Asthma is a chronic condition involving the respiratory system in which the airway occasionally constricts, becomes inflamed, and is lined with excessive amounts of mucus, often in response to one or more triggers. Asthma is the most common chronic disease affecting children and young adults. It is a complex genetic disorder with a heterogeneous phenotype, largely attributed to the interactions among many genes and between these genes and the environment. Asthma-related traits include clinical symptoms of asthma, such as coughing, wheezing, and dyspnea; bronchial hyperresponsiveness (BHR) as assessed by methacholine challenge test; serum IgE levels; atopy; and atopic dermatitis.
Asthma can be diagnosed on the basis of typical findings in a patient's clinical history and examination. Asthma is strongly suspected if a patient suffers from eczema or other allergic conditions or has a family history of asthma. However, before diagnosing someone as asthmatic, alternative possibilities should be considered.
Multiple loci and candidate genes have been implicated in the causation of asthma and asthma-related traits (ASRT), including: ASRT1, associated with a mutation in the PTGDR gene on chromosome 14q24; ASRT2, associated with mutation in the GPRA gene on 7p15-p14; ASRT3, which has been mapped to chromosome 2p; ASRT4, which has been mapped to chromosome 1p31; and ASRT5, associated with variation in the IRAK3 gene on 12q14.3. ASRT6 is associated with markers on chromosome 17q21 and transcript levels of ORMDL3. Polymorphisms in the HNMT gene and the ADRB2 gene have also been associated with susceptibility to asthma.
Djidjik et al. (2008) investigated the role of NOS1 -84G>A and NOS3 -786T>C, 894G>T and 27 base pair (bp) repeat polymorphisms in 125 patients suffering from asthma and/or rhinitis and mono-sensitized against Dermatophagoides pteronyssinus (Dpter) and 111 controls from Algeria. Results indicated a higher frequency of the -786 C NOS3 allele in patients than in controls [corrected P value (Pc) = 0.04], especially in female cases (Pc=0.02) and that the 'ab' genotype of the 27-bp polymorphism was significantly associated with specific immunoglobulin E production against Dpter (P = 0.006) and demonstrating a possible participation of NOS3 gene polymorphism in the pathogenesis of respiratory allergic disorders.
Ellul-Micallef and Al-Ali (1984) studied the first 1000 consecutive patients diagnosed with bronchial asthma referred to the central allergy unit in Kuwait. These included 569 Kuwait patients (307 females); in 281 of whom the asthma developed before reaching 10-years of age. Positive skin-prick tests were elicited in 81% of the Kuwaiti patients, of which 80% reacted positively to pollen grains. About 47% of the skin test positive Kuwaiti patients had a family history of asthma, a statistic that reached to 64% when only Bedouins were considered. Most attaches were observed between March and October. Ellul-Micallef and Al-Ali (1984) speculated that this could be due to abundance of pollen, frequent sandstorms, and/or the sudden change in temperature and humidity between the outside environment and the air-conditioned interiors encountered in this season.
In 1989, El Shirbiny performed a study to determine the levels of serum alpha-1-apantitrypsin [alpha 1AT] and the phenotypes of protease inhibitor [PI] in asthmatic patients and healthy controls. The M "normal" phenotype was less frequent in patients with bronchial asthma (82%) than in non-asthmatic controls (98%). On the other hand the Z phenotype, which is linked to severe alpha 1AT deficiency, was far more prevalent in the patients group (10%) than in the controls (1.6%). Upon clinical investigation of patients with the M or Z phenotypes, no significant relationships could be detected between these phenotypes and the following clinical parameters: type of asthma, severity of the disease, steroid dependency, smoking habits or age at onset. Still the higher frequency of deficient phenotypes in the asthmatic group may indicate a certain degree of causality that could be made conspicuous by the harsh environmental conditions in Kuwait.
A study by Al Kordy et al. (1994) compared bronchial asthma prevalence among Kuwaitis and expatriates over 5 years (1983-1988). Kuwaiti males and females had higher relative rates of 2.91 and 1.9 times respectively than expatriates with the age of onset ranging between 30 and 39. This trend is reversed when the age of onset is > 60, i.e., Kuwaiti rates were less than these of expatriates. Comparisons within other age of onset groups rendered insignificant differences. Interestingly extrinsic asthma was more frequent among expatriates [12%] than in Kuwaitis [8%].
Behbehani et al. (2000) studied the prevalence of asthma and allergic diseases in 3110 students in Kuwait aged between 13 and 14 years. They calculated modest prevalence rates of wheeze ever, current wheeze with the past year, and a diagnosis of asthma as 30%, 16%, and 17%, respectively. Multiple logistic regression identified male gender and a diagnosis of allergic rhinitis to be associated with a diagnosis of asthma. Later, Owayed et al. (2007) conducted a similar study among 2882 children and found decreased prevalence rates of wheeze ever, and current wheeze with the past year at as 13% and 8%, respectively, while the rate of physician diagnosis of asthma remained the same at 16%.
Ezeamuzie et al. (2000) investigated the prevalence of allergen-specific IgE, and the characteristic of sensitization among 533 randomly selected Kuwaiti asthmatics. The overall frequency of positive specific IgE to at least one allergen was 87.2%, compared to 24.1% in age and sex-matched controls. Pollens elicited the maximum positive response (76%), followed by house-dust allergens (66%), and molds (26%). Males had significantly higher rates for the allergens, whereas no significant differences could be detected between the different age groups. Molds had overall the lowest rate of positivity, although they were more frequently associated with severe asthma. Ezeamuzie et al. (2000) concluded that pollens of local horticultural plants and cockroaches constituted the bulk of the sensitizing allergens among extrinsic asthmatics in Kuwait. Hijazi et al. (2002) also studied the clinical features and common triggers of asthma among 135 asthmatics under 13-years old in Kuwait. The study identified that asthma was more common in boys, cough and wheezing were the most common presenting symptoms, URT infections, exercise and cigarette smoke were the most common triggers, humid weather and winter season were associated with exacerbated symptoms, and pollens, house dust mites, molds and cockroaches were the major sensitizing allergens. The interesting observations made in this study included the early age of asthma in spite of the high rate of breast feeding, a marked delay in diagnosis, under-treatment, and subjection to complementary and alternative medicine. Al-Mousawi et al. (2004) studied risk factors associated with asthma and sensitization in Kuwait, and found that despite low allergen exposure, the pattern of childhood asthma followed in Kuwait was similar to those seen in Western populations. They also established that pet ownership markedly increased sensitization to pets.
Al-Riyami et al. (2003) investigated the prevalence and severity of symptoms of asthma, allergic rhinitis and eczema in Omani schoolchildren using the International Study of Asthma and Allergies in Childhood (ISAAC) Phase I questionnaire. An Arabic version of the ISAAC Phase I questionnaire was completed by parents of 3893 children aged 6-7 years and self-completed by 3174 children aged 13-14 years, randomly selected from a nationwide sample of public schools. The prevalence rates of reported diagnoses of asthma, allergic rhinitis and eczema were higher in older children (20.7%, 10.5% and 14.4% compared with 10.5%, 7.4% and 7.5%, respectively, in young children).
Dawod and Hussain (1995) studied the profile of asthma among 414 (67.4% boys) children in Qatar below the age of 13-years suffering from asthma and compared the results with those from other countries. Of these, 274 children (66.2%) were Qatari nationals. Mean age of the patients was 6.15 years, which was lower than that reported from other developing countries. About 92% of the 414 patients had their first asthmatic episode within 5-years of their life, of which 52% experienced it within the first year of their life. This is earlier than that reported from other countries, and could be due to early diagnosis in Qatar, and to the high level of consanguinity in the country. Most common features in the patients were noticed to be noisy and musical breathing, nocturnal coughing, and dyspnea. The most common precipitating factor was found to be upper respiratory infections (95.2%), most probably viral in origin, weather changes (82.2%), dust exposure (65.7%), and exercise (41.6%). Interestingly, fumes were found to be the precipitating factor in 36% of the patients, with fumes from Bokhour representing 54% of these cases. Winter season was found to result in more episodes. A positive family history of allergic diseases was seen in 86% of the patients, specifically asthma in 74%, allergic rhinitis in 47%, atopic dermatitis in 23%, and food allergy in 6% of the cases. Growth patterns in the children were noted to be normal for age, although eosinophilic count was elevated in 36.6% of the patients and 61.6% had elevated serum IgE levels. Positive skin tests were obtained for house dust mites, house dust, cockroaches, molds, and food, most notably eggs.
El-Tonsy et al. (1998) studied 87 patients (33 Qatari and 54 other nationalities; 73 males and 14 females;76 adults and 11 children; aged 2-56 years) with alopecia areata (AA). They found out two patients (2.4%) to have bronchial asthma, and nine patients (10.3%) were found to have a family history for bronchial asthma.
Bener et al. (2005) studied the genetic and environmental risk factors associated with asthma in Qatari school children between 6-12 years with the use of ISAAC questionnaires. A total of 3,500 Qatari schoolchildren, aged between 6 and 14 years, were selected from both rural and urban areas, based on a stratified, random sampling technique. Great care was taken to avoid bias due to sampling errors. Parents of all selected subjects were asked to fill questionnaires intending to diagnose asthma or other allergic conditions in their child. The response rate was 93.8%, with 3,283 of the subjects returning properly filled questionnaires. Males constituted 52.3% of the study group. A high prevalence of asthma (649 subjects; 19.8%) was diagnosed in the study population. More boys were asthmatic than girls. Parents also reflected almost the same incidence of asthma. Stepwise logistic regression analysis revealed the major predictors of asthma to be allergy to pets, certain food or medicine, smoking history of parents or siblings, and a history of asthma in mother, father, or siblings, history of asthma in second degree relatives. The study revealed that a family history of asthma contributed more to the development of the disease when compared to environmental factors. This was exemplified by the fact that 42.4% of either parent was found to be asthmatic if more than one of their children was affected, while only 23.3% had asthma when only one child was affected. This underlined the hypothesis of asthma being an inherited disorder. Interestingly, siblings showed a statistically significant higher prevalence rate of asthma than did parents of affected children. In a further study, Bener and Janahi (2005) studied the association between asthma, allergic rhinitis, and eczema in this same sample group. This study found that 21.6% of children with asthma had asthmatic mothers, while 18.2% had asthmatic fathers. Of the non-asthmatic children, on the other hand, only 9.4% and 6.8%% of the mothers and fathers had asthma. In addition, it was also noticed that 26.5% of the children with asthma had mothers who had allergic rhinitis, while 25.3% had fathers with the condition. Asthmatic children were also found to have increased frequency of siblings with asthma (36.6%), allergic rhinitis (16.4%), and eczema (29.1%). The results prompted Bener and Janahi (2005) to suggest that the three diseases share a common genetic defect. In year 2006, Janahi et al. further analyzed the results form the same study group. Janahi et al. (2006) noted that a prevalence rate of 19.8% is very similar to that reported from Oman, but higher than earlier reports from Saudi Arabia and UAE. Interestingly, the prevalence was found to decrease with increasing age. Males were found to be more susceptible to asthma, especially among the youngest age group (6-8 years). Among the parents, prevalence of asthma was found to be higher among the mothers (11.8%) than the fathers (9%). Almost 64% of affected children had at least one affected sibling. Asthma was found to be closely associated with allergic rhinitis and chest infections, with 71.9% of the asthmatic subjects also having either one or both of the other conditions. Janahi et al. (2006) concluded that the high prevalence rate of asthma in Qatar could be due to the high consanguinity rate, modified environmental factors (greening the environment and increase in domestication of animals), and/or increase in obesity.
Al-Marri (2006) studied all asthma hospitalizations in Qatar for the year 2002 and compared their epidemiologic features with similar hospitalizations in other countries. A total of 275 hospitalizations due to asthma (53% male) were recorded in that year in Qatar, of which 200 (73%) were Qatari nationals. Al-Marri (2006) interpreted this high percentage of Qatari nationals due to the possibility of asthmatic expatriate laborers being sent home. The hospitalization rate for the Qatari nationals was calculated to be 154 per 100,000 of the population, similar to rates reported from USA and Saudi Arabia in separate studies. The mean age of patients was 29.6 years, which was higher than that seen in the Saudi population. Al-Marri (2006) attributed this to the presence of pediatric 24 hour observance units in Qatar. Females had a higher rate of hospital admission than males, as opposed to Saudi data. The mean length of hospital stay for Qatari patients was 10 days. Peak hospitalizations were noticed in December-January, with a secondary peak in March. Most patients, in addition, were found to have comorbid conditions, pointing out to the high prevalence of asthma in Qatar. Only two of these patients died in the hospital, resulting in a very low mortality rate.
Bener et al. (1992) aimed to study the heredity of asthma in the Saudi population. A total of 1035 schoolchildren (ranging in age from 7-12 years) were recruited for the study. The parents of these children answered a questionnaire regarding bronchial asthma, hay fever and eczema in their children as well as a family history of respiratory allergy. Statistical analysis was carried out and it was found that the rate of asthma and hay fever were significantly higher among the siblings of the cases than their parents (p<0.001). Hay fever, asthma and eczema were found at increased rates among siblings and offspring of affected fathers or mothers. The authors concluded that these results supported the hypothesis that bronchial asthma and hay fever are inherited in the Saudi population, but were unable to determine the mode of inheritance.
El Mouzan et al (2008) conducted a study to find out whether the risk of bronchial asthma in children is increased by parental consanguinity. The study included 103 Saudi households with children having physician-diagnosed bronchial asthma, matched with an equal number of families with no children with asthma. The results came up to show that parental consanguinity does not increase the risk of bronchial asthma in children.
Chouchane et al. (1999) conducted a study to investigate the role of a repeat polymorphism in the IL4 gene in the pathogenesis of asthma among Tunisians. A total of 145 asthma patients (49 females, 86 males) were included in the study, and were classified into mild or moderate/severe asthma according to the clinical features before treatment and the lung function. In addition, a group of 160 healthy subjects (63 females, 97 males; mean age: 14 yrs) with no familial history of asthma was also selected for the study as control. The control subjects showed no specific IgE reaction. Genomic DNA, extracted from the blood of the subjects was amplified using a PCR primer intending to type a repeat polymorphism in intron 2 of the IL4 gene. Three allelic forms were identified: A1 (171 bp), A2 (161 bp), and A3 (149 bp). The patient group showed a high number of A1/A3 genotype, whereas the control group showed a significant decrease in the A3/A3 genotype. The frequency of the A1 allele was therefore, significantly increased in the patient population. Four patients with the A1 allele were selected for family studies. In two of these families, the IL4 A1 allele showed a recessive mode of inheritance, with only homozygous A1/A1 members showing the disease. In the two other families, members with the A1/A3 genotype were found to be asthmatic. In addition, in patients with moderate/severe asthma, the frequency of the A1 allele and the A1/A3 genotype was found to be significantly higher (0.36 and 0.475) as compared to patients with mild asthma (0.08 and 0.075). The relative risk of moderate/severe asthma associated with the A1/A3 genotype was found to be 3.94, while with the A3/A3 genotype, it was 0.165. Chouchane et al. (1999) explained the association found between the polymorphism and asthma as arising either from the IL4 intron 2 carrying a mast-cell specific enhancer, or by the polymorphism being in linkage disequilibrium with a locus contributing to the onset of asthma.
Bener et al. (1994) studied the prevalence of asthma among United Arab Emirates school children aged 6-14 years. A cross-sectional study of 850 school children living in both urban and rural areas (average age 9.36 +/- 2.11 years, 46.8% boys and 53.2% girls) was conducted using self-administered questionnaires between October 1992 and May 1993. The population sample had a high prevalence rate of diagnosed asthma (13.6%), breathlessness or tightness in chest (9.7%), allergic rhinitis (22.9%), and nocturnal cough (8.9%). Allergic rhinitis was the most frequently seen respiratory illness when compared to other respiratory symptoms. The frequency of asthma, allergic rhinitis and eczema among parents reflected the same pattern as that seen in the children. Prevalence rate of asthma was not significantly higher in fathers (5.9%) than in mothers (5.3%). The differences between the sexes were not significant in any of the age group studied for any of the allergic conditions, except for diagnosed asthma in which the prevalence rate in males was significantly higher than that in females. On the whole, the prevalence rate of all the conditions increased with age. But the frequency of allergic rhinitis symptoms was significantly higher in mothers (16%) than in fathers (10.8%). Additionally, Abdulrazzaq et al. (1994) investigated the association of asthma, allergic rhinitis, and eczema in United Arab Emirates (UAE) schoolchildren with allergic conditions in their parents. For this, they conducted a cross-sectional, population-based study among schoolchildren aged 6-14 years in Al-Ain City, UAE. The field survey was conducted from October 1992 to May 1993. A questionnaire was distributed to 850 UAE government school students from representative, randomly selected schools with a majority of UAE nationals. It was found that 13.1% of asthmatic children had mothers with asthma (relative risk (RR) = 2.67; 95% confidence intervals (CI) = 1.65-4.35), and 15.2% had fathers who were asthmatic (RR = 2.85; 95% CI = 1.81-4.49). This contrasted with 4.4% of nonasthmatic children who had fathers with asthma, and 4.1% who had mothers with asthma. A similar pattern was seen with symptoms of allergic rhinitis when it was found that 34.3% of children who had asthma had mothers with allergic rhinitis (RR: 2.74; 95% CI: 1.90-3.94). The corresponding figure for fathers was 12.7% (RR: 0.92; 95% CI: 0.5-1.7). The frequency of either parent of the asthmatic children having allergic rhinitis was 28.6%; for both parents, it was 14.5%. It was also found that asthmatic children had 12.5% of their fathers, 32.8% of their mothers, 26.4% of either of their parents, and 33.3% of both their parents suffering from allergic rhinitis. Two years later, Bener et al. (1996) investigated the familial and environmental risk factors associated with asthma among United Arab Emirates schoolchildren aged 6-14 years. For this, a cross-sectional study of 850 schoolchildren living in both urban and rural areas (average age 9.36 +/- 2.11 years; 46.8% boys, 53.2% girls) was conducted using self-administered questionnaires between October 1992 and May 1993. The population sample had a high prevalence rate of diagnosed asthma (13.6%) and allergic rhinitis (22.9%). The frequency of asthma, allergic rhinitis, and eczema among parents and siblings reflected the same pattern as that seen in the children. Environmental risk factors associated with asthma were pets, medicine, plants, dust storm, physical exercise, humidity, and perfume. All other factors, such as foods, climate, and parental smoking, showed no apparent relation to the development of asthma. The logistic regression analysis showed that parental asthma, plants, perfume, dust storm, humidity, and pets were the only significant predictors after adjusting for sex and other confounding covariates in the model.
Al-Maskari et al. (2000) studied the prevalence of asthma, wheezing, hay fever, and eczema among primary school children aged 6-13 years in United Arab Emirates (UAE). For this, a cross-sectional study on school children was performed using the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaires. Government primary school children in seven Emirates, in UAE. Subjects were selected by a multi-stage stratified sampling design. Only 3200 children aged 6-13 years agreed to participate and responded to the study. The prevalence of physician diagnosed asthma was 13%, in addition, the wheeze by history was 15.6%, the prevalence of nocturnal cough was 21%, the prevalence of eczema was 11%, and hay fever was 14.9%. Al-Maskari et al. (2000) concluded that parental asthma but not parental atopy was associated with an increased risk of asthma and wheezing in children.
Joseph et al. (2009) explored the effect of consanguinity on childhood asthma by studying the asthma prevalence in children between 6 and 14 years of age among local Arab families of the United Arab Emirates where consanguinity is known to be highly prevalent. A total of 1136 children [650 (57.2%) males and 486 (42.8%) females] from 295 families were included in this study. The prevalence of childhood asthma was found to be higher among children in consanguineous families (43.3%) compared to non-consanguineous (22.6%, p < 0.001). A significant correlation between the degree of consanguinity and the number of asthmatic children per family (p = 0.0002) was observed. Girls from consanguineous families had found to be proportionately more asthmatic (42.9%, p < 0.001) compared to boys (23.1%, p = 0.539). Joseph et al. (2009) also found that paternal asthma in consanguineous families increased asthma risk for both boys and girls (p = 0.021 for boys, p < 0.001 for girls), while maternal asthma had no significant impact on asthma in offspring. The significant asthma predictors for girls from the consanguineous families were found to be the degree of consanguinity and paternal asthma. The only predictor for boys was found to be paternal asthma. Joseph et al. (2009) concluded that these interesting observations merit further studies on both larger samples and in other consanguineous communities for confirmation.
Alsowaidi et al. (2010) investigated the prevalence of asthma and its independent risk factors among adolescents and adults in Al-Ain, UAE. A two-stage, randomly selected survey was used to distribute 10,000 questionnaires to adolescents and their parents. Logistic regression was applied to assess asthma prevalence and independent associations with age, gender, education, nationality and family history. A total of 6,543 subjects were included in the final analysis. Median age was found to be 30 years (range: 8-93 years); 53% were found to be male. The overall self-reported prevalence of asthma was found to be 13%. Direct standardization with the UAE population as the reference yielded a prevalence of 12%. By applying logistic regression, Alsowaidi et al. (2010) found that family history and UAE nationality (about 50% of nationals were of Bedouin origin) as the main risk factors for asthma. Also, by applying logistic regression, they found a significant (p = 0.001) interaction between gender and age as following: in the group aged 13-19 years, males had a significantly higher prevalence of asthma [17 and 14%; adjusted odds ratio (OR): 1.45; 95% confidence interval (CI): 1.10-1.90]; in the group aged >19 years, males had a significantly lower prevalence of asthma (11 and 13%; adjusted OR: 0.77; 95% CI: 0.60-0.95) than females. The findings of this study indicate a prevalence of asthma comparable to findings of earlier studies. Alsowaidi et al. (2010) also noted that the higher prevalence in adolescent males compared to females may possibly be due to sex-specific lifestyle factors and that strong predictors of asthma, such as family history and UAE nationality, may indicate modernization and possible genetic susceptibility, warranting further studies in this population.
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