Faculty Bibliography

Background: Therapies targeting the inflammatory process revealed inconsistent results in Idiopathic Pulmonary Fibrosis (IPF). Aerosolized Interferon Gamma (IFN-y) has been proposed as a novel therapy. Additionally, changes in the host airway microbiome have been associated with inflammatory tone and, in IPF, may be associated with disease progression.We evaluate whether treatment with aerosolized IFN-y impacts the lower airway microbiome or host immune phenotype. Methods: Patients with IPF were enrolled in an aerosolized IFNy trial. Patients underwent a bronchoscopy at baseline and after 6 months. 16S rRNA sequencing of BAL samples were used to evaluate the lower airway microbiome. Cytokines were measured by Luminex on plasma, BAL fluid and BAL cell supernatant. Findings: IFN-y treatment did not change alpha or beta diversity of the lung microbiome and few taxonomic changes in low abundant taxa occurred (Figure 1). The measured cytokines were unchanged in plasma, however, there was an increase in IFN-y and a decrease in Fit 3 Ligand, IFN-A2 and IL- 5 in BAL cell supernatant, and TNF-B in BAL. Multiple correlations between taxa and inflammatory cytokines were found. Network analysis showed correlations were more abundant between lung microbial taxa and local inflammatory cytokines (either in BAL or by ex vivo BAL cell production) than between lung microbial taxa and systemic inflammatory cytokines. Importantly, analysis showed persistent of these association post IFN treatment. Interpretation: This data suggests that the lower airway microbiome has an independent effect on host immune tone and thus may provide a novel therapeutic target for treatment of IPF

BACKGROUND AND OBJECTIVES/OBJECTIVE:Over 70% of smokers visit a physician annually, and physicians are well-positioned to assist patients in smoking cessation. Residency offers the ideal setting to train physicians in best practices for treatment of nicotine dependence. We hypothesized that experiential learning during a smoking cessation medical clinic (SCMC) rotation would be associated with an improvement in smoking cessation practice of internal medicine (IM) interns in outpatient primary care and inpatient settings. METHODS:This was a prospective study performed at a large university-affiliated hospital. Forty IM interns rotated through SCMC. After a lecture on nicotine addiction and treatment, interns treated SCMC patients under direct supervision of an attending pulmonologist. Interns' smoking cessation practices before and after SCMC rotation were evaluated through chart review over 1 year. Upon study completion, a survey to assess confidence was administered. Paired t tests measured changes in rates of identifying smokers, offering pharmacological treatment and counseling. RESULTS:A total of 5,622 outpatient and 683 inpatient charts of interns' encounters with patients were reviewed. Following SCMC rotation, there was an increase in identifying active smokers (7.1% versus 18.7%), prescribing therapy for smoking cessation (6.5% versus 18.0%), and providing counseling (30.9% versus 42.3%) to outpatients. For inpatients, there was an increase in nicotine replacement during admission (12.9% versus 37.4%) and prescription of therapy upon discharge (5.7% versus 16.1%). Interns reported confidence in providing appropriate counseling and treatment. CONCLUSIONS:SCMC experience positively impacted smoking cessation treatment by IM interns, causing a measurable change in their practice.

INTRODUCTION: Extensively Drug Resistant Tuberculosis (XDR-TB), is uncommon in developed countries with only 63 cases reported in the US between 1993-2011. Treatment is tailored to culture sensitivities with second line anti-tuberculosis (anti-TB) drugs. We report the first case in United States of compassionate use of bedaquiline for the treatment of pulmonary XDR-TB. CASE PRESENTATION: A 30 year-old man, former smoker, with diabetes, presented with fevers and hemoptysis one month after immigrating to New York from a high incidence country. His chest x-ray revealed bilateral cavitary upper lobe infiltrates (Figure 1). Sputum smears for acid-fast bacilli were positive as were cultures for Mycobacterium Tuberculosis. He was empirically started on first-line anti-TB drugs, and his regimen was modified as results from susceptibility testing became available eventually revealing XDR-TB. He was ultimately treated with pyrazinamide, ethionamide, paraminosalycilic acid, cycloserine, capreomycin, amoxicillin/clavulanic, meropenem and linezolid. As a result of multiple adverse effects from his XDR-TB treatment, especially linezolid induced demyelinating peripheral neuropathy, bedaquiline was obtained through a compassionate use program in order to maintain an effective treatment regimen for XDR-TB after the discontinuation of linezolid. He tolerated bedaquiline well experiencing only mild transaminitis and successfully completed his XDR-TB treatment. DISCUSSION: Three cases in the literature pertain to the compassionate use of bedaquiline. In each of these cases, bedaquiline was added in place of a fourth agent in a treatment regimen when there were no additional options remaining. QTC prolongation and increased risk of death have been noted in patients receiving bedaquiline. High incidences of nausea (35.3% vs. 25.7%) and hepatotoxicity (8.8% vs. 1.9%) have also been reported with bedaquiline when compared to placebo. CONCLUSIONS: Bedaquiline is a novel agent for the treatment of Pre-XDR or XDR Tuberculosis. In our patient bedaquiline was added to an effective XDR regimen to ameliorate the side effect profile in order to allow for the successful completion of therapy