Associations between Nitric Oxide Synthase Genes and Exhaled NO-Related Phenotypes according to Asthma Status

International audienceBACKGROUND: The nitric oxide (NO) pathway is involved in asthma, and eosinophils participate in the regulation of the NO pool in pulmonary tissues. We investigated associations between single nucleotide polymorphisms (SNPs) of NO synthase genes (NOS) and biological NO-related phenotypes measured in two compartments (exhaled breath condensate and plasma) and blood eosinophil counts. METHODOLOGY: SNPs (N = 121) belonging to NOS1, NOS2 and NOS3 genes were genotyped in 1277 adults from the French Epidemiological study on the Genetics and Environment of Asthma (EGEA). Association analyses were conducted on four quantitative phenotypes: the exhaled fraction of NO (Fe(NO)), plasma and exhaled breath condensate (EBC) nitrite-nitrate levels (NO2-NO3) and blood eosinophils in asthmatics and non-asthmatics separately. Genetic heterogeneity of these phenotypes between asthmatics and non-asthmatics was also investigated. PRINCIPAL FINDINGS: In non-asthmatics, after correction for multiple comparisons, we found significant associations of Fe(NO) levels with three SNPs in NOS3 and NOS2 (P ≤ 0.002), and of EBC NO2-NO3 level with NOS2 (P = 0.002). In asthmatics, a single significant association was detected between Fe(NO) levels and one SNP in NOS3 (P = 0.004). Moreover, there was significant heterogeneity of NOS3 SNP effect on Fe(NO) between asthmatics and non-asthmatics (P = 0.0002 to 0.005). No significant association was found between any SNP and NO2-NO3 plasma levels or blood eosinophil counts. CONCLUSIONS: Variants in NO synthase genes influence Fe(NO) and EBC NO2-NO3 levels in adults. These genetic determinants differ according to asthma status. Significant associations were only detected for exhaled phenotypes, highlighting the critical relevance to have access to specific phenotypes measured in relevant biological fluid

Performance of population specific job exposure matrices (JEMs): European collaborative analyses on occupational risk factors for chronic obstructive pulmonary disease with job exposure matrices (ECOJEM)

OBJECTIVES—To compare the performance of population specific job exposure matrices (JEMs) and self reported occupational exposure with data on exposure and lung function from three European general populations.
METHODS—Self reported occupational exposure (yes or no) and present occupation were recorded in the three general population surveys conducted in France, The Netherlands, and Norway. Analysis was performed on subjects, aged 25-64, who provided good forced expiratory volume in 1 second (FEV(1)) tracings and whose occupations were performed by at least two people, in the French (6217 men and 5571 women), the Dutch (men from urban (854) and rural (780) areas), and the Norwegian (395 men) surveys. Two population specific JEMs, based on the percentage of subjects who reported themselves exposed in each job, were constructed for each survey and each sex. The first matrix classified jobs into three categories of exposure according to the proportion of subjects who reported themselves exposed in each job (P10-50 JEM, low < 10%, moderate 10-49%, high ⩾ 50%). For the second matrix, a dichotomous variable was constructed to have the same statistical power as the self reported exposure—that is, the exposure prevalence (p) was the same with both exposure assessment methods (Pp JEM). Relations between occupational exposure, as estimated by the two JEMs and self reported exposure, and age, height, city, and smoking adjusted FEV(1) score were compared.
RESULTS—Significant associations between occupational exposure estimated by the population specific JEM and lung function were found in the French and the rural Dutch surveys, whereas no significant relation was found with self reported exposure. In populations with few subjects in most jobs, exposure cannot be estimated with sufficient precision by a population specific JEM, which may explain the lack of relation in the Norwegian and the Dutch (urban area) surveys.
CONCLUSION—The population specific JEM, which was easy to construct and cost little, seemed to perform better than crude self reported exposures, in populations with sufficient numbers of subjects per job.


Keywords: job exposure matrix; occupational exposure; lung functio

Application of the New Asthma-Specific Job Exposure Matrix: A Study in Quebec Apprentice Cohort Exposed to Isocyanates.

International audienceBackground: Recently, the first asthma-specific Job Exposure Matrix (JEM) was updated to occupational asthma-specific JEM (OAsJEM). Our study aimed to evaluate the association between continued exposure to isocyanates and incident work-related chest symptoms in former car-painting apprentices and to compare the associations using the first and new OAsJEMs.Methods: We used data from an inception cohort of male car-painting apprentices. Post-apprenticeship exposure to isocyanate during follow-up was evaluated using the first asthma-specific JEM (“exposed”=1 or “not exposed”=0) and the new OAsJEM (high=2, medium=1, and none=0). Association between occupation exposure to isocyanate and incidence of work-related rhinoconjunctival and chest symptoms were evaluated through cox regression models, adjusted for age, smoking, wheezing, and non-specific bronchial hyperresponsiveness.Results: The agreement between the two JEMs (exposed vs non-exposed to isocyanate) was perfect (kappa coefficient=0.946, p<0.001). There were only five subjects who were classified as non-exposed based on the first JEM, but had a medium exposure to isocyanate based on the new OAsJEM. Exposure to isocyanate increased the risk of occupational chest symptoms in the high-exposure category (hazard ratio [HR] 2.7, 95% CI 1.1 – 6.6) and the medium category (HR 2.9, 95% CI 0.3 – 30.0) compared to the reference group based on the new OAsJEM, whereas an HR of 2.5 (95% CI 1.0-6.2) was observed from the first JEM. Both JEMs yielded an inconclusive association between exposure to isocyanates and the risk for work-related rhino-conjunctivitis.Conclusion: The asthma-specific JEM and OAsJEM consistently showed that isocyanate exposure increased the risk of incident work-related chest symptoms

P123 Asthma control in severe asthma and occupational exposures to inhalable asthmagens

International audienc