Sensitization to inhaled allergens in asthmatic children in southern Jordan: a cross-sectional study

Bronchial asthma is one of the most common chronic disorders in children, and it imposes a great burden on global health. It is a major cause of frequent admissions to hospital and emergency room visits among the pediatric population, leading to significant morbidity and mortality in children worldwide [1]. Thus, bronchial asthma has a substantial impact on the health and quality of life of children as well as the economy [2‐4].

In Jordan, it is estimated that 10% of the population has been diagnosed with bronchial asthma. According to an official report of the Jordanian Ministry of Health, most of these patients are children under the age of 15 years. One study estimated the prevalence of bronchial asthma in children in the capital city and rural northern Jordan to be approximately 9% [4]. Although the prevalence of asthma among school children was found to be 3% in the city of Al-Karak, southern Jordan, up to 16% children have had one or more wheezing episodes in their lifetime [5]. In the latter study, 36% reported symptoms of at least one allergic condition. Prevalence studies on childhood asthma at a national level are still lacking.

Bronchial asthma is caused by a complicated interaction between several environmental and genetic factors. In general, the triggering factors of asthma are classified as allergic (atopic) and non-allergic [6]. Atopy is defined as an individual’s intrinsic propensity to generate immunoglobulin E (IgE) antibodies in response to an exposure to certain allergens, with a higher tendency for developing typical allergic diseases, such as asthma, rhinitis, conjunctivitis, and atopic dermatitis. Generally, atopy is confirmed by the presence of serum allergen-specific IgE antibodies or positive skin prick tests (SPTs) [6]. Atopic asthma is the most common form of asthma in the pediatric population and is distinguished by the presence of eosinophils in the airways associated with specific IgE antibodies to several allergens, as verified by serology or SPT [7].

Sensitization to at least one inhaled allergen in atopic children is a prognostic and predictive indicator for developing asthma and for the persistence of asthma into late childhood and adulthood [8, 9]. For example, a previous study reported 50 to 95% sensitization to inhaled allergens in several patients with bronchial asthma [10]. Allergens trigger asthma attacks in 60 to 90% of atopic children and in 50% of atopic adults [11‐13]. These inhaled allergens include seasonal pollen, mold spores, dust mites, and animal dander allergens. Identifying sensitization to inhaled allergens in children with asthma can assist in planning an environmental control strategy, titration of therapy (i.e., seasonal exacerbations), or referring patients for an immunotherapy regimen [13‐15].

The present study determined the prevalence in Al-Karak of sensitization to inhaled allergens in children with bronchial asthma and wheezing episodes to investigate the effect of positive sensitization on the severity and control of asthma symptoms and to screen for other associated allergic conditions.

The present study included a total of 277 children with asthma and wheezing episodes. Demographics, GINA classification, and clinical profile are shown in Table 1. Of these 277 children, 186 (67%) had a positive SPT, 41 (15%) for a single allergen and 145 (52%) for multiple allergens (Fig. 1). A significant increase in the sensitivity with age was observed upon comparing SPT results among different age groups (χ² = 24.7, p < 0.001) (Fig. 2). The maximum frequency of sensitivity was 86% in the group aged 10 years or older (Fig. 2).

Figure 3 represents the frequency of sensitization for each allergen tested. Olive pollen had the highest frequency of sensitization (18%) followed by cat fur (13.5%) and D. pteronyssinus (11.9%). The sensitivity of patients to different groups of allergens (pollens, animal dander, mites, cereals, and molds) is described in Fig. 4. A skin reactivity to pollens was found in half of the children (144; 52%), with olive pollen causing the most common positive reaction (50; 18%), as shown in Figs. 3 and 4. There was a significant increase in the sensitivity with age to pollens (χ² = 45.9, p < 0.001), animal dander (χ² = 14.95, p = 0.005), and mites (χ² = 17.32, p = 0.002), as shown in Fig. 5. The mean atopic index (AI) for each allergen group is shown in Fig. 6. The AI represents the total number of allergens out of the 11 tested to which the subjects exhibited positive responses. There was a significant difference in the mean AI among all age groups (f-test = 7.8 and p < 0.010).

Of the total number of children included in the study, 185 (66.8%) were boys and 92 (33.2%) were girls. No significant difference in the positive SPT responses was noted between boys and girls (68 and 65%, respectively; Table 2). Nevertheless, more boys were reported to be asthmatic with atopy compared to girls (126 boys/60 girls) in the present study (Table 2). According to the GINA classification of bronchial asthma, most of the children had intermittent asthma (115; 41.5%), followed by mild persistent (74; 26.7%) and moderate persistent asthma (70; 25%) (Table 1).

The most common concomitant allergic condition among children was allergic rhinitis (198; 71.5%), followed by allergic conjunctivitis (83; 30%) and eczema (73; 26%) (Table 1). A positive SPT response was significantly higher among children who had concomitant conjunctivitis (65; 78.3%) (χ² = 6.58, p = 0.01). However, there were no significant differences in the SPT reactivity among children with concomitant allergic rhinitis, atopic dermatitis and eczema, or food allergies (Table 2). A family history of bronchial asthma was reported in 112 children (40%) as shown in Table 1. Seventy-seven (68.8%) children with a family history of asthma reported a positive SPT; however, this was not predictive of SPT reactivity (Table 2).

Based on the results obtained using multiple logistic regression, we concluded that only age and concomitant allergic conjunctivitis were significant predictors of sensitization to inhaled allergens.

When children with positive SPT were assessed for severity according to the GINA classification, most asthmatic children above the age of 4 years (n = 170) were found to have intermittent asthma (40%), followed by mild persistent (25.9%) and moderate persistent asthma (28.9%), and only 5.3% of them had severe persistent asthma (Table 2). These findings were not significantly different when compared to the SPT-negative group (p > 0.05). One hundred four children (66.25%) were admitted to the hospital with an asthma exacerbation during the past 12 months compared to 53 (33.8%) children with a negative SPT. Systemic steroids were used to treat acute exacerbations in 116 (67%) children with a positive SPT compared to 56 (32.3%) children with a negative SPT. Neither admission to hospital nor use of systemic steroids was significantly different between positive-SPT and-negative SPT children (p > 0.05).

In addition, the mean ACT score was less than 19 (poor asthma control) in both SPT-positive and SPT-negative groups with no significant difference between the two groups (16.5 ± 5 and 17.08 ± 5), respectively (p > 0.05) (Table 2).

The present study found that sensitization to inhaled allergens is present in almost two-thirds of children with bronchial asthma and wheezing episodes. These findings are consistent with the results of previous studies [20‐23]. Most children with a positive SPT were sensitive to multiple inhaled allergens, similar to the findings in other reports [24, 25]. Children with negative skin reactivity to SPT may lack atopy or be sensitized to other allergens not tested in this study. We analyzed the clinical and demographic characteristics of these children to identify possible predictive values for a positive SPT and found only age and concomitant allergic conjunctivitis to be significant predictors. Older children reported more positive SPT results for different groups of allergens (pollens, mites, and animal dander). This finding might be attributable to the natural history of atopic disorders (the allergic march), where exposure to indoor allergens occurs earlier in childhood and exposure to outdoor allergens, particularly tree pollens and grasses, occurs later and increases with age [26]. Furthermore, this may suggest that asthma in children with atopy is more likely to persist into later childhood and adulthood than non-atopic asthma. Covar et al. followed children in the Childhood Asthma Management Program study for 4 years and found that remission was associated with a lack of atopic sensitization [27].

The incidence of asthma and atopy in boys was higher, a finding consistent with a previous report [28]. However, there was no significant difference in SPT reactivity between boys and girls. In accordance with our findings, a study from Jordan that evaluated skin reactivity to 18 inhaled allergens in patients with allergic rhinitis found that most patients had sensitization to more than one inhaled allergen [29]. In the latter study, pollens of a grass mix, thistle weed, and olive tree were the most common seasonal allergens, while cat allergen was the most common perennial allergen, followed by house dust mites (D. pteronyssinus). These findings are consistent with our study, showing that olive tree pollen, cat fur allergen, and house dust mites (D. pt) were the most common inhaled allergens in children from Al-Karak.

In the present study, allergic rhinitis was found to be the most common allergic condition associated with bronchial asthma, occurring in approximately two-thirds of children. These findings are similar to those of previous reports [30] and emphasize the importance of screening all children with bronchial asthma for allergic rhinitis to determine the appropriate treatment for both conditions, thereby improving symptom control [30]. Although allergic rhinitis failed to show a predictive value for skin prick reactivity in our study, concomitant allergic conjunctivitis was a predictive variable for positive SPT. Several of the children included in the present study with positive sensitization also had a positive family history for one or more allergic conditions, indicating a genetic predisposition to asthma and atopy [9]. However, a family history of asthma was not predictive of skin test reactivity, which could be explained by the complexity of the interrelationship between the genetics and epigenetics of asthma [31].

As for the relationship between allergen sensitization and asthma severity, many studies have demonstrated that the presence of atopy has a linear relationship with asthma morbidity and that sensitization to allergens can be used as a marker for asthma severity [32‐36]. Allergen sensitization to molds, cockroach, pet dander, and inhaled food-derived allergens has been reported to be associated with severe asthma episodes [37]. Exposure to environmental molds may lead to life threatening asthma episodes [38‐40]. In addition, “thunderstorm asthma” was shown to be associated with severe symptoms resulting from massive and abrupt exposure to inhaled allergens [41].

However, the findings of the current study do not support this relationship. There was no statistically significant difference between SPT-positive and SPT-negative asthmatic children in terms of GINA classification, ACT score, admission to hospital or the use of systemic steroids within the past 12 months. This could be explained, in part, by the lack of more objective measures to assess the severity of asthma (e.g., spirometry for forced expiratory volume in the first second [FEV1]) and atopy (e.g., quantitative serum IgE level). In addition, most children in this study presented to the clinic with their care givers when their asthma symptoms were uncontrolled, rather than for a regular follow-up, which resulted in low clinical scores. Moreover, our allergen panel did not include some important allergens like cockroaches and various types of fungi (e.g., Aspergillus spp), which can be strongly associated with severe asthma in addition to house dust mites and seasonal pollens.

Atopy is considered a significant burden in regards to childhood asthma. Most children with asthma and wheezy episodes in the present study had sensitization to one or more inhaled allergens. The two strains of house dust mites, olive pollen, and cat fur were the most common inhaled allergens. Age had a predictive value for allergen sensitization, as older children reported more positive SPT results. Allergic conjunctivitis was the only concomitant allergic condition that correlated with skin test reactivity. With regard to allergen sensitization and asthma severity, we could not demonstrate a significant relationship. Based on the findings of the present study, we concluded that allergen sensitization is highly prevalent in children with asthma and wheezing episodes. Therefore, physicians should be encouraged to perform allergen testing on all children with asthma. Additionally, families should be instructed to avoid allergens when possible to limit exposure of their atopic children to asthma triggers. The association of asthma with other allergic conditions, especially allergic rhinitis and conjunctivitis, is common and medical personnel should address these conditions during evaluation and treatment. Researchers are advised to conduct further studies with a larger population size including patients from other parts of Jordan to assess the prevalence and pattern of sensitization in children with bronchial asthma in order to improve asthma control and the quality of life of these children.