PURPOSE: Alpha-1-antitrypsin (AAT) deficiency, an underrecognized genetic disorder with airway and pulmonary parenchymal manifestations, causes more frequent and severe disease with exposure to tobacco smoke. Massive irritant inhalation during/after the World Trade Center collapse (WTC) caused spirometric reduction in Fire Department of New York (FDNY) rescue workers. We hypothesized that post-WTC spirometric decline may be accelerated in AAT-deficient rescue workers.
METHODS: One hundred and fifty-one WTC-exposed workers were enrolled 10-11/2001 with annual spirometric follow-up till 2005. AAT testing was offered 09/2005 (N=90; 60% retention).Blood AAT level (immunoassay) and/or AAT phenotype (isoelectric focusing) were determined in a nationally accredited laboratory (Alpha Center, Salt Lake City, UT). Subjects with a Z allele (N=4) were categorized as severely deficient, those with an S and no Z allele (N=7) as moderately deficient, and those without S and Z allele or normal blood level (N=79) as normal. Post-WTC FEV1 declines were (A) difference between last and first measurements (2-point rates), and (B) gender-, race-, height-, smoking-, age-, and WTC exposure- (arrival time and work assignment) adjusted with mixed linear random effects (MLRE) modeling (adjusted rates).
RESULTS: Severely AAT-deficient subjects had significantly faster post-WTC FEV1 declines than subjects without severe deficiency (i.e., normal/moderately deficient), both as 2-point (p=0.003, Fig.1A) and adjusted rates (p=0.006, Fig.1B). Moderately AAT-deficiency subjects had post-WTC FEV1 declines between severely AAT-deficient and normal subjects, with significant linear trend, both as 2-point (p=0.003, Fig.2A) and adjusted rates (p=0.004, Fig.2B). Pre-WTC, AAT deficient subjects did not show accelerated adjusted FEV1 declines. Analyses with FVC as outcome variable yielded similar results.
CONCLUSION: Severe and moderate AAT deficiency in FDNY rescue workers was associated with significantly faster FEV1 decline during the first 4 years after the irritant WTC exposure.
CLINICAL IMPLICATIONS: If our findings are substantiated, subjects with significant occupational inhaled irritant exposure or with chronic inflammatory airway disease may require higher than currently accepted AAT blood levels to prevent accelerated pulmonary function deterioration.
DISCLOSURE: Gisela Banauch, None.