BOSTON The current epidemic of pediatric asthma cannot be attributed solely to an increase in allergen exposure. More likely it is a combination of societal factors that have changed during the past 40 years, ranging from decreased indoor ventilation to the introduction of broad-spectrum antibiotics.
"Clearly, there continues to be a profound association between asthma and sensitization to indoor allergens," said Thomas A. E. Platts-Mills, MD, PhD, head of allergy and immunology at the University of Virginia in Charlottesville. "However, the evidence that a simple increase in indoor allergens has caused the increase in asthma is not as clear as it was."
Platts-Mills listed indoor environmental changes such as increases in energy efficiency, which decreased ventilation; more carpeting and furnishings; and an increase in room temperature, as factors that contribute to the epidemic.
Since 1960, broad-spectrum antibiotics have also affected asthma rates. "It has now become routine for children to be treated so that the course of infections is dramatically shortened," said Platts-Mills, who spoke about the natural history of pediatric asthma at the American College of Allergy, Asthma and Immunology annual meeting here. "But bacterial infections are thought to induce TH1 responses by a mechanism that includes high levels of IL-12 production from macrophages."
The question then becomes "whether antibiotic treatment will change the immune response to bacteria and in some way increase the TH2 response to inhalants." Taken one step further, Platts-Mills contemplated whether the widespread use of antibiotics in children has influenced the development of chronic sinusitis.
Dietary changes have also been suggested as a culprit, specifically increased sodium or decreased consumption of fish. Rounding out the suspect list is outdoor air pollution, indoor passive smoking and a sedentary lifestyle.
"Intervention studies to influence the prevalence of asthma in a community are now a high priority," he said. However, designers of such studies should consider all the changes that have occurred in our society since 1950.
Other factors that influence the development of asthma are the structure and size of the lungs; the relationship between exposure and sensitization to inhaled allergens; genetic considerations; and nonspecific enhancers of the immune or inflammatory response that can increase the severity of symptoms.
Small lungs increase the risk of acute respiratory episodes in the first two years of life, but that declines and does not appear to be a significant determinant of asthma in childhood. "Given that the primary cause of acute episodes of wheezing in the first two years is infection with respiratory syncytial virus (RSV), it seems likely that the effect of small airway size is mechanical," said Platts-Mills.
As for sensitization to indoor allergens, the traditional view maintains that children first develop positive skin tests to dust mite or cat allergens between the ages of 2 and 6 years old. "It is assumed that exposure over the preceding months or years is relevant to this. But we showed that the concentration of mite allergen at ages 1 and 2 was a good predictor of sensitization at age 10," said Platts-Mills.
A significant association between month of birth and sensitization has also been documented in several studies. "This strongly suggests that there is a window of time in early childhood when inhaled allergens can be recognized and processed," said Platts-Mills. "Clearly, this could represent priming of T cells without significant production of antibodies."
Two reports in the last four years suggest that infants might be sensitized even before birth, if T cell proliferative responses to dust mite antigens using chord blood lymphocytes are positive. "However, calculation of the quantities of allergen inhaled by the mother makes this difficult to understand," explained the practitioner.
"If the mother inhales 50 ng/day, then the serum concentration would be of the order of 10 pg/mL. It is very difficult to understand how these concentrations would be recognized by the fetus. Furthermore, these authors found less consistent response to over albumin or ß-lactoglobulin," he said.
The one predominately outdoor allergen that has been strongly associated with epidemics of asthma is alternaria. However, studies suggest that indoor alternaria may offer the major exposure. Cockroaches have also been linked among African-Americans, but not among Caucasians. The dust mite is the dominant sensitization in both races.
Can antigen exposure, other than inhaled allergens, during the first two years of life change the immune response to inhalants? "The obvious candidates are viral infections, bacterial infections and immunization," said Platts-Mills, noting that the most studied viral infection in early childhood is RSV. "This virus not only induces acute episodes of bronchitis, but also induces a profound immune response."
Whether the infant makes a TH1 or TH2 response to early viral infections may be highly relevant, whereas "the clinical symptoms at the time of the first infection with RSV may be almost irrelevant to subsequent events," he said.
The development of asthma occurs "either by increasing exposure or by changing responsiveness or by increasing symptoms in sensitized individuals," said Platts-Mills. "Even though it's clear that the asthmatic children are allergic, the simple move to say that allergen exposure must have increased cannot be directly substantiated."
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