Heliox therapy in bronchiolitis: phase III multicenter double-blind randomized controlled trial.

BACKGROUND AND OBJECTIVE: Supportive care remains the mainstay of therapy in bronchiolitis. Earlier studies suggest that helium-oxygen therapy may be beneficial, but evidence is limited. We aimed to compare efficacy of 2 treatment gases, Heliox and Airox (21% oxygen + 79% helium or nitrogen, respectively), on length of hospital treatment for bronchiolitis. METHODS: This was a multicenter randomized blinded controlled trial of 319 bronchiolitic infant subjects randomly assigned to either gas; 281 subjects completed the study (140 Heliox, 141 Airox), whose data was analyzed. Treatment was delivered via facemask (nasal cannula, if the facemask intolerant) ± continuous positive airway pressure (CPAP). Severe bronchiolitics received CPAP from the start. Primary end point was length of treatment (LoT) required to alleviate hypoxia and respiratory distress. Secondary end-points were proportion of subjects needing CPAP; CPAP (LoT); and change in respiratory distress score. RESULTS: Analysis by intention to treat (all subjects); median LoT (inter-quartile range, days): Heliox 1.90 (1.08-3.17), Airox 1.87 (1.11-3.34), P = .41. Facemask tolerant subgroup: Heliox 1.46 (0.85-1.95), Airox 2.01 (0.93-2.86), P = .03. Nasal cannula subgroup: Heliox 2.51 (1.21-4.32), Airox 2.81 (1.45-4.78), P = .53. Subgroup started on CPAP: Heliox 1.55 (1.38-2.01), Airox 2.26 (1.84-2.73), P = .02. Proportion of subjects needing CPAP: Heliox 17%, Airox 19%, O.R. 0.87 (0.47-1.60), P = .76. Heliox reduced respiratory distress score after 8 hours (mixed models estimate, -0.1298; P < .001). The effect was greater for facemask compared with nasal cannula (mixed models estimate, 0.093; P = .04). CONCLUSIONS: Heliox therapy does not reduce LoT unless given via a tight-fitting facemask or CPAP. Nasal cannula heliox therapy is ineffective.

Health-related quality of life in a clinical sample of obese children and adolescents.

BACKGROUND: Obesity affects ethnic minority groups disproportionately, especially in the pediatric population. However, little is known about the impact of obesity on health-related quality of life (HRQoL) in children and adolescents from mixed-ethnic samples. The purpose of this study was to: 1) measure HRQoL in a mixed-ethnic clinical sample of obese children and adolescents, 2) compare HRQoL assessments in obese participants and healthy controls, and 3) compare HRQoL in obese children and adolescents according to their pubertal status. METHODS: A clinical sample of children and adolescents with obesity (n = 96) and healthy children and adolescents attending local schools (n = 444) completed the Pediatric Quality of Life Inventory (PedsQL; UK version 4). Age-appropriate versions were self-administered by children and adolescents aged 8-18 years, and interview administered to children aged 5-7 years. Multiple regression analyses controlling for age, gender, pubertal status, and ethnicity were used to compare the PedsQL scores of the two samples. RESULTS: The clinical sample of obese children and adolescents had poorer HRQoL scores on all dimensions of the PedsQL compared to the healthy controls (p < 0.005). Subsequent analyses also demonstrated that in this sample of mixed-ethnic children and adolescents, prepubescent obese children achieved the poorest scores in the emotional functioning dimension. CONCLUSIONS: Obesity significantly impacts on physical, emotional, social and school functioning of mixed-ethnic children and adolescents. Clinicians need to be aware of the significant impact of obesity on all aspects of functioning. More effort is required to target interventions to improve the quality of life of children with obesity.

Symptom-pattern phenotype and pulmonary function in preschool wheezers.

BACKGROUND: Pulmonary function in preschool wheezing phenotypes based on wheeze onset and duration and atopic status has been extensively described but has not been studied in symptom-pattern phenotypes of episodic (viral) and multiple-trigger wheeze. OBJECTIVE: We investigated whether multiple-trigger wheezers were more likely to have abnormal pulmonary function and increased fraction of exhaled nitric oxide (FeNO) than episodic (viral) wheezers and whether multiple-breath wash-out was more sensitive at detecting abnormal pulmonary function than specific airways resistance (sR(aw)) in preschool wheezers. METHODS: FeNO, multiple-breath wash-out indices (lung clearance index [LCI] and conductive airways ventilation inhomogeneity [S(cond)]) and sR(aw) were measured in healthy children and those with recurrent wheeze aged 4 to 6 years. Subgroup analysis was performed according to current symptom-pattern (multiple-trigger vs episodic [viral]), atopic status (atopic vs nonatopic), and wheeze status (currently symptomatic vs asymptomatic). RESULTS: Seventy-two control subjects and 62 wheezers were tested. Multiple-trigger wheezers were associated with an average increase of 11% (95% CI, 7% to 18%; P < .001) in LCI, 211% (95% CI, 70% to 470%; P < .001) in S(cond), and 15% (95% CI, 3% to 28%; P = .01) in sR(aw) compared with episodic (viral) wheezers. Pulmonary function in episodic (viral) wheezers did not differ significantly from control subjects. The presence of current atopy or wheeze was associated with higher FeNO (P = .05) but did not influence pulmonary function significantly. On average, LCI was abnormal in 39% (95% CI, 32% to 45%), S(cond) was abnormal in 68% (95% CI, 61% to 74%), and sR(aw) was abnormal in 26% (95% CI, 16% to 35%) of multiple-trigger wheezers. CONCLUSIONS: Multiple-trigger wheeze is associated with pulmonary function abnormalities independent of atopic and current wheeze status. S(cond) is the most sensitive indicator of abnormal pulmonary function in preschool wheezers.

Randomised controlled trial of nasal continuous positive airways pressure (CPAP) in bronchiolitis.

AIMS: To compare continuous positive airways pressure (CPAP) with standard treatment (ST) in the management of bronchiolitis. METHODS: Children <1 year of age with bronchiolitis and capillary PCO2 >6 kPa were recruited and randomised to CPAP or ST and then crossed over to the alternative treatment after 12 h. ST was intravenous fluids and supplemental oxygen by nasal prongs or face mask. The change in PCO2 was compared between the groups after 12 and 24 h. Secondary outcomes were change in capillary pH, respiratory rate, pulse rate and the need for invasive ventilatory support. RESULTS: 29 of 31 children completed the study. PCO2 after 12 h fell by 0.92 kPa in children treated with CPAP compared with a rise of 0.04 kPa in those on ST (p<0.015). If CPAP was used first, there was a significantly better reduction in PCO2 than if it was used second. There were no differences in secondary outcome measures. CPAP was well tolerated with no complications identified. CONCLUSIONS: This study suggests that CPAP compared with ST improves ventilation in children with bronchiolitis and hypercapnoea.

Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor.

BACKGROUND: A single family has been described in which obesity results from a mutation in the leptin-receptor gene (LEPR), but the prevalence of such mutations in severe, early-onset obesity has not been systematically examined. METHODS: We sequenced LEPR in 300 subjects with hyperphagia and severe early-onset obesity, including 90 probands from consanguineous families, and investigated the extent to which mutations cosegregated with obesity and affected receptor function. We evaluated metabolic, endocrine, and immune function in probands and affected relatives. RESULTS: Of the 300 subjects, 8 (3%) had nonsense or missense LEPR mutations--7 were homozygotes, and 1 was a compound heterozygote. All missense mutations resulted in impaired receptor signaling. Affected subjects were characterized by hyperphagia, severe obesity, alterations in immune function, and delayed puberty due to hypogonadotropic hypogonadism. Serum leptin levels were within the range predicted by the elevated fat mass in these subjects. Their clinical features were less severe than those of subjects with congenital leptin deficiency. CONCLUSIONS: The prevalence of pathogenic LEPR mutations in a cohort of subjects with severe, early-onset obesity was 3%. Circulating levels of leptin were not disproportionately elevated, suggesting that serum leptin cannot be used as a marker for leptin-receptor deficiency. Congenital leptin-receptor deficiency should be considered in the differential diagnosis in any child with hyperphagia and severe obesity in the absence of developmental delay or dysmorphism.

Spirometry in the diagnosis of asthma in children.

PURPOSE OF REVIEW: To review the diagnostic accuracy of lung function measurements made using spirometry for childhood asthma, recent guidelines for the measurement and interpretation of spirometric lung function tests and recent developments for diagnosing asthma. RECENT FINDINGS: Measurements of lung function and bronchial lability made using spirometry may not perform any better than other tests such as skin prick testing, or measurements of exhaled nitric oxide for diagnosing asthma. New guidelines are available. SUMMARY: Spirometry is a simple, robust and widely available tool for investigating lung function. There are published guidelines for making measurements and their interpretation. The place of spirometry in the diagnosis of asthma, however, needs clarification. The diagnostic profiles of measurements of bronchodilator responsiveness and bronchial hyperreactivity made using spirometry, although reasonable, are not perfect. In schoolchildren, they are no better than knowledge of aeroallergen sensitization when considering a diagnosis of asthma.

Pressure oscillation amplitude after interruption of tidal breathing as an index of change in airway mechanics in preschool children.

Bronchodilator reversibility testing using change in airway resistance during interruption (Rint) is feasible in preschool children. Analysis of postocclusion oscillations of the mouth pressure-time transient (Pmo(t)), recorded during airflow interruption, may offer an alternative index of change in airway mechanics. We analyzed Pmo(t) oscillation amplitude in three different ways: 1) difference between the first relative maximum and minimum (AMxMn); 2) detection of the dominant frequency using Fourier analysis (AFS); and 3) curve-fitting based on a mathematical model (ACurv). In 25 asymptomatic asthmatic children, aged 2.5-5.6 years, who had undertaken reversibility testing, the correlation coefficients between baseline Rint and amplitude were: AMxMn r = -0.84, AFS r = -0.82, ACurv r = -0.84. The coefficient of variation (CoV) of readings contributing to baseline Rint measurement, as median (range), was 12% (5-24%), which was not significantly different from AFS or ACurv (P > 0.05). All parameters were significantly different postbronchodilator (P < 0.001). Using the sensitivity index, i.e., the change after intervention divided by the baseline standard deviation, ACurv was the most sensitive and Rint the least sensitive, with median (range) at 2.72 (-0.84 to 12.10) and 1.91 (-1.17 to 9.50), respectively (P = 0.005). Our results suggest that oscillation amplitude analysis may provide a sensitive index of change in airway mechanics in preschool children undertaking bronchodilator reversibility testing.

Environmental factors relevant to difficult asthma.

Symptom persistence in difficult asthmatics may be related to their home environment. If sensitised asthmatics are to benefit from indoor allergen avoidance measures, these must be rigorous and drug adherence satisfactory. This is difficult for many families. The relationship between traffic pollution, asthma diagnosis and symptom severity is persuasive but requires objective validation. Overall, it seems that house dust mite control and tobacco smoke avoidance are important for asthmatics and advice about how to avoid these adverse factors must be given. Whether these measures are effective in difficult asthmatics and whether moving house makes any difference is unknown.

Randomized controlled trial of fluticasone in preschool children with intermittent wheeze.

Preschool children with intermittent wheeze are often prescribed inhaled corticosteroids, although there is no proven benefit. Measurement of airway resistance by the interrupter technique can be used to objectively assess response to treatment. If lung function improves, treatment may be justified. Children with intermittent wheeze aged 2 to