Asthma is defined as a condition with clinical symptoms of cough, wheeze and shortness of breath characterized by variable airflow limitation (obstruction), increased responsiveness of the airways to various external stimuli (twitchiness) and inflammation, with mucous and cells primarily eosinophilic in the airways.
Inflammation is the primary cause of asthma and if that inflammation continues, it leads to permanent changes in the airways making them more hyperreactive (twitchy).
Our current understanding of asthma suggests that the inflammation in the airways is primarily eosinophilic in nature. It seems likely that in future that understanding will change and other cells such as the neutrophil will prove to be important such as in viral induced asthma of the pre-school child.
Virtually the only mechanism for creating eosinophilic asthma in children is allergy.
The allergens that are the most important for creating the eosinophilic inflammation in the airways of children with asthma are the indoor perennial allergens, mites, dander, moulds and cockroaches plus the outdoor seasonal tree leaf moulds, alternaria and cladosporium.
The data supporting these conclusions will be outlined below.
Although the relationship between allergy and asthma has been suggested for a long time, there was great scepticism and the formal proof is relatively recent in origin. In 1988, we showed that there was a dose relationship between degree of allergy and severity of asthma[1]. We hypothesized that if allergy were a factor in aggravating asthma, we should find that allergy (defined by symptoms and numbers of positive prick skin tests) increased with increasing severity of asthma. One hundred twenty-three children with asthma were graded according to clinical severity (the amount and type of medication used for treatment) and compared to a group of 29 normal individuals, 48 patients with allergic rhinitis, and 52 patients with cystic fibrosis. There was an increase in the number and size of positive skin tests with increasing severity of asthma. Similarly, there was increased reporting of allergic symptoms, such as sensitivity to animals with increasing severity of asthma. These data suggested that atopy is associated with asthma in a crude dose-response fashion. This relationship has been confirmed recently by Arshad, et al. [2]PEDIATRICS 108 No. 2 August 2001.
We reported similar findings in pre-school children where highly allergic children had more significant asthma requiring maintenance inhaled steroid [3]. Later more powerful epidemiologic data confirmed the relationship between allergy and asthma. The New Zealand study by Malcolm Sears and colleagues [4] along with the NHANES studies [5], [6] were the first epidemiologic studies to assess the strength of relationship between allergy and asthma and to regress to determine the most significant allergens.
The epidemiologic studies suggested that allergens such as dust mite, cat and alternaria were more strongly associated with asthma while sensitivity to pollen was associated with allergic rhinitis and not asthma. Further studies on the cohort of New Zealand children with asthma showed a relationship between airway hyperreactivity as assessed by methacholine challenge with levels of serum IgE [7],[8], or positive skin tests, particularly mite, cat, dog, aspergillus[9]. The study of this population of childhood asthmatics identified atopy as a major determinant of airway hyperreactivity[10].
The relationship between allergy and asthma in childhood has been reproduced in numbers of studies from around the world using differing techniques. There is general agreement that the perennial indoor allergens and seasonal mould allergens have a more important relationship to asthma than the pollens with the most important allergens varying slightly from study to study probably depending on the prevalence of allergens in a given climatic area. Peat et al. found that asthma severity and morbidity in large sample of Australian school children was directly related to dust mite sensitivity but not sensitivity to grass pollen [11]. They measured the level of dust mite allergen level in the homes and found that the levels were very high. Moreover sensitivity to dust mite and the degree of sensitivity as measured by the size of skin test wheals was the major determinant of current asthma.
Further study of the data on children with asthma gathered in the Second National Health and Nutrition Survey (NHANES II) of children in the United States, documented the relationship between allergen sensitivity and decreased lung function [12].
It is now accepted that allergy plays a major role in childhood asthma. The Childhood Asthma Management Program is an on-going long-term study of childhood asthma. That study has confirmed that sensitivity to certain allergens, particularly cat, dog or alternaria, was associated with increased bronchial hyperreactivity[13]. A study from Melbourne Australia has been following asthmatic children from age 7 in the 1960s to the present. That study clearly shows that allergy is related to the severity and persistence of asthma [14]. This cohort of children has been followed every seven years since they were enrolled into the study at age 7. Each time they have been studied it has been apparent that there is a close relationship between allergy and childhood asthma.
The Third National Health and Nutrition Examination Survey continued to examine the relationship between allergy and asthma in children. They attempted to determine the important residential risk factors for asthma and calculate how much less asthma there would be if the appropriate residential factors were eliminated. They estimated that elimination of such risk factors would result in a 39% decline in doctor-diagnosed asthma among US children less than 6 years old [15] and 44% in older children and adolescents [16]. They determined that in older children, predictors of doctor-diagnosed asthma included a history of allergy to a pet, presence of a pet in the household, and immediate hypersensitivity to dust mite, Alternaria, and cockroach allergens. Family history of atopy and diagnosis of allergic rhinitis were also predictors for asthma.
The risk factors in childhood asthma was studied in Sweden [17]. Significant risk factors for incident asthma, that is cases of asthma showing up over the course of the year of study were, a positive skin test, low birth weight and family history of asthma. Having or having had pets at home was associated with a decreased risk for asthma and wheezing based on prevalent cases, although it was associated with an increased risk for incidence of wheezing. Remission of asthma, which was reported by 10% of the children with current asthma during 1 year, was associated with a negative skin test. They concluded that the incidence of asthma at the age of 8 years was high, but remission was also common. Important risk factors for the development of asthma at this age were type 1 allergy, low birth weight, and family history of asthma. They suggested that in a region where sensitivity to domestic animals is a strong risk factor for asthma, the presence of pets in the home may have different effects in early childhood compared with later in childhood. This latter conclusion is still controversial since there are several studies examining asthma in young allergic children where the wheezing was directly related to sensitivity to a pet in the home.
A risk factor study for asthma in children age 7 - 9 in New Zealand [18], found that sensitization to Dermatophagoides farinae, Dermatophagoides pteronyssinus and cat were independently associated with current asthma.
Henderson et al in a case-control study[19] examined 343 children ranging from 7 to 12 yr of age and recruited from a general pediatric practice. Positive skin tests for allergy were observed in 35% of a random sample of children without recurrent wheezing, and in 77% and 90% of children who had experienced from two to four episodes and five or more episodes, respectively, of recent wheezing. By logistic regression analysis, sensitization to dust mite (odds ratio [OR]: 5.2; 95% CI: 3.0 to 9.0), cat (OR: 15.5; 95% CI: 3.4 to 70.8), and Alternaria (OR: 6.8; 95% CI: 2.1 to 21.5) antigens was consistently associated with recurrent wheezing. Sensitization to pollen antigen(s), observed in 60% of allergic children, was not associated with wheezing.
Squillace SP et al studied adolescents with asthma in the state of Virginia USA[full text, 20]. Marginal analysis identified elevated total IgE and dust mite, cat, and cockroach sensitization as significant risk factors for asthma. Using multiple regression, only dust mite sensitization was independently associated with asthma (odds ratio = 6.6; p < 0.0001). Dust from 81% of the houses contained high levels of mite allergen (> 2 micrograms/g), while approximately 40% of the children were exposed to cat and 17% were exposed to cockroach allergen. In this population, there was no significant association between asthma and race, socioeconomic status, home smoking, sensitization to outdoor allergens, or allergen concentration in the child's home.
Halonen et al. studied the factors associated with childhood asthma in children raised in a semi-arid environment where the children commonly had positive skin tests to Alternaria[21]. On logistic regression, only Alternaria showed independent association for increased risk of asthma while Bermuda grass and Mulberry tree showed a similar association with allergic rhinitis. These data suggested that in areas where there was not a lot of sensitization to mites and animal dander, the mould Alternaria was the major allergenic drive for asthma.
The group from the Isle of Wight studied the relationship of allergy and childhood asthma in a large birth cohort[2]. They found that allergic disease such as asthma was strongly associated with atopy and the prevalance of asthma increased in relation to the number of positive skin tests a child had.
The data very strongly supports the role of allergy to indoor allergens in childhood asthma. When combined with data showing that very young children with viral induced asthma out grow the asthma if they are not allergic and if there is no smoking in the home (See PRESCHOOL ASTHMA) along with data showing that allergy is responsible for eosinophilic inflammation in the airways of children with asthma, there is a strong basis for implicating allergy in at least aggravating and maintaining asthma. Moreover the studies have consistently shown that indoor allergens, mite, dander, cockroach and the seasonal mould alternaria have the greatest negative effect on asthma. For these reasons allergy control in the home is strongly recommended in the management of childhood asthma.
Go to Allergy Control in the home.