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MEDICAL BIOLOGY: ON ASTHMA PREVENTION

The following points are made by Fernando D. Martinez (New Engl. J. Med. 2003 349:1473):

1) Patients with asthma and their caregivers are currently faced with a remarkable paradox. Considerable progress has been made during the past 20 years in the pharmacotherapy, educational tools, and environmental measures available for the control of symptoms of asthma. As a result of these advances, more than 90 percent of patients with asthma now have the potential to lead a normal life. The bad news, however, is the absence of any universally accepted strategy for the prevention of the disease. With the exception, perhaps, of measures for the avoidance of infrequent forms of asthma caused by very specific types of exposure (e.g., occupational or aspirin-induced asthma), no single action has been irrefutably demonstrated to decrease the risk of the development of persistent asthma in persons who do not already have the disease.

2) The greatest obstacle to the development of approaches for the prevention of asthma has been the lack of a clear understanding of its natural history. In the past, the cross-sectional surveys on which we have relied have proved misleading. These types of surveys are based heavily on patients' recall of past events, which is particularly susceptible to bias. Most adults, for example, have no direct memory of events that occurred during their preschool years. It is thus not surprising that until quite recently it was widely believed that chronic asthma was equally likely to begin at any age. In addition, asthma was considered to be a progressive disease: the longer it lasted, it was thought, the more likely it was that irreversible changes would develop in the structure and function of the lungs.(1)

3) These conceptions had important consequences from the point of view of public health. Asthma is a disease in which both genetic and environmental factors have important roles,(2) and thus considerable attention was paid to the search for environmental causes of the disease that could affect persons of all ages. On the basis of the results of cross-sectional studies, factors such as environmental tobacco smoke,(3) air pollution,(4) and exposure to common aeroallergens(5) that were known to trigger asthma symptoms in persons who already had the disease were widely reputed to cause it as well.

4) The publication in recent years of the results of adequately powered, well-designed longitudinal studies with follow-up starting during the first years of life has produced a remarkable change in our understanding of asthma, its beginnings, its clinical expression, and its evolution. First, most persons of any age who have chronic, persistent asthma have their first symptoms during their preschool years. Environmental factors, acting during early life and interacting with specific "asthma genes," are apparently crucial for the development of the chronic, persistent form of the disease.(2) The identification of these factors will thus be crucial for a primary-prevention strategy, which will necessarily be focused on events that occur in infancy and early childhood.

5) A second conclusion has to do with the timing of the changes in lung function that are characteristic of the disease. As a group, patients with asthma have lower values than persons without asthma on several measures of lung function, including the ratio of the forced expiratory volume in one second to the forced vital capacity. These deficits are strongly associated with the severity of disease and are believed to represent alterations in lung function and structure that contribute to the persistence of symptoms of asthma. Until recently, the origin of these deficits was not well understood. It now appears that lower levels of lung function are already present by the early school years in patients in whom persistent asthma will ultimately develop, with no further deterioration after that age.

6) A third but not less important conclusion that may be derived from longitudinal studies is that the most common clinical expression of asthma -- namely, episodic wheezing -- has a high frequency in developed countries. There is an urgent need for tools with which to identify young children with symptoms of asthma who are at high risk for the development of the more persistent forms of the disease, so that potential preventive measures can be targeted to those who will benefit the most. The prevention of asthma will require interventions focused on the types of early environmental exposure that predispose children to or protect them against the onset and progression of the disease.

References (abridged):

1. Agertoft L, Pedersen S. Effects of long-term treatment with an inhaled corticosteroid on growth and pulmonary function in asthmatic children. Respir Med 1994;88:373-381

2. Patino CM, Martinez FD. Interactions between genes and environment in the development of asthma. Allergy 2001;56:279-286

3. Cook DG, Strachan DP. Health effects of passive smoking. 10. Summary of effects of parental smoking on the respiratory health of children and implications for research. Thorax 1998;54:357-366

4. Mortimer KM, Neas LM, Dockery DW, Redline S, Tager IB. The effect of air pollution on inner-city children with asthma. Eur Respir J 2002;19:699-705

5. Rosenstreich DL, Eggleston P, Kattan M, et al. The role of cockroach allergy and exposure to cockroach allergen in causing morbidity among inner-city children with asthma. N Engl J Med 1997;336:1356-1363

New Engl. J. Med. http://www.nejm.org

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ON HOUSE PETS AND RISK OF ALLERGIC SENSITIZATION

The following points are made by D.R. Ownby et al (J. Am. Med. Assoc. 2002 288:963):

1) The increasing prevalence of asthma in the United States and other developed countries over the last few decades has been a cause for concern.(1,2) While many factors appear to be involved in the development of childhood asthma, allergic sensitization to common allergens has consistently been shown to be related to the risk of developing asthma and to the risk of asthma persisting from childhood into adulthood.(3-5) Many studies have attempted to elucidate relationships between environmental exposures, especially during infancy, and the risk of allergic sensitization in later life. These studies are based on the theory that an individual's genetic predisposition to allergic disease is activated or enhanced by early allergen exposure. The outcome of interactions between genetic influences and allergen exposures may be influenced by other environmental exposures, such as passive exposure to environmental tobacco smoke. If these relationships were better understood it might become possible to reduce the prevalence of allergic sensitization and perhaps asthma in children.

2) Exposure to dogs and cats during infancy has been thought to increase the risk of subsequent allergy to these animals. This assumption is primarily based on a few retrospective studies reporting an increased likelihood of allergic sensitization following exposure during infancy. Some studies, however, have suggested that exposure to dogs or cats during infancy is associated with reduced risk of allergic disease. Others have shown that children growing up on farms, especially farms with animals, were less likely to be allergic than were children growing up in urban environments.

3) The authors report a study to evaluate the relationship between dog and cat exposure in the first year of life and allergic sensitization at 6 to 7 years of age. The subjects consisted of a prospective birth cohort study of healthy, full-term infants enrolled in a health maintenance organization in suburban Detroit, Michigan, who were born between April 15, 1987, and August 31, 1989, and followed up yearly to a mean age of 6.7 years. Of 835 children initially in the study at birth, 474 (57%) completed follow-up evaluations at age 6 to 7 years. Main outcome measures: Atopy, defined as any skin prick test positivity to 6 common aeroallergens (dust mites [Dermatophagoides farinae, D pteronyssinus], dog, cat, short ragweed [Ambrosia artemisiifolia], and blue grass [Poa pratensis]); seroatopy, defined as any positive allergen-specific IgE test result for the same 6 allergens or for Alternaria species. From the results, the authors conclude that exposure to 2 or more dogs or cats in the first year of life may reduce subsequent risk of allergic sensitization to multiple allergens during childhood.

References (abridged):

1. Mannino DM, Homa DM, Akinbami LJ, Moorman JE, Gwynn C, Redd SC. Surveillance for asthma United States, 1980-1999. Mor Mortal Wkly Rep CDC Surveill Summ. 2002;51:1-13

2. Yunginger JW, Reed CE, O'Connell EJ, Melton LJ III, O'Fallon WM, Silverstein MD. A community-based study of the epidemiology of asthma: incidence rates, 1964-1983. Am Rev Respir Dis. 1992;146:888-894

3. Sears MR, Burrows B, Flannery EM, Herbison GP, Holdaway MD. Atopy in childhood, I: gender and allergen related risks for development of hay fever and asthma. Clin Exp Allergy. 1993;23:941-948

4. Platts-Mills TA, Vervloet D, Thomas WR, Aalberse RC, Chapman MD. Indoor allergens and asthma: report of the third international workshop. J Allergy Clin Immunol. 1997;100:S2-S24

5. Litonjua AA, Sparrow D, Weiss ST, O'Connor GT, Long AA, Ohman JL Jr. Sensitization to cat allergen is associated with asthma in older men and predicts new-onset airway hyperresponsiveness. Am J Respir Crit Care Med. 1997;156:23-27

J. Am. Med. Assoc. http://www.jama.com

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