Dataset Information

Blood Leukocyte Concentrations, FEV₁ Decline, and Airflow Limitation. A 15-Year Longitudinal Study of World Trade Center-exposed Firefighters.

ABSTRACT:

Rationale

Rescue/recovery work at the World Trade Center disaster site (WTC) caused a proximate decline in lung function in Fire Department of the City of New York firefighters. A subset of this cohort experienced an accelerated rate of lung function decline over 15 years of post-September 11, 2001 (9/11) follow-up.

Objectives

To determine if early postexposure blood leukocyte concentrations are biomarkers for subsequent FEV₁ decline and incident airflow limitation.

Methods

Individual rates of forced expiratory volume in 1 second (FEV₁) change were calculated for 9,434 firefighters using 88,709 spirometric measurements taken between September 11, 2001, and September 10, 2016. We categorized FEV₁ change rates into three trajectories: accelerated FEV₁ decline (FEV₁ loss >64 ml/yr), expected FEV₁ decline (FEV₁ loss between 0 and 64 ml/yr), and improved FEV₁ (positive rate of change >0 ml/yr). Occurrence of FEV₁/FVC less than 0.70 after 9/11 defined incident airflow limitation. Using regression models, we assessed associations of post-9/11 blood eosinophil and neutrophil concentrations with subsequent FEV₁ decline and airflow limitation, adjusted for age, race, smoking, height, WTC exposure level, weight change, and baseline lung function.

Results

Accelerated FEV₁ decline occurred in 12.7% of participants (1,199 of 9,434), whereas post-9/11 FEV₁ improvement occurred in 8.3% (780 of 9,434). Higher blood eosinophil and neutrophil concentrations were each associated with accelerated FEV₁ decline after adjustment for covariates (odds ratio [OR], 1.10 per 100 eosinophils/μl; 95% confidence interval [CI], 1.05-1.15; and OR, 1.10 per 1,000 neutrophils/μl; 95% CI, 1.05-1.15, respectively). Multivariable-adjusted linear regression models showed that a higher blood neutrophil concentration was associated with a faster rate of FEV₁ decline (1.14 ml/yr decline per 1,000 neutrophils/μl; 95% CI, 0.69-1.60 ml/yr; P < 0.001). Higher blood eosinophil concentrations were associated with a faster rate of FEV₁ decline in ever-smokers (1.46 ml/yr decline per 100 eosinophils/μl; 95% CI, 0.65-2.26 ml/yr; P < 0.001) but not in never-smokers (P for interaction = 0.004). Higher eosinophil concentrations were also associated with incident airflow limitation (adjusted hazard ratio, 1.10 per 100 eosinophils/μl; 95% CI, 1.04-1.15). Compared with the expected FEV₁ decline group, individuals experiencing accelerated FEV₁ decline were more likely to have incident airflow limitation (adjusted OR, 4.12; 95% CI, 3.30-5.14).

Conclusions

Higher post-9/11 blood neutrophil and eosinophil concentrations were associated with subsequent accelerated FEV₁ decline in WTC-exposed firefighters. Both higher blood eosinophil concentrations and accelerated FEV₁ decline were associated with incident airflow limitation in WTC-exposed firefighters.

SUBMITTER: Zeig-Owens R

PROVIDER: S-EPMC5802620 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceThe World Trade Center (WTC) attacks on September 11, 2001, created an unprecedented environmental exposure to known and suspected carcinogens suggested to increase the risk of multiple myeloma. Multiple myeloma is consistently preceded by the precursor states of monoclonal gammopathy of undetermined significance (MGUS) and light-chain MGUS, detectable in peripheral blood.ObjectiveTo characterize WTC-exposed firefighters with a diagnosis of multiple myeloma and to conduct a screening study for MGUS and light-chain MGUS.Design, setting, and participantsCase series of multiple myeloma in firefighters diagnosed between September 11, 2001, and July 1, 2017, together with a seroprevalence study of MGUS in serum samples collected from Fire Department of the City of New York (FDNY) firefighters between December 2013 and October 2015. Participants included all WTC-exposed FDNY white, male firefighters with a confirmed physician diagnosis of multiple myeloma (n = 16) and WTC-exposed FDNY white male firefighters older than 50 years with available serum samples (n = 781).ExposuresWTC exposure defined as rescue and/or recovery work at the WTC site between September 11, 2001, and July 25, 2002.Main outcomes and measuresMultiple myeloma case information, and age-adjusted and age-specific prevalence rates for overall MGUS (ie, MGUS and light-chain MGUS), MGUS, and light-chain MGUS.ResultsSixteen WTC-exposed white male firefighters received a diagnosis of multiple myeloma after September 11, 2001; median age at diagnosis was 57 years (interquartile range, 50-68 years). Serum/urine monoclonal protein isotype/free light-chain data were available for 14 cases; 7 (50%) had light-chain multiple myeloma. In a subset of 7 patients, myeloma cells were assessed for CD20 expression; 5 (71%) were CD20 positive. In the screening study, we assayed peripheral blood from 781 WTC-exposed firefighters. The age-standardized prevalence rate of MGUS and light-chain MGUS combined was 7.63 per 100 persons (95% CI, 5.45-9.81), 1.8-fold higher than rates from the Olmsted County, Minnesota, white male reference population (relative rate, 1.76; 95% CI, 1.34-2.29). The age-standardized prevalence rate of light-chain MGUS was more than 3-fold higher than in the same reference population (relative rate, 3.13; 95% CI, 1.99-4.93).Conclusions and relevanceEnvironmental exposure to the WTC disaster site is associated with myeloma precursor disease (MGUS and light-chain MGUS) and may be a risk factor for the development of multiple myeloma at an earlier age, particularly the light-chain subtype.

Project description: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.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.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.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.

Project description:Rate of FEV1 decline in COPD is heterogeneous and the extent to which inhaled corticosteroids (ICS) influence the rate of decline is unclear. The majority of previous reviews have investigated specific ICS and non-ICS inhalers and have consisted of randomised control trials (RCTs), which have specific inclusion and exclusion criteria and short follow up times. We aimed to investigate the association between change in FEV1 and ICS-containing medications in COPD patients over longer follow up times.MEDLINE and EMBASE were searched and literature comparing change in FEV1 in COPD patients taking ICS-containing medications with patients taking non-ICS-containing medications were identified. Titles, abstract, and full texts were screened and information extracted using the PICO checklist. Risk of bias was assessed using the Cochrane Risk of Bias tool and a descriptive synthesis of the literature was carried out due to high heterogeneity of included studies.Seventeen studies met our inclusion criteria. We found that the difference in change in FEV1 in people using ICS and non-ICS containing medications depended on the study follow-up time. Shorter follow-up studies (1 year or less) were more likely to report an increase in FEV1 from baseline in both patients on ICS and in patients on non-ICS-containing medications, with the majority of these studies showing a greater increase in FEV1 in patients on ICS-containing medications. Longer follow-up studies (greater than 1 year) were more likely to report a decline in FEV1 from baseline in patients on ICS and in patients on non-ICS containing medications but rates of FEV1 decline were similar.Further studies are needed to better understand changes in FEV1 when ICS-containing medications are prescribed and to determine whether ICS-containing medications influence rate of decline in FEV1 in the long term. Results from inclusive trials and observational patient cohorts may provide information more generalisable to a population of COPD patients.

Project description:Study objectivesThe presence of flow limitation during sleep is associated with adverse health consequences independent of obstructive sleep apnea (OSA) severity (apnea-hypopnea index, AHI), but remains extremely challenging to quantify. Here we present a unique library and an accompanying automated method that we apply to investigate flow limitation during sleep.MethodsA library of 117,871 breaths (N = 40 participants) were visually classified (certain flow limitation, possible flow limitation, normal) using airflow shape and physiological signals (ventilatory drive per intra-esophageal diaphragm EMG). An ordinal regression model was developed to quantify flow limitation certainty using flow-shape features (e.g. flattening, scooping); breath-by-breath agreement (Cohen's ƙ); and overnight flow limitation frequency (R2, %breaths in certain or possible categories during sleep) were compared against visual scoring. Subsequent application examined flow limitation frequency during arousals and stable breathing, and associations with ventilatory drive.ResultsThe model (23 features) assessed flow limitation with good agreement (breath-by-breath ƙ = 0.572, p < 0.001) and minimal error (overnight flow limitation frequency R2 = 0.86, error = 7.2%). Flow limitation frequency was largely independent of AHI (R2 = 0.16) and varied widely within individuals with OSA (74[32-95]%breaths, mean[range], AHI > 15/h, N = 22). Flow limitation was unexpectedly frequent but variable during arousals (40[5-85]%breaths) and stable breathing (58[12-91]%breaths), and was associated with elevated ventilatory drive (R2 = 0.26-0.29; R2 < 0.01 AHI v. drive).ConclusionsOur method enables quantification of flow limitation frequency, a key aspect of obstructive sleep-disordered breathing that is independent of the AHI and often unavailable. Flow limitation frequency varies widely between individuals, is prevalent during arousals and stable breathing, and reveals elevated ventilatory drive. Clinical trial registration: The current observational physiology study does not qualify as a clinical trial.

Dataset Information

Blood Leukocyte Concentrations, FEV₁ Decline, and Airflow Limitation. A 15-Year Longitudinal Study of World Trade Center-exposed Firefighters.

Rationale

Objectives

Methods

Results

Conclusions

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OmicsDI is part of the ELIXIR infrastructure

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Dataset Information

Blood Leukocyte Concentrations, FEV1 Decline, and Airflow Limitation. A 15-Year Longitudinal Study of World Trade Center-exposed Firefighters.

Rationale

Objectives

Methods

Results

Conclusions

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Blood Leukocyte Concentrations, FEV₁ Decline, and Airflow Limitation. A 15-Year Longitudinal Study of World Trade Center-exposed Firefighters.