Thorax 61:514-520 doi:10.1136/thx.2005.054643
  • Cystic fibrosis

Inducible NO synthase expression is low in airway epithelium from young children with cystic fibrosis

  1. A Moeller1,2,
  2. F Horak Jr1,4,
  3. C Lane1,
  4. D Knight6,
  5. A Kicic1,3,
  6. S Brennan5,
  7. P Franklin3,
  8. J Terpolilli1,
  9. J H Wildhaber2,
  10. S M Stick1
  1. 1Department of Respiratory Medicine, Princess Margaret Hospital for Children, Perth, Western Australia
  2. 2Division of Respiratory Medicine, University Children’s Hospital, Zurich, Switzerland
  3. 3School of Paediatrics and Child Health, University of Western Australia, Nedlands, Western Australia
  4. 4Department of General Pediatrics, University Children’s Hospital, Vienna, Austria
  5. 5Telethon Institute for Child Health Research, Centre for Child Health Research, University of Western Australia, Western Australia
  6. 6James Hogg iCAPTURE Centre for Cardiovascular and Respiratory Research, St Paul’s Hospital, Vancouver, BC, Canada
  1. Correspondence to:
    Dr A Moeller
    Department of Respiratory Medicine, University Children’s Hospital Zurich, Steinwiesstrasse 75, CH-8032 Zurich, Switzerland; alexander.moeller{at}
  • Received 19 October 2005
  • Accepted 19 February 2006
  • Published Online First 3 March 2006


Background: This is the first study to measure inducible nitric oxide synthase (iNOS) gene and protein expression quantitatively in primary epithelial cells from very young children with cystic fibrosis (CF). Low levels of exhaled nitric oxide (NO) in CF suggest dysregulation of NO production in the airway. Due to the importance of NO in cell homeostasis and innate immunity, any defect in the pathway associated with CF would be a potential target for treatment.

Methods: Cells were obtained by tracheobronchial brushing from 40 children with CF of mean (SD) age 2.1 (1.5) years and from 12 healthy non-atopic children aged 3.4 (1.2) years. Expression of iNOS mRNA was measured using quantitative PCR and iNOS protein by immunofluorescence and Western blot analysis.

Results: Inducible NOS mRNA expression was significantly lower in CF patients with and without bacterial infection than in healthy children (0.22 and 0.23 v 0.76; p = 0.002 and p = 0.01, respectively). Low levels of iNOS gene expression were accompanied by low levels of iNOS protein expression as detected by Western blot analysis.

Conclusions: These results support the findings of previous studies in adult patients with advanced disease, cell lines, and animal models. Our findings reflect the situation in children with mild lung disease. They indicate that low iNOS expression may be an innate defect in CF with potential consequences for local antimicrobial defence and epithelial cell function and provide evidence for an approach to treatment based on increasing epithelial NO production or the sensitivity of NO dependent cellular processes.


  • Published Online First 3 March 2006

  • A Moeller was supported by a grant from the Swiss National Research Foundation. F Horak was supported by a grant of the Austrian Science Foundation. The study was supported by the Cystic Fibrosis Australia Research Trust.

  • Competing interests: none.

  • A Moeller and F Horak have equal first author responsibility for this study.