Search

Pulmonary function tests are seldom performed in preschool children with asthma. The aim of this multicenter study was to compare pulmonary function in 74 preschool children with asthma (height of 90-130 cm) and 84 healthy control subjects. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (interrupter technique) were measured. As compared with control children, children with asthma had a significantly higher resistance (0.77 +/- 0.20 vs. 0.92 +/- 0.22 kPa. L-1. second, p < 0.001) and significantly lower specific expiratory interrupter conductance (p < 0.005) values. Resistance values were significantly higher in children with asthma with than without symptoms on exertion (p < 0.05). The effect of bronchodilator administration, expressed as the percentage of baseline and predicted resistance values, was significantly greater in children with asthma than in control subjects (-18.6 +/- 13.6% vs. -11.2 +/- 15.2%, p

Rationale: Although children with primary ciliary dyskinesia (PCD) typically have low nasal nitric oxide (nNO), some children with indisputable PCD may have unexplained high nNO concentrations. Objectives: To look for relationships between nNO measures and genetic findings (and cilia motility or ultrastructure when available) in children with PCD with known genotypes. Methods: We retrospectively studied 73 children with PCD (median age, 9.5 [range, 2.1-18.2] yr). nNO was the mean value of a plateau reached while the velum was closed (nNO-VC; threshold, 77 nl ⋅ min -1 ) or was calculated as the average of five peaks obtained during tidal breathing (threshold, 40 nl ⋅ min -1 ). Ciliary beat was classified as either motile (including dyskinetic pattern) or immotile, depending on whether motility was present or absent in all cilia, or as a mixture of motile and immotile cilia. Genotypes were classified as pathogenic mutations in genes known to be associated with high nNO (mild genotype), biallelic truncating mutations in other genes (severe mutations), or putative hypomorphic pathogenic mutations (missense, single amino acid deletion, or moderate splicing mutations) in at least one allele believed to be possibly associated with residual production of a functional protein. Results: nNO was above the discriminant threshold in 16 of 73 (21.9%) children (11 nNO-VC and 5 nNO during tidal breathing). High nNO was less frequent in children with severe mutations (2 of 42) than in those with mild genotypes (7 of 10) or at least one hypomorphic mutation (7 of 21) ( P  < 0.0001). Median (interquartile range) nNO-VC values ( n  = 60) were significantly different in the three genotype groups: severe mutations, 18 (10-26) nl ⋅ min -1 ( n  = 36); possible residual functional protein production (putative hypomorphic mutations), 23 (16-68) nl ⋅ min -1 ( n  = 17); and mild genotypes, 139 (57-216) nl ⋅ min -1 ( n  = 7) ( P  = 0.0002). The higher the cilia motility, the higher the nNO-VC (16 [10-23], 23 [17-56], and 78 [45-93] nl ⋅ min -1 in patients with immotile, dyskinetic motile and immotile, and dyskinetic motile cilia, respectively; P  < 0.0001), while nNO values were scattered across different ultrastructure defects ( P  = 0.07). Conclusions: In children with PCD, high nNO values were linked not only to specific genes but also to potentially hypomorphic mutations in other genes (with possible functional protein production). nNO values increased with the proportion of motile cilia.

Rationale: Although the effects of traffic-related air pollution on respiratory exacerbations have been well documented, its impact on lung function in childhood remains unclear., Objectives: Our aim was to investigate the associations of prenatal, early, and lifetime traffic-related air pollution exposure with lung function at 8-9 years studying possible effect modification by sex, sensitization at 8-9 years, and early lower respiratory tract infections., Methods: We conducted this study among 788 children from the PARIS (Pollution and Asthma Risk: an Infant Study) birth cohort. Lung function tests were performed during the medical examination at 8-9 years. Traffic-related air pollution exposure during each trimester of pregnancy was estimated using nitrogen oxides background measurements. Postnatal traffic-related air pollution exposure was assessed by a nitrogen oxides air dispersion model at both residential and daycare/school addresses. Associations between lung function and traffic-related air pollution exposure were analyzed by multiple linear regression models., Results: Higher prenatal nitrogen oxides levels, especially during the second trimester of pregnancy, were associated with a lower forced expiratory flow at 25-75% of the forced vital capacity, but there were no significant associations between prenatal nitrogen oxide levels and forced vital capacity, forced expiratory volume during 1 second, or the forced expiratory volume during 1 second/forced vital capacity ratio overall. Postnatal traffic-related air pollution exposure was associated with lower lung function among children with early lower respiratory tract infections or sensitization at 8-9 years, but not in the full cohort. In children with early repeated lower respiratory tract infections, an interquartile increase in lifetime nitrogen oxides exposure was associated with both a lower forced expiratory volume during 1 second (-62.6 ml; 95% confidence interval = -107.0 to -18.1) and forced vital capacity (-55.7 ml; 95% confidence interval = -109.5 to -1.8), but was not associated with the forced expiratory volume during 1 second/forced vital capacity ratio. There was an association between greater early postnatal nitrogen oxide exposure and a lower forced expiratory volume during 1 second/forced vital capacity ratio among sensitized children (-0.65%; 95% confidence interval = -1.25 to -0.05)., Conclusions: This study sheds new light, suggesting associations between postnatal traffic-related air pollution exposure and reduced lung function may be enhanced by early, repeated lower respiratory tract infections or allergic sensitization.

Rationale: Airway wall structure in preschoolers with severe recurrent wheeze is poorly described., Objectives: To describe airway wall structure and inflammation in preschoolers with severe recurrent wheeze., Methods: Flexible bronchoscopy was performed in two groups of preschoolers with severe recurrent wheeze: group 1, less than or equal to 36 months (n = 20); group 2, 36-59 months (n = 29). We assessed airway inflammation, reticular basement membrane (RBM) thickness, airway smooth muscle (ASM), mucus gland area, vascularity, and epithelial integrity. Comparisons were then made with biopsies from 21 previously described schoolchildren with severe asthma (group 3, 5-11.2 yr)., Measurements and Main Results: RBM thickness was lower in group 1 than in group 2 (3.3 vs. 3.9 μm; P = 0.02), was correlated with age (P < 0.01; ρ = 0.62), and was higher in schoolchildren than in preschoolers (6.8 vs. 3.8 μm; P < 0.01). ASM area was lower in preschoolers than in schoolchildren (9.8% vs. 16.5%; P < 0.01). Vascularity was higher in group 1 than in group 2 (P = 0.02) and group 3 (P < 0.05). Mucus gland area was higher in preschoolers than in schoolchildren (16.4% vs. 4.6%; P < 0.01). Inflammatory cell counts in biopsies were not correlated with airway wall structure. ASM area was higher in preschoolers with atopy than without atopy (13.1% vs. 7.7%; P = 0.01). Airway morphometrics and inflammation were similar in viral and multiple-trigger wheezers., Conclusions: In preschoolers with severe recurrent wheeze, markers of remodeling and inflammation are unrelated, and atopy is associated with ASM. In the absence of control subjects, we cannot determine whether differences observed in RBM thickness and vascularity result from disease or normal age-related development.

Although pulmonary function testing plays a key role in the diagnosis and management of chronic pulmonary conditions in children under 6 years of age, objective physiologic assessment is limited in the clinical care of infants and children less than 6 years old, due to the challenges of measuring lung function in this age range. Ongoing research in lung function testing in infants, toddlers, and preschoolers has resulted in techniques that show promise as safe, feasible, and potentially clinically useful tests. Official American Thoracic Society workshops were convened in 2009 and 2010 to review six lung function tests based on a comprehensive review of the literature (infant raised-volume rapid thoracic compression and plethysmography, preschool spirometry, specific airway resistance, forced oscillation, the interrupter technique, and multiple-breath washout). In these proceedings, the current state of the art for each of these tests is reviewed as it applies to the clinical management of infants and children under 6 years of age with cystic fibrosis, bronchopulmonary dysplasia, and recurrent wheeze, using a standardized format that allows easy comparison between the measures. Although insufficient evidence exists to recommend incorporation of these tests into the routine diagnostic evaluation and clinical monitoring of infants and young children with cystic fibrosis, bronchopulmonary dysplasia, or recurrent wheeze, they may be valuable tools with which to address specific concerns, such as ongoing symptoms or monitoring response to treatment, and as outcome measures in clinical research studies.

Pulmonary function tests have rarely been assessed in preschool children with cystic fibrosis (CF). The objective of this multicenter study was to compare pulmonary function in 39 preschool children with CF (height, 90-130 cm; 16 homozygous Delta F508) and in 79 healthy control children. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (Rint(exp)) (interrupter technique) were measured. As compared with control children, children with CF had significantly higher Rint(exp), expressed as absolute values and as Z-scores (1.05 +/- 0.36 versus 0.80 +/- 0.20 kPa.L(-1). second, p < 0.0001; and 1.31 +/- 1.72 versus 0.19 +/- 0.97, p < 0.0001), and significantly lower specific expiratory interrupter conductance (1.29 +/- 0.34 versus 1.63 +/- 0.43 kPa(-1). second, p < 0.0001). The effect of the bronchodilator salbutamol on Rint(exp) was not significantly different between children with CF and control children. Rint(exp) Z-scores were significantly higher in children with CF who were exposed to passive smoke (n = 8) (p < 0.03). Children with CF and with a history of respiratory symptoms (n = 31) had significantly higher functional residual capacity Z-scores (p < 0.02) and lower specific expiratory interrupter conductance Z-scores (p < 0.04). Genotype did not influence the data. We conclude that Rint(exp) and functional residual capacity measurements may help to follow young children with CF who are unable to perform reproducible forced expiratory maneuvers.

The interrupter technique estimates flow resistance. It entails occlusion of the airways during tidal breathing while flow and mouth pressure are recorded. This noninvasive technique is easy to use in young children. The aim of the present study was to measure inspiratory and expiratory interrupter resistance (Rint(insp), Rint(exp)) before and after bronchodilator administration in young healthy white children. We designed a multicenter study using a standardized procedure for Rint measurements. Centers in five French cities studied 91 children (48 boys and 43 girls; height, 92 to 129 cm; mean age 5.3 +/- 1.4 years). Mean values were not significantly different for Rint(insp) and Rint(exp) (0.78 +/- 0.21 versus 0.78 +/- 0.20 KPa x L(-1) x second). However, the difference between Rint(insp) and Rint(exp) decreased significantly with age and being positive before 5 years and negative later on (p < 0.02). Rint(insp) and Rint(exp) decreased significantly with height (Rint(insp) [KPa x L(-1) x second] = 2.289 - 1.37. 10(-2) x H [cm], Rint(exp) [KPa. L(-1) x second] = 2.021 - 1.12.10(-2) x H [cm]; p < 0.001). Bronchodilator (salbutamol) administration significantly decreased Rint(insp) and Rint(exp) (p < 0.001). Bronchodilator-induced changes (% of predicted values) in mean Rint(insp) and mean Rint(exp) were -15% (95% confidence interval, -46 to +15%) and -12% (95% confidence interval, -46 to +22%), respectively. Sex did not affect pre- or postbronchodilator values. Data from the present study may prove useful for testing lung function in young children with respiratory disorders who failed to cooperate with forced expiratory maneuvers.