Increased Airway Wall Thickness is Associated with Adverse Longitudinal First–Second Forced Expiratory Volume Trajectories of Former World Trade Center workers

Abstract

Rationale Occupational exposures at the WTC site after September 11, 2001 have been associated with several presumably inflammatory lower airway diseases. In this study, we describe the trajectories of expiratory air flow decline, identify subgroups with adverse progression, and investigate the association of a quantitative computed tomography (QCT) imaging measurement of airway wall thickness, and other risk factors for adverse progression. Methods We examined the trajectories of expiratory air flow decline in a group of 799 former WTC workers and volunteers with QCT-measured (with two independent systems) wall area percent (WAP) and at least 3 periodic spirometries. We calculated individual regression lines for first–second forced expiratory volume (FEV1), identified subjects with rapidly declining and increasing (“gainers”), and compared them to subjects with normal and “stable” FEV1 decline. We used multivariate logistic regression to model decliner vs. stable trajectories. Results The mean longitudinal FEV1slopes for the entire study population, and its stable, decliner, and gainer subgroups were, respectively, −35.8, −8, −157.6, and + 173.62 ml/year. WAP was associated with “decliner” status (ORadj 1.08, 95% CI 1.02, 1.14, per 5% increment) compared to stable. Age, weight gain, baseline FEV1 percent predicted, bronchodilator response, and pre-WTC occupational exposures were also significantly associated with accelerated FEV1 decline. Analyses of gainers vs. stable subgroup showed WAP as a significant predictor in unadjusted but not consistently in adjusted analyses. Conclusions The apparent normal age-related rate of FEV1 decline results from averaging widely divergent trajectories. WAP is significantly associated with accelerated air flow decline in WTC workers.

Increased pulmonary artery diameter is associated with reduced FEV1 in former World Trade Center workers

“…Although that could result from toxicant induced injury, as has been proposed for tobacco related chronic obstructive pulmonary disease, another potential explanation is that increased PAAr reflects obesity (with or without metabolic syndrome) associated pulmonary hypertension, and a post hoc analysis showed that PAAr was significantly associated with obesity (data not shown). Our studies in this cohort have demonstrated the adverse effect of obesity and weight gain on longitudinal follow up, the prevalence of obesity and the metabolic syndrome is known to be substantial in this cohort, and a case‐control study among WTC firefighters demonstrated associations of metabolic syndrome biomarkers with adverse respiratory outcomes (FEV 1 % less than predicted lower limit of normal) …”

“…We have demonstrated that pulmonary arterial enlargement, as indicated by the PAAr, is associated with an FEV 1 below the predicted lower limit of normal, even after adjustment for several known predictors of lung function, such as bronchodilator hyperresponsiveness, wall area percent, baseline BMI, arrival at the WTC within 48 hours and shorter WTC occupational exposure duration, and smoking status.…”

“…We selected a substantial number of important covariates and potential confounders. WAP is an indicator of proximal airway wall thickening, which can result from inflammatory changes, and be a common feature to the different WTC‐related lower airway diseases, and we previously demonstrated that WAP was significantly associated with adverse respiratory outcomes in this WTC occupational cohort . To the extent that significant BDR also reflects bronchial inflammation, it would also be expected to be associated with adverse expiratory flow outcomes, and BDR has been associated with increased susceptibility to tobacco‐smoke pulmonary toxicity .…”

“…We initially determined sex‐specific PAAr cutoff values that maximized the Youden J index (sensitivity + specificity−1) in bivariate analyses with our outcome of interest, FEV 1 < LLN . We then classified subjects dichotomously according to whether or not their PAAr exceeded their sex‐specific cutoff value, and used a logistic regression model to estimate the odds of having a FEV 1 < LLN, adjusting for important covariates . Although some of the predictors were correlated, significant multicollinearity was excluded by the variance inflation factor method.…”

“…In this study, we sought to utilize a novel QCT measurement of PAAr to test the hypothesis that an increased ratio is associated with FEV 1 < LLN in with a substantially larger group of similarly exposed WTC workers and volunteers, also adjusting for a larger number of very important predictors of adverse respiratory health effects in this patient group …”