The Prevalence of Asthma, Allergic Rhinitis, and Atopy in Antalya, Turkey ABSTRACT Bronchial asthma is a common inflammatory disorder

of the airways that causes serious morbidity and mortality. The prevalence of the disorder has been increasing, especially in developed countries. The population-based asthma prevalence studies provide data from Ankara, Istanbul, Gaziantep, Trabzon, Izmir, and Kayseri in our country and asthma prevalence ranges between 1.4 and 3%. However, the prevalence of adult asthma in our city was not known. We aimed to determine the prevalence of asthma, allergic rhinitis, and atopy in the adult population of Antalya and compare the data with other countries and other regions of our country. The European Commission Respiratory Health Survey, the first study to assess the geographical variation in asthma and allergic diseases, provided comparablendata from 22 countries and 140,000 individuals. Therefore, the European Commission Respiratory Health Survey protocol was preferred in our study. The first stage consisted of 1000 subjects; of these 1000 subjects, 200 subjects were randomly selected for the second stage. The response rates were 99.5 and 55.4% for stages I and II, respectively. The current prevalence of asthma, allergic rhinitis, and atopy in Antalya was 9.4, 27.7, and 31.1%, respectively. The most prevalent type of sensitization was mite allergy detected in 31 (20.9%) subjects. Sensitization to more than one allergen was frequent in subjects with asthma and allergic rhinitis. Bronchial asthma, allergic rhinitis, and atopy are frequent in our city and when compared with previous studies performed in Turkey, the highest results were in Antalya. (Allergy and Athma Proc 26:403-409, 2005) Bronchial asthma is a common chronic inflammatory disorder of the airways that causes serious morbidity and mortality. The prevalence of asthma has increased, especially in developed countries.1-3 The prevalence of childhood and adult asthma has been reported to be between 0.1 and 30% and 1.2 and 56%, respectively.2,4 Although the exact etiology is not known, genetic predisposition, environmental factors, and some triggering agents are considered to play role in pathogenesis. 2-8 This potentially preventable disorder, possibly caused by environmental exposure of, especially, inhaled allergens, makes the prevalence studies for asthma attractive. 2-5 Most of the studies reporting asthma prevalence in Turkey are childhood studies and most of the adult studies have used the European Commission Respiratory Health Survey (ECHRS) protocol.9 However, only a few of these studies bear all the items of the protocol; many of them lack skin tests, immunoglobulin E (IgE) levels, or bronchoprovacation tests. The prevalence of adult asthma reported from different parts of Turkey ranges between 0.3 and 14.5%. 10-28 However, the prevalence of asthma in the adult population in our city is not known. In this study, we aimed to determine the prevalence of asthma, allergic rhinitis, and atopy in the adult population of Antalya using the internationally approved ECHRS protocol and compare the data with other countries and other regions of our country.

MATERIALS AND METHOD The study was performed in the Department of Chest Diseases of the Akdeniz University Medical Faculty in Antalya between November 2002 and June 2003. From 31 primary health care centers scattere throught the city, 100 different ddresses of 20 to 44 years old men and women were randomly selected. A comprehensive training was given to six interviewers who were medical students. Interviewers administered the screening questionnaire of the ECHRS protocol to 10 subjects aged20-44 years old, living at each selected address and at the nearest nine addresses. Questions about their smoking status were added to the screening questionnaire. A total of 1000 subjects were interviewed. In the second stage, we obtained information using the main questionnaire of the ECHRS protocol and performed physical examinations and clinical tests of 200 randomly selected subjects that responded to stage I. in light of response rates reported by previous studies made by the ECHRS protocol, the response rate was estimated to be low and a high number of subjects (500) were randomly selected and called, but only 148 subjects participated in stage II. 8,29 Subjects who did not respond to telephone calls on 3 separate days at various hours or subjects who gave a wrong telephone number in stage I were excluded from stage II. Detailed information on the questionnaire and clinical tests were given to subjects who responded to telephone calls. All responders were assured that the clinical tests were free. The subjects who agreed to participate in stage II were invited to the hospital. Written informed consent was obtained from all participants. The main questionnaire, physical examination, pulmonary function test, skin-prick tests, and blood sampling were performed at the same visit. The spirometric measurements were doing using Microspiro 3000 spirometry equipment (Micro Medical Ltd., Rochester, England) in a sitting position. The best forced vital capacity, forced expiratory volume in 1 second FEV1, FEV1/forced vital capacity, maximum midexpiratoryflow, and peak expiratpry flow rate values from three consecutive sessions were recorded. Skin tests were performed by puncture method. The allergens included house-dust mites, trees, weeds, grass pollens, animal epithelia, and mold antigens. Indurations wider than or equal to histamine control were accepted as positive. After 3-6 hours of waiting in room air, 5mL of venous blood obtained from the participans was centrifuged at 2500 rpm for 10 minutes. Serum samples were stored at -200C until the test day. On the test day, samples melted at room temperature and total IgE levels were measured by the fluoroimmunoassay method with UniCap 100 System (Pharmacia & Upjohn, Uppsala, Sweden). According to the manufucturers recommendations, values 100 kU/L were accepted as positive. Statistical analysis was performed by chi-square test and logistic regression analysis using the SPSS 12.0 package program (SPSS, Inc., Istanbul, Turkey).

RESULTS Among 995 subjects (99.5%) who participated in the first screening stage, 670 (60.7%) were women and 325 (32.5%) were men. The most frequent symptom in the screening questionnaire was wheezing (Table I). The prevalence of current asthma according to the answers given to questions five and six was 9.4%. Twenty-two (2.21%) of the participants were receiving medication for asthma but denied having an asthma attack in the last year. Current smokers constituted 37.7% of the participants; 29.5% of the participants were women and 54.7% of the participants were men. The prevalence of smoking was significantly higher among man (p<.005). No clear associtation has been detected between smoking and current asthma; however, smoking > 10 year was associated with a higher prevalence of wheezy breathing. Among 500 subjects randomly selected for the second stage, 78 subjects (15.6%) had declared a wrong telephone number on the screening questionnaire and 165 subjects (33%) id not respond to telephone calls made on three separate days at various hours. Among the remaining 267 subjects 148 subjects (55.4%) agreed to participating in the scond stage of the study. Fiftyfive (37.2%) of these 148 participants were men and 93 (62.8%) were women. The ratio of women/men was 1.69. The current asthma prevalence in the second stage was 25% and tended to be higher among women compared with men (27.9% versus 20%, respectively); however, this difference was not statistically significant (p = 0.78). the age of onset for asthma was similar in both sex groups. No significant difference was observed between age groups for wheezing, asthma, atopy prevalences. Among 37 subjects with asthma, 22 reported two attacks, 13 reported one attack in the last 12 months, and 2 denied asthma attack in the last year. Mean attack number was 1.63 5.71. Attacks were more frequent in the spring (p > 0.000001). More than treequarters of attacks occurred in March and April. Among the patients with asthma, 22 were receiving asthma medication and 31 had been offered asthma medication but refused to adhere to treatment. Current medications received were inhaler therapies for 21 patients, pills for 16 patients, and inhaler therapies plus pills for 6 patients. Inhaler therapies included 2-agonists in 86.3% of patients, inhaler steroids in 50% of patients, and combined bronchodilators (inhaler steroids plus 2-agonists) in 13.6% of patients. Atopy was detected in 46 subjects (31.1%). Mean IgE level was 122.37 231.28 kU/L. This value was higher in men (152283.98 versus 105.54 195.06). Among the participants in the second stage, 56 subjects (37.8%) had allergic rhinitis; asthma and allergic rhinitis together were present in 27 subjects (18.2%). A high proportion of subjects with asthma (72.9%) also had allergic rhinitis, whereas 48.2% of the subjects with rhinitis and asthma. A significantly higher prevalence of asthma was found in subjects with reported nasal allergy (p < 0.0000001). similarly, there was a strong relationship between asthma and atopy (p < 0.000001). A statistically significant association between asthma and parental atopy, asthma or allergic diseases, could not be determined with chi-square test, but in logistic

regression analysis history of paternal allergy was found to be a statistically significant risk factor. In the second stage, prevalence of smoking for at least 1 year was 44.5% and prevalence of current smoking was slightly lower (31.08%). There was no association between smoking for at least 1 year or current smoking and asthma or atopy. However, smoking significantly increased prevalence of wheezy breathing, expectoration of sputum on most days for 3 motnhs or in the mornings in the winter (p < 0.01). Exposure to environmental tobacco smokes in childhood or prenatally did not effect asthma or atopy prevalence, but prenatal exposure was reported by only 12 subjects. Mite sensitization was found to be the most frequent allergen sensitization. Dermatophagoides pteronyssinus and D. farinae sensitizations were detected in 30 (20.2%) and 27 (18.2%) subjects, respectively. Twenty-four (16.2%) subjects were sensitive to both allergens. The rest of the results of the skin-prick tests are given in Table II, and the association of allergen sensitizations with asthma and allergic rhinitis are given in Fig. 1. All of the five subjects with aspergillud allergy also were sensitive to Alternaria and three of them were sensitive to cladospor. None of the subjects revealed characteristic findings of allergic bronchopulmonary aspergillosis. Skin-prick test positivity to any allergen was detected in 43 subjects (29.05%). History of food allergy was present in nine subjects (6.0%), all of whom experienced local reactions. The same was true for 25 subjects (16.8%) with insect allergy. Dyspnea after ingestion of drugs was reported by seven subjects (4.7%) and five of those subjects had asthma. Drugs that cause allergy were as follows: acetyl-salicylic acid in four subjects, nonsteroidal antiinflammatory drugs in two subjects, and -blockers in one subject. There was no association between asthma or allergy and attending a nursery in childhood, which was reported by only three subjects. FEV1 values were significantly lower in subjects with asthma. In 24 subjects (64.8%) with asthma, findings of airway obstruction were detected by either spirometry or physical examination. Because they were almost the same for all the participants, we could not evaluate the effect of gas cooking, damp dweelings, and housing conditions on the prevalence of asthma or atopy. In logistic regression analysis allergic rhinitis, skin test, and paternal allergy history positivity were found to be significantly associated with the presesnce of asthma (Table III).

TABLE I Distribution of Responses to the Screening Questions Q1. Wheeze Q1.1. Wheeze with breathlessness

Q1.2. Wheeze without a cold Q2. Waking with tightness in the chest Q3. Waking with breathlessness Q4. Waking with cough Q5. Attack of asthma Q6. Treatment for asthma Q7. Nasal allergies and hay fever

TABLE II Results of the Skin-Prick Tests Aeroallergens D. pteronyssinus D. farinae Acarus silo Cockroach/Blatella germanica Tree pollens (early) Tree pollens (middle) Olive (Olea europaea) Zea mays Mixture of Mediterranean grass Grass pollens Hay dust Aspergillus fumigates Alternaria alternata Cladosporium herbarum

Wool Dog epithelium Cat epithelium Cow ephitelium Budgerigar feathers Goat epithelium Poultry

Figure 1. Distribution of aeroallergen sensitivity in subjects with asthma and allergic rhinitis. Allergens follow the order in Table II. Athma; allergic rhinitis; dp, Dermatophagoides pteronyssinus; ac, acarus silo; ea, early tree pollens; zm, zea mays; ao, Mediterranean grass mixture; sm, hay dust; alt, Alternaria alternate; yn, wool; kd, cat epithelium; mu, budgerigar feathers; km, poultry.

Table III Risk Factors for Presence of Asthma, Results of the Logistic Regression Analysis Risk Factor Sex (female) Current smoker Skin test positivity Allergic rhinitis Childhood infection Occupational exposure Damp dwellings Number of siblings Paternal smoking during childhood Maternal smoking during childhood Odds Ratio

History of maternal allergy History of paternal allergy Atopy (T/IgE > 100 kU/L) *Indicates significant p values

DISCUSSION The prevalence of asthma and other allergic diseases varies widely according to the study population, definition of the disease, disease-related symptoms, and methods of diagnosis. To overcome the potential problems that may arise in assessment of data from epidemiological studies, especially in questionnaire-based ones, execution of standardize questionnaire-based ones, execution of standardized questionnaires, study, and analysis protocols have been suggested.1,4 The ECHRS is the first study to asses the geographical variation in asthma and allergic diseases in adult using the identical and standardized protocol. Moreover, information from 22 different countries and nearly 140,000 individuals are available from studies that have used the ECHRS protocol.1,29 Prevalence is the percent of subjects in a population with symptoms that are looked for, and current prevalence is the percent with symptoms during the previous 12 months unless another period is indicated.30 In our study, the current prevalence of asthma, allergic rhinitis, and atopy was found to be 9.4, 27.7, and 31.3%, respectively. The response rates of subjects were 99.5 and 55.4% for stages I and II, respectively. The median response rate for other countries was 78% (54-100%) for stage I and 65% (12-90%) for stage II.8,29 The high response rate in the first stage of our study is probably because of the faceto-face interview executed by trained interviewers. The relatively low response rate in the second stage may be because of the necessity of subjects to be in the hospital during working hours. Also, the asymptomatic subjects were reluctant to participate in stage II. A sixfoldnvariation in asthma prevalence was found in the ECHRS; the prevalence of asthma and respiratory symptoms were highest in Australia and New Zealand and lowest in Estonia, parts of Spain, Algeria, and India. The prevalence of nasal allergies varied between 9.5% (Algeria) and 40.9% (Australia).8 In our city, the prevalence of asthma, allergic rhinitisnassal allergies, and wheezy breathing was 9.4, 27.7, and 23.2%, respectively. When compared with existing data, the prevalences are among the highest in other European countries. Also, data from different regions of our country such as Ankara, Istanbul, Eskisehir, Gaziantep, Trabzon, Izmir, Kayseri, Afyon, Adana, Sivas, and Kocaeli and from Turkish immigrants living in different European countries reveal asthma prevalences ranging between 0.3 and 54.1%. when

only the values belonging to population based studies made in Turkey are overviewed, the asthma prevalence ranges between 1.4 and 3%.10-28 There is a tendency of Turkish people to unite asthma and chronic obstructive pulmonary disease as if they are two parts of the same disease asthmatiform bronchitis. However, because the questionnaires were performed by trained interviewers, we think that the high prevalence of asthma in our city could not just be attributes to this limited tendency and the conflict in terminology. Moreover, the highest prevalence of childhood asthma detected by the International Study of Asthma and Allergies in Childhood protocol in Turkey, which is one of most important risk factors for adult asthma, has been reported from our city (14.8%).27 The high percent of women in our study may be another factor for the high asthma prevalence. This high ratio of women in the study group possibly may reflect the high ratio of employment among men in our country in contrast to women. Our attempts to have an equal number of subjects from both sexes, such as interviewing on weekends and at late hours, have failed. However, in logistic regression analysis sex failed to arise as a significant risk factor. Asthma prevalence was 25% in the second stage of the study. This value was between 1.2 and 13% in other countries.29 The difference in our results may be due to the high proportion of women and reluctance of asymptomatic subjects in participating in the second stage. Other potential problems may be subjective symptom recognition or recall and tendency o hide illnesses for social reasons. In the study of Celik et al., similarly, more than a twofold increase was observed in asthma prevalence in the second stage.18 In the second stage, atopy (total IgE > 100) was present in 46 subjects (31.1%). Specific IgE levels could not be measured because of financial problems. Skin test positivity for any allergen was detected in 43 subjects (29.05%). The median prevalence of skin test positivity for any allergen in other countries was 33.1% (16.2-44.5%).31 The prevalence of atopy and skin test positivity, such as the prevalence of asthma and nasal allergies, was high in our city. Because all of these pathologies may accompany each other, this finding was not a surprise. And in logistic regression, skin test positivity, allergic rhinitis, and history of paternal allergy were found to be the significant risk factors for the presence of asthma.