Charles A. Read

Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial

Summary BACKGROUND Twelve months of oral cyclophosphamide (CYC) has been shown to alter the progression of scleroderma-related interstitial lung disease (SSc-ILD) when compared to placebo. However, toxicity was a concern and without continued treatment the efficacy disappeared by 24 months. We hypothesized that a two-year course of mycophenolate mofetil (MMF) would be safer, better tolerated and produce longer lasting improvements than CYC. METHODS Patients with SSc-ILD meeting defined dyspnea, pulmonary function and high-resolution computed tomography (HRCT) criteria were randomized in a double-blind, two-arm trial at 14 medical centers. MMF (target dose 1500 mg twice daily) was administered for 24 months in one arm and oral CYC (target dose 2·0 mg/kg/day) administered for 12 months followed by placebo for 12 months in the other arm. The primary endpoint, change in forced vital capacity as a percent of the predicted normal value (FVC %) over the course of 24 months, was assessed in a modified intention-to-treat analysis using an inferential joint model combining a mixed effects model for longitudinal outcomes and a survival model to handle non-ignorable missing data. The study was registered with ClinicalTrials.gov, number NCT00883129, and is closed. RESULTS Between November, 2009, and January, 2013, 142 patients were randomized. 126 patients (63 MMF; 63 CYC) with acceptable baseline HRCT studies and at least one outcome measure were included in the analysis. The adjusted FVC % (primary endpoint) improved from baseline to 24 months by 2.17 in the MMF arm (95% CI, 0.53–3.84) and 2·86 in the CYC arm (95% confidence interval 1·19–4·58) with no significant between-treatment difference (p=0·24), indicating that the trial was negative for the primary endpoint. However, in a post-hoc analysis of the primary endpoint, within-treatment improvements from baseline to 24 months were noted in both the CYC and MMF arms. A greater number of patients on CYC than on MMF prematurely withdrew from study drug (32 vs 20) and failed treatment (2 vs 0), and the time to stopping treatment was significantly shorter in the CYC arm (p=0·019). Sixteen deaths occurred (11 CYC; 5 MMF) with most due to progressive ILD. Leukopenia (30 vs 4 patients) and thrombocytopenia (4 vs 0 patients) occurred more often in patients treated with CYC. In post-hoc analyses, within- (but not between-) treatment improvements were also noted in defined secondary outcomes including skin score, dyspnea and whole-lung HRCT scores. INTERPRETATION Treatment of SSc-ILD with MMF for two years or CYC for one year both resulted in significant improvements in pre-specified measures of lung function, dyspnea, lung imaging, and skin disease over the 2-year course of the study. While MMF was better tolerated and associated with less toxicity, the hypothesis that it would have greater efficacy at 24 months than CYC was not confirmed. These findings support the potential clinical impact of both CYC and MMF for progressive SSc-ILD, as well as the current preference for MMF due to its better tolerability and toxicity profile. FUNDING National Heart, Lung and Blood Institute/National Institutes of Health with drug supply provided by Hoffmann-La Roche/Genentech.

Adult Bronchoscopy Training: Current State and Suggestions for the Future: CHEST Expert Panel Report

BACKGROUNDnThe determination of competency of trainees in programs performing bronchoscopy is quite variable. Some programs provide didactic lectures with hands-on supervision, other programs incorporate advanced simulation centers, whereas others have a checklist approach. Although no single method has been proven best, the variability alone suggests that outcomes are variable. Program directors and certifying bodies need guidance to create standards for training programs. Little well-developed literature on the topic exists.nnnMETHODSnTo provide credible and trustworthy guidance, rigorous methodology has been applied to create this bronchoscopy consensus training statement. All panelists were vetted and approved by the CHEST Guidelines Oversight Committee. Each topic group drafted questions in a PICO (population, intervention, comparator, outcome) format. MEDLINE data through PubMed and the Cochrane Library were systematically searched. Manual searches also supplemented the searches. All gathered references were screened for consideration based on inclusion criteria, and all statements were designated as an Ungraded Consensus-Based Statement.nnnRESULTSnWe suggest that professional societies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. Bronchoscopy training programs should incorporate multiple tools, including simulation. We suggest that ongoing quality and process improvement systems be introduced and that certifying agencies move from a volume-based certification system to skill acquisition and knowledge-based competency assessment for trainees. We also suggest that assessment of skill maintenance and improvement in practice be evaluated regularly with ongoing quality and process improvement systems after initial skill acquisition.nnnCONCLUSIONSnThe current methods used for bronchoscopy competency in training programs are variable. We suggest that professional societies and certifying agencies move from a volume- based certification system to a standardized skill acquisition and knowledge-based competency assessment for pulmonary and thoracic surgery trainees.

Mediastinal Pseudocyst Associated with Chronic Pleural Effusions

We present a patient who had chronic, bilateral pleural effusions without evidence of parenchymal, retrocardiac or mediastinal masses. A CAT scan of the abdomen and chest revealed the extension of a large abdominal pseudocyst through the diaphragm into the posterior mediastinum. The pseudocyst resolved with conservative management.

Laryngeal mucosa-associated lymphoid tissue (MALT) lymphoma associated with bronchial MALT lymphoma: a case series and review of the literature

The objective of this study is to describe the management of two adults with laryngeal mucosa-associated lymphoid tissue (MALT) lymphoma and concurrent bronchial MALT lymphoma and to review the literature pertaining to laryngeal lymphoma and discuss appropriate evaluation and treatment options. This is a retrospective case series where a retrospective chart review was performed. Demographic data collected includes presenting symptoms, age at presentation, gender, comorbidities, course of illness, and follow-up. Operative reports, serial endoscopic examinations, and serial CT images were used to monitor for recurrence. Between 2004 and 2006, two adult subjects were diagnosed and treated for false vocal cord MALT lymphoma with concurrent low-grade bronchial MALT lymphoma. Both patients were treated with surgical debulking, adjunctive rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) chemotherapy, and external beam radiation. At most recent follow-up, there was no endoscopic, clinical, or radiologic evidence of recurrence. Surgical debulking, RCHOP chemotherapy, and external beam radiation show promising results in treating false vocal cord laryngeal MALT lymphomas with concurrent low-grade bronchial MALT lymphomas. Bronchoscopy and laryngoscopy should be included in the evaluation of a patient with a laryngeal or bronchial MALT lymphoma for staging and optimal treatment since MALT lymphoma can be multifocal in both larynx and bronchus as shown in this case series.

An unusual case of persistent extrinsic bronchial compression.

Bronchomalacia is defined as diffuse or segmental bronchial weakness and easy compressibility. We present a rare case of a 67-year-old man with chronic cough as a consequence of focal bronchomalacia caused by persistent extrinsic compression of the left lower lobe bronchus by the descending aorta and the left lower lobe branch of the pulmonary artery. Focal bronchomalacia discovered during adulthood is most often acquired and can be attributed to extrinsic compression by abnormal blood vessels due to hypertension and lung transplantation or to bronchial disease processes. The natural history of bronchomalacia is typically progressive.