Sputum inflammatory profile before and after specific inhalation challenge in individuals with suspected occupational asthma

PLoS One. 2013 Nov 13;8(11):e78304. doi: 10.1371/journal.pone.0078304. eCollection 2013.

Abstract

Background: The aim of this study was to establish the sputum inflammatory profile and changes in levels of leukotriene B₄ (LTB₄) and a panel of Th1/Th2 cytokines in subjects with suspected occupational asthma (OA) following specific inhalation challenge (SIC) to high-molecular-weight (HMW) and low-molecular-weight (LMW) agents.

Material and methods: Fifty-one consecutive subjects undergoing SIC for suspected OA were enrolled. Sputum induction was performed the day before and 24 h after exposure to the offending agent. Total and differential cell counts were assessed. LTB₄ and a 10 Th1/Th2 cytokines were measured in sputum supernatant.

Results: Thirty-four patients tested positive to SIC and were diagnosed with OA (in 10 due to HMW agents and in 24 to LMW agents). SIC was negative in 17 subjects. As compared to baseline an increase was found in the percentage of sputum eosinophils and neutrophils, and in IL-10 concentration after SIC (p = 0.0078, p = 0.0195, and p = 0.046, respectively), and a decrease was seen in LTB₄ level (p = 0.0078) in patients with OA due to HMW agents. An increase in the percentage of sputum neutrophils after SIC (p = 0.0040) was observed in subjects without OA exposed to LMW agents. IL-8 levels after SIC were higher in patients without OA compared with patients with OA (p = 0.0146).

Conclusion: When conducting airway inflammation studies in OA, patients should be divided according to the causal agent (HMW or LMW). In OA patients exposed to HMW agents, an increase in the number of neutrophils can be found in parallel to the increase of eosinophils, although this does not contradict an IgE-mediated mechanism. Exposure to LMW agents can result in increased neutrophilic inflammation in patients with airway diseases unrelated to OA. There is variability in the responses observed in patients with OA exposed to LMW agents.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adolescent
  • Adult
  • Asthma, Occupational / diagnosis
  • Asthma, Occupational / immunology
  • Asthma, Occupational / metabolism*
  • Biomarkers / metabolism
  • Cytokines / metabolism*
  • Eosinophils / immunology
  • Female
  • Humans
  • Leukocyte Count
  • Leukotriene B4 / metabolism*
  • Male
  • Methacholine Chloride / administration & dosage
  • Middle Aged
  • Molecular Weight
  • Neutrophils / immunology
  • Sputum / immunology
  • Sputum / metabolism*
  • Th1 Cells / immunology
  • Th1 Cells / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Young Adult

Substances

  • Biomarkers
  • Cytokines
  • Methacholine Chloride
  • Leukotriene B4

Grants and funding

MJC is a researcher supported by the Miguel Servet programme from Instituto de Salud Carlos III (CP12/03101). This project was supported by the FIS PI05100 (Instituto de Salud Carlos III), the Sociedad Española de Patología Respiratoria (SEPAR), the Fundació Catalana de Pneumologia (FUCAP), and the Societat Catalana de Pneumologia (SOCAP). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.