A case-crossover design to examine the role of aeroallergens and respiratory viruses on childhood asthma exacerbations requiring hospitalisation: The MAPCAH study

Bircan Erbas, SC Dharmage, M O’Sullivan, Md Akram, Ed Newbigin, P Taylor, Don Vicendese, Rob J Hyndman, ML Tang, Michael J Abramson
(2012) Journal of Biometrics and Biostatistics, S7-018


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 the feasibility and validity of a case crossover study of children admitted to hospital for asthma to examine interacting effects of time varying environmental exposures. 

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. Non-participants were slightly younger at admission (mean age 4.3, 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”. Of those recruited, 46% were sensitized to any pollen, 14% were sensitized to fungi, and 22% tested positive to egg or peanut allergens. 68% of children had positive NTS for human rhinovirus (HRV) at admission and 22% were still positive nine weeks later. Parental history of asthma and hay fever was common.  Children who skin-tested positive to any pollen were slightly older (mean 6.4 years, SD 3.6, p<0.001).

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 summer(p<0.002). More admissions occurred during the grass pollen season in our study than in general asthma hospital admissions across Victoria (36% 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.

Key words: case crossover design, asthma, respiratory viral infections, internal validity