Elevated exhaled nitric oxide in newborns of atopic mothers precedes respiratory symptoms

Am J Respir Crit Care Med. 2006 Dec 15;174(12):1292-8. doi: 10.1164/rccm.200606-782OC. Epub 2006 Sep 14.


Rationale: Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in asthma. Its role in the disease process before the onset of respiratory symptoms remains unclear.

Objectives: To examine whether elevated NO in newborns with clinically naive airways is associated with subsequent respiratory symptoms in infancy.

Methods: We measured exhaled NO concentration and output after birth and prospectively assessed respiratory symptoms during infancy in a birth cohort of 164 unselected healthy neonates. We examined a possible association between NO and respiratory symptoms using Poisson regression analysis.

Results: In infants of atopic mothers, elevated NO levels after birth were associated with increased risk of subsequent respiratory symptoms (risk ratio [RR], 7.5; 95% confidence interval [CI], 1.7-32.4 for each nl/s increase in NO output; p = 0.007). Similarly, a positive association between NO and symptoms was seen in infants of smoking mothers (RR, 6.6; 95% CI, 2.3-19.3; p = 0.001), with the strongest association in infants whose mothers had both risk factors (RR, 21.8; 95% CI, 5.8-81.3; p < 0.001).

Conclusions: The interaction of NO with maternal atopy and smoking on subsequent respiratory symptoms is present early in life. Clinically, noninvasive NO measurements in newborns may prove useful as a new means to identify high-risk infants. Future confirmation of a role for NO metabolism in the evolution of respiratory disease may provide an avenue for preventative strategies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asthma / diagnosis*
  • Asthma / physiopathology
  • Breath Tests*
  • Female
  • Humans
  • Hypersensitivity
  • Infant
  • Infant, Newborn / physiology*
  • Nitric Oxide*
  • Pregnancy
  • Pregnancy Complications*
  • Prospective Studies*
  • Regression Analysis
  • Risk Factors
  • Smoking


  • Nitric Oxide