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PAPERS: Rosalind M Green, Adnan Custovic, Gwen Sanderson, Jenny Hunter, Sebastian L Johnston, and Ashley Woodcock Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study BMJ 2002; 324: 763 [Abstract] [Full text]

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Allergens and Viral Infections in precipitating acute asthma in adults

S K Agarwal   (29 March 2002)

Statistical concerns

Adam Jacobs   (1 April 2002)

Allergens and Viral Infections in precipitating acute asthma in adults 29 March 2002
S K Agarwal, Head, Department of Chest Diseases, Institute of Medical Sciences, BHU, Varanasi Send response to journal: Re: Allergens and Viral Infections in precipitating acute asthma in adults	The Editor, In a study by Green et al(1) allergens and viruses have been found to act together to exacerbate asthma thereby indicating that domestic exposure to allergens may act synergistically with viruses in sensitized patients, increasing the risk of hospital admission. This is in contrast to other study by Stein et al (2) where no significant relationship of respiratory syncytial virus causing lower respiratory tract infection and allergic sensitization was found. Respiratory syncytial virus significantly increased the risk for wheezing during the first 10 years of life (2); the risk decreased with age, however, and was no longer significant by 13 years of age. In the study by Green et al (1) all patients taken were of more than 16 years. Moreover, the workers have also given significance to pets in adults whereas in another study (3) in 412 Swedish children, exposure to pets during the first year of life resulted in lower incidence of allergic rhinitis at 7 to 9 years of age and a decreased frequency of asthma at 12 to 13 years of age. Reference: 1.Green RM, Custovic A, Sanderson G et al.Synergism between allergens and viruses and risk of hospital admission with asthma: case- control study BMJ 2002; 324:763 2. Stein RT, Sherill D, Morgan WJ et al. Respiratory syncytial virus in early life and risk of wheeze and allergy by age 13 years. Lancet. 1999; 354:541-545. 3. Hesselmar B, Aberg N, Aberg, N et al. Does early exposure to cat or dog protect against later allergy development? Clin Exp Allergy 1999, 29:611-617.
Statistical concerns 1 April 2002
Adam Jacobs, Director Dianthus Medical Limited, SW19 3TZ Send response to journal: Re: Statistical concerns	Green et al conclude that allergens and viruses act synergistically in causing exacerbations of asthma [1]. However, I am concerned about the statistical methods that led them to that conclusion. My first concern is that they seem to describe an individually matched case–control study, but none of their statistical methods takes account of the matching. For example, logistic regression is inappropriate for a matched case–control study; conditional logistic regression should have been used instead [2]. Another problem is that the paper seems to suffer seriously from multiple hypothesis testing. I counted no less than 76 P values in the tables, and I think there were a few more in the text. We would therefore expect a few significant results to occur by chance alone. This makes it hard to interpret P values of borderline significance, especially as Green et al do not state clearly what their primary hypothesis is. My final concern is that Green et al do not make clear exactly how they tested for synergy between allergens and viruses. Their conclusion apparently rests on the significance of the odds ratio for ‘the combination of sensitisation and high exposure to one or more allergens and detection of viruses’ in their logistic regression model. However, this is appropriate only if the logistic regression model is already adjusted for sensitisation, exposure to allergens, detection of viruses, and the combination of sensitisation and exposure to allergens. If I read their description correctly, then they seem to have adjusted for the first three of those, but it is not at all clear whether they have adjusted for the combination. If they have not, then they have not shown whether viruses act synergistically with the other exposures; they have merely shown that the combination of all three exposures is synergistic, but this does not necessarily add to their finding that sensitisation and exposure to allergens are synergistic with each other. References: 1. Green RM, Custovic A, Sanderson G, Hunter J, Johnston SL, Woodcock A. Synergism between allergens and viruses and risk of hospital admission with asthma: case-control study BMJ 2002; 324: 763–766 2. Clayton D, Hills M. Statistical models in epidemiology. Oxford: Oxford University Press, 1993. p 290–297