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Exhaled nitric oxide in endotoxin-exposed adults: effect modification by smoking and atopy
  1. L A M Smit,
  2. D Heederik,
  3. G Doekes,
  4. I M Wouters
  1. Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, Utrecht University, Utrecht, The Netherlands
  1. Lidwien Smit, Institute for Risk Assessment Sciences, Division of Environmental Epidemiology, PO Box 80178, 3508 TD Utrecht, The Netherlands; L.A.Smit{at}


Objectives: Occupational exposure to endotoxin is associated with non-allergic asthma and other airway inflammatory reactions. Little is known about the role of mucosal nitric oxide (NO) production in endotoxin-induced airway inflammation. The objective was to explore exposure–response relationships between occupational endotoxin exposure and fractional concentrations of exhaled NO (FENO) and study the role of FENO as an intermediate factor in the relationship between endotoxin exposure and asthma-like symptoms.

Methods: FENO was measured online in 425 farmers and agricultural processing workers. For each participant (cumulative) endotoxin level was modelled on the basis of 249 personal measurements and job history. Atopy was assessed as specific serum IgE to common inhalant allergens, and other health data and personal characteristics by standardised questionnaires.

Results: A significant positive exposure–response relationship was found between endotoxin and FENO, but only in non-atopic, non-smoking subjects (p = 0.001). FENO was significantly associated with current wheeze and other asthma-like symptoms irrespective of atopy and current smoking. Associations between endotoxin exposure and symptoms changed slightly after adjusting for FENO.

Conclusions: A positive association was found between occupational endotoxin exposure and exhaled nitric oxide in non-smoking, non-atopic adults. Increased FENO was associated with asthma-like symptoms, but the role of FENO as an intermediate factor between endotoxin exposure and airway symptoms appears to be limited.

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  • Funding: This study was funded by the Netherlands Asthma Foundation (grant no.

  • Competing interests: None.

  • Ethics approval: The study protocol was approved by the local medical ethics committee.