Distinguishing phenotypes of childhood wheeze and cough using latent class analysis

Airway disease in childhood comprises a heterogeneous group of disorders. Attempts to distinguish different phenotypes have generally considered few disease dimensions. The present study examines phenotypes of childhood wheeze and chronic cough, by fitting a statistical model to data representing multiple disease dimensions. From a population-based, longitudinal cohort study of 1,650 preschool children, 319 with parent-reported wheeze or chronic cough were included. Phenotypes were identified by latent class analysis using data on symptoms, skin-prick tests, lung function and airway responsiveness from two preschool surveys. These phenotypes were then compared with respect to outcome at school age. The model distinguished three phenotypes of wheeze and two phenotypes of chronic cough. Subsequent wheeze, chronic cough and inhaler use at school age differed clearly between the five phenotypes. The wheeze phenotypes shared features with previously described entities and partly reconciled discrepancies between existing sets of phenotype labels. This novel, multidimensional approach has the potential to identify clinically relevant phenotypes, not only in paediatric disorders but also in adult obstructive airway diseases, where phenotype definition is an equally important issue.

Nonacid reflux episodes reaching the pharynx are important factors associated with cough

BACKGROUND: Gastroesophageal reflux is implicated in the pathogenesis of asthma and chronic cough. To date most studies have focused on acid reflux measured by pH below the upper esophageal sphincter (UES). The aim of this study was to assess the relationship between cough and reflux through the UES into the pharynx. METHODS: Thirty-seven patients with asthma (19) and chronic cough (18) were recruited from the respiratory clinic. Reflux was monitored using a combined multichannel intraluminal impedance and pH probe by detecting (1) bolus reflux episodes within the esophagus and in the pharynx and (2) acidic reflux episodes within the esophagus and in the pharynx. All acid suppressive therapy was stopped for at least 7 days before the study. Demonstration of cough being linked to reflux was achieved using the symptom association probability (SAP). This was calculated using a 2-minute association window between symptoms and bolus entry into the esophagus. SAP was considered positive if >95%. RESULTS: A positive SAP for cough was noted in 7/26 patients reporting symptoms on the day of monitoring. Compared with SAP-negative patients, SAP-positive patients had both a greater number [median (interquartile range), 5(2 to 8) vs. 2(0 to 4), P<0.05] and a higher proportion of reflux episodes crossing the UES into the pharynx [25%(14% to 28%) vs. 7% (2% to 14%), P<0.02]. There was no difference in the number of reflux episodes or acid exposure time in the distal esophagus between SAP-positive and SAP-negative patients. Only 1% to 2% of episodes were detected by the pharyngeal pH sensor. CONCLUSIONS: Impedance detected pharyngeal reflux episodes are important factors in symptom production in cough patients.

Comparison of phenotypes of childhood wheeze and cough in 2 independent cohorts

BACKGROUND Among children with wheeze and recurrent cough there is great variation in clinical presentation and time course of the disease. We previously distinguished 5 phenotypes of wheeze and cough in early childhood by applying latent class analysis to longitudinal data from a population-based cohort (original cohort). OBJECTIVE To validate previously identified phenotypes of childhood cough and wheeze in an independent cohort. METHODS We included 903 children reporting wheeze or recurrent cough from an independent population-based cohort (validation cohort). As in the original cohort, we used latent class analysis to identify phenotypes on the basis of symptoms of wheeze and cough at 2 time points (preschool and school age) and objective measurements of atopy, lung function, and airway responsiveness (school age). Prognostic outcomes (wheeze, bronchodilator use, cough apart from colds) 5 years later were compared across phenotypes. RESULTS When using a 5-phenotype model, the analysis distinguished 3 phenotypes of wheeze and 2 of cough as in the original cohort. Two phenotypes were closely similar in both cohorts: Atopic persistent wheeze (persistent multiple trigger wheeze and chronic cough, atopy and reduced lung function, poor prognosis) and transient viral wheeze (early-onset transient wheeze with viral triggers, favorable prognosis). The other phenotypes differed more between cohorts. These differences might be explained by differences in age at measurements. CONCLUSIONS Applying the same method to 2 different cohorts, we consistently identified 2 phenotypes of wheeze (atopic persistent wheeze, transient viral wheeze), suggesting that these represent distinct disease processes. Differences found in other phenotypes suggest that the age when features are assessed is critical and should be considered carefully when defining phenotypes.

The therapy of pre-school wheeze: appropriate and fair?

The current study aimed to assess prevalence and distribution of use of asthma medication for wheeze in pre-school children in the community. We sent a postal questionnaire to the parents of a random population-based sample of 4,277 UK children aged 1-5 years; 3,410 participated (children of south Asian decent were deliberately over-represented). During the previous 12 months, 18% of the children were reported to have received bronchodilators, 8% inhaled corticosteroids (ICS) and 3% oral corticosteroids. Among current wheezers these proportions were 55%, 25%, and 12%, respectively. Use of ICS increased with reported severity of wheeze, but did not reach 60% even in the most severe category. In contrast, 42% of children receiving ICS reported no or very infrequent recent wheeze. Among children with the episodic viral wheeze phenotype, 17% received ICS compared with 40% among multiple-trigger wheezers. Use of ICS by current wheezers was less common in children of South Asian ethnicity and in girls. Although a high proportion of pre-school children in the community used asthma inhalers, treatment seemed to be insufficiently adjusted to severity or phenotype of wheeze, with relative under-treatment of severe wheeze with ICS, especially in girls and South Asian children, but apparent over-treatment of mild and episodic viral wheeze and chronic cough.

A parent-completed respiratory questionnaire for 1-year-old children: repeatability

BACKGROUND AND AIMS: There are few standardised questionnaires for the assessment of respiratory symptoms in preschool children. We have developed and tested the short-term repeatability of a postal questionnaire on respiratory symptoms for 1-year-old children. METHODS: A newly developed postal questionnaire for the assessment of wheeze and other respiratory symptoms was sent to parents of a population-based random sample of 4300 children aged 12-24 months. After an interval of 3 months, a random sample of 800 respondents received the questionnaire a second time. The responses were compared using Cohen's kappa (kappa) to assess agreement corrected for chance. RESULTS: The first questionnaire was returned by 3194 (74%) families, the second one by 460/800 (58%). Repeatability was excellent (kappa 0.80-0.96) for questions on household characteristics, environmental exposures and family history, good (kappa 0.61-0.80) for questions on prevalence, severity and treatment of wheeze, and moderate (kappa 0.39-0.66) for chronic cough and upper respiratory symptoms. CONCLUSIONS: This short postal questionnaire designed for use in population-based studies has excellent repeatability for family and household characteristics and good repeatability for questions on wheeze. Short-term changes in symptom status might be responsible for variable answers on recent chronic cough and upper respiratory symptoms. Overall, the questionnaire is a valuable instrument for community-based research on respiratory symptoms in 1 to 2-year-old children.