiorespiratory fitness was determined according to the treadmill exercise duration. The 20-year difference in cardiorespiratory fitness was used as the fitness measurement. At year 25, chest CT was performed to assess bronchiectasis and was used as the primary outcome. Multivariable logistic models were performed to determine the association between cardiorespiratory fitness changes and bronchiectasis. Results Of 2177 selected participants (at year 0: mean age, 25 years ± 4 [standard deviation]; 1224 women), 209 (9.6%) had bronchiectasis at year 25. After adjusting for age, race-sex group, study site, body mass index, pack-years smoked, history of tuberculosis, pneumonia, asthma and myocardial infarction, peak lung function, and cardiorespiratory fitness at baseline, preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT at year 25 (per 1-minute-longer treadmill duration from year 0 to year 20: odds ratio [OR], 0.88; 95% CI: 0.80, 0.98; P = .02). A consistent strong association was found when cough and phlegm were included in bronchiectasis (OR, 0.72; 95% CI: 0.59, 0.87; P < .001). Conclusion In a long-term follow-up, the preservation of cardiorespiratory fitness was associated with lower odds of bronchiectasis at CT. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Stojanovska in this issue.

Pseudomonas aeruginosa associated with severity of non-cystic fibrosis bronchiectasis measured by the modified bronchiectasis severity score (BSI) and the FACED: The US bronchiectasis and NTM Research Registry (BRR) study.

RATIONALE: Non-cystic fibrosis bronchiectasis (NCFB) is characterized by dilated bronchi, poor mucus clearance and susceptibility to bacterial infection. Pseudomonas aeruginosa (PA) is one of the most frequently isolated pathogens in patients with NCFB. The purpose of this study was to evaluate the association between presence of PA and disease severity in patients within the US Bronchiectasis and Nontuberculous mycobacteria (NTM) Research Registry (BRR). METHODS: Baseline US BRR data from adult patients with NCFB collected between 2008 and 2018 was used for this study. The presence of PA was defined as one or more positive PA cultures within two years prior to enrollment. Modified Bronchiectasis Severity Index (m-BSI) and modified FACED (m-FACED) were computed to evaluate severity of bronchiectasis. Unadjusted and multivariable multinomial regression models were used to assess the association between presence of PA and severity of bronchiectasis. RESULTS: Average age of the study participants (n = 1831) was 63.7 years (SD = 14.1), 91.5% white, and 78.8% female. Presence of PA was identified in 25.4% of the patients. Patients with presence of PA had significantly lower mean pre-bronchodilator FEV1% predicted compared to those without PA (62.8% vs. 73.7%, p < .0001). In multivariate analyses, patients with presence of PA had significantly greater odds for having high (ORadj = 6.15 (95%CI:3.98-9.50) and intermediate (ORadj = 2.06 (95%CI:1.37-3.09) severity vs. low severity on m-BSI. CONCLUSION: The presence of PA is common in patients with NCFB within the Bronchiectasis and NTM Research Registry. Severity of bronchiectasis is significantly greater in patients with PA which emphasizes high burden of the disease.

Nutrition and Markers of Disease Severity in Patients With Bronchiectasis.

BACKGROUND: Increasing numbers of patients are being diagnosed with bronchiectasis, yet much remains to be elucidated about this heterogeneous patient population. We sought to determine the relationship between nutrition and health outcomes in non-cystic fibrosis (non-CF) bronchiectasis, using data from the U.S. Bronchiectasis Nontuberculous Mycobacterial Research Registry (U.S. BRR). METHODS: This was a retrospective, observational, longitudinal study using 5-year follow-up data from the BRR. Bronchiectasis was confirmed on computed tomography (CT). We stratified patients into nutrition categories using body mass index (BMI), and correlated BMI to markers of disease severity. RESULTS: Overall, n = 496 patients (mean age 64.6- ± 13 years; 83.3% female) were included. At baseline 12.3% (n = 61) were underweight (BMI < 18.5kg/m2), 63.9% (n = 317) had normal weight (BMI ≥ 18.5kg/m2 and <25.0kg/m2), 17.3% (n = 86) were overweight (BMI ≥ 25.0kg/m2 and < 30.0kg/m2), and 6.5% (n= 32) were obese (BMI ≥ 30kg/m2). Men were overrepresented in the overweight and obese groups (25.6% and 43.8% respectively, p < 0.0001). Underweight patients had lower lung function (forced expiratory volume in 1 second [FEV1] % predicted) than the other weight groups (64.5 ± 22, versus 73.5 ± 21, 68.5 ± 20, and 76.5 ± 21 in normal, overweight, and obese groups respectively, p = 0.02). No significant differences were noted between BMI groups for other markers of disease severity at baseline, including exacerbation frequency or hospitalization rates. No significant differences were noted in BMI distribution between patients with and without Pseudomonas, non-tuberculous mycobacteria, or by cause of bronchiectasis. The majority of patients demonstrated stable BMI over 5 years. CONCLUSIONS: Although underweight patients with bronchiectasis have lower lung function, lower BMI does not appear to relate to other markers of disease severity in this patient population.

Airway Clearance Techniques in Bronchiectasis: Analysis From the United States Bronchiectasis and Non-TB Mycobacteria Research Registry.

BACKGROUND: In patients with bronchiectasis, airway clearance techniques (ACTs) are important management strategies. RESEARCH QUESTION: What are the differences in patients with bronchiectasis and a productive cough who used ACTs and those who did not? What was the assessment of bronchiectasis exacerbation frequency and change in pulmonary function at 1-year follow up? STUDY DESIGN AND METHODS: Adult patients with bronchiectasis and a productive cough in the United States Bronchiectasis and NTM Research Registry were included in the analyses. ACTs included the use of instrumental devices and manual techniques. Stratified analyses of demographic and clinical characteristics were performed by use of ACTs at baseline and follow up. The association between ACT use and clinical outcomes was assessed with the use of unadjusted and adjusted multinomial logistic regression models. RESULTS: Of the overall study population (n = 905), 59% used ACTs at baseline. A greater proportion of patients who used ACTs at baseline and follow up continuously had Pseudomonas aeruginosa (47% vs 36%; P = .021) and experienced an exacerbation (81% vs 59%; P < .0001) or hospitalization for pulmonary illness (32% vs 22%; P = .001) in the prior two years, compared with those patients who did not use ACTs. Fifty-eight percent of patients who used ACTs at baseline did not use ACTs at 1-year follow up. There was no significant change in pulmonary function for those who used ACTs at follow up, compared with baseline. Patients who used ACTs at baseline and follow up had greater odds for experiencing exacerbations at follow up compared with those patients who did not use ACTs. INTERPRETATION: In patients with bronchiectasis and a productive cough, ACTs are used more often if the patients have experienced a prior exacerbation, hospitalization for pulmonary illness, or had P aeruginosa. There is a significant reduction in the use of ACTs at 1-year follow up. The odds of the development of a bronchiectasis exacerbation are higher in those patients who use ACTs continuously, which suggests more frequent use in an ill bronchiectasis population.

Changes in respiratory symptoms during 48-week treatment with ARD-3150 (inhaled liposomal ciprofloxacin) in bronchiectasis: results from the ORBIT-3 and -4 studies.

It is not known if inhaled antibiotics improve respiratory symptoms in patients with bronchiectasis. In the recent phase-3 ORBIT trials, 48 weeks' treatment with ARD-3150 (inhaled liposomal ciprofloxacin) did not significantly improve symptoms using the prespecified method of analysis comparing baseline symptoms to those after 48 weeks, when patients had been off treatment for 28 days. This method of analysis does not take account of possible improvements in symptoms while on active treatment.A post hoc analysis of two identical randomised trials of ARD-3150 (ORBIT-3 and -4) administered 28 days on and 28 days off in patients with bronchiectasis and chronic Pseudomonas aeruginosa infection. The quality-of-life bronchiectasis respiratory symptom scale (QOL-B-RSS), which has a one-week recall period, was administered every 28 days. We examined whether respiratory symptoms improved during on-treatment periods and the relationship of changes in QOL-B-RSS to changes in bacterial load using a mixed-model repeated measures approach.ARD-3150 treatment resulted in a significant improvement in respiratory symptoms during the on-treatment periods with concordant results between ORBIT-3 (estimate 1.4 points, se 0.49; p=0.004) and ORBIT-4 (estimate 1.1 point, se 0.41; p=0.006). The proportion of patients achieving a symptom improvement above the minimum clinically important difference was higher with ARD-3150 compared with placebo during on-treatment cycles (p=0.024). Changes in respiratory symptoms were correlated with changes in bacterial load in the treatment group (r=-0.89, p<0.0001). Individual estimates for decrements in the QOL-B RSS during exacerbation were -9.4 points (se 0.91) in ORBIT-3 and -10.8 points (0.74) in ORBIT-4 (both p<0.0001).Inhaled ARD-3150 resulted in significant improvements in respiratory symptoms during the on-treatment periods which were lost during off-treatment periods. These results supports the concept that reducing bacterial load can improve respiratory symptoms in patients with bronchiectasis.

Relationship between Symptoms, Exacerbations, and Treatment Response in Bronchiectasis.

Rationale: Bronchiectasis guidelines regard treatment to prevent exacerbation and treatment of daily symptoms as separate objectives.Objectives: We hypothesized that patients with greater symptoms would be at higher risk of exacerbations and therefore that a treatment aimed at reducing daily symptoms would also reduce exacerbations in highly symptomatic patients.Methods: Our study comprised an observational cohort of 333 patients from the East of Scotland (2012-2016). Either symptoms were modeled as a continuous variable or patients were classified as having high, moderate, or low symptom burden (>70, 40-70, and <40 using the St. George's Respiratory Questionnaire symptom score). The hypothesis that exacerbation reductions would only be evident in highly symptomatic patients was tested in a post hoc analysis of a randomized trial of inhaled dry powder mannitol (N = 461 patients).Measurements and Main Results: In the observational cohort, daily symptoms were a significant predictor of future exacerbations (rate ratio [RR], 1.10; 95% confidence interval [CI], 1.03-1.17; P = 0.005). Patients with higher symptom scores had higher exacerbation rates (RR, 1.74; 95% CI, 1.12-2.72; P = 0.01) over 12-month follow-up than those with lower symptoms. Inhaled mannitol treatment improved the time to first exacerbation (hazard ratio, 0.56; 95% CI, 0.40-0.77; P < 0.001), and the proportion of patients remaining exacerbation free for 12 months of treatment was higher in the mannitol group (32.7% vs. 14.6%; RR, 2.84; 95% CI, 1.40-5.76; P = 0.003), but only in highly symptomatic patients. In contrast, no benefit was evident in patients with lower symptom burden.Conclusions: Highly symptomatic patients have increased risk of exacerbations, and exacerbation benefit with inhaled mannitol was only evident in patients with high symptom burden.

The Clinical Features of Bronchiectasis Associated with Alpha-1 Antitrypsin Deficiency, Common Variable Immunodeficiency and Primary Ciliary Dyskinesia--Results from the U.S. Bronchiectasis Research Registry.

OBJECTIVE: This study compares and contrasts the clinical features of non-cystic fibrosis bronchiectasis with 3 uncommon disorders known to be associated with bronchiectasis but with distinctly different underlying defined pathophysiologic derangements, namely severe alpha-1 antitrypsin deficiency (AATD), common variable immunodeficiency (CVI) and primary ciliary dyskinesia (PCD). METHODS: The Bronchiectasis Research Registry provides a central database for studying patients with non-cystic fibrosis bronchiectasis. This report consists of information from 13 U.S. sites pertaining to the 3 study diagnoses. Patients with AATD (SZ and ZZ phenotypes only), CVI (patients with IgG≤500), PCD (history of physician diagnosed Kartagener's syndrome or PCD), and patients with confirmed absence of the above 3 diagnoses (idiopathic control group) were included in the study. Descriptive statistics were computed for the main demographic and clinical characteristics of the sample stratified by group. Values between the groups were compared using Kruskal-Wallis test, and Chi-squared/ Fisher's exact tests respectively. The significance level was set at 0.05. Software SAS 9.4 was used to perform the statistical analyses. RESULTS: Of the 2170 participants in the database enrolled as of January 2017, 615 respondents had sufficient data and were included in the analyses. Patients with PCD (n=79, mean age 41.9 years [standard deviation (SD)=14.5]) were significantly younger than patients with AATD (n=58, mean age 66.9 [SD=10.7]), CVI (n=18, mean age 66.7 years [SD=10.5]) or the idiopathic group (n=460, mean age 64.2 [SD=15.9]), p<.0001. Compared to other groups, those with PCD had lower pulmonary function (forced expiratory volume in 1 second [FEV1] forced vital capacity [FVC] and FEV1/FVC ratio) (p<0.01), and a greater proportion of them reported having exacerbations and/or hospitalizations in the past 2 years (p<0.01). Overall, Pseudomonas aeruginosa and Staphylococcus aureus were the organisms most commonly isolated from sputum. Mycobacterial infection was most commonly reported in those with AATD. CONCLUSION: This report from the U.S. Bronchiectasis Research Registry compares and contrasts differences in the clinical features of patients suffering from 3 rare conditions, with different underlying causes, to those without. The group with PCD had more symptoms, greater morbidity, lower lung function and more commonly were infected by Pseudomonas aeruginosa. A greater percentage of those with AATD reported mycobacterial lung involvement.

Bronchiectasis.

Bronchiectasis is an important clinical syndrome because of its increasing prevalence, substantial economic burden on health care, and associated morbidity. Until recently, the disease was considered an orphan and essentially neglected from a therapeutic standpoint, but many recent advances have been made in the field. Several national registries have formed to provide databases from which to study patients with bronchiectasis. Experts published a consensus definition of a bronchiectasis-specific exacerbation that will serve as a unified definition for future clinical trials. Several inhaled antibiotic trials aimed at reducing exacerbation frequency have been completed. Researchers have investigated nonculture techniques, such as 16S ribosomal RNA (rRNA) and whole genome sequencing, to characterize the microbiological characteristics. Studies of anti-Pseudomonas antibodies are providing interesting insight into varying host responses to chronic Pseudomonas infection. After three successful trials demonstrating that macrolides reduce exacerbations in bronchiectasis, other antiinflammatory agents have been investigated, and a trial of a novel antiinflammatory drug is ongoing. A relatively robust study has been published in airway clearance, a therapy that is accepted universally as beneficial but that has never been accompanied by strong evidence. To build on the successes with bronchiectasis thus far, investigators must develop better definitions of phenotypes of bronchiectasis. In this regard, clinical tools have been developed to quantify disease severity and predict prognosis. Studies of different clinical phenotypes of bronchiectasis in patients with bronchiectasis have been published. With continued advances in the field of bronchiectasis, there is hope that evidenced-based therapies will become available.

The Prevalence and Significance of Staphylococcus aureus in Patients with Non-Cystic Fibrosis Bronchiectasis.

RATIONALE: Staphylococcus aureus is commonly cultured from the sputum of patients with bronchiectasis; however, little is known about the prevalence of the organism in these patients, the characteristics of patients who have grown the organism, or its implications. OBJECTIVES: Determine the relationship between S. aureus and pulmonary function, frequency of exacerbations, and frequency of hospitalization in patients with bronchiectasis Methods: The Bronchiectasis Research Registry is a database of adults with non-cystic fibrosis bronchiectasis identified from 13 sites within the United States. Baseline and follow-up demographic, spirometric, microbiologic, and therapeutic data were entered into a central web-based database. Patients were grouped into three cohorts based on their previous respiratory cultures at the time of entry into the Registry: 1) no prior S. aureus or glucose-nonfermenting gram-negative bacilli (NF-GNB) (Pseudomonas, Stenotrophomonas, or Burkholderia spp.); 2) prior S. aureus at least once; or 3) no prior S. aureus but prior NF-GNB at least once. The association between S. aureus isolation and pulmonary function and frequency of exacerbations and hospital admissions was assessed, both at baseline and after 1 year of follow-up. RESULTS: S. aureus was cultured from 94 of 830 patients (11.3%) included in the analysis. Patients who had grown S. aureus before entry into the Registry had a frequency of prior exacerbations and baseline pulmonary function that was between that of patients who had grown NF-GNB and those who had grown neither NF-GNB or S. aureus. Similarly, at the first follow-up visit after study entry, patients who had grown S. aureus had a frequency of exacerbations and hospitalizations that was between those of patients who had grown NF-GNB and those who had grown neither NF-GNB nor S. aureus. However, in multivariate analysis, S. aureus was not associated with pulmonary function, frequency of exacerbation, or hospital admissions. There were no significant differences in patient characteristics or outcomes between patients who had methicillin-sensitive and methicillin-resistant S. aureus. CONCLUSIONS: Staphylococcus aureus does not appear to be an independent risk factor for severe disease in patients with bronchiectasis enrolled in the Bronchiectasis Research Registry.

Pulmonary exacerbation in adults with bronchiectasis: a consensus definition for clinical research.

There is a need for a clear definition of exacerbations used in clinical trials in patients with bronchiectasis. An expert conference was convened to develop a consensus definition of an exacerbation for use in clinical research.A systematic review of exacerbation definitions used in clinical trials from January 2000 until December 2015 and involving adults with bronchiectasis was conducted. A Delphi process followed by a round-table meeting involving bronchiectasis experts was organised to reach a consensus definition. These experts came from Europe (representing the European Multicentre Bronchiectasis Research Collaboration), North America (representing the US Bronchiectasis Research Registry/COPD Foundation), Australasia and South Africa.The definition was unanimously approved by the working group as: a person with bronchiectasis with a deterioration in three or more of the following key symptoms for at least 48 h: cough; sputum volume and/or consistency; sputum purulence; breathlessness and/or exercise tolerance; fatigue and/or malaise; haemoptysis AND a clinician determines that a change in bronchiectasis treatment is required.The working group proposes the use of this consensus-based definition for bronchiectasis exacerbation in future clinical research involving adults with bronchiectasis.

Acute exacerbations in the INPULSIS trials of nintedanib in idiopathic pulmonary fibrosis.

Time to first investigator-reported acute exacerbation was a key secondary end-point in the INPULSIS trials of nintedanib in patients with idiopathic pulmonary fibrosis (IPF).We used the INPULSIS trial data to investigate risk factors for acute exacerbation of IPF and to explore the impact of nintedanib on risk and outcome of investigator-reported and adjudicated confirmed/suspected acute exacerbations. Mortality following these events and events adjudicated as not acute exacerbations was analysed using the log rank test.Risk of acute exacerbations was most strongly associated with the following variables: baseline forced vital capacity (higher risk with lower value), baseline supplemental oxygen (higher risk with use), baseline antacid medication (higher risk with use), treatment (higher risk with placebo), and for confirmed/suspected acute exacerbations, cigarette smoking. Mortality was similar following investigator-reported and adjudicated confirmed/suspected acute exacerbations. Nintedanib had no significant effect on risk of mortality post-exacerbation.Investigator-reported acute exacerbations of IPF are associated with similar risk factors and outcomes as adjudicated confirmed/suspected acute exacerbations.

Pharmacotherapy for Non-Cystic Fibrosis Bronchiectasis: Results From an NTM Info & Research Patient Survey and the Bronchiectasis and NTM Research Registry.

BACKGROUND: Non-cystic fibrosis bronchiectasis ("bronchiectasis") is a chronic inflammatory lung disease often associated with nontuberculous mycobacteria (NTM) infection. Very little data exist to guide bronchiectasis management decisions. We sought to describe patterns of inhaled corticosteroid (ICS) and antibiotic therapy in the United States. METHODS: We invited 2,000 patients through NTM Info & Research (NTMir) to complete an anonymous electronic survey. We separately queried baseline clinical and laboratory data from the US Bronchiectasis and NTM Research Registry (BRR). RESULTS: Among 511 NTMir survey responders with bronchiectasis, whose median age was 67 years, 85 (17%) reported asthma and 99 (19%) reported COPD. History of ICS use was reported by 282 (55%), 171 (61%) of whom were treated 1 year or longer, and 150 (53%) were currently taking ICSs. Fewer reported ever taking azithromycin for non-NTM bronchiectasis (203 responders [40%]) or inhaled tobramycin (78 responders [15%]). The median age of 1,912 BRR patients was 69 years; 528 (28%) had asthma and 360 (19%) had COPD. Among 740 patients (42%) without NTM, 314 were taking ICSs at baseline. Among patients without NTM who were taking ICSs, only 178 (57%) had a concurrent diagnosis of COPD or asthma that could explain ICS use. Fewer were taking suppressive macrolides (96 patients [13%]), and of the 70 patients (10%) taking inhaled suppressive antibiotics, 48 (68%) had chronic Pseudomonas aeruginosa infection. CONCLUSIONS: ICS use was common in two national samples of patients with bronchiectasis, with relatively few patients taking suppressive antibiotic therapies. Further research is needed to clarify the safety and effectiveness of these therapies in patients with bronchiectasis.

Adult Patients With Bronchiectasis: A First Look at the US Bronchiectasis Research Registry.

OBJECTIVES: We sought to describe the characteristics of adult patients with bronchiectasis enrolled in the US Bronchiectasis Research Registry (BRR). METHODS: The BRR is a database of patients with non-cystic-fibrosis bronchiectasis (NCFB) enrolled at 13 sites in the United States. Baseline demographic, spirometric, imaging, microbiological, and therapeutic data were entered into a central Internet-based database. Patients were subsequently analyzed by the presence of NTM. RESULTS: We enrolled 1,826 patients between 2008 and 2014. Patients were predominantly women (79%), white (89%), and never smokers (60%), with a mean age of 64 ± 14 years. Sixty-three percent of the patients had a history of NTM disease or NTM isolated at baseline evaluation for entry into the BRR. Patients with NTM were older, predominantly women, and had bronchiectasis diagnosed at a later age than those without NTM. Gastroesophageal reflux disease (GERD) was more common in those with NTM, whereas asthma, primary immunodeficiency, and primary ciliary dyskinesia were more common in those without NTM. Fifty-one percent of patients had spirometric evidence of airflow obstruction. Patients with NTM were more likely to have diffusely dilated airways and tree-in-bud abnormalities. Pseudomonas and Staphylococcus aureus isolates were cultured less commonly in patients with NTM. Bronchial hygiene measures were used more often in those with NTM, whereas antibiotics used for exacerbations, rotating oral antibiotics, steroid use, and inhaled bronchodilators were more commonly used in those without NTM. CONCLUSIONS: Adult patients with bronchiectasis enrolled in the US BRR are described, with differences noted in demographic, radiographic, microbiological, and treatment variables based on stratification of the presence of NTM.

Inhaled mannitol for non-cystic fibrosis bronchiectasis: a randomised, controlled trial.

RATIONALE: Bronchiectasis is characterised by excessive production of mucus and pulmonary exacerbations. Inhaled osmotic agents may enhance mucociliary clearance, but few long-term clinical trials have been conducted. OBJECTIVES: To determine the impact of inhaled mannitol on exacerbation rates in patients with non-cystic fibrosis (CF) bronchiectasis. Secondary endpoints included time to first exacerbation, duration of exacerbations, antibiotic use for exacerbations and quality of life (QOL) (St George's Respiratory Questionnaire, SGRQ). METHODS: Patients with non-CF bronchiectasis and a history of chronic excess production of sputum and ≥2 pulmonary exacerbations in the previous 12 months were randomised (1:1) to 52 weeks treatment with inhaled mannitol 400 mg or low-dose mannitol control twice a day. Patients were 18-85 years of age, baseline FEV1 ≥40% and ≤85% predicted and a baseline SGRQ score ≥30. MAIN RESULTS: 461 patients (233 in the mannitol and 228 in the control arm) were treated. Baseline demographics were similar in the two arms. The exacerbation rate was not significantly reduced on mannitol (rate ratio 0.92, p=0.31). However, time to first exacerbation was increased on mannitol (HR 0.78, p=0.022). SGRQ score was improved on mannitol compared with low-dose mannitol control (-2.4 units, p=0.046). Adverse events were similar between groups. CONCLUSIONS: Mannitol 400 mg inhaled twice daily for 12 months in patients with clinically significant bronchiectasis did not significantly reduce exacerbation rates. There were statistically significant improvements in time to first exacerbation and QOL. Mannitol therapy was safe and well tolerated. TRIAL REGISTRATION NUMBER: NCT00669331.

Non-cystic fibrosis bronchiectasis.

There is renewed interest in non-cystic fibrosis bronchiectasis, which is a cause of significant morbidity in adults and can be diagnosed by high-resolution chest computed tomography scan. No longer mainly a complication after pulmonary infection with Mycobacterium tuberculosis, diverse disease processes and mechanisms have been demonstrated to result in the chronic cough, purulent sputum production, and airway dilation that characterize this disease. Improved understanding of the role of mucus stasis in causing bacterial colonization has led to increased emphasis on the use of therapies that enhance airway clearance. Inhalational antibiotics reduce the bacterial burden associated with a worse outcome. Low-dose, chronic macrolide therapy has been shown to decrease exacerbation frequency and airway inflammation. For the first time, a number of therapies for non-cystic fibrosis bronchiectasis are undergoing testing in clinical research trials designed specifically for this population. This concise clinical review focuses on the major etiologies, diagnostic testing, microbiology, and management of patients with adult non-cystic fibrosis bronchiectasis. Systematic evaluation identifies a specific cause in the majority of patients and may affect subsequent treatment. We outline current therapies and review the data that support their use.