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Elevated Exhaled Nitric Oxide in Newborns of Atopic Mothers Precedes Respiratory Symptoms

Departments of Pediatrics and Social and Preventive Medicine, University of Bern, Bern, Switzerland

Correspondence and requests for reprints should be addressed to Urs Frey, M.D., Ph.D., Pediatric Respiratory Medicine, Department of Pediatrics, University of Berne Inselspital, 3010 Bern, Switzerland. E-mail: urs.frey{at}insel.ch

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.

Key Words: allergy • asthma • cough • wheeze

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Exhaled nitric oxide (NO) is a well-known marker of established airway inflammation in allergic asthma. It is not known yet whether NO plays a role in the evolution of the disease before the onset of respiratory symptoms. What This Study Adds to the Field In infants of atopic and smoking mothers, changes in NO metabolism occur before the onset of clinical symptoms. This suggests that NO plays a role in respiratory disease pathogenesis and may help to identify high-risk infants.

 

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