Journal of Biometrics & Biostatistics

A Case-Crossover Design to Examine the Role of Aeroallergens and Respiratory Viruses on Childhood Asthma Exacerbations Requiring Hospitalization: The Mapcah Study

Abstract

Background: Few case-control studies of time dependent environmental exposures and respiratory outcomes have been performed. Small sample sizes pose modeling challenges for estimating interactions. In contrast, case cross-over studies are well suited where control selection and responses are low, time consuming and costly.

Objective: To demonstrate feasibility in daily recruitment of children admitted to hospital with asthma and validity  of the case crossover methodology for hospital based studies. Methods: The Melbourne Air Pollen Children and Adolescent Health (MAPCAH) study recruited incident asthma admissions of children and adolescents aged 2–17 years to a tertiary hospital. A case was defined by date of admission, and eligible cases served as their own controls. We used bi-directional sampling design for control selection. At time of admission, participants underwent skin prick tests and nasal/throat swabs (NTS) to test for respiratory viruses.Questionnaires collected data on asthma management, family history and environmental characteristics. Daily concentrations of ambient pollen, air pollution and weather variables were also available.  Results: 644 children were recruited. More than half (63%) were male with mean age 5.2(SD 3.3) years. Nonparticipants were slightly younger at admission (mean age 4.4, SD 2.8, p<0.001), although the absolute differences were small. Participants and non-participants were well balanced on gender. The most common reason for refusal to participate in the study was “causing further distress to child by skin prick testing”. Gender and age distributions were similar to the overall admissions to the tertiary hospital as well as in Victoria. Our study slightly under-represented winter admissions (p<0.001), and was over-represented in spring (p<0.001). More admissions occurred during the grass pollen season in our study than in general asthma hospital admissions across Victoria (42% versus 22%, p<0.001). Conclusions: The case cross-over method is a highly feasible design for a reasonably sized hospital based study of children with asthma. MAPCAH has robust internal validity and strong generalizability. Collection of data on respiratory viruses and pollen exposure at the time of admission on children with asthma provides important information that will have clinical and public health impacts.