Occupational asthma phenotypes identified by increased fractional exhaled nitric oxide after exposure to causal agents

Background: The added value of fractional exhaled nitric oxide (FENO) remains controversial in the investigation of occupational asthma (OA). Objective: We sought to assess whether or not the increase of FENO levels following positive specific inhalation challenge (SIC) was restricted to phenotypes of subjects sharing common clinical characteristics by using a statistical cluster analysis. Methods: Subjects were investigated for possible OA in a tertiary center using SICs from 2006 to 2012. FENO levels and sputum eosinophil counts were assessed at baseline and 24 hours after SIC. We performed a 2-step cluster analysis of the subgroup of subjects with OA. A multivariate logistic regression was performed in order to identify the variables associated with an increase in FENO in subjects with OA. Results: One hundred and seventy-eight subjects underwent SIC; 98 had a positive test. The cluster analysis performed in the OA subgroup identified 3 clusters. Despite a positive SIC, there was no increase in the FENO levels after exposure to occupational agents in Cluster 3, in which subjects were only exposed to low-molecular-weight (LMW) agents. The molecular weight of the agent (high molecular weight vs LMW) was the only factor associated with an increase in FENO (OR: 4.2 [1.1-16.8]) in subjects with a positive SIC. Conclusion: An increase in FENO after exposure to agents causing OA seems to occur more consistently in subjects with OA caused by high molecular weight than in those with OA due to LMW.