[A pilot trial on the treatment of gastroesophageal reflux-related cough in infants].

OBJECTIVE: Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheezing. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms. METHODS: Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB. RESULTS: Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported. CONCLUSIONS: In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.

A pilot trial on the treatment of gastroesophageal reflux-related cough in infants.

BACKGROUND: Diagnosing asthma in infancy is largely made on the basis of the symptoms of cough and wheeze. A similar presentation can be seen in neurologically normal infants with excessive gastroesophageal reflux (GER). There are no randomized placebo controlled studies in infants using proton pump inhibitors (PPI) alone or in addition to prokinetic agents. OBJECTIVES: The primary objective was to confirm the presence of excessive GER in a population of infants that also had respiratory symptoms suggestive of asthma. Second, in a randomized placebo-controlled fashion, we determined whether treatment of GER with bethanacol and omeprazole could improve these respiratory symptoms. METHODS: Infants (n=22) with a history of chronic cough and wheeze were enrolled, if they had evidence of GER by history and an abnormal pH probe or gastric emptying scan. Infants were randomly allocated to four treatment groups: placebo/placebo (PP), omeprazole plus bethanacol (OB), omeprazole/placebo (OP), bethanacol/placebo (BP). Evaluations by clinic questionnaire and exam, home diary, and pH probe data were done before, after study-medication and after open label of OB. RESULTS: Nineteen children were studied. PP did not affect GER or respiratory symptoms, and did not decrease GER measured by pH probe. In contrast, OB decreased GER as measured by pH probe indices and parental assessment. In association, OB significantly decreased daytime coughing and improved respiratory scores. No adverse effects were reported. CONCLUSIONS: In infants with a clinical presentation suggestive of chronic GER-related cough, the use of omeprazole and bethanacol appears to be viable therapeutic option.

Early life factors associated with incidence of physician-diagnosed asthma in preschool children: results from the Canadian Early Childhood Development cohort study.

Background. Asthma is a common childhood illness. The objective of this study is to determine the incidence of physician-diagnosed asthma in preschool years and its relationship to host, prenatal and postnatal factors, early childhood factors, parental factors, household factors and demographic factors. Methods. The study sample was comprised of 8,499 infants and toddlers (<2 years at baseline) enrolled in the Canadian Early Childhood Development Study. Incidence of asthma was determined when the children were in preschool age (2 to 5 years). Results. The 4-year cumulative incidence at preschool age was 13.7% for physician-diagnosed asthma. History of early childhood wheezing before 2 years of age was a significant risk factor for incidence of asthma in preschool years (hazard ratio (HR): 2.32; 95% confidence interval (CI): 2.04-2.65). Factors that were protective for the development of asthma were breastfeeding more than 3 months (HR: 0.82; 95% CI: 0.69-0.97); history of nose or throat infection often in childhood (HR: 0.79; 95% CI: 0.67-0.93); early daycare attendance (HR: 0.85; 95% CI: 0.74-0.98); presence of two or more siblings at birth, (HR: 0.79; 95% CI: 0.64-0.97); and dwelling in rural non- central metropolitan areas (HR: 0.81; 95% CI: 0.69-0.95). Male sex, low birth weight, childhood allergy, single parent, maternal smoking during pregnancy, maternal medication use, parental atopy, and low SES at baseline were significant risk factors for the incidence of physician-diagnosed asthma in preschool years. Conclusion. This study emphasizes the role of wheezing in infant and toddler age on early onset of asthma during preschool years. The results also provide additional importance of early exposures to environmental factors such as early infections, daycare attendance, and rural environment in the development of proper immune dynamics to prevent asthma.

Predictors for wheezing phenotypes in the first decade of life.

BACKGROUND AND OBJECTIVE: This study examined prenatal, perinatal and early childhood predictors of wheezing phenotypes in the first decade of life. METHODS: Information on current wheezing, was collected prospectively from five surveys conducted every 2 years over the first decade of life. Five wheezing phenotypes were defined: non-wheezers, preschool, primary-school, intermittent and persistent wheezers. Logistic regression with adjustment for survey design was used to determine the predictors of wheezing phenotypes. RESULTS: Data on 2711 children were used in the analysis. Early respiratory infection, the child's allergy and parental asthma were significant risk factors for preschool, intermittent and persistent wheeze. The child's allergy and parental asthma had stronger associations with persistent wheeze than with preschool wheeze. Breastfeeding was a significant predictor of both preschool and intermittent wheezing. Daycare attendance was a risk factor for preschool wheeze but a protective factor for primary-school wheezing. Crowding at home was a protective factor for both preschool and primary-school wheeze. Parental smoking was a significant factor for preschool wheeze. CONCLUSION: This study identified different predictors for each wheezing phenotype with some degree of overlap. The observed differential effects for these conditions raises the possibility that there are different aetiologies for asthma among children.

Reduced risk of physician-diagnosed asthma among children dwelling in a farming environment.

BACKGROUND AND OBJECTIVE: Living in a farm environment has been reported to be associated with lower prevalence of asthma, based on the results of cross-sectional studies. The objective of this longitudinal study was to determine whether living in a farm environment is associated with lower incidence of asthma among children. METHODS: A total of 13 524 asthma-free children aged 0-11 years were drawn from the Cycle 1 (1994/1995) of the Canadian National Longitudinal Survey of Children and Youth (NLSCY). Subjects were categorized as dwelling in rural farming, rural non-farming and non-rural environments. Incidence of physician-diagnosed asthma was determined at Cycle 2 (1996/1997). Bootstrap logistic regression method was used to adjust for design effect in the NLSCY. RESULTS: The 2-year cumulative incidence of asthma was 2.3%, 5.3% and 5.7% among children living in farming, rural non-farming and non-rural environments, respectively. From the multivariate analysis with adjustment for important confounders, children from a farming environment had a reduced risk of asthma compared with children from rural non-farming environment with odds ratios (OR) of 0.22 (95% CI: 0.07-0.74) and 0.39 (95% CI: 0.24-0.65) for children with and without parental history of asthma, respectively. Children living in a non-rural environment with parental history of asthma had an increased risk of asthma incidence when compared with children living in rural non-farming environment (OR = 2.51, 95% CI: 1.56-4.05). CONCLUSION: This longitudinal study expands on observational study results which suggest a reduced risk of developing asthma associated with living in a farming environment.

Clinical correlations and pulmonary function at 8 years of age after severe neonatal respiratory failure.

OBJECTIVES: The aim of this study was to determine the pulmonary sequelae of severe neonatal respiratory failure. STUDY DESIGN: This was a multicenter, prospective study. Fifty-four survivors of neonatal respiratory failure (oxygenation indices >25 on two occasions), completed pulmonary function testing at 8 years of age. Thirty-one (57%) received extracorporeal membrane oxygenation (ECMO). Pulmonary outcome was based on spirometry and lung volume data. Pulmonary outcome for each diagnostic and treatment group is reported as mean and as percent predicted. Individually subjects were also classified based on spirometry, as either normal, obstructed (defined as forced expiratory volume (FEV(1)) in 1 sec:forced vital capacity (FVC) of <80 % predicted, or with reduced FVC (FCV of <80% predicted) with normal FEV(1)/FVC. Risk for adverse outcome was determined using univariate analysis. RESULTS: Mean FVC, FEV(1) and FEV(25-75) were reduced in the total cohort. The reduction was greatest in the subgroup with CDH and the group treated with ECMO. Assessed individually, 54% of subjects had normal spirometry and lung volumes, 19% airflow obstruction, and 27% reduced FVC. Poorer pulmonary outcome was linked to ECMO, congenital diaphragmatic hernia (CDH), birth weight for gestational age <10th percentile, duration of hospitalization, or need for prolonged supplemental oxygen. CONCLUSION: Neonates with severe respiratory failure due to CDH or needing ECMO and small for gestation are at increased risk of poorer pulmonary outcome and require close follow-up.