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Allergic Bronchopulmonary Aspergillosis As a Cause of Bronchial Asthma in Children

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Allergic Bronchopulmonary Aspergillosis As a Cause of Bronchial Asthma in Children Egypt J Pediatr Allergy Immunol 2012;10(2):95-100. Original article Allergic bronchopulmonary aspergillosis as a cause of bronchial asthma in children Background: Allergic bronchopulmonary aspergillosis (ABPA) occurs in Dina Shokry, patients with asthma and cystic fibrosis. When aspergillus fumigatus spores Ashgan A. are inhaled they grow in bronchial mucous as hyphae. It occurs in non Alghobashy, immunocompromised patients and belongs to the hypersensitivity disorders Heba H. Gawish*, induced by Aspergillus. Objective: To diagnose cases of allergic bronchopulmonary aspergillosis among asthmatic children and define the Manal M. El-Gerby* association between the clinical and laboratory findings of aspergillus fumigatus (AF) and bronchial asthma. Methods: Eighty asthmatic children were recruited in this study and divided into 50 atopic and 30 non-atopic Departments of children. The following were done: skin prick test for aspergillus fumigatus Pediatrics and and other allergens, measurement of serum total IgE, specific serum Clinical Pathology*, aspergillus fumigatus antibody titer IgG and IgE (AF specific IgG and IgE) Faculty of Medicine, and absolute eosinophilic count. Results: ABPA occurred only in atopic Zagazig University, asthmatics, it was more prevalent with decreased forced expiratory volume Egypt. at the first second (FEV1). Prolonged duration of asthma and steroid dependency were associated with ABPA. AF specific IgE and IgG were higher in the atopic group, they were higher in Aspergillus fumigatus skin Correspondence: prick test positive children than negative ones .Wheal diameter of skin prick Dina Shokry, test had a significant relation to the level of AF IgE titer. Skin prick test Department of positive cases for aspergillus fumigatus was observed in 32% of atopic Pediatrics, Faculty of asthmatic children. Conclusion: ABPA occurs in 1/3 of atopic asthmatic Medicine, Zagazig children and is related to the duration and severity of asthma. University, Egypt. E-mail: dinaa1111@ Keywords: Aspergillosis, bronchial asthma, children. yahoo.com condition under which aspergillus fumigatus INTRODUCTION colonizes the respiratory tract in patients Allergic bronchopulmonary aspergillosis (ABPA) developing ABPA is a factor associated with the 7 was first reported in England during 19521, since pathophysiology of the disease . then a number of cases have been diagnosed and Improved diagnostic methods and awareness reported from many countries2,3. This pulmonary have led to recent reports of higher prevalence of disorder arises from an allergic response to multiple ABPA in patients suffering from chronic asthma (1- antigens expressed by aspergillus fumigatus4. In 40%) and 7-15% of cystic fibrosis (CF) 8,9,10 temperate climates, aspergillus is one of the patients . ABPA leads to poorly controlled common indoor allergens responsible for asthma. asthma with pulmonary exacerbations and Swimming pools and basements that are moist and detrimental consequences; dependence on oral- humid for prolonged periods of time harbor these corticosteroids increases the risk for secondary 11 fungi. ABPA may develop in individuals with infections . In rare cases, ABPA disease has also episodic obstructive lung disease such as asthma been reported to complicate other lung diseases and cystic fibrosis that produce thick tenacious including idiopathic bronchiectasis, chronic 6,12,13 sputum5. The factors underlying the development of obstructive pulmonary disease (~38%) . ABPA remain unclear. The role of genetic factors, Moreover, ABPA has also been reported in patients mucous quality, preactivation of epithelial cells and with pulmonary aspergilloma and chronic 14 the extent to which this activation facilitates the necrotizing pulmonary aspergillosis . The development of aspergillus spores into hyphae, prevalence of AF hypersensitivity is even higher in 15 bronchial penetration of aspergillus, the immune patients with acute severe asthma (~51%) . response and bronchiolar inflammation that leads to Aspergillus fumigatus-sensitized asthmatic patients 16,17 destruction are not yet fully understood6. The have been reported to have poor lung function . 95 Shokry et al. It has been noted that proteases activate as chest infection. Pulmonary function tests to protease activated receptors (PARs) which are G- prove the diagnosis and assess the severity of protein coupled receptors present on the airway asthma as FEV1 ≥80%: intermittent or mild asthma, cells and other cells such as mast cells, eosinophils, 60-80%: moderate asthma, <60%: severe asthma25. neutrophils, macrophages and lymphocytes18. To The apparatus used was master screen Viasys date, four PARs have been identified; PAR-2 is the Health Care GmBh, Germany. most important in allergic airway disease owing to Stool analysis was done to exclude parasitic its increased expression on the airways of asthmatic infestations. Chest x-rays were obtained as needed. patients19. Interestingly, injured airway epithelial Skin prick test for all children, absolute cells also secrete trypsin, a PAR-2 agonist that eosinophilic count, serum total IgE and specific further aggravates allergic inflammatory responses. serum anti fumigatus IgE and IgG were done. Genetic association studies have shown that All sera were tested for AF specific antibodies polymorphisms in the SP-A and MBL gene lead to using UniCAP 100 assay (CAP; Pharmacia/Upjohn, a predisposition to develop ABPA19,20. ABPA can Kalamazoo, MI). A.fumigatus total extract and occur at any age in individuals with atopy. Patients recombinant AF allergens Asp f1, f2, f3, f4, and f6 have recurrent episodes of asthma exacerbation coupled ImmunoCAPs were used to detect specific with wheezing and chest infiltrates. They have IgE in the sera, according to the protocol systemic manifestations such as fever, malaise and recommended by the manufacturer. An anorexia. Sputum production is characterized by ImmunoCAP class of 1 or more (35 mgA/L) was chunks of green or beige colored sputum plugs. considered to be positive. The same lot of Mucus plugging results in partial obstruction of ImmunoCAPs and reagents were used for all the airways leading to bronchiectasis as a study26,27,28. complication21. Allergy skin test Reagents: Allergen 8 Coca's extracted allergens METHODS were used, saline (0.9% NaCl) was used as a This study was carried out at the Pulmonology Unit, negative control and histamine (histamine acid Pediatric Department and at Allergy and phosphate 1 mg/ml) was used as a positive control. Immunology Unit, Microbiology Department, For the intradermal skin test, 1/1000 W/V (100 µl Zagazig University during the period from of 1/10 W/V of diluted extract to 9900 µl saline) of 29 September 2008 to October 2011. diluted extract was used . The allergens used were: This study included 80 asthmatic children house dust, human hair, smoke, wool, cotton, mixed diagnosed according to National Asthma Education fungi (Aspergillus niger, Aspergillus flavus, and and Prevention Programme 22. Their ages ranged Aspergillus fumigatus), mixed pollens and hay dust. from 3 to 14 years. The severity of asthma was The procedure of skin intradermal test: The classified according to GINA guidelines for asthma skin of the volar surface of the forearm was cleaned severity23,24. and marked, 0.1 ml of 1/1000 dilution of each Asthmatic children were divided into: Group extract, negative and positive controls were injected (1): Fifty atopic children according to positive intradermally; after15 minutes the tested sites were family history, history of atopy to a specific inspected. Fully developed erythema and wheal allergen, positive skin prick test to one or more reactions were remeasured after 30 minutes. The allergens, eosinophilia and elevated IgE level and mean wheal size was represented as (X + x)/2 (X is Group (2): Thirty non- atopics diagnosed by the maximum diameter, and x is the perpendicular exclusion of atopy, precipitation of asthma by diameter). Mean wheal size of greater than or equal 30 exercise, cold air or hormonal changes. Informed to 3 mm was regarded as positive . No consents were taken from the parents or care-givers antihistamines were taken in the last 48 hours prior of all children. to the test, so as not to affect the result. Exclusion criteria were: Children with parasitic Serum Total IgE infestations, or those taking any medication other It was measured using RIDASCREEN® 31 than anti-asthma drugs and children with Spezifisches IgE kit by EIA technique . Analytical immunocompromised disorders. sensitivity and specificity of the kit were 0.24 IU/ml The following were done: History taking to and 91.2% respectively. find if there was positive family history of asthma, assess asthma severity and differentiate between Statistical analysis atopic and non-atopic asthmatics. Thorough clinical Data were presented as mean ± standard deviation examination to exclude any other cause of distress (X± SD), median and range or percentage (%). All 96 ABPA and asthma in children statistical comparisons were performed using the positive which represented (32%). Total IgE, student's t test, X2, Z test, Fisher's exact test and specific IgE (AF), IgG (AF) and eosinophilic count Kruskal-Wallis H test. Data were checked and were statistically higher in the atopic group (table analyzed using Statistical Package of Social 1). SPT AF positive cases were associated with Science (SPSS) for windows version 8. P values prolonged duration of asthma. History of steroid less than 0.05 were considered
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