Faculty Bibliography

Rationale Lengthy multi-drug, toxic, and low efficacy regimens limit management of pulmonary nontuberculous mycobacterial (PNTM) disease. Objective This phase 2 study investigated efficacy and safety of liposomal amikacin for inhalation (LAI) in treatment-refractory PNTM (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 multi-drug regimen for 84 days. Both groups could receive open-label LAI for 84 additional days. Primary endpoint was change from baseline to day 84 on a semi-quantitative mycobacterial growth scale. Other endpoints included sputum conversion, 6-minute walk distance, and adverse events. Measurements and Main Results Modified intent-to-treat population included 89 (LAI=44; placebo=45) patients. Average age was 59 years, 88% were female, 92% were Caucasian; 80 and 59 patients completed study drug dosing during the double-blind and open-label phases, respectively. Primary endpoint was not achieved (P=0.072); however, a greater proportion of the LAI group demonstrated >/=1 negative sputum cultures (32% [14/44] vs. 9% [4/45]; P=0.006) and improvement in 6-minute walk test (+20.6 vs. -25.0 meters; P=0.017) at day 84. Treatment effect was predominantly in patients without cystic fibrosis with MAC and was sustained 1 year post-LAI. Most adverse events were respiratory and in some patients led to drug discontinuation. Conclusions Although the primary endpoint was not reached, LAI added to a multi-drug regimen produced improvements in sputum conversion and 6-minute walk distance vs. placebo with limited systemic toxicity in patients with refractory MAC lung disease. Further research is needed. Clinical trial registration available at www.clinicaltrials.gov, ID NCT01315236.

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.

RATIONALE: Most trainees in combined Pulmonary and Critical Care Medicine fellowship programs complete in-training examinations (ITE) that tests knowledge in both disciplines. Whether ITE scores predict performance on the American Board of Internal Medicine (ABIM) Pulmonary Disease and Critical Care Medicine Certification Examinations is unknown. OBJECTIVES: To determine whether Pulmonary and Critical Care Medicine ITE scores predict performance on subspecialty board certification examinations independent of trainee demographics, program director competency ratings, fellowship program characteristics, and prior medical knowledge assessments. METHODS: 1st and 2nd year fellows that enrolled in the study from 2008 to 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 ABIM 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 2nd year fellows was matched to their certification examination score and yielded 1,484 physicians for pulmonary disease and 1,331 for critical care medicine. Second year fellows' ITE score (beta = 0.24, p < 0.001) and Internal Medicine Certification Examination score (beta = 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: OR = 1.12 [95% CI: 1.07, 1.16]; Internal Medicine Certification Examination: OR = 1.01 [95% CI: 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 1st year fellows on the subspecialty certification examinations was comparable to 2nd 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.