50 Years Ago in The Journal of Pediatrics:
The diagnosis of asthma in infancy
Article Outline
Buffum WP. J Pediatr 1958;52:264-266.
Buffum made a number of important observations of the natural history of wheezing beginning in infants. He reported that the risk factors for the 60% of children who persisted to wheeze included atopy, positive family history of atopy/asthma, and atopic dermatitis.
Reed reviewed a number of epidemiologic studies on the natural history of wheezing in children.1 The factors that predicted persistence and severity of childhood asthma included family history of asthma/atopy, elevated immunoglobulin E (IgE) levels, and positive allergy skin test results. In the Tucson study, infantile wheezing was divided into (1) transient wheezing; (2) nonatopic wheezing; and (3) atopic asthma.2, 3 Transient and nonatopic wheezing was typically associated with viral infections. Children with transient wheezing usually did not have a history of wheezing beyond age 3 years of age, and the children with nonatopic wheezing had diminished wheezing. The children who continued to have wheezing were more likely to have a family history of asthma and elevated IgE levels. In addition, atopic dermatitis was not infrequently the first atopic disease in the so-called “atopic march.”
Atopy is associated with increased risk of persistent wheezing in most studies. This may be sensitization to foods, as Buffum described, with subsequent sensitivity to aeroallergens. In the Tucson study, sensitization to Alternaria was associated with persistent wheezing and severity of asthma.4 In other studies, sensitization to house dust mites showed a strong correlation with persistent wheezing.5 Sensitivity to increased number of aeroallergens has also been associated with persistent wheezing. A number of studies have identified genetic risks, including interleukin-4 (IL-4), IL-4 receptor, and IL-13 polymorphisms that are associated with increased IgE levels.
Buffum reported that transient wheezing was associated with respiratory viral infections. Recently, in the Childhood Onset Asthma Study, wheezing with rhinovirus in the first year of life was associated with risk of persistent wheezing at 3 years of age.6 Although respiratory syncytial virus was associated with wheezing in infancy, it was not associated with risk of persistent wheezing.
Environmental exposures may affect asthma outcome. These include exposure in infancy to endotoxins from animal contacts that protect against progression of wheezing. The hypothesis is that endotoxin interacting with Toll-like receptor 4 and CD14 skews allergen T cell responses to a Th1 response, the so-called “hygiene hypothesis.”
In conclusion, many of the risk factors that Buffum reported 50 years ago for asthma in children have been validated by subsequent studies. Current studies are examining the molecular basis for genetic risks for the development of atopy and asthma in relationship to host-environment interactions.
References
- . The natural history of asthma. J Allergy Clin Immunol. 2006;118:543–548
- . Tucson Children’s Respiratory Study: 1980 to present. J Allergy Clin Immunol. 2003;111:661–675
- Outcome of asthma and wheezing in the first 6 years of life: follow-up through adolescence. Am J Respir Crit Care Med. 2005;172:1253–1258
- . Alternaria as a major allergen for asthma in children raised in a desert environment. Am J Respir Crit Care Med. 1997;155:1356–1361
- . Exposure to house-dust mite allergen (Der p I) and the development of asthma in childhood (A prospective study). N Engl J Med. 1990;323:502–507
- Rhinovirus illnesses during infancy predict subsequent childhood wheezing. J Allergy Clin Immunol. 2005;116:571–577
PII: S0022-3476(07)00946-8
doi:10.1016/j.jpeds.2007.09.049
© 2008 Mosby, Inc. All rights reserved.
