Published ahead of print on September 14, 2006, doi:10.1164/rccm.200606-782OC Am. J. Respir. Crit. Care Med., Volume 174, Number 12, December 2006, 1292-1298 A more recent version of this article appeared on December 15, 2006
Submitted on June 13, 2006 Elevated Exhaled Nitric Oxide in Newborns of Atopic Mothers Precedes Subsequent Respiratory SymptomsPhilipp Latzin1,1 Department of Pediatrics, University of Berne, Bern, Switzerland; Department of Social and Preventive Medicine, University of Berne, Bern, Switzerland, 2 Department of Social and Preventive Medicine, University of Berne, Bern, Switzerland, 3 Department of Pediatrics, University of Berne, Bern, Switzerland * To whom correspondence should be addressed. E-mail: urs.frey{at}insel.ch.
Rationale Exhaled nitric oxide is a well-known marker of established airway inflammation in asthma. Its role in the disease process prior to the onset of respiratory symptoms remains unclear. Objectives To examine whether elevated nitric oxide in newborns with clinically naive airways is associated with subsequent respiratory symptoms in infancy. Methods We measured exhaled nitric oxide 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 nitric oxide and respiratory symptoms using Poisson regression analysis. Results In infants of atopic mothers elevated nitric oxide levels after birth were associated with increased risk of subsequent respiratory symptoms (risk ratio 7.5; CI 1.7 - 32.4 for each nL/s increase in nitric oxide output; p = 0.007). Similarly, a positive association between nitric oxide and symptoms was seen in infants of smoking mothers (risk ratio 6.6; CI 2.3 - 19.3; p = 0.001), with the strongest association in infants whose mothers had both risk factors (risk ratio 21.8; CI 5.8 - 81.3; p < 0.001). Conclusions The interaction of nitric oxide with both maternal atopy and smoking on subsequent respiratory symptoms is already present early in life. Clinically, non-invasive nitric oxide measurements in newborns may potentially prove useful as a new means to identify high-risk infants. Future confirmation of a role for nitric oxide metabolism in the evolution of respiratory disease may provide an avenue for preventative strategies. Key words: allergy, asthma, cough, wheeze
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