Rise in pediatric asthma linked to range of causes

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Rise in pediatric asthma linked to range of causes

Decreased indoor ventilation and broad-spectrum antibiotics may be two

factors.

by Bob Kronemyer

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January 1997

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 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.

Antibiotics affect

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.

Size of lungs

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. "

In utero sensitization

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. "

Changes Related to Increase in Asthma

Increase in indoor allergens:

Passive smoke

Pet dander

Changes in the Home:

Decreased ventilation

More carpeting and furniture

Higher temperatures

Use of broad-spectrum antibiotics

Changes in Diet:

Increased sodium

Decreased fish

Outdoor air pollution

Changes in Lifestyle:

More sedentary activities

Increased obesity

Decreased outdoor activity