Asthma, a chronic inflammatory airway disorder, is one of the most prevalent respiratory conditions in children worldwide, affecting an estimated 10–15% of this population. It is characterized by reversible airflow obstruction, airway hyperresponsiveness, and persistent inflammation. While asthma itself poses significant challenges in terms of morbidity and quality of life, its association with certain pulmonary complications further exacerbates disease outcomes. One such complication is Allergic Bronchopulmonary Aspergillosis (ABPA), a hypersensitivity reaction to the fungus Aspergillus fumigatus.

ABPA is an immunologically mediated condition resulting from a complex interplay between a genetically predisposed host and environmental exposure to Aspergillus fumigatus. This ubiquitous saprophytic fungus colonizes the airways and triggers an exaggerated immune response in susceptible individuals. The resulting immune cascade leads to tissue damage, central bronchiectasis, and progressive lung impairment if untreated. Although ABPA is commonly associated with adult populations, emerging evidence indicates that children with asthma are also at significant risk, with potentially severe long-term sequelae if the condition is not diagnosed and managed promptly.

The diagnosis of ABPA in children presents unique challenges. The clinical presentation often mimics uncontrolled asthma, characterized by persistent cough, wheezing, recurrent pulmonary infiltrates, and, occasionally, hemoptysis. Laboratory markers such as elevated total IgE levels, Aspergillus fumigatus-specific IgE, peripheral eosinophilia, and positive serum precipitins are critical in confirming the diagnosis. Radiological imaging, particularly high-resolution computed tomography (HRCT) of the chest, reveals hallmark features like central bronchiectasis and high-attenuation mucus plugging. Despite these diagnostic advances, ABPA remains underdiagnosed in resource-limited settings, including India, due to limited awareness and accessibility to specialized diagnostic tools.

The management of ABPA in children revolves around reducing inflammation, mitigating fungal colonization, and preventing disease progression. Systemic corticosteroids remain the mainstay of therapy, often combined with antifungal agents like itraconazole to reduce fungal load. However, treatment outcomes are variable, with relapses frequently reported, necessitating long-term monitoring and individualized therapeutic approaches. In recent years, biologics such as omalizumab and dupilumab have shown promise in refractory cases, although their utility in pediatric populations remains to be fully established.

In India, where the burden of respiratory diseases is disproportionately high due to environmental factors like air pollution, biomass fuel exposure, and overcrowding, the prevalence and impact of ABPA in children with asthma are not well-documented. Most of the existing literature focuses on adult populations or single-center studies, leaving a significant gap in understanding the pediatric spectrum of the disease.

This multicenter study aims to address these gaps by evaluating the clinical manifestations, diagnostic findings, and therapeutic outcomes of ABPA in children with asthma across three tertiary care hospitals in India. By analyzing data from diverse geographic and demographic settings, the study seeks to provide insights into the burden of ABPA in the Indian pediatric population, identify challenges in diagnosis and management, and propose strategies for improving outcomes.

METHODS

This prospective observational study was conducted at three tertiary care hospitals located across India over a period of three years, from January 2020 to December 2023. The study focused on children aged 6 to 18 years who were diagnosed with asthma and met the diagnostic criteria for Allergic Bronchopulmonary Aspergillosis (ABPA) based on the Rosenberg-Patterson criteria. Children with cystic fibrosis or other chronic pulmonary diseases were excluded from the study.

Data collection encompassed several domains. Clinical parameters were recorded, including symptoms such as chronic cough, wheezing, fever, and hemoptysis, as well as the overall control of asthma. Laboratory investigations included measurements of serum total IgE levels and Aspergillus fumigatus-specific IgE, peripheral eosinophil counts, and sputum cultures to detect Aspergillus fumigatus. Radiological assessments were performed using high-resolution computed tomography (HRCT) of the chest to identify features such as central bronchiectasis, pulmonary infiltrates, and high-attenuation mucus plugging. Treatment outcomes were monitored over a six-month period, focusing on the response to corticosteroids and itraconazole therapy.

Statistical analysis was conducted using SPSS software (version 25). Continuous variables were expressed as mean ± standard deviation (SD), while categorical variables were presented as percentages. Descriptive and inferential statistics were employed to analyze the data and identify significant patterns or correlations within the study population.

Statistical Analysis

Descriptive and inferential statistics were performed using SPSS (version 25). Continuous data were presented as mean ± SD, and categorical data as percentages.

RESULTS

Demographic and Clinical Features

A total of 120 children were included in the study. The demographic and clinical characteristics are summarized in Table 1.

Table 1. Demographic and Clinical Characteristics of Study Population

The bar graph summarizes the prevalence of symptoms in the study population. The percentages correspond to the values from Table 1.

Laboratory Findings

Laboratory data are summarized in Table 2.

Table 2. Laboratory Characteristics of ABPA Cases

The horizontal bar graph summarizes the laboratory characteristics of ABPA cases from Table 2.

Radiological Findings

HRCT findings revealed the following abnormalities (Table 3).

Table 3. HRCT Chest Findings in ABPA Cases

Treatment Outcomes

Treatment outcomes are summarized in Table 4.

Table 4. Treatment Outcomes

DISCUSSION

Allergic bronchopulmonary aspergillosis (ABPA) is a significant, though often underrecognized, complication in children with asthma. This study provides valuable insights into the clinical manifestations, diagnostic features, and management outcomes of ABPA in a pediatric population across three tertiary hospitals in India. By comparing our findings with previous studies, we aim to better understand the clinical spectrum of ABPA and evaluate its management in the Indian context.

Clinical Manifestations

In our study, the most common symptoms reported were chronic cough (100%), wheezing (87.5%), and recurrent fever (71%), with hemoptysis observed in 33% of children. These symptoms are consistent with those reported in other studies, which suggest that ABPA in children frequently presents with upper and lower respiratory tract manifestations similar to uncontrolled asthma. For instance, a study by Agarwal et al. (2013) reported that cough and wheezing were the predominant presenting symptoms, observed in nearly 90% of their pediatric ABPA cases. The presence of hemoptysis, although less common, has been identified as a more specific feature of ABPA and was noted in 22–40% of pediatric cases in previous reports (Shah et al., 2016). This finding highlights the variability of ABPA presentation, where children may exhibit diverse clinical features, often overlapping with exacerbations of asthma.

A key challenge in diagnosing ABPA in children with asthma lies in the overlap of symptoms with those of poorly controlled asthma. Therefore, a high index of suspicion is essential, especially in children with poorly responsive asthma or those who exhibit atypical symptoms such as recurrent pulmonary infiltrates or persistent fever, which were seen in 70% and 71% of our study cohort, respectively. The study by Stevens et al. (2003) also reported that recurrent pulmonary infiltrates were a common finding in ABPA, correlating with increased airway inflammation and the presence of Aspergillus fumigatus in the airway. These findings suggest that clinicians must consider ABPA in children with asthma who do not respond adequately to standard asthma treatment.

Laboratory Findings

Our study found that all children with ABPA had elevated total serum IgE levels (mean 4,500 IU/mL), which is consistent with the literature, where high total IgE levels are a hallmark of ABPA. In a study conducted by Diba et al. (2020), elevated total IgE levels were found in nearly 95% of children with ABPA. Total IgE levels above 1,000 IU/mL are typically considered diagnostic for ABPA when accompanied by clinical features. Notably, 77% of our cohort also exhibited eosinophilia (eosinophil count >500 cells/µL), further supporting the immunological nature of the disease. Elevated eosinophil counts are commonly observed in ABPA due to the allergic and inflammatory response to Aspergillus fumigatus antigens, as also reported by Agarwal et al. (2013).

The diagnosis of ABPA is further supported by the detection of specific IgE antibodies to Aspergillus fumigatus, which were positive in all study participants. This finding aligns with previous studies that emphasize the diagnostic utility of Aspergillus fumigatus-specific IgE in confirming ABPA. The presence of specific IgE is a strong indicator of sensitization to Aspergillus and is generally regarded as an essential component of the diagnostic criteria for ABPA. Furthermore, sputum culture positivity for Aspergillus fumigatus was noted in 37.5% of cases, a finding that is lower than in some other studies. For instance, a study by Batta et al. (2015) reported sputum culture positivity in up to 60% of pediatric ABPA cases. This discrepancy may be due to the variation in the sensitivity of sputum cultures and the possibility that many patients were not actively colonized by the fungus at the time of sampling.

Radiological Findings

Radiological investigations, particularly HRCT, are crucial in diagnosing ABPA. In our cohort, central bronchiectasis was observed in 55% of children, and recurrent pulmonary infiltrates were seen in 70%. These findings are consistent with other studies, such as the one by Casserly et al. (2014), which reported central bronchiectasis in 50–60% of pediatric ABPA cases. Central bronchiectasis, in particular, is considered a characteristic feature of ABPA, reflecting long-standing airway damage due to chronic inflammation and fungal colonization. In contrast, non-specific radiological findings such as atelectasis or consolidation can be seen in other respiratory infections, making it essential to differentiate ABPA from other causes of pneumonia or asthma exacerbations.

High-attenuation mucus plugging, another common finding in ABPA, was observed in 37.5% of our patients. The presence of this finding has been linked to fungal colonization and mucus hypersecretion, which obstructs airways and exacerbates symptoms (Stevens et al., 2003). This feature can be particularly useful in differentiating ABPA from other causes of chronic cough or asthma exacerbation, providing a more direct indication of fungal involvement.

Management and Treatment Outcomes

In this study, systemic corticosteroids and itraconazole were the primary treatment modalities for ABPA. Corticosteroids successfully managed acute symptoms in 78% of patients, with a similar response rate seen in other studies such as the one by Shah et al. (2016), where corticosteroids provided symptom relief in 70–80% of pediatric ABPA cases. Itraconazole, used as an adjunctive therapy to control fungal colonization, had a positive response in 77% of cases. The combination of systemic corticosteroids and antifungals remains the standard treatment for ABPA, as these therapies address both the inflammatory and fungal components of the disease.

However, despite initial treatment success, a relapse rate of 22% was observed in our cohort, which is consistent with findings from other studies. In a study by Diba et al. (2020), a similar relapse rate of 20% was reported in pediatric ABPA cases following corticosteroid treatment. Relapses are commonly attributed to the chronic nature of ABPA and the tendency for Aspergillus fumigatus to persist in the airways despite treatment. This highlights the importance of long-term monitoring and possibly maintenance therapy in children with ABPA to prevent recurrent episodes.

While corticosteroids and antifungal agents are effective, newer therapies, including biologics like omalizumab (an anti-IgE antibody) and dupilumab (an anti-IL-4/IL-13 monoclonal antibody), have shown promise in managing refractory ABPA, particularly in adults. Their role in pediatric ABPA remains an area of ongoing research, and studies comparing biologics with conventional therapies are eagerly awaited.

Comparative Analysis and Implications for Practice

When comparing our findings with the global literature, it becomes clear that ABPA remains underdiagnosed and undertreated in many regions, especially in low- and middle-income countries like India. In settings with limited diagnostic infrastructure, the reliance on serum IgE levels and radiological findings is crucial in identifying this condition. However, our study emphasizes the need for heightened awareness among clinicians, particularly pediatric pulmonologists and allergists, to recognize ABPA early and initiate appropriate treatment.

Additionally, this study highlights the importance of a multidisciplinary approach in managing ABPA, involving pediatricians, pulmonologists, microbiologists, and immunologists. Early referral to specialized centers for confirmatory testing and treatment initiation can significantly improve outcomes, as evidenced by the relatively high success rates of corticosteroid and itraconazole therapy in our cohort.

This multicenter study highlights the significant burden of ABPA in children with asthma, underlining the need for increased clinical vigilance and early intervention to prevent long-term pulmonary damage. The combination of clinical, laboratory, and radiological findings remains the cornerstone of ABPA diagnosis. Although conventional therapies like corticosteroids and itraconazole are effective in managing symptoms and preventing complications, the high relapse rate suggests a need for long-term management strategies and consideration of newer treatment options. Further research on the role of biologics and maintenance therapies is essential for improving outcomes in pediatric ABPA.

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