Faculty Bibliography

OBJECTIVES: In a cohort of rescue/recovery workers exposed to the dust that resulted from the collapse of the World Trade Center (WTC), we assessed how a diagnosis of obstructive airways disease (OAD) affected the likelihood of a subsequent diagnosis of chronic rhinosinusitis (CRS) or gastroesophageal reflux disease (GERD). We also assessed whether OAD acted as a mediator of the association between exposure to the WTC rescue/recovery effort and CRS and GERD diagnoses. METHODS: In this prospective cohort study, we analyzed Fire Department of the City of New York physician diagnoses of OAD, CRS, and GERD that were first documented between September 11, 2001, and September 10, 2011, among 8,968 WTC-exposed firefighters. We used piecewise exponential survival models to evaluate whether OAD was a risk factor for either CRS or GERD and to assess OAD as a possible mediator. RESULTS: An OAD diagnosis significantly increased the risks for subsequent CRS [relative rate (RR), 4.24; 95% CI, 3.78-4.76] and GERD (RR, 3.21; 95% CI, 2.93-3.52) diagnoses. Further, 21% of the WTC exposure effect (high vs. low intensity) on GERD and 13% of the effect (high vs. low intensity) on CRS were mediated by a prior OAD diagnosis. CONCLUSION: Individuals with an OAD diagnosis had elevated risks for subsequent diagnoses of CRS or GERD. Part of the effect of WTC exposure on CRS and GERD diagnoses is mediated by prior diagnoses of OAD; this mediation effect of OAD may reflect biological pathways or healthcare utilization practices.

OBJECTIVE: To determine whether lung function trajectories after 9/11/2001 (9/11) differed by sex or race/ethnicity in World Trade Center-exposed Fire Department of the City of New York emergency medical service (EMS) workers. METHOD: Serial cross-sectional study of pulmonary function tests (PFTs) taken between 9/11 and 9/10/2015. We used data from routine PFTs (forced expiratory volume in 1 s (FEV1) and FEV1% predicted), conducted at 12-18 month intervals. FEV1 and FEV1% predicted were assessed over time, stratified by sex, and race/ethnicity. We also assessed FEV1 and FEV1% predicted in current, former and never-smokers. RESULTS: Among 1817 EMS workers, 334 (18.4%) were women, 979 (53.9%) self-identified as white and 939 (51.6%) were never-smokers. The median follow-up was 13.1 years (IQR 10.5-13.6), and the median number of PFTs per person was 11 (IQR 7-13). After large declines associated with 9/11, there was no discernible recovery in lung function. In analyses limited to never-smokers, the trajectory of decline in adjusted FEV1 and FEV1% predicted was relatively parallel for men and women in the 3 racial/ethnic groups. Similarly, small differences in FEV1 annual decline between groups were not clinically meaningful. Analyses including ever-smokers were essentially the same. CONCLUSIONS: 14 years after 9/11, most EMS workers continued to demonstrate a lack of lung function recovery. The trajectories of lung function decline, however, were parallel by sex and by race/ethnicity. These findings support the use of routine, serial measures of lung function over time in first responders and demonstrate no sex or racial sensitivity to exposure-related lung function decline.

INTRODUCTION: Azithromycin (AZM) reduces pulmonary inflammation and exacerbations in patients with COPD having emphysema. The antimicrobial effects of AZM on the lower airway microbiome are not known and may contribute to its beneficial effects. Here we tested whether AZM treatment affects the lung microbiome and bacterial metabolites that might contribute to changes in levels of inflammatory cytokines in the airways. METHODS: 20 smokers (current or ex-smokers) with emphysema were randomised to receive AZM 250 mg or placebo daily for 8 weeks. Bronchoalveolar lavage (BAL) was performed at baseline and after treatment. Measurements performed in acellular BAL fluid included 16S rRNA gene sequences and quantity; 39 cytokines, chemokines and growth factors and 119 identified metabolites. The response to lipopolysaccharide (LPS) by alveolar macrophages after ex-vivo treatment with AZM or bacterial metabolites was assessed. RESULTS: Compared with placebo, AZM did not alter bacterial burden but reduced alpha-diversity, decreasing 11 low abundance taxa, none of which are classical pulmonary pathogens. Compared with placebo, AZM treatment led to reduced in-vivo levels of chemokine (C-X-C) ligand 1 (CXCL1), tumour necrosis factor (TNF)-alpha, interleukin (IL)-13 and IL-12p40 in BAL, but increased bacterial metabolites including glycolic acid, indol-3-acetate and linoleic acid. Glycolic acid and indol-3-acetate, but not AZM, blunted ex-vivo LPS-induced alveolar macrophage generation of CXCL1, TNF-alpha, IL-13 and IL-12p40. CONCLUSION: AZM treatment altered both lung microbiota and metabolome, affecting anti-inflammatory bacterial metabolites that may contribute to its therapeutic effects. TRIAL REGISTRATION NUMBER: NCT02557958.

BACKGROUND: World Trade Center (WTC)-exposed rescue/recovery workers endured massive respiratory insult from inhalation of particulate matter and gases, resulting in respiratory symptoms, loss of lung function, and, for many, bronchial hyperreactivity (BHR). The persistence of respiratory symptoms and lung function abnormalities has been well-documented, whereas persistence of BHR has not been investigated. METHODS: A total of 173 WTC-exposed firefighters with bronchial reactivity measured within 2 years after September 11, 2001 (9/11) (baseline methacholine challenge test), were reevaluated in 2013 and 2014 (follow-up methacholine challenge test). FEV1 measurements were obtained from the late pre-9/11, early post-9/11, and late post-9/11 periods. Respiratory symptoms and corticosteroid treatment were recorded. RESULTS: Bronchial reactivity remained stable (within 1 doubling dilution) for most (n = 101, 58%). Sixteen of 28 (57%) with BHR (provocative concentration of methacholine producing a 20% decline in FEV1 <8 mg/mL) at baseline had BHR at follow-up, and an additional 27 of the 145 (19%) without BHR at baseline had BHR at follow-up. In multivariable models, we found that BHR baseline was strongly associated with BHR follow-up (OR, 6.46) and that BHR at follow-up was associated with an estimated 15.4 mL/y greater FEV1 decline than experienced by those without BHR at follow-up. Annual FEV1 decline was moderated by corticosteroid use. CONCLUSIONS: Persistent BHR and its deleterious influence on lung function suggest a role for airway inflammation in perpetuation of WTC-associated airway disease. In future massive occupational exposure to inorganic dust/gases, we recommend early and serial pulmonary function testing, including measurements of bronchial reactivity, when possible, and inhaled corticosteroid therapy for those with symptoms or pulmonary function tests consistent with airway disease.