Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

Singh, Ankura; Liu, Charles; Putman, Barbara; Zeig‐Owens, Rachel; Hall, Charles B.; Schwartz, Theresa; Webber, Mayris P.; Cohen, Hillel W.; Berger, Kenneth I.; Nolan, Anna; Prezant, David J.; Weiden, Michael D.

doi:10.1016/j.chest.2018.07.002

Cited by 40 publications

(54 citation statements)

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“…The report by Singh et al 4 in this issue of CHEST contributes to our understanding as to how a specific environmental exposure in the setting of particular risk factors can lead to various clinical airway outcomes. As a result of the September 2011 terrorist attack on the World Trade Center (WTC) in New York City, rescue and recovery workers suffered unprecedented exposure to respirable particulates, combustion by-products, and caustic fumes.…”

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confidence: 97%

“…Singh et al 4 report predictors of asthma/COPD overlap, asthma, and COPD among WTC-exposed firefighters. The source population consisted of 9,598 male firefighters.…”

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confidence: 99%

“…The cohort had no history of asthma or COPD prior to exposure. 4 Four groups of participants emerged: a group with a post-bronchodilator FEV 1 increase of > 12% and 200 mL from baseline defined as asthma, a group with a post-bronchodilator FEV 1 /FVC ratio < 0.7 and no significant change with bronchodilator defined as COPD, and participants who met both criteria were defined as asthma/COPD overlap; the fourth group was asymptomatic postexposure. In the cohort of 2,137 exposed firefighters, the prevalence of isolated asthma, COPD, and asthma/COPD overlap was found to be 9.6%, 10.1%, and 4.6%, respectively.…”

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confidence: 99%

“…The study by Singh et al 4 is the longest cohort study of WTC-exposed firefighters that evaluated predictors of exposure associated with asthma/COPD overlap, asthma, and COPD phenotypes. First, lung function emerged as a significant risk factor for disease.…”

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confidence: 99%

“…Blood eosinophils were shown to be an important risk factor for ACO, with increased presentation reported in patients with a history of smoking and elevated blood eosinophil levels prior to and/or following the particulate exposure. 4 Serum cytokines were also measured and showed that early post-9/11 levels of type 2 and T-helper 17 serum cytokines IL-5, IL-13, IL-17, IL-23, and IL-6 were not associated with any of the three outcomes. Although higher early post-9/11 serum IgE levels were initially associated with incident asthma/ COPD overlap, this result was not significant after adjustment for multiple comparisons.…”

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Asthma/COPD Overlap

Sam

Kraft

2018

Chest

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confidence: 97%

“…Singh et al 4 report predictors of asthma/COPD overlap, asthma, and COPD among WTC-exposed firefighters. The source population consisted of 9,598 male firefighters.…”

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confidence: 99%

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confidence: 99%

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Asthma/COPD Overlap

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Kraft

2018

Chest

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Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long‐acting beta agonists

Goldfarb

Putman

Lahousse

et al. 2021

American J Industrial Med

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Background Greater than average loss of one‐second forced expiratory volume (FEV1) is a risk factor for asthma, chronic obstructive pulmonary disease (COPD), and asthma/COPD overlap syndrome in World Trade Center (WTC)‐exposed firefighters. Inhaled corticosteroids and long‐acting beta agonists (ICS/LABA) are used to treat obstructive airways disease but their impact on FEV1‐trajectory in this population is unknown. Methods The study population included WTC‐exposed male firefighters who were treated with ICS/LABA for 2 years or longer (with initiation before 2015), had at least two FEV1 measurements before ICS/LABA initiation and two FEV1 measurements posttreatment between September 11, 2001 and September 10, 2019. Linear mixed‐effects models were used to estimate FEV1‐slope pre‐ and post‐treatment. Results During follow‐up, 1023 WTC‐exposed firefighters were treated with ICS/LABA for 2 years or longer. When comparing intervals 6 years before and 6 years after treatment, participants had an 18.7 ml/year (95% confidence interval [CI]: 11.3–26.1) improvement in FEV1‐slope after adjustment for baseline FEV1, race, height, WTC exposure, weight change, blood eosinophil concentration, and smoking status. After stratification by median date of ICS/LABA initiation (January 14, 2010), earlier ICS/LABA‐initiators had a 32.5 ml/year (95% CI: 19.5–45.5) improvement in slope but later ICS/LABA‐initiators had a nonsignificant FEV1‐slope improvement (7.9 ml/year, 95% CI: −0.5 to 17.2). Conclusions WTC‐exposed firefighters treated with ICS/LABA had improved FEV1 slope after initiation, particularly among those who started earlier. Treatment was, however, not associated with FEV1‐slope improvement if started after the median initiation date (1/14/2010), likely because onset of disease began before treatment initiation. Research on alternative treatments is needed for patients with greater than average FEV1‐decline who have not responded to ICS/LABA.

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Serum Th‐2 cytokines and FEV₁ decline in WTC‐exposed firefighters: A 19‐year longitudinal study

Weiden

Singh

Goldfarb

et al. 2021

American J Industrial Med

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Background Accelerated‐FEV1‐decline, defined as rate of decline in FEV1 > 64 ml/year, is a risk factor for asthma and chronic obstructive pulmonary disease in World Trade Center (WTC)‐exposed firefighters. Accelerated‐FEV1‐decline in this cohort is associated with elevated blood eosinophil concentrations, a mediator of Th‐2 response. We hypothesized that an association exists between Th‐2 biomarkers and FEV1 decline rate in those with accelerated‐FEV1‐decline. Methods Serum was drawn from Fire Department of the City of New York (FDNY) firefighters 1–6 months (early) (N = 816) and 12–13 years (late) (N = 983) after 9/11/2001. Th‐2 biomarkers IL‐4, IL‐13, and IL‐5 were assayed by multiplex Luminex. Individual FEV1 decline rates were calculated using spirometric measurements taken: (1) between 9/11/2001 and 9/10/2020 for the early biomarker group and (2) between late measurement date and 9/10/2020 for the late biomarker group. Associations of early and late Th‐2 biomarkers with subsequent FEV1 decline rates were analyzed using multivariable linear regression controlling for demographics, smoking status, and other potential confounders. Results In WTC‐exposed firefighters with accelerated‐FEV1‐decline, IL‐4, IL‐13, and IL‐5 measured 1–6 months post‐9/11/2001 were associated with greater FEV1 decline ml/year between 9/11/2001 and 9/10/2020 (−2.9 ± 1.4 ml/year per IL‐4 doubling; −8.4 ± 1.2 ml/year per IL‐13 doubling; −7.9 ± 1.3 ml/year per IL‐5 doubling). Among late measured Th‐2 biomarkers, only IL‐4 was associated with subsequent FEV1 decline rate (−4.0 ± 1.6 ml/year per IL‐4 doubling). Conclusions In WTC‐exposed firefighters with accelerated‐FEV1‐decline, elevated serum IL‐4 measured both 1–6 months and 12–13 years after 9/11 is associated with greater FEV1 decline/year. Drugs targeting the IL‐4 pathway may improve lung function in this high‐risk subgroup.

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Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

Abstract: In WTC-exposed firefighters, elevated blood eosinophil and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific T-helper cell type 2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.

Cited by 40 publications

References 41 publications

Asthma/COPD Overlap

Asthma/COPD Overlap

Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long‐acting beta agonists

Serum Th‐2 cytokines and FEV₁ decline in WTC‐exposed firefighters: A 19‐year longitudinal study

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Predictors of Asthma/COPD Overlap in FDNY Firefighters With World Trade Center Dust Exposure

Abstract: In WTC-exposed firefighters, elevated blood eosinophil and IL-4 levels are associated with subsequent asthma/COPD overlap. Disease-specific T-helper cell type 2 biomarkers present years before diagnosis suggest patient-intrinsic predisposition to irritant-associated asthma/COPD overlap.

Cited by 40 publications

References 41 publications

Asthma/COPD Overlap

Asthma/COPD Overlap

Lung function decline before and after treatment of World Trade Center associated obstructive airways disease with inhaled corticosteroids and long‐acting beta agonists

Serum Th‐2 cytokines and FEV1 decline in WTC‐exposed firefighters: A 19‐year longitudinal study

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Product

Resources

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Serum Th‐2 cytokines and FEV₁ decline in WTC‐exposed firefighters: A 19‐year longitudinal study