Adnan Majid

Relapsing Polychondritis and Airway Involvement

OBJECTIVE To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP). METHODS Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008. RESULTS RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention. CONCLUSION In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

Effect of Endobronchial Coils vs Usual Care on Exercise Tolerance in Patients With Severe Emphysema: The RENEW Randomized Clinical Trial

IMPORTANCE Preliminary clinical trials have demonstrated that endobronchial coils compress emphysematous lung tissue and may improve lung function, exercise tolerance, and symptoms in patients with emphysema and severe lung hyperinflation. OBJECTIVE To determine the effectiveness and safety of endobronchial coil treatment. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial conducted among 315 patients with emphysema and severe air trapping recruited from 21 North American and 5 European sites from December 2012 through November 2015. INTERVENTIONS Participants were randomly assigned to continue usual care alone (guideline based, including pulmonary rehabilitation and bronchodilators; n = 157) vs usual care plus bilateral coil treatment (n = 158) involving 2 sequential procedures 4 months apart in which 10 to 14 coils were bronchoscopically placed in a single lobe of each lung. MAIN OUTCOMES AND MEASURES The primary effectiveness outcome was difference in absolute change in 6-minute-walk distance between baseline and 12 months (minimal clinically important difference [MCID], 25 m). Secondary end points included the difference between groups in 6-minute walk distance responder rate, absolute change in quality of life using the St Georges Respiratory Questionnaire (MCID, 4) and change in forced expiratory volume in the first second (FEV1; MCID, 10%). The primary safety analysis compared the proportion of participants experiencing at least 1 of 7 prespecified major complications. RESULTS Among 315 participants (mean age, 64 years; 52% women), 90% completed the 12-month follow-up. Median change in 6-minute walk distance at 12 months was 10.3 m with coil treatment vs -7.6 m with usual care, with a between-group difference of 14.6 m (Hodges-Lehmann 97.5% CI, 0.4 m to ∞; 1-sided P = .02). Improvement of at least 25 m occurred in 40.0% of patients in the coil group vs 26.9% with usual care (odds ratio, 1.8 [97.5% CI, 1.1 to ∞]; unadjusted between-group difference, 11.8% [97.5% CI, 1.0% to ∞]; 1-sided P = .01). The between-group difference in median change in FEV1 was 7.0% (97.5% CI, 3.4% to ∞; 1-sided P < .001), and the between-group St Georges Respiratory Questionnaire score improved -8.9 points (97.5% CI, -∞ to -6.3 points; 1-sided P < .001), each favoring the coil group. Major complications (including pneumonia requiring hospitalization and other potentially life-threatening or fatal events) occurred in 34.8% of coil participants vs 19.1% of usual care (P = .002). Other serious adverse events including pneumonia (20% coil vs 4.5% usual care) and pneumothorax (9.7% vs 0.6%, respectively) occurred more frequently in the coil group. CONCLUSIONS AND RELEVANCE Among patients with emphysema and severe hyperinflation treated for 12 months, the use of endobronchial coils compared with usual care resulted in an improvement in median exercise tolerance that was modest and of uncertain clinical importance, with a higher likelihood of major complications. Further follow-up is needed to assess long-term effects on health outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01608490.

Tracheobronchoplasty for Severe Tracheobronchomalacia: A Prospective Outcome Analysis

RATIONALE Central airway stabilization with silicone stents can improve respiratory symptoms in patients with severe symptomatic tracheobronchomalacia (TBM) but is associated with a relatively high rate of complications. Surgery with posterior tracheobronchial splinting using a polypropylene mesh has also been used for this condition but to date has not been evaluated prospectively and objectively for patient outcomes. OBJECTIVES To evaluate the effect of surgical tracheobronchoplasty on symptoms, functional status, quality of life, lung function, and exercise capacity in patients with severe and symptomatic TBM. METHODS A prospective observational study in which baseline measurements were compared to those obtained 3 months after surgical tracheobronchoplasty. MEASUREMENTS AND MAIN RESULTS Of 104 referred patients to our complex airway center for severe TBM, 77 had baseline measurements. Of this group, 57 patients had severe malacia and underwent stent placement for central airway stabilization. Of those, 37 patients reported improvement in respiratory symptoms and 35 were considered for surgical tracheobronchoplasty. Two patients were excluded from surgery for medical reasons. Median age was 61 years (range, 39 to 83 years), 20 patients were men, 11 patients (31%) had COPD, 9 patients (26%) had asthma, and 4 patients (11%) had Mounier-Kuhn syndrome. Thirty-three patients (94%) presented with severe dyspnea, 26 patients (74%) with uncontrollable cough, and 18 patients (51%) reported recurrent pulmonary infections. Two patients (3%) presented with respiratory failure requiring mechanical ventilation. After surgery, quality of life scores improved in 25 of 31 patients (p < 0.0001), dyspnea scores improved in 19 of 26 patients (p = 0.007), functional status scores improved in 20 of 31 patients (p = 0.003), and mean exercise capacity improved in 10 patients (p = 0.012). CONCLUSIONS In experienced hands, surgical central airway stabilization with posterior tracheobronchial splinting using a polypropylene mesh improves respiratory symptoms, health-related quality of life, and functional status in highly selected patients with severe symptomatic TBM.

Success and failure rates of tumor genotyping techniques in routine pathological samples with non-small-cell lung cancer

INTRODUCTION Identification of some somatic molecular alterations in non-small-cell lung cancer (NSCLC) has become evidence-based practice. The success and failure rate of using commercially available tumor genotyping techniques in routine day-to-day NSCLC pathology samples is not well described. We sought to evaluate the success and failure rate of EGFR mutation, KRAS mutation, and ALK FISH in a cohort of lung cancers subjected to routine clinical tumor genotype. METHODS Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 381 patient-tumor samples. RESULTS From these 381 patients with lung cancer, the mean age was 65 years, 61.2% were women, 75.9% were white, 27.8% were never smokers, 73.8% had advanced NSCLC and 86.1% had adenocarcinoma histology. The tumor tissue was obtained from surgical specimens in 48.8%, core needle biopsies in 17.9%, and as cell blocks from aspirates or fluid in 33.3% of cases. Anatomic sites for tissue collection included lung (49.3%), lymph nodes (22.3%), pleura (11.8%), bone (6.0%), brain (6.0%), among others. The overall success rate for EGFR mutation analysis was 94.2%, for KRAS mutation 91.6% and for ALK FISH 91.6%. The highest failure rates were observed when the tissue was obtained from image-guided percutaneous transthoracic core-needle biopsies (31.8%, 27.3%, and 35.3% for EGFR, KRAS, and ALK tests, respectively) and bone specimens (23.1%, 15.4%, and 23.1%, respectively). In specimens obtained from bone, the failure rates were significantly higher for biopsies than resection specimens (40% vs. 0%, p=0.024 for EGFR) and for decalcified compared to non-decalcified samples (60% vs. 5.5%, p=0.021 for EGFR). CONCLUSIONS Tumor genotype techniques are feasible in most samples, outside small image-guided percutaneous transthoracic core-needle biopsies and bone samples from core biopsies with decalcification, and therefore expansion of routine tumor genotype into the care of patients with NSCLC may not require special tissue acquisition or manipulation.

Gas Embolism Following Bronchoscopic Argon Plasma Coagulation: A Case Series

Thermal ablation using argon plasma coagulation (APC) is a commonly used modality in the bronchoscopic management of central airway obstruction and hemoptysis. In experienced hands, APC is considered to be a relatively safe tool. Reported complications associated with APC use are rare and include hemorrhage, airway perforation, or airway fires. Systemic gas embolism has been reported with APC during laparoscopic hepatic surgeries, and we have reported one case of systemic gas embolism with cardiovascular collapse in the past. We now report the first case series of systemic, life-threatening gas embolism occurring as a complication of bronchoscopic application of APC.

Adequacy of lymph node transbronchial needle aspirates using convex probe endobronchial ultrasound for multiple tumor genotyping techniques in non-small-cell lung cancer.

Introduction: Adequate tumor acquisition is essential to identify somatic molecular alterations in non–small-cell lung cancer (NSCLC), such as epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) translocations. The success and failure rates for tumor genotyping of tissue obtained from fine-needle aspirates of nodal tissue using a convex probe endobronchial ultrasound (CP-EBUS) and other diagnostic modalities in routine NSCLC care have not been described. Methods: Clinicopathologic data, tumor genotype success and failure rates were retrospectively compiled and analyzed from 207 patient-tumor samples sent for routine tumor genotype in clinical practice, including 42 patient-tumor samples obtained from hilar or mediastinal lymph nodes using CP-EBUS. Results: The median age of the patients was 65 years, 62.3% were women, 77.8% were white, 26.6% were never smokers, 73.9% had advanced NSCLC, and 84.1% had adenocarcinoma histology. Tumor tissue was obtained from CP-EBUS–derived hilar or mediastinal nodes in 42 cases (20.2% of total). In this latter cohort, the overall success rate for EGFR mutation analysis was 95.2%, for Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation 90.5%, and for ALK fluorescence in situ hybridization 90.5%. In the complete 207 tumors, the success rate for EGFR was 92.3%, for KRAS 91.8%, and for ALK 89.9%. The failure rates were not significantly different when comparing CP-EBUS–derived nodal tissue versus all other samples or versus surgical biopsies of mediastinal nodes, but were significantly lower than image-guided percutaneous transthoracic core-needle biopsies. Conclusions: The success rate of multiple tumor genomic analyses techniques for EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples obtained from hilar or mediastinal lymph nodes by means of CP-EBUS exceeds 90%, and this method of tissue acquisition is not inferior to other specimen types. Tumor genotype techniques are feasible in most CP-EBUS–derived samples and therefore further expansion of routine tumor genotype for the care of patients with NSCLC may be possible using targeted sample acquisition through CP-EBUS.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA): An overview and update for the cytopathologist

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) has emerged as a minimally invasive technique for evaluating the mediastinum and staging patients with lung cancer. In the hands of an experienced operator, the procedure is safe and provides excellent sensitivity, specificity, and predictive diagnostic values. In conjunction with endoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA), a nearly complete mediastinal evaluation can be performed in a minimally invasive fashion. This strategy results in improved lymph node staging, markedly reduced need for mediastinoscopy, and fewer futile thoracotomies compared with a traditional surgical staging procedure. The procedure is cost effective and provides excellent cytologic specimens that have proven well suited for ancillary testing, such as immunohistochemistry and tumor genotyping. EBUS‐TBNA, initially used as a tool to sample the lymph nodes adjacent to the airway walls, has now become instrumental in sampling lesions in the mediastinum, hilum, and lung parenchyma, where previously more than 1 procedure would have been necessary. Looking forward, expanded use of this procedure is likely to revolutionize the access to cytology‐proven staging and restaging of lung cancer and other thoracic malignancies in a minimally invasive fashion. Cancer (Cancer Cytopathol) 2014;122:561–576.

Tracheobronchomalacia: current concepts and controversies.

Tracheobronchomalacia (TBM) results from weakness of the airway walls and/or supporting cartilage and affects both adult and pediatric populations. Diagnosing TBM is challenging because symptoms are nonspecific and overlap with those of other chronic respiratory disorders. Recent advances in multidetector computed tomography have facilitated the noninvasive diagnosis of TBM, and concurrent advances in management have improved clinical outcomes and created a need for greater awareness of the posttreatment appearance of the airways. This review discusses the physiology, histopathology, epidemiology, and clinical features of TBM; it also describes current methods of diagnosis, available therapies, and postoperative imaging evaluation.

Smoking status and self-reported race affect the frequency of clinically relevant oncogenic alterations in non-small-cell lung cancers at a United States-based academic medical practice

INTRODUCTION The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient-tumor sample pairs. METHODS Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient-tumor samples. RESULTS Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort. CONCLUSIONS The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC.

Central Airway Stabilization for Tracheobronchomalacia Improves Quality of Life in Patients With COPD

BACKGROUND Tracheobronchomalacia (TBM) is characterized by excessive collapsibility of the central airways, typically during expiration. TBM may be present in as many as 50% of patients evaluated for COPD. The impact of central airway stabilization on symptom pattern and quality of life is poorly understood in this patient population. METHODS Patients with documented COPD were identified from a cohort of 238 patients assessed for TBM at our complex airway referral center. Pulmonary function testing, exercise tolerance, and health-related quality-of-life (HRQOL) measures were assessed at baseline and 2 to 4 weeks following tracheal stent placement/operative tracheobronchoplasty (TBP). Severity of COPD was classified according to the GOLD (Global Initiative for Chronic Obstructive Lung Disease) staging system. RESULTS One hundred three patients (48 women) with COPD and moderately severe to severe TBM were identified. Statistically and clinically significant improvements were seen in HRQOL measures, including the transitional dyspnea index (stent, P = .001; TBP, P = .008), the St. George Respiratory Questionnaire (stent, P = .002; TBP, P < .0001), and the Karnofsky performance score (stent, P = .163; TBP, P < .0001). The improvement appeared greatest following TBP and was seen in all GOLD stages. Clinical improvement was also seen in measured FEV(1) and exercise capacity as assessed by 6-min walk test. CONCLUSIONS Central airway stabilization may provide symptomatic benefit for patients with severe COPD and concomitant severe airway malacia. Operative airway stabilization appears to impart the greatest advantage. Long-term follow-up study is needed to fully ascertain the ultimate efficacy of both stenting and surgical airway stabilization in this patient group.