Five-Year Outcomes Among U.S. Bronchiectasis and Nontuberculous Mycobacterial 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. OBJECTIVE: To assess the impact of NTM on 5-year clinical outcomes and mortality in patients with bronchiectasis. METHODS: Patients in the United States Bronchiectasis and Nontuberculous Mycobacteria 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 forced expiratory volume in 1 second % predicted, age, hospitalization within 2 years before baseline, body mass index, and gender (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 irrespective 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.

Long-term Safety and Tolerability of Omadacycline for the Treatment of Mycobacterium abscessus Infections.

Background: Mycobacterium abscessus is a virulent human pathogen. Treatment is complex and often poorly tolerated with suboptimal rates of eradication, highlighting the need for improved therapeutics. This study reports clinical experience with omadacycline for treatment of M abscessus infections at five large nontuberculous mycobacterial (NTM) disease clinics across the United States to better understand long-term safety and tolerability. Methods: We conducted a multicenter retrospective chart review of adults with M abscessus infections. All patients treated with omadacycline as part of a multidrug therapeutic regimen through December 2021 were included. Clinical data from time of omadacycline initiation and up to 12 months of follow-up were collected. Descriptive statistics were performed. Results: Analysis included 117 patients. Among patients with M abscessus isolate subspeciation, 58 of 71 (81.7%) were M abscessus spp abscessus. In isolates with reported drug susceptibility testing, 15 of 70 (21.4%) had confirmed susceptibility to macrolides. The most common site of infection was lungs. Median duration omadacycline treatment was 8 months (range, 0.25-33 months; interquartile range, 4-15 months). Omadacycline was discontinued in 60 patients (51.3%); 20 completed planned treatment course, 23 experienced intolerance or adverse event leading to drug cessation, and 17 stopped due to cost, death (unrelated to NTM infection or therapy), or another reason. In those with pulmonary disease, 44 of 95 (46%) had 1 or more negative cultures at time of final microbiological assessment, with 17 of 95 (18%) achieving culture conversion. Conclusions: This study reports data supporting long-term safety and tolerability of omadacycline along with signal of effectiveness in treatment of M abscessus infections.

Role of small airway dysfunction in unexplained exertional dyspnoea.

Background: Isolated small airway abnormalities may be demonstrable at rest in patients with normal spirometry; however, the relationship of these abnormalities to exertional symptoms remains uncertain. This study uses an augmented cardiopulmonary exercise test (CPET) to include evaluation of small airway function during and following exercise to unmask abnormalities not evident with standard testing in individuals with dyspnoea and normal spirometry. Methods: Three groups of subjects were studied: 1) World Trade Center (WTC) dust exposure (n=20); 2) Clinical Referral (n=15); and Control (n=13). Baseline evaluation included respiratory oscillometry. Airway function during an incremental workload CPET was assessed by: 1) tidal flow versus volume curves during exercise to assess for dynamic hyperinflation and expiratory flow limitation; and 2) post-exercise spirometry and oscillometry to evaluate for airway hyperreactivity. Results: All subjects demonstrated normal baseline forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC). Dyspnoea was reproduced during CPET in WTC and Clinical Referral groups versus Control without abnormality in respiratory pattern and minute ventilation. Tidal flow-volume curves uncovered expiratory flow limitation and/or dynamic hyperinflation with increased prevalence in WTC and Clinical Referral versus Control (55%, 87% versus 15%; p<0.001). Post-exercise oscillometry uncovered small airway hyperreactivity with increased prevalence in WTC and Clinical Referral versus Control (40%, 47% versus 0%, p<0.05). Conclusions: We uncovered mechanisms for exertional dyspnoea in subject with normal spirometry that was attributable to either small airway dysfunction during exercise and/or small airway hyperreactivity following exercise. The similarity of findings in WTC environmentally exposed and clinically referred cohorts suggests broad relevance for these evaluations.

Cardiovascular Critical Care Training: A Collaboration between Intensivists and Cardiologists.

With growing patient complexity, the cardiovascular intensive care unit (CICU) of today has evolved substantially from the coronary care unit (CCU) of decades ago. The growing burden of noncardiac critical illness and highly specialized acute cardiovascular disease requires a degree of expertise beyond that afforded through a general cardiology training program. Therefore, the American Heart Association (AHA) has proposed a CICU staffing model to include dedicated cardiac intensivists; in the present day, "dual-trained" physicians are extremely sparse. Guidance on designing critical care fellowships for cardiologists is limited but will require collaboration between cardiologists and medical intensivists. Here, we review the evolution of the CICU, describe training pathways, and offer guidance on creating a cardiology critical care training program.

Amikacin Liposome Inhalation Suspension for Refractory Mycobacterium avium Complex Lung Disease: Sustainability and Durability of Culture Conversion and Safety of Long-term Exposure.

BACKGROUND: In the CONVERT study, treatment with amikacin liposome inhalation suspension (ALIS) added to guideline-based therapy (GBT) met the primary end point of increased culture conversion by month 6 in patients with treatment-refractory Mycobacterium avium complex lung disease (ALIS plus GBT, 29% [65/224] vs GBT alone, 8.9% [10/112]; P < .0001). RESEARCH QUESTION: In patients who achieved culture conversion by month 6 in the CONVERT study, was conversion sustained (negative sputum culture results for 12 months with treatment) and durable (negative sputum culture results for 3 months after treatment) and were there any additional safety signals associated with a full treatment course of 12 months after conversion? STUDY DESIGN AND METHODS: Adults were randomized 2:1 to receive ALIS plus GBT or GBT alone. Patients achieving culture conversion by month 6 continued therapy for 12 months followed by off-treatment observation. RESULTS: More patients randomized to ALIS plus GBT (intention-to-treat population) achieved conversion that was both sustained and durable 3 months after treatment vs patients randomized to GBT alone (ALIS plus GBT, 16.1% [36/224] vs GBT alone, 0% [0/112]; P < .0001). Of the patients who achieved culture conversion by month 6, 55.4% of converters (36/65) in the ALIS plus GBT treated arm vs no converters (0/10) in the GBT alone arm achieved sustained and durable conversion (P = .0017). Relapse rates through 3 months after treatment were 9.2% (6/65) in the ALIS plus GBT arm and 30.0% (3/10) in the GBT alone arm. Common adverse events among ALIS plus GBT-treated patients (dysphonia, cough, dyspnea, hemoptysis) occurred mainly within the first 8 months of treatment. INTERPRETATION: In a refractory population, conversion was sustained and durable in more patients treated with ALIS plus GBT for 12 months after conversion than in those treated with GBT alone. No new safety signals were associated with 12 months of treatment after conversion. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT02344004; URL: www.clinicaltrials.gov.

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.

Clinical Outcomes in Critically Ill Coronavirus Disease 2019 Patients: A Unique New York City Public Hospital Experience.

To explore demographics, comorbidities, transfers, and mortality in critically ill patients with confirmed severe acute respiratory syndrome coronavirus 2. DESIGN: Retrospective cohort study. SETTING: Data were collected from a large tertiary care public hospital ICU that is part of the largest public healthcare network in the United States. PATIENTS: One-hundred thirty-seven adult (≥ 18 yr old) ICU patients admitted between March 10, 2020, and April 7, 2020, with follow-up collected through May 18, 2020. INTERVENTIONS: None. MEASUREMENTS: Demographic, clinical, laboratory, treatment, and outcome data extracted from electronic medical records. MAIN RESULTS: The majority of patients were male (99/137; 72.3%) and older than 50 years old (108/137; 78.9%). The most reported ethnicity and race were Hispanic (61/137; 44.5%) and Black (23/137; 16.7%). One-hundred six of 137 patients had at least one comorbidity (77.4%). One-hundred twenty-one of 137 (78.1%) required mechanical ventilation of whom 30 (24.8%) moved to tracheostomy and 46 of 137 (33.6%) required new onset renal replacement therapy. Eighty-two of 137 patients (59.9%) died after a median of 8 days (interquartile range 5-15 d) in the ICU. Male sex had a trend toward a higher hazard of death (hazard ratio, 2.1 [1.1-4.0]) in the multivariable Cox model. CONCLUSIONS: We report a mortality rate of 59.9% in a predominantly Hispanic and Black patient population. A significant association between comorbidities and mortality was not found in multivariable regression, and further research is needed to study factors that impact mortality in critical coronavirus disease 2019 patients. We also describe how a public hospital developed innovative approaches to safely manage a large volume of interhospital transfers and admitted patients.

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.

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.

Amikacin Liposome Inhalation Suspension for Treatment-Refractory Lung Disease Caused by Mycobacterium avium Complex (CONVERT). A Prospective, Open-Label, Randomized Study.

Rationale: Improved therapeutic options are needed for patients with treatment-refractory nontuberculous mycobacterial lung disease caused by Mycobacterium avium complex (MAC). Objectives: To evaluate the efficacy and safety of daily amikacin liposome inhalation suspension (ALIS) added to standard guideline-based therapy (GBT) in patients with refractory MAC lung disease. Methods: Adults with amikacin-susceptible MAC lung disease and MAC-positive sputum cultures despite at least 6 months of stable GBT were randomly assigned (2:1) to receive ALIS with GBT (ALIS + GBT) or GBT alone. Once-daily ALIS was supplied in single-use vials delivering 590 mg amikacin to the nebulizer. The primary endpoint was culture conversion, defined as three consecutive monthly MAC-negative sputum cultures by Month 6. Measurements and Main Results: Enrolled patients (ALIS + GBT, n = 224; GBT-alone, n = 112) were a mean 64.7 years old and 69.3% female. Most had underlying bronchiectasis (62.5%), chronic obstructive pulmonary disease (14.3%), or both (11.9%). Culture conversion was achieved by 65 of 224 patients (29.0%) with ALIS + GBT and 10 of 112 (8.9%) with GBT alone (odds ratio, 4.22; 95% confidence interval, 2.08-8.57; P < 0.001). Patients in the ALIS + GBT arm versus GBT alone were more likely to achieve conversion (hazard ratio, 3.90; 95% confidence interval, 2.00-7.60). Respiratory adverse events (primarily dysphonia, cough, and dyspnea) were reported in 87.4% of patients receiving ALIS + GBT and 50.0% receiving GBT alone; serious treatment-emergent adverse events occurred in 20.2% and 17.9% of patients, respectively. Conclusions: Addition of ALIS to GBT for treatment-refractory MAC lung disease achieved significantly greater culture conversion by Month 6 than GBT alone, with comparable rates of serious adverse events. Clinical trial registered with www.clinicaltrials.gov (NCT02344004).

Evaluation of the airway microbiome in nontuberculous mycobacteria disease.

Aspiration is associated with nontuberculous mycobacterial (NTM) pulmonary disease and airway dysbiosis is associated with increased inflammation. We examined whether NTM disease was associated with a distinct airway microbiota and immune profile.297 oral wash and induced sputum samples were collected from 106 participants with respiratory symptoms and imaging abnormalities compatible with NTM. Lower airway samples were obtained in 20 participants undergoing bronchoscopy. 16S rRNA gene and nested mycobacteriome sequencing approaches characterised microbiota composition. In addition, inflammatory profiles of lower airway samples were examined.The prevalence of NTM+ cultures was 58%. Few changes were noted in microbiota characteristics or composition in oral wash and sputum samples among groups. Among NTM+ samples, 27% of the lower airway samples were enriched with Mycobacterium A mycobacteriome approach identified Mycobacterium in a greater percentage of samples, including some nonpathogenic strains. In NTM+ lower airway samples, taxa identified as oral commensals were associated with increased inflammatory biomarkers.The 16S rRNA gene sequencing approach is not sensitive in identifying NTM among airway samples that are culture-positive. However, associations between lower airway inflammation and microbiota signatures suggest a potential role for these microbes in the inflammatory process in NTM disease.

Management of nontuberculous mycobacterial pulmonary disease.

PURPOSE OF REVIEW: To highlight recent original research and specialty society guidelines regarding the diagnosis and treatment of nontuberculous mycobacterial (NTM) pulmonary disease. RECENT FINDINGS: The prevalence of NTM pulmonary disease has risen in recent years. The prevalence of individual NTM species varies geographically, although Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MABC) remain among the most commonly encountered in many regions. Diagnosis and treatment of NTM pulmonary disease can be complex but guideline-based recommendations have been published. However, adherence to guideline recommendations is poor. Drug susceptibility testing plays a role with important caveats for treatment. Alternative therapies are being explored with older antimycobacterial drugs like clofazimine, which has demonstrated efficacy and tolerability for treatment-refractory NTM infections, and a novel formulation of amikacin for inhalation which may be better tolerated than parenteral administration. Several studies have shown that patients will have recurrences as high as 48%, and that these are not solely relapses but many cases are reinfections with a new organism. United States and European research registries of patients with non-cystic fibrosis bronchiectasis are expected to provide needed data on clinical characteristics of patients at risk for NTM pulmonary disease. SUMMARY: The evidence base for optimal management of NTM pulmonary disease is expanding but notable gaps in the literature remain.

Effects of Chest Physical Therapy in Patients with Non-Tuberculous Mycobacteria.

Antibiotic therapy against non-tuberculous mycobacteria (NTM) is prolonged and can be associated with toxicity. We sought to evaluate whether chest physical therapy (PT) was associated with clinical improvement in patients with NTM not receiving anti-mycobacterial pharmacotherapy. A retrospective review of 77 subjects that were followed from June 2006 to September 2014 was performed. Baseline time point was defined as the first positive sputum culture for NTM; symptoms, pulmonary function, and radiology reports were studied. Subjects were followed for up to 24 months and results analyzed at specified time points. Half of the subjects received chest PT at baseline. Cough improved at 12 (p = 0.001) and 24 months (p = 0.003) in the overall cohort when compared with baseline, despite lack of NTM antibiotic treatment. Cough decreased at 6 (p = 0.01), 9 (p = 0.02), 12 (p = 0.02) and 24 months (p = 0.002) in subjects that received chest PT. Sputum production also improved at 24 months in the overall cohort (p = 0.01). There was an increase in the percent change of total lung capacity in subjects that received chest PT (p = 0.005). Select patients with NTM may have clinical improvement with chest PT, without being subjected to prolonged antibiotic therapy. Future studies are warranted to prospectively evaluate outcomes in the setting of non-pharmacologic treatment and aid with the decision of antibiotic initiation.

Randomized Trial of Liposomal Amikacin for Inhalation in Nontuberculous Mycobacterial Lung Disease.

RATIONALE: Lengthy, multidrug, toxic, and low-efficacy regimens limit management of pulmonary nontuberculous mycobacterial disease. OBJECTIVES: In this phase II study, we investigated the efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory pulmonary nontuberculous mycobacterial (Mycobacterium avium complex [MAC] or Mycobacterium abscessus) disease. METHODS: During the double-blind phase, patients were randomly assigned to LAI (590 mg) or placebo once daily added to their multidrug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. The primary endpoint was change from baseline to Day 84 on a semiquantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute-walk distance, and adverse events. MEASUREMENTS AND MAIN RESULTS: The modified intention-to-treat population included 89 (LAI = 44; placebo = 45) patients. The average age of the sample was 59 years; 88% were female; 92% were white; and 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. The primary endpoint was not achieved (P = 0.072); however, a greater proportion of the LAI group demonstrated at least one negative sputum culture (14 [32%] of 44 vs. 4 [9%] of 45; P = 0.006) and improvement in 6-minute-walk test (+20.6 m vs. -25.0 m; P = 0.017) at Day 84. A treatment effect was seen predominantly in patients without cystic fibrosis with MAC and was sustained 1 year after LAI. Most adverse events were respiratory, and in some patients it led to drug discontinuation. CONCLUSIONS: Although the primary endpoint was not reached, LAI added to a multidrug regimen produced improvements in sputum conversion and 6-minute-walk distance versus placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research in this area is needed. Clinical trial registered with www.clinicaltrials.gov (NCT01315236).

Pulmonary and Critical Care In-Service Training Examination Score as a Predictor of Board Certification Examination Performance.

RATIONALE: Most trainees in combined pulmonary and critical care medicine fellowship programs complete in-service training examinations (ITEs) that test knowledge in both disciplines. Whether ITE scores predict performance on the American Board of Internal Medicine Pulmonary Disease Certification Examination and Critical Care Medicine Certification Examination is unknown. OBJECTIVES: To determine whether pulmonary and critical care medicine ITE scores predict performance on subspecialty board certification examinations independently of trainee demographics, program director competency ratings, fellowship program characteristics, and prior medical knowledge assessments. METHODS: First- and second-year fellows who were enrolled in the study between 2008 and 2012 completed a questionnaire encompassing demographics and fellowship training characteristics. These data and ITE scores were matched to fellows' subsequent scores on subspecialty certification examinations, program director ratings, and previous scores on their American Board of Internal Medicine Internal Medicine Certification Examination. Multiple linear regression and logistic regression were used to identify independent predictors of subspecialty certification examination scores and likelihood of passing the examinations, respectively. MEASUREMENTS AND MAIN RESULTS: Of eligible fellows, 82.4% enrolled in the study. The ITE score for second-year fellows was matched to their certification examination scores, which yielded 1,484 physicians for pulmonary disease and 1,331 for critical care medicine. Second-year fellows' ITE scores (ß = 0.24, P < 0.001) and Internal Medicine Certification Examination scores (ß = 0.49, P < 0.001) were the strongest predictors of Pulmonary Disease Certification Examination scores, and were the only significant predictors of passing the examination (ITE odds ratio, 1.12 [95% confidence interval, 1.07-1.16]; Internal Medicine Certification Examination odds ratio, 1.01 [95% confidence interval, 1.01-1.02]). Similar results were obtained for predicting Critical Care Medicine Certification Examination scores and for passing the examination. The predictive value of ITE scores among first-year fellows on the subspecialty certification examinations was comparable to second-year fellows' ITE scores. CONCLUSIONS: The Pulmonary and Critical Care Medicine ITE score is an independent, and stronger, predictor of subspecialty certification examination performance than fellow demographics, program director competency ratings, and fellowship characteristics. These findings support the use of the ITE to identify the learning needs of fellows as they work toward subspecialty board certification.

Reduced lung function in smokers in a lung cancer screening cohort with asbestos exposure and pleural plaques.

BACKGROUND: While low dose computed tomography (LDCT) screening for lung cancer is recommended for high-risk smokers, ages 55-74 years, information about asbestos exposure may not be routinely elicited. Asbestos exposure is associated with declining respiratory function over time; however, the effect of a history of asbestos exposure in LDCT screening cohorts is limited. We report the relationship between asbestos exposure and pulmonary function in a cohort of heavy smokers with a history of occupational asbestos exposure, hypothesizing that these subjects will have additional decreased pulmonary function. We also examined relationships between spirometric measurements and the presence of isolated pleural plaques. METHODS: A cross-sectional study was performed using data from the NYU Lung Cancer Biomarker Center cohort to compare study subjects with a history asbestos exposure primarily in the period since 1970 when tighter federal standards were in place (n = 359) to those without asbestos exposure (n = 1038) with respect to pulmonary function, LDCT lung imaging findings, and clinical symptoms. We further classified individuals with asbestos exposure by length of exposure time to examine the effect of duration of exposure on pulmonary function. Lastly, for asbestos-exposed participants, we examined the association of spirometric measurements with the presence of absence of isolated pleural plaques. RESULTS: Individuals with asbestos exposure had decreased FVC % predicted compared to those with no asbestos exposure (76% vs. 85% predicted, P < 0.01) and FEV1 % predicted (64% vs. 67% predicted, P < 0.01). Since there was no change in FEV1 /FVC ratio, the findings are consistent with restrictive impairment. Those with ≥20 years of exposure had a lower mean FVC % predicted compared to those with less than 20 years of exposure (74% vs. 78% predicted, P = 0.017). Individuals with asbestos exposure were more likely to have pleural plaques (P < 0.001) on CT. Those with isolated pleural plaques had lower mean % predicted FEV1 (P = 0.005) and FVC (P = 0.001) compared to those without pleural plaques. CONCLUSIONS: Occupational asbestos exposure in a cohort of heavy smokers was associated with a significant restrictive decline in pulmonary function, with longer duration of exposure associated with greater decline. The presence of isolated pleural plaques was also associated with reduced lung function.

Successful treatment of ulcerative bronchiolitis in a woman with refractory Mycobacterium intracellulare infection.

We present a case of a woman with medically refractory ulcerative colitis (UC) who developed severe bronchiectasis, bronchitis, bronchiolitis and Mycobacterium intracellulare (MAC) infection 2 years after total colectomy. Despite being on optimal therapy for her MAC and sterilising multiple consecutive sputum cultures, she remained highly symptomatic, and this led to further investigations that revealed the presence of UC-related airways disease. Addition of immunosuppressive therapy to her antimycobacterial treatment resulted in sustained and complete clinical remission of her disease. To our knowledge, this is the only case published in the literature that describes a case of successful treatment of concomitant UC-related pulmonary disease and symptomatic MAC.