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The attack on the World Trade Center (WTC) on 9/11/2001 produced a massive dust cloud with acute exposure, and the rubble pile burning over 3 months exposed more than 300,000 residents, rescue workers, and clean-up workers. Firefighters in the New York City Fire Department had significant respiratory symptoms characterized by cough, dyspnea, gastroesophageal reflux, and nasal stuffiness with a significant 1-year decline in FVC and FEV(1). Bronchial hyperreactivity measured by methacholine challenge correlated with bronchial wall thickening on CT scans. Compared with the NHANES III data for FVC and FEV(1), 32% of 2,000 WTC dust-exposed residents and clean-up workers were below the lower 5th percentile. The most common abnormality was a low FVC pattern, a finding similar to that also described for individuals in rescue and recovery activities. Among those complaining of respiratory symptoms and normal spirometry, almost half had abnormalities detected with impedance oscillometry consistent with distal airways' disease. Follow-up with the WTC Health Registry and the WTC Environmental Health Center will help discern whether treatment with anti-inflammatory medications or bronchodilators in those with respiratory symptoms may prevent the development of chronic obstructive pulmonary disease

BACKGROUND: The World Trade Center (WTC) collapse produced a massive exposure to respirable particulates in New York City Fire Department (FDNY) rescue workers. This group had spirometry examinations pre-September 11, 2001, and post-September 11, 2001, demonstrating declines in lung function with parallel declines in FEV(1) and FVC. To date, the underlying pathophysiologic cause for this has been open to question. METHODS: Of 13,234 participants in the FDNY-WTC Monitoring Program, 1,720 (13%) were referred for pulmonary subspecialty evaluation at a single institution. Evaluation included 919 full pulmonary function tests, 1,219 methacholine challenge tests, and 982 high-resolution chest CT scans. RESULTS: At pulmonary evaluation (median 34 months post-September 11, 2001), median values were FEV(1) 93% predicted (interquartile range [IQR], 83%-101%), FVC 98% predicted (IQR, 89%-106%), and FEV(1)/FVC 0.78 (IQR, 0.72-0.82). The residual volume (RV) was 123% predicted (IQR, 106%-147%) with nearly all participants having normal total lung capacity, functional residual capacity, and diffusing capacity of carbon monoxide. Also, 1,051/1,720 (59%) had obstructive airways disease based on at least one of the following: FEV(1)/FVC, bronchodilator responsiveness, hyperreactivity, or elevated RV. After adjusting for age, gender, race, height and weight, and tobacco use, the decline in FEV(1) post-September 11, 2001, was significantly correlated with increased RV percent predicted (P < .0001), increased bronchodilator responsiveness (P < .0001), and increased hyperreactivity (P = .0056). CT scans demonstrated bronchial wall thickening that was significantly associated with the decline in FEV(1) post-September 11, 2001 (P = .024), increases in hyperreactivity (P < .0001), and increases in RV (P < .0001). Few had evidence for interstitial disease. CONCLUSIONS: Airways obstruction was the predominant physiologic finding underlying the reduction in lung function post-September 11, 2001, in FDNY WTC rescue workers presenting for pulmonary evaluation

OBJECTIVES: Particulate matter (PM) exposure causes adverse health effects. The WTC collapse led to significant PM exposure and lung injury (Weiden et al. Chest 2009). The mechanism by which WTC PM causes pulmonary morbidity is not understood. We are investigating the differential cytokine effects on human alveolar cells, comparing ambient PM of WTC to ambient PM from NYC, South Bronx (SB) and Sterling Forest (SF), a rural area northwest of NYC. METHODS AND POPULATION: AM were obtained from Bronchoalveolar lavage (BAL) by adherence overnight. AM were exposed to 50mug/mL suspensions of WTC, SB, and SF PM2.5. Media alone was the negative control and 40 ng/mL of LPS was the positive control. After 24hrs, supernatants were collected and analyzed in duplicate using Human Cytokine Panel I (Millipore) on a Luminex-200. RESULTS: Fold induction of mediators was expressed as ratios of PM exposure/media alone. Exposure to WTC PM was markedly more inflammatory than SB and SF. The most significant inductions were of the leukocyte growth factors (GM-CSF, G-CSF), a promoter of angiogenesis (VEGF), the chemokine (RANTES) and the potent multifunctional cytokine IL-6. LPS caused a greater induction for all of the analytes when compared to WTC PM except for IL-1ra. SIGNIFICANCE OF STUDY: WTC PM2.5 produces a marked inflammatory effect in comparison to PM2.5 from both NYC, SB and rural sites. The large number of cytokines induced by WTC PM may drive airway injury and may be biomarkers for lung injury. WTC PM has been observed in induced sputum obtained 9 months after 9/11/2001 and so the elaboration of cytokines may underlie the severe and long lasting health effects produced by exposure to WTC PM

INTRODUCTION: Traditionally, Mycobacterium abscessus pulmonary disease has poor long term response to current antibiotic regimens. The data regarding the clinical efficacy of linezolid and aerosolized amikacin in M. abscessus pulmonary disease is limited. CASE PRESENTATION: A 52 year-old Caucasian female presented in 2004 with scant hemoptysis and intermittent night sweats. Her past medical history was unremarkable. She denied history of pneumonias. She did not smoke tobacco. She worked as a middle school secretary. Computed tomographic (CT) evaluation of the chest showed significant bronchiectasis in the right middle lobe with irregular opacities throughout the right upper lobe and right lower lobe. She was treated empirically with levofloxacin for recurrent episodes of infection with a presumed response. In 2007, she had more severe hemoptysis with several teaspoons of bright red blood that woke her up from sleep at night. M. chelonae and M. abscessus were identified in her sputum and she was started on clarithromycin combined with ciprofloxacin. In 2008, pulmonary function tests showed evidence of decreasing diffusing capacity. Chest CT showed interval increase in the nodular densities primarily in the right middle lobe and many were cavitating. She required hospitalization in 2009 for increasing hemoptysis and underwent IR embolization of branches of the right bronchial artery and right internal mammary artery. Nebulized amikacin 250 mg daily was started along with linezolid 600 mg daily. After 6 months of moxifloxacin, clarithromycin, nebulized amikacin, and linezolid, chest CT in late 2009 showed improvement and there was no further hemoptysis. DISCUSSIONS: Intermittent courses of parenteral therapy combined with and followed by an oral macrolide, aerosolized amikacin, and linezolid may be used to suppress infection and control disease progression of M. abscessus pulmonary disease. (1) Cost and side effects may limit the feasibility of prolonged treatment with parenteral antibiotic therapy. Aminoglycosides exhibit significant concentration-dependent bactericidal activity against nontuberculous mycobacteria. Extended parenteral therapy with aminoglycosides has been avoided due to the substantial risks of nephrotoxicity, ototoxicity, and vestibular toxicity. Aerosolized antibiotic delivery offers the potential advantage of achieving high drug concentrations in the lung with low systemic absorption and diminished risk of systemic toxicities. Aerosolized antibiotics have been used with notable success in the treatment of chronic Pseudomonas aeruginosa infection in patients with cystic fibrosis. In an observational case series, six HIV-negative patients with Mycobacterium avium intracellulare pulmonary infections who had failed standard therapy were administered aerosolized amikacin at 15 mg/kg daily in addition to standard multi-drug macrolide-based oral therapy. Five responded to therapy and achieved symptomatic improvement. Four were sputum culture negative after 6 months of therapy. (2) Approximately 50% of M. abscessus isolates are susceptible or exhibit intermediate susceptibility in vitro to the oxazolidinone linezolid. A small number of patients with M. abscessus lung disease have been treated with linezolid and a companion drug, usually a macrolide, with varied results. Impediments to long-term use of linezolid include the cost and potential side effects of chronic therapy which include peripheral neuropathy and anemia. Once daily dosing of linezolid 600mg instead of the traditional twice daily dosing is currently used by some to treat mycobacterial disease with seemingly fewer side effects and retained antimycobacterial activity. CONCLUSION: Preliminary case series suggest that nonparenteral agents including oral macrolides, aerosolized amikacin, and linezolid may be effective for the treatment of M. abscessus pulmonary disease