Exhaled Nitric Oxide Differentiates Airway Diseases in the First Two Years of Life

Abstract

Fractional exhaled nitric oxide (FE NO ) levels are increased in children and adults with asthma, whereas low levels have been found in cystic fibrosis and primary ciliary dyskinesia. The aim of this study was to investigate whether FE NO measurements could distinguish between children below the age of 2 with different airway diseases. FE NO measurements were performed in 118 infants aged between 4.6 and 25.2 mo: 74 infants with recurrent wheezing (RW), 24 with bronchopulmonary dysplasia (BPD), and 20 with cystic fibrosis (CF). FE NO was measured also in 100 healthy controls aged between 1.1 and 7.7 mo. Geometric mean (95% confidence interval) FE NO values were 10.4 (9.1-12.0) parts per billion (ppb) in healthy infants, 18.6 (15.6 -22.2) ppb in wheezy infants, 11.7 (8.2-16.8) ppb in BPD infants and 5.9 (3.4 -10.1) ppb in CF infants. FE NO in wheezers was higher than in controls, BPD, and CF (p ϭ 0.009, p ϭ 0.038, and p Ͻ 0.001, respectively). Atopic wheezers showed higher FE NO than nonatopic wheezers (p ϭ 0.04). CF infants had lower FE NO than healthy controls and BPD infants (p ϭ 0.003 and p ϭ 0.043, respectively). FE NO values in BPD and control infants were not different. We conclude that FE NO is helpful to differentiate various airway diseases already in the first 2 y of life. T he fractional concentration of nitric oxide in exhaled air (FE NO ) has been suggested as a marker of bronchial eosinophilic inflammation. Increased FE NO levels have been found in asthmatic adults (1) and children with symptoms of asthma and atopy (2). Guidelines for the measurement of FE NO are available for both adults and children (3,4), and normal values for healthy children between 4 and 17 y of age have been recently published (5). Although in the last decade there has been a growing interest in measuring FE NO in noncooperative young children as well, few studies have investigated FE NO as a marker of bronchial inflammation in children below the age of 2 y. It has been shown that infants with recurrent wheeze have elevated levels of FE NO during exacerbations that rapidly decrease after steroid therapy (6), suggesting that eosinophilic airway inflammation is present in early childhood wheeze. Low FE NO levels have been found in infants with CF (7), primary ciliary dyskinesia (8) and rhinorrhea (9). A recent study by Baraldi and co-workers (10) showed that school-age children with BPD and airflow limitation had lower FE NO levels than healthy matched controls and asthmatic children, suggesting that airflow limitation in children with BPD might not be related to ongoing inflammation as is the case in asthma. It is well known that infants with BPD have an early inflammatory response followed by chronic inflammation and airways remodeling (11-13). Only one study previously reported high FE NO levels in infants with chronic lung disease (14).The aim of the present study was to measure FE NO in infants below the age of 2 y and to evaluate whether FE NO could be used to differentiate airways diseases in the first 2 y of ...

NO kidding: exhaled nitric oxide fraction in preschool children

“…The results were in line with earlier studies suggesting an association between FeNO early in life and respiratory symptoms, lung function, airways reactivity and/or asthma later in life [7][8][9][10][11]. The different populations studied, the different techniques used to measure FeNO and the different outcomes assessed may explain conflicting results with other studies [12][13][14]. CHAWES et al [12] showed that elevated FeNO at 1 month of age did precede transient early wheeze, but not persistent wheeze, and was unrelated to atopy.…”

“…Another message from this study could be that measuring FeNO before 1 year of age for routine clinical care may be of little value, because at that age FeNO does not discriminate sufficiently between the various categories of patients, demonstrating too much overlap, as was observed by GABRIELE et al [14].…”

Definition, assessment and treatment of wheezing disorders in preschool children: an evidence-based approach

“…Exhaled nitric oxide and other assessments of airways inflammation Elevated exhaled nitric oxide fractions (FeNO) have been found in wheezing infants, especially when they are atopic [70,71], and these normalise during treatment with ICSs [72] and montelukast [73,74]. FeNO in infants are affected by environmental exposures and genetic predisposition to atopy [75].…”

Wheezing in infancy: epidemiology, investigation, and treatment

“…As medidas de fração de óxido nítrico exalado (FeNO) em lactentes, principalmente atópicos, foram elevadas e reduziram após o tratamento farmacológico para asma. Valores padronizados estão disponíveis apenas para crianças com 4 anos ou mais de vida devido à necessidade de colaboração 56,57 . O exame de escarro induzido ainda não foi estudado em todos os grupos de crianças pré-escolares.…”