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Published ahead of print on March 20, 2008, doi:10.1164/rccm.200709-1419OC

Am. J. Respir. Crit. Care Med., Volume 177, Number 12, June 2008, 1358-1363

A more recent version of this article appeared on June 15, 2008
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Submitted on September 25, 2007
Accepted on March 20, 2008

Dimensions of Respiratory Symptoms in Pre-school Children: Population-based Birth Cohort Study

Jaclyn A Smith1*, Richard Drake2, Angela Simpson1, Ashley Woodcock1, Andrew Pickles3, and Adnan Custovic1

1 Respiratory Research Group, University of Manchester, Manchester, United Kingdom, 2 Division of Psychiatry, University of Manchester, Manchester, United Kingdom, 3 Biostatistics, Health Methodology Research Group, University of Manchester, Manchester, United Kingdom

* To whom correspondence should be addressed. E-mail: jacky.smith{at}manchester.ac.uk.

Rationale: A focus on distinctive collections of symptoms may be more informative of the probability of respiratory disease than individual and possibly transient phenotypes. However, such collections or components of overall symptomatology need to be valid, and their relationship established with the known risk factors and physiological measures. Objectives: To analyse detailed parentally-reported respiratory symptoms by Principal Component Analysis (PCA) and derive symptom components; to examine the relationship of such components with measures of lung physiology and atopy. Methods: Unselected, population-based birth cohort (n=946) Measurements: Interviewer-administered questionnaires, lung function (specific airway resistance-sRaw), airway reactivity (dry air challenge) and atopic status obtained at ages three and five years; PCA and multivariate ANOVA used to analyse the data. Main Results: The four-component solution (wheeze, cough, colds, chronic symptoms) explained 53.2% of the variance in symptoms at age three, and five-component (wheeze, wheeze with irritants, wheeze with allergens, cough, chest congestion) 49.8% at age five. The multivariate analysis revealed novel relationships between symptoms, risk factors for asthma and measures of lung function. At age three, sRaw, and the interaction between maternal asthma and child's atopy were not only related to wheeze, but also independently to the cough component. At age five, overall wheeze and allergic wheeze were related to lung function and airway reactivity; child's atopy was only related to symptoms when considered as a continuous trait. Conclusions: Our analysis supports the need to move beyond the presence or absence of individual symptoms. Syndromes of co-existing symptoms more likely reflect underlying pathophysiological processes. Clinical Trial Registry Information: ID #ISRCTN72673620 registered at http://www.controlled-trials.com


Key words: Principle components analysis, wheeze phenotypes, childhood asthma, cough







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