Aspergillus colonization increases with age in children with cystic fibrosis [1]. Prevalence of allergic bronchopulmonary aspergillosis (ABPA) ranges from 2% to 15%. Older age, poor nutritional status, atopy, use of inhaled antibiotics, inhaled corticosteroid, long-term azithromycin therapy, RhDNase therapy, and Pseudomonas infection are some risk factors [2]. Cystic fibrosis is increasingly being diagnosed in Indian sub-continent and there is paucity of data from the region.

This cross-sectional study was conducted in Pediatric chest clinic of All India Institute of Medical Sciences, New Delhi, India. The study was approved by the Institutional ethics committee. Informed written consent was taken. Clinical evaluation, spirometry, chest radiograph, sputum, total IgE, specific IgE for Aspergillus fumigatus, IgG precipitins and skin prick test (SPT) were done. ImmunoCAP test was used for estimation of total IgE, A. fumigatus specific IgE and common aeroallergen [3]. IgG precipitins were assayed by agar gel double diffusion method [4]. SPT was done using A. fumigatus extracts (All Cure Pharma Pvt. Ltd. Bahadurgarh, Haryana) [5].

Colonization with Aspergillus species was present in six (18.2%) patients. Fifteen (45.5%) patients were sensitized to A. fumigatus. Six patients were diagnosed as ABPA by minimal diagnostic criteria giving prevalence of 18.2% (95% CI 6.9% - 35.4%). Out of six ABPA diagnosed patients, 3 were in acute stage, 2 in exacerbation and 1 in remission [10].

Table I compares the clinical and investigational profile of children diagnosed to be having ABPA with those not having it. ABPA was more often seen in patients with low CF score, age >12 years, reversibility after bronchodialator, atopy, and eosinophilia. Patient with ABPA had a trend towards lower FEV1 and FVC. Immediate skin reactivity to A. fumigatus was seen in 14 patients. Measures of correlation between IgE specific for A. fumigatus and skin prick test showed no discordance. There was 87.5% agreement between the two tests with a kappa value of 0.74. A similar agreement (85.4%; kappa 0.68) was seen between total serum IgE level (>500) and IgE specific for Aspergillus fumigatus (>3.5 KU). IgG precipitins were negative in all patients.

TABLE I Comparison of Risk Factors Between ABPA and Non-ABPA Group

Aspergillus species causing illness in children with CF has a wide spectrum ranging from ABPA, colonization, IgE sensitization and chronic bronchitis [7]. IgE sensitization of aspergillus is associated with a more rapid decline of pulmonary function [8]. Colonization of A. fumigatus is frequent with reported prevalence of 40% but only 1% to 11% may develop ABPA [1]. Though there is increasing recognition of CF in India, there is paucity of information about Aspergillus in children with CF [11]. We observed prevalence of colonization and ABPA in 6 (18.2%) patients each in CF. ABPA was more often seen in patients with low CF score, age >12 years, airway reversibility, atopy, and high eosinophil count.

Various studies from Europe and United States have reported prevalence of ABPA ranging from 2%-15% [12-14]. The high prevalence of ABPA in our study may be due to low BMI, regular use of azithromycin and ICS or frequent requirement of antibiotics for pulmonary infections. Lower colonization rate (18%) with aspergillus in present study could be because of stringent criteria of two sputum samples collected on two consecutive days were positive instead of two positive cultures over a period of one year used in other studies [8].

There was statistically significant correlation between SPT and IgE specific A. fumigatus indicating that SPT can be reliably done in screening for ABPA in resource limited countries.

In our study, none of the patients had positive test for precipitins. Such negative results were seen in two previous studies [7,14], which can be due to less potent antigens or poor IgG response.

Limitations of present study include: diagnosis of bronchiectasis by X-ray rather than high resolution CT scans, and use of IgG precipitins rather than IgG anti-Af ELISAs [15] Present study provides data on different aspects of Aspergillus infection in children with CF from India.

Acknowledgements: SRL diagnostics, India for performing the assays for total and specific IgE.

Contributors: VK and DR: conceived and designed the study, data collection and analysis; VK: drafted the initial manuscript. DR, RL and SK: revision of manuscript and data analysis. IX: microbiological and serological investigations; SK: revised the manuscript for important intellectual content. He will act as guarantor of the study. All authors approved the final manuscript.

Funding: None; Competing interest: None stated.