Abstract INTRODUCTION. Keywords: atopic asthma, children, fungus sensitization ORIGINAL ARTICLE

Transcription

1 ORIGINAL ARTICLE Fungus Sensitizations: Specific IgE to 4 Different Fungi among Asthmatic Children in North Taiwan Yu-Ting Yu, Shyh-Dar Shyur, Hwai-Chih Yang, Szu-Hung Chu, Yu-Hsuan Kao, Hou-Ling Lung, Wei-Te Lei, Li-Ching Fang, Chien-Hui Yang Department of Pediatrics, Mackay Memorial Hospital, Taipei, Taiwan Abstract Introduction: Asthma is the only well-documented IgE-mediated disease involving airborne fungal allergens. Increased asthmatic symptoms, hospitalization and emergency department visit have been reported after fungal exposure. This study aims to evaluate the characteristics of fungus sensitization in atopic asthmatic children. Material and Method: 109 asthmatic children aged 7 to 13 years with specific IgE positive to at least one of Dermatophagoides pteronyssinus, Dermatophagoides farinae, cat dander, dog dander and cockroach were included. Then data regarding specific IgE for Alternaria alternata, Candida albicans, Aspergillus fumigatus and Cladosporium herbarum, total IgE level, asthma severity, symptom score and pulmonary function parameters were analyzed. Result: Sensitization rate to least one of four fungi was 31.2%, and sensitized children had significant lower FVC% (96.20±15.63 v.s ±14.39; p=0.014) and non-statistically significant higher asthma symptom scores (4.85±2.72 v.s. 4.51±2.37; p=0.254), higher Log total IgE (2.60±0.57 v.s. 2.55±0.53; p=0.328), lower FEV1% pred. (92.07±18.72 v.s ±19.67; p=0.054) and lower FEF 25-75% pred. (52.10±19.68 v.s ±19.79; p=0.407). Dermatophagoides pteronyssinus and Dermatophagoides farinae sensitization degrees were moderate and severe (93/107, 86.92% v.s 94/107, 87.85%), but the other majority of antigens belong to mild sensitization (66.67%-100%). Children with C. albicans sensitization showed significant higher Log total IgE (2.79±0.44 v.s. 255±0.53; p =0.022) compared to children without any fungus sensitization. Conclusion: Prevalence of sensitization to at least one of four fungi in atopic asthmatic children of north Taiwan is 31.2%. In these children, lower FVC% was noted. Children with sensitization of C. albicans also showed statistically significant higher level of Log total IgE. (J Pediatr Resp Dis 2012;8: ) Keywords: atopic asthma, children, fungus sensitization INTRODUCTION Asthma is a common chronic inflammatory lung disease, and is a major public health problem. In Taiwan, prevalence of asthma has risen gradually in past 30 yr. 1-3 Fungal sensitization had been contributed to the persistence of active symptoms of asthma. However, Correspondence: Shyh-Dar Shyur, MD. Department of Pediatrics, Mackay Memorial Hospital, Taipei. 92, Sec. 2, Chung-Shan North Road, Taipei 104, Taiwan. Tel: Fax: abc1016@ms2.mmh.org.tw. Received: October 1, Accepted: November 19, Journal compilation 2012 Taiwan Society of Pediatric Pulmonology the precise prevalence of fungal sensitivity in atopic asthmatic patients is unclear. In previous reports from Europe and America, sensitization rate of fungus can be 12-80% among atopic patients and 20-25% among patients with persistent asthma requiring specialist referral. 4-7 Recent opinion recognized that sensitization to fungi is an important factor in patients with allergic respiratory tract diseases, playing a major role in the development, persistence, and severity of lower airway disease, particularly asthma. 5 Our study was aimed to evaluate both the prevalence and the related factors associated with fungus sensitization in atopic asthmatic children in north Taiwan. The correlation of the fungus

2 Yu YT, et al. sensitization with different aeroallergens sensitization was also investigated. METHODS All children aged 7-13 years with diagnosis of asthma with specific IgE positive to at least one of the five allergens including D. pteronyssinus, D. farinae, cat dander, dog dander and cockroach were enrolled in our pediatric outpatient clinic, Mackay Memorial Hospital, Taipei, Taiwan. The diagnosis of asthma was made according to guidelines of the Global Initiative for Asthma. The asthma disease severity was graded to mild intermittent, mild persistent, moderate persistent and severe persistent (Table 1). The symptoms score was assigned from 0 to the highest 16 points (Table 2). Pulmonary function tests were performed on all patients including assessments of the FEV1 (forced expiratory volume in 1 sec), FVC (forced vital capacity), FEV1/FVC (forced expiratory flow in 1 sec/forced vital capacity ratio) and FEF 25-75% (forced expiratory flow, 25-75%). All pulmonary-function tests were performed using the SensorMedics 2130 spirometer. Table1. Classification of asthma severity Severity Frequency of symptoms % predicted Variability Day Night FEV 1 /PEFR PEFR% Intermittent < 1/wk 2/m 80 < 20 Mild persistent 1/wk < 1/day > 2/m Moderate persistent 1/day 1/wk > 30 Severe persistent Frequent Frequent 60 > 30 Table2. Asthma Symptom Score Cough score (night time) 1= mild (cough was present but did not disturb sleep) 2= moderate (patient awoke once because of cough) 3= severe (patient awoke more than once because of cough) 4= extremely severe (patient experienced insomnia on most nights) Shortness of breath score (early in the morning) 1= mild (occasional shortness of breath that did not require medication) 2= moderate (occasional shortness of breath that required medication) 3= severe (frequent shortness of breath that required medication) 4= extremely severe (persistent shortness of breath that required multiple doses of medication) Wheeze or dyspnea score (day time) 1= mild (occasional wheeze) 2= moderate (occasional wheeze and dyspnea that did not disturb) 3= severe (persistent wheeze and dyspnea that hampered normal activities) 4= extremely severe (wheeze and dyspnea that left the patient totally unable to perform normal activities) Cough score (day time) 1= mild (occasional cough that did not disturb normal activities) 2= moderate (frequent cough that did not disturb normal activities) 3= severe (frequent cough that disturbed normal activities) 4= extremely severe (persistent cough) 113

3 Fungus sensitization in children In laboratory examinations, we checked serum total IgE and specific IgE to fungi including Alternaria alternata, Candida albicans, Aspergillus fumigatus and Cladosporium herbarum. The normal range of total IgE was less 100 IU/ml. The Pharmacia CAP system (Modal Auto-CAP V1 Pharmacia, Upssala, Sweden) was used to quantify specific IgE antibody concentration in the serum. The degree of hypersensitivity was classified according to concentrations of specific IgE: class 0 (< 0.35 kua/l), class1 ( kua/l), class 2 ( kua/l). class 3 ( kua/l), class 4 ( kua/l), class 5 ( kua/l), class 6 (>100 kua/l). Class 1-2 were categorized as mild, class 3-4 as moderate, class 5-6 as severe. Quantitative variables were compared using Student s t-test. The differences between groups were considered significant if p-values were smaller than Calculations were done using the Statistical Package for Social Science Software version 12 (SPSS, Chicago, Illinois, USA). Table 3. Gender Female 33/109 (30.28%) Male 76/109 (69.72%) Age (y/o) Min. 7 Max Mean±SD 9.5±1.7 Disease Severity Mild intermittent 6/109 (5.50%) Mild persistent 22/109 (20.18%) Moderate persistent 56/109 (51.38%) Severe persistent 25/109 (22.94%) Serum total IgE level (IU/ml) Mean±SD ± Table 4. House dust mites D. p D. f Cat dander Dog dander Fungus Cockroach C.herbarum A.fumigatus C.albicans A.alternata Class Class Class Class Class Class Class Positive result No: % 98.17% 98.17% 10.09% 11.01% 23.85% 7.34% 9.17% 22.94% 25.69% D. p: Dermatophagoides pteronyssinus D. f: Dermatophagoides farinae C. herbarum: Cladosporium herbarum A. fumigatus: Aspergillus fumigatus C. albicans: Candida albicans A. alternata: Alternaria alternata 114

4 Yu YT, et al. RESULTS A total of 109 asthmatic children with specific IgE positive to at least one of the five inhaled allergens, aged from 7 to 12.9 years (average 9.5 ±1.7 years) were enrolled. The ratio of boys to girls was 2.30:1. Table 3 presented the clinical characteristics and laboratory findings. The sensitized rates to the aeroallergens in asthmatic children tested on CAP tests. On CAP testing, the rates of sensitization to the allergens tested were presented in Table 4. The most prevalent sensitizations were D. pteronyssinus (107/109, 98.17%) and D. farinae (107/109, 98.17%), followed by A. alternata (28/109, 25.69%), cockroaches (26/109, 23.85%), C. albicans (25/109, 22.94%), dog danders (12/109, 11.01%), cat danders (11/109, 10.09%), A. fumigatus (10/109, 9.17%) and C. herbarum (8/109, 7.34%). A total of 31.2% (34/109) of patients were positive for at least one species of fungus. The degree of sensitization for D. pteronyssinus and D. farinae were moderate and severe(93/107, 86.92% v.s 94/107, 87.85%), but for the others majority of them belong to mild sensitization(cat dander 8/11, 72.73%; dog dander 8/12, 66.67%; cockroach 23/26, 88.46%; Alternaria alternate 28/28, 100%; Candida albicans 24/25, 96%; Aspergillus fumigatus 10/10, 100%; and Cladosporium herbarum 7/8, 87.5%). Characteristics of subjects with and without fungus sensitization There were no statistically significant differences among subjects with and without fungus sensitization with regard to sex or age. In children with sensitization to at least one of fungi, it had a trend of higher asthma symptom scores (4.85±2.72 v.s. 4.51±2.37; p=0.254), higher Log total IgE (2.60±0.57 v.s. 2.55±0.53; p=0.328), and lower performance in some sections of pulmonary function test (FEV1 % pred., 92.07±18.72 v.s ±19.67; p=0.054; FEF % pred., 52.10±19.68 v.s ±19.79; p=0.407). However, all these differences are not statistically significant. In children with sensitization to at least one of fungi, lower FVC% (96.20±15.63 v.s ±14.39; p=0.014) was noted significantly compared with children without fungal sensitization. (Table 5) Between the four fungal allergens, children with sensitization of C. albicans showed statistically significant higher level of Log total IgE (2.79±0.44 v.s. 255±0.53; p =0.022) compared to children without any fungus sensitization. DISCUSSION It is known that sensitivity to fungi, especially Alternaria and Cladosporium species, is associated with the development, persistence, and severity of atopic asthma. In addition, sensitivity to Aspergillus fumigatus has been associated with severe persistent asthma in adults. 5 Therefore, the importance of fungal allergen should be considered and included in the topic of indoor environment control for childhood asthma. Skin prick tests (SPTs) and serum specific IgE tests are used to determine sensitization to various fungi. In vitro measurement of specific IgE antibodies can be useful in patients with fungal sensitization. 8 In our study, the sensitization rate of any of four fungal allergens was 31.2% in atopic asthmatic children, which is comparable with previous studies. 4-7 Besides, a trend of higher asthma symptom scores, higher Log total IgE, and lower performance in some sections of pulmonary function test (FEV1, FEF 25-75%) were noted, but all of these are lacking of statistically significance. In previous studies 9-11 performed for the relationship between inhaled allergen sensitization and pulmonary function in children, sensitization to Altenaria or Aspergillus is often not related to statistically significant decrease in performance of FEV1 and FEF 25-75%, and the findings is compatible with the result of our study. However, these studies didn t report the performance of FVC% on children with fungus sensitization. Therefore, the finding of significant lower FVC% in children with fungal sensitization in this study still need further appropriate investigation. In our report, we also found these with sensitization of C. albicans showed statistically significant higher level of Log total IgE (2.79±0.44 v.s. 255±0.53; p =0.022). In conclusion, our study is the first report of investigating fungal allergens and other clinical parameters in atopic asthmatic children in north Taiwan. We found the prevalence of sensitization 115

5 Table 5. Clinical characteristics and laboratory findings C. Herbarum (N=8) A. fumigatus (N=10) C. Albicans (N=25) A. Alternata (N=28) Any fungus sensitization (N=34) Fungus sensitization in children No fungus sentitization (N=75) Age 9.95 ± ± ± ± ± ± Gender Female 2 (25%) 2 (20%) 7 (28%) 8 (28.57%) 10 (29.41%) 23 (30.67%) Male 6 (75%) 8 (80%) 18 (72%) 20 (71.43%) 24 (70.59%) 52 (69.33%) Log total IgE 2.83± ± ± ± ± ± Asthma severity Mild intermittent 0 (0%) 0 (0%) 1 (4%) 1 (3.57%) 1 (2.94%) 5 (6.67%) Mild persistent 1 (12.5%) 1 (10%) 4 (16%) 3 (10.71%) 5 (14.71%) 17 (22.67%) Moderate persistent 3 (37.5%) 4 (40%) 11 (44%) 13 (46.43%) 17 (50%) 39 (52%) Severe persistent 4 (50%) 5 (50%) 9 (36%) 11 (39.29%) 11 (32.35%) 14 (18.67%) Symptom score 5.38± ± ± ± ± ± Pulmonary function FVC% pred ± ± ± ± ± ± FEV1% pred ± ± ± ± ± ± FEV1/FVC 82.78± ± ± ± ± ± FEF 25-75% pred ± ± ± ± ± ± p to at least one of four fungi is up to 31.2%, which is comparable with studies from European and American countries. Besides, higher symptom scores and lower performance of some sections of pulmonary function test were found in patients with sensitization. These findings indicate that the role of fungal sensitization should not be underscored in atopic asthma of Taiwanese children. Further effort of detection of fungal sensitization, indoor environmental control of fungi (including tiled or clean walls, air conditioners, dehumidifiers and cleaning of carpets) 12 and treatment of associated respiratory tract diseases may give the chance of improving the symptoms or life quality in these sensitized individuals. REFERENCES 1. Chang YT, Hwang CY, Chen YJ, et al. Prevalence of Atopic Dermatitis, Allergic Rhinitis and Asthma in Taiwan: A National Study 2000 to Acta Derm Venereol 2010;90: Lee MF, Song PP, Hwang GY, Lin SJ, Chen YH. Sensitization to Per a 2 of the American cockroach correlates with more clinical severity among airway allergic patients in Taiwan. Ann Allergy Asthma Immunol 2012;108: Yeh KW, Fang W, Huang JL. Increasing the hospitalization of asthma in children not in adults - from a national survey in Taiwan Pediatr Allergy Immunol 2008;19: Ahluwalia SK, Matsui EC. The indoor environment and its effects on childhood asthma. Curr Opin Allergy Clin Immunol 2011;11: Knutsen AP, Bush RK, Demain JG, et al. Fungi and allergic lower respiratory tract diseases. J Allergy Clin Immunol 2012;129: Pasqualotto AC, Powell G, Niven R, Denning DW. The effects of antifungal therapy on severe asthma with fungal sensitization and allergic bronchopulmonary aspergillosis. Respirology 2009;14: Zock JP, Jarvis D, Luczynska C, Sunyer J, Burney P. Housing characteristics, reported mold exposure, and asthma in the European Community Respiratory Health Survey. J Allergy Clin Immunol 2002;110:

6 Yu YT, et al. 8. O Driscoll BR, Powell G, Chew F, et al. Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma. Clin Exp Allergy 2009;39: Benghida R, Ghezzo H, Malo JL. Sensitization to Aspergillus fumigatus and functional outcome of asthma. Rev Mal Respir 2007;24: Choi SY, Sohn MH, Yum HY, Kwon BC, Kim KE. Correlation between inhalant allergen-specific IgE and pulmonary function in children with asthma. Pediatr Pulmonol 2005; 39: Schwartz J, Weiss ST. Relationship of skin test reactivity to decrements in pulmonary function in children with asthma or frequent wheezing. Am J Respir Crit Care Med 1995;152: From the Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma Available from: 117