Predictive value of childhood airway hyper-responsiveness to indirect stimuli: 10-year longitudinal study.

BACKGROUND: Airway hyper-responsiveness (AHR) is a common feature in asthma. The use of AHR in predicting active asthma or the persistence of AHR in childhood is poorly understood. By analyzing longitudinal connections including different measures of AHR, lung function, and inflammation markers, we sought to identify the best available method for predicting persistence of AHR and identification of later active asthma. METHODS: We tested 105 asthmatic children aged 3-7 years with fractional exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and AHR evaluated by indirect methods (hypertonic saline and exercise challenge). Ten years later, 64 children participated in the follow-up visit and were tested with FeNO, IOS, spirometry, and methacholine challenge. At both study visits, blood samples were collected, and a questionnaire was completed. RESULTS: Asthma was in remission in 66% of patients at adolescence. AHR measured by hypertonic saline challenge at preschool age was associated with asthma symptoms (OR 10.2; 95% CI 2.8, 37.3) but not with AHR estimated with methacholine challenge 10 years later. AHR measured by exercise challenge was not associated with AHR or recent asthma symptoms in adolescence. Preschool eosinophilia continued until adolescence in 87% of patients but was not associated with AHR or subjective signs of asthma 10 years later. Wheezy preschoolers with atopy had a higher risk for AHR in adolescence (OR 4.1; 95% CI 1.0, 16.2). CONCLUSION: Results from hypertonic saline challenge are associated with persistent asthma symptoms even after a decade. AHR measured by indirect methods at preschool age did not predict AHR in adolescence.

Airway hyperresponsiveness in young children with respiratory symptoms: A five-year follow-up.

BACKGROUND: Recurrent wheezing in early life is transient in most children. The significance of airway hyperresponsiveness (AHR) in persistence of respiratory symptoms from infancy to early childhood is controversial. OBJECTIVE: We evaluated whether AHR in wheezy infants predicts doctor-diagnosed asthma (DDA) or AHR at the age of 6 years. METHODS: Sixty-one wheezy infants (age 6-24 months) were followed up to the median age of 6 years. Lung function and AHR with methacholine challenge test were assessed at infancy and 6 years. The exercise challenge test was performed at the age of 6 years. Atopy was assessed with skin prick tests. RESULTS: At 6 years, 21 (34%) of the children had DDA. Children with DDA had higher logarithmic transformed dose-response slope (LOGDRS) to methacholine in infancy than children without DDA (0.047 vs 0.025; P = .033). Furthermore, AHR to methacholine in infancy and at 6 years were associated with each other (r = 0.324, P = .011). Children with exercise-induced bronchoconstriction (EIB) at 6 years were more reactive to methacholine in infancy than those without EIB (P = .019). CONCLUSION: Increased AHR in symptomatic infants was associated with increased AHR, DDA, and EIB at median the age of 6 years, suggesting early establishment of AHR.

Abnormal lung function at preschool age asthma in adolescence?

BACKGROUND: Asthma often begins early in childhood. However, the risk for persistence is challenging to evaluate. OBJECTIVE: This longitudinal study relates lung function assessed with impulse oscillometry (IOS) in preschool children to asthma in adolescence. METHODS: Lung function was measured with IOS in 255 children with asthma-like symptoms aged 4-7 years. Baseline measurements were followed by exercise challenge and bronchodilation tests. At age 12-16 years, 121 children participated in the follow-up visit, when lung function was assessed with spirometry, followed by a bronchodilation test. Asthma symptoms and medication were recorded by a questionnaire and atopy defined by skin prick tests. RESULTS: Abnormal baseline values in preschool IOS were significantly associated with low lung function, the need for asthma medication, and asthma symptoms in adolescence. Preschool abnormal R5 at baseline (z-score ≥1.645 SD) showed 9.2 odds ratio (95%CI 2.7;31.7) for abnormal FEV1/FVC, use of asthma medication in adolescence, and 9.9 odds ratio (95%CI 2.9;34.4) for asthma symptoms. Positive exercise challenge and modified asthma-predictive index at preschool age predicted asthma symptoms and the need for asthma medication, but not abnormal lung function at teenage. CONCLUSION: Abnormal preschool IOS is associated with asthma and poor lung function in adolescence and might be utilised for identification of asthma persistence.

Small airway oscillometry indices: Repeatability and bronchodilator responsiveness in young children.

INTRODUCTION: The impulse oscillometry (IOS) indices absolute and relative difference between respiratory resistance at 5 and 20 Hz (R5-20 and R5-20%, respectively) and the area under the reactance curve (AX) are postulated to reflect small airway function. Data on their cutoff values to evaluate bronchodilator responsiveness (BDR) or between-visit changes after interventions are limited in young children. METHODS: We evaluated the BDR of 103 healthy children aged 2-7 years, who received either salbutamol (n = 84) or placebo (n = 19) in order to determine cutoff values for BDR of R5-20, R5-20%, and AX. We then determined the repeatability within and between two IOS measurements 7-14 days apart in young children aged 4-8 years with asthmatic symptoms (n = 43), including cutoff values for significant between-visit changes. RESULTS: The investigated IOS parameters showed marked BDR (fifth percentile cutoff of 75-110% of the baseline value) in healthy children, whereas no significant changes were seen after inhalation of placebo. The agreement within the triplicate IOS measurement was excellent (ICC > 0.80), and the agreement of results between visits was good (ICC > 0.60). A change in R5-20, R5-20%, and AX of 0.65, 1.08, and 0.84 z-scores, respectively, would exceed 95% confidence intervals for between-visit variability. CONCLUSION: We introduce cutoff values for BDR of R5-20, R5-20%, and AX, and their repeatability indices and cutoff limits for significant between-visit changes. These IOS parameters may show greater variability than the conventional IOS indices during follow-up, but the between-visit agreement remains good, providing potentially useful endpoints for monitoring lung function in young children.

Sensitivity of newly defined impulse oscillometry indices in preschool children.

INTRODUCTION: Early origins of chronic obstructive pulmonary disease have been recognized. Impulse oscillometry (IOS) is suitable for assessment of lung function also in preschool children, and some novel indices have been connected to assessment of small airway function. However, limited data exist on the sensitivity of these new indices to detect lung function deficits in young symptomatic children. METHODS: IOS measurements of 103 healthy preschool children were evaluated to establish reference equations for the difference between respiratory resistance at 5 and 20 Hz (R5-20), the relative difference of R5-20 (R5-20%), and area under the reactance curve (AX). Thereafter, IOS results of children with late-onset troublesome lung symptoms (n = 20), a history of early wheeze (n = 37), or a history of bronchopulmonary dysplasia (BPD, n = 8) were compared to healthy children. RESULTS: None of the patient groups differed from healthy regarding respiratory resistance at 5 Hz (R5), and only children with a history of BPD differed from healthy regarding respiratory reactance at 5 Hz (X5). In contrast, z-scores of R5-20, R5-20%, and AX were significantly higher in all patient groups than in healthy children (P < 0.001), showing improved sensitivity (20-55%) compared to R5 and X5 (5-6%). CONCLUSION: R5-20, R5-20%, and AX are superior to conventional IOS parameters in distinguishing children with current or past lower respiratory tract symptoms from healthy, and may prove valuable for screening early lung function deficits. Pediatr Pulmonol. 2017;52:598-605. © 2016 Wiley Periodicals, Inc.

Aberrant small airways function relates to asthma severity in young children.

BACKGROUND: Frequency dependence of resistance (R5-20) assessed by impulse oscillometry (IOS) is suggested to be a measure of small airways. Small airways involvement during induced bronchoconstriction has been shown to reflect severity of asthma in adults. OBJECTIVE: Our aim was to evaluate if methacholine (Mch) induced changes in R5-20 are associated with the severity of exercise induced bronchoconstriction (EIB) in young children. METHODS: A total of 109 children aged 3-8 years were studied, 95 with obstructive symptoms and 14 in good health, to assess small airways function during a Mch challenge. R5-20 and other IOS resistance and reactance parameters were measured at baseline and after the Mch challenge. In a standardized exercise test, the children were grouped according to the severity of EIB expressed as the percentage increase in resistance at 5 Hz (ΔR5) after exercise, indicating either no EIB (ΔR5 < 40%, n = 84), moderate EIB (ΔR5 40-80%, n = 13) and severe EIB (ΔR5 > 80%, n = 12). RESULTS: The baseline R5-20 was not associated with the severity of EIB, but during Mch induced bronchoconstriction the change in R5-20 was significantly higher in children with severe EIB (2.61 fold increase) than in children with moderate EIB (1.48) or no EIB (1.74, p = 0.036). No significant associations were found in changes of other IOS parameters. The children with severe EIB also used more short-acting beta-agonists during the past two months than the other two groups (p < 0.001). CONCLUSION: Frequency dependence of resistance (R5-20) measured by IOS during the Mch induced bronchoconstriction and more frequent use of beta-agonists are associated with severe EIB in young children.

Assessing direct and indirect airway hyperresponsiveness in children using impulse oscillometry.

BACKGROUND: Airway hyperresponsiveness (AHR) is a hallmark of asthma but its assessment is usually restricted to older children who are capable of performing the maneuvers involved in spirometry. In younger children, a feasible option to perform the lung function measurement is impulse oscillometry (IOS), which requires less cooperation. OBJECTIVE: To evaluate whether assessment of AHR by IOS could differentiate children with various obstructive symptoms from one another. METHODS: One hundred twenty-one children (median age 6.0 years, range 3.7-8.1 years) were examined: 31 with probable asthma characterized by current troublesome lung symptoms, 61 with a history of early wheezing disorder (recurrent wheezing ≤24 months of age), 15 with a history of bronchopulmonary dysplasia, and 14 healthy controls. Indirect AHR was assessed by exercise and mannitol challenge tests, and direct AHR was assessed with methacholine using IOS. AHR to exercise was defined as an increase of at least 40% in respiratory resistance at 5 Hz. In the mannitol and methacholine challenges, the dose causing an increase of 40% in respiratory resistance at 5 Hz was calculated. RESULTS: AHR to exercise was good at differentiating children with current troublesome lung symptoms from those in the other groups (P < .001). AHR to methacholine separated children with current troublesome lung symptoms, early wheezing disorder, and bronchopulmonary dysplasia from the controls (P < .001), whereas the mannitol test did not distinguish among the study groups (P = .209). CONCLUSION: The methacholine and exercise challenge tests with IOS identify children with probable asthma characterized by troublesome lung symptoms and therefore may represent a practical aid in the evaluation of AHR in young children.

Maternal smoking affects lung function and airway inflammation in young children with multiple-trigger wheeze.

BACKGROUND: Exposure to tobacco smoke is a well-known risk factor for childhood asthma and reduced lung function, but the effect on airway inflammation in preschool-aged children is unclear. OBJECTIVE: To examine the effect of parental smoking on lung function and fractional concentration of exhaled nitric oxide (Feno) in relation to both parental reports and children's urine cotinine concentrations in preschool-aged children with multiple-trigger wheeze. METHODS: A total of 105 3- to 7-year-old children with multiple-trigger wheeze and lung function abnormalities were recruited. Lung function was assessed by impulse oscillometry, and Feno measurements were performed. Exposure to tobacco smoke was determined by parental reports and measurement of children's urinary cotinine concentrations. RESULTS: Forty-three percent of the children were exposed to environmental tobacco smoke according to parental reports. The Feno level was significantly higher in children with a smoking mother (n = 27) than in children with a nonsmoking mother (23.4 vs 12.5 ppb, P = .006). The Feno level expressed as z score and the cotinine level correlated significantly (P = .03). Respiratory resistance at 5 Hz was higher in children exposed to maternal smoking than in others (0.99 vs 0.88 kPas/L, P = .005). Urinary cotinine concentrations reflected well parental reports on their daily smoking and increased relative to the number of cigarettes smoked in the family (P < .01). Atopy was found in 75% of the children, but it was not associated with the Feno value (P = .65). CONCLUSION: Maternal smoking was associated with increased Feno value and poorer lung function in steroid-naive preschool children with multiple-trigger wheeze. Larger controlled trials are needed to generalize the results.

Can we use portable nitric oxide analyzer in young children?

OBJECTIVE: Management of asthma could be improved by measuring exhaled nitric oxide (FENO). Portable hand-held FENO analyzer (NIOX MINO) is practical and small and could be used also in the primary care office. It has demonstrated good repeatability and correlation with stationary device (NIOX) in adults and school aged children, but so far there have been no reports on young children. The aim of this study was to compare conventional chemiluminescence device (NIOX) with a hand-held electrochemical device (NIOX MINO) in young children. DESIGN: Paired measurements of FENO were performed with the stationary chemiluminescence-based analyzer (NIOX) and with portable electrochemical device (NIOX MINO) in children with asthmatic symptoms and age-matched controls. RESULTS: Fifty-five children with mean (range) age of 5.7 (3.9-8.5) years were evaluated with both devices. Measurements were successful with both devices in 40 out of 57 children. NIOX MINO was more difficult to use than NIOX in this age group, success rates being 73% and 93%, respectively (P = 0.004). The reproducibility was similar and there was a close correlation between FENO measured by the two devices (r = 0.97, P < 0.001). However, Bland-Altman plot demonstrated limits of agreement that were relatively wide compared to low levels of FENO in the sample. Both devices were sensitive enough to distinguish higher FENO levels in children with asthmatic symptoms, compared to healthy controls. CONCLUSIONS: We conclude that NIOX MINO can be used as a screening tool for the assessment of airway inflammation in children from the age of 4 years, but its applicability is limited by lower measurement success rate and relatively poor accuracy and detection limit at low levels of FENO.