Acute respiratory effects in firefighters.

BACKGROUND: Associations between acute respiratory inflammatory responses, changes in bronchial hyperresponsiveness, serum pneumoprotein levels, and exposure to fire smoke were studied. METHODS: The study comprised 51 firefighters. Blood samples were taken within 24 hr following exposure to fire smoke, and after a week and 3 months. Sputum was induced within 5 days post-exposure and subjects underwent spirometry and methacholine provocation one week post-exposure. Exposure was registered by a questionnaire. RESULTS: No changes were observed following smoke exposure in bronchial hyperresponsiveness and serum pneumoprotein levels. Nevertheless, in a sizable proportion of the firefighters (44%) elevated sputum neutrophil levels (≥60%) were found. Serum IL-8 concentrations were higher 24 hr post-exposure compared to pre-exposure. Elevated neutrophil levels in sputum were associated with elevated serum IL-8 (ß = 0.010, P = 0.004) and TNFα (ß = 0.005, P = 0.034) levels within 24 hr post-exposure and IL-8 elevation lasted up to 3 months. CONCLUSIONS: Acute exposure to fire smoke induces acute neutrophilic airway and long-lasting systemic inflammation in healthy firefighters in the absence of bronchial hyperresponsiveness.

Serum pneumoproteins in firefighters.

Serum Clara cell protein (CC16) and surfactant-associated protein A (SP-A) were measured in a cross-sectional study in 402 firefighters. For the population as a whole, no associations were detected between serum pneumoproteins and smoke exposure. SP-A levels were increased in symptomatic subjects exposed to fire smoke within 2 days before testing. SP-A levels were higher after an inhalation incident ever. CC16 was negatively associated with the number of fires fought in the last 12 months in current nonsmokers. These associations between pneumoprotein levels reiterate the importance of adequate use of self-contained breathing apparatus by firefighters.

The role of ELOVL1 in very long-chain fatty acid homeostasis and X-linked adrenoleukodystrophy.

X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene encoding the peroxisomal ABC transporter adrenoleukodystrophy protein (ALDP). X-ALD is characterized by the accumulation of very long-chain fatty acids (VLCFA; > or =C24) in plasma and tissues. In this manuscript we provide insight into the pathway underlying the elevated levels of C26:0 in X-ALD. ALDP transports VLCFacyl-CoA across the peroxisomal membrane. A deficiency in ALDP impairs peroxisomal beta-oxidation of VLCFA but also raises cytosolic levels of VLCFacyl-CoA which are substrate for further elongation. We identify ELOVL1 (elongation of very-long-chain-fatty acids) as the single elongase catalysing the synthesis of both saturated VLCFA (C26:0) and mono-unsaturated VLCFA (C26:1). ELOVL1 expression is not increased in X-ALD fibroblasts suggesting that increased levels of C26:0 result from increased substrate availability due to the primary deficiency in ALDP. Importantly, ELOVL1 knockdown reduces elongation of C22:0 to C26:0 and lowers C26:0 levels in X-ALD fibroblasts. Given the likely pathogenic effects of high C26:0 levels, our findings highlight the potential of modulating ELOVL1 activity in the treatment of X-ALD.