Cystic fibrosis complicated by allergic bronchopulmonary aspergillosis in a Chinese adolescent: a case report and literature review
Yuhai Dang1#
, Zhenfeng Deng2#, Ke Wang1, Jin Luo1, Chao Wang1, Feiyang Long1, Jinliang Kong1
Contributions: (I) Conception and design: Y Dang; (II) Administrative support: J Kong; (III) Provision of study materials or patients: J Luo, K Wang; (IV) Collection and assembly of data: C Wang, F Long; (V) Data analysis and interpretation: Z Deng; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.
#These authors contributed equally to this work.
Background: Cystic fibrosis (CF) predisposes patients to allergic bronchopulmonary aspergillosis (ABPA). The objective of this study is to enhance the recognition of CF-related ABPA (CF-ABPA) in adolescents through a detailed case study. A multidisciplinary management approach is essential. Early diagnosis and intervention could substantially improve outcomes, warranting further longitudinal research on optimized treatment protocols.
Case Description: A 15-year-old patient presenting with persistent respiratory symptoms underwent a series of diagnostic tests, including serum immunoglobulin E (IgE) testing, chest computed tomography (CT), bronchoscopy, bronchoalveolar lavage metagenomic next-generation sequencing (mNGS), and whole-exome sequencing to identify CFTR mutations. The diagnostic findings revealed markedly elevated serum IgE levels (2,359.0 IU/mL), the presence of bronchiectasis with mucus plugging on CT imaging, and mNGS detection of Aspergillus fumigatus with an abundance of 97.28%. The diagnosis of CF-ABPA was confirmed by identification of a pathogenic CFTR mutation. Later antifungal therapy and corticosteroids produced notable clinical improvement.
Conclusions: CF was under-recognized historically, but this case shows that it is a clinically important cause of bronchiectasis and ABPA in Chinese adolescents. The identification of Aspergillus was accurate with the mNGS. Genetic test confirmed that the subject is a CF patient with compound heterozygous mutations in CFTR gene. The finding urges the clinician to have a high index of suspicion for the CF-ABPA in those with asthma-like refractory symptoms with structural lung disease. When diagnosed early and accurately, antifungal therapy and inhaled corticosteroids can be administered timely. The patient experienced a notable improvement both clinically and radiologically, as well as functionally. The future work should promote awareness of this clinical entity and systematic screening of similar patients in China. Further multicenter studies are necessary to formulate diagnostic and therapeutic guides for CF-ABPA in Asia.
Keywords: Cystic fibrosis (CF); allergic bronchopulmonary aspergillosis (ABPA); adolescent; whole-exome sequencing; case report
Received: 08 July 2025; Accepted: 09 October 2025; Published online: 22 January 2026.
doi: 10.21037/acr-2025-175
Highlight box
Key findings
• A 15-year-old Chinese male with chronic respiratory symptoms was diagnosed with cystic fibrosis (CF) complicated by allergic bronchopulmonary aspergillosis (ABPA).
• Genetic testing identified compound heterozygous pathogenic mutations in the CFTR gene (c.1210-11delinsGTG and c.1210 11T>G).
• Metagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid detected Aspergillus fumigatus with 97.28% relative abundance.
• Combination therapy with voriconazole and inhaled corticosteroids/bronchodilators led to rapid clinical and radiological improvement.
What is known and what is new?
• CF is historically underrecognized in China. ABPA is a known complication in CF patients, often presenting with asthma-like symptoms and bronchiectasis.
• This case highlights the feasibility and diagnostic importance of combining mNGS for pathogen identification and whole-exome sequencing for CFTR analysis in the Chinese adolescent population. It also demonstrates that CF should be considered in Chinese patients with bronchiectasis and ABPA, even in the absence of a typical CF phenotype or family history.
What is the implication, and what should change now?
• There is a critical need to enhance physician awareness of CF and CF-related ABPA in non-Caucasian populations, especially among adolescents with unexplained bronchiectasis or refractory asthma.
• Routine screening for Aspergillus sensitization and early genetic testing for CFTR mutations should be integrated into the diagnostic workflow for such patients in China.
• A multidisciplinary management approach is essential, and future efforts should focus on generating real-world evidence for CFTR modulator efficacy in Chinese-specific mutations.
Introduction
Cystic fibrosis (CF) occurs because of mutations in a gene called CFTR that causes abnormal secretions in the lung and digestive system (1). One complication which may arise in CF is allergic bronchopulmonary aspergillosis (ABPA). It can occur in 10–15% of patients (2). ABPA occurs when there is a hypersensitive reaction to Aspergillus, which causes damage in the lung and often leads to bronchiectasis (3). A 15-year-old boy with CF-related ABPA (CF-ABPA) might have presented as an asthmatic (4,5). The patient who presented with a sputum cough and wheezing was diagnosed with a CFTR mutation and Aspergillus sensitization (6). The importance of timely diagnosis of ABPA in CF patients is to avoid accelerated decline in lung function (7). The case shows the benefit of genetics and specialist consultation in CF-ABPA, allowing CF to be considered a main differential in a young case of bronchiectasis having features of ABPA, especially when treatment for asthma is not effective. We present this article in accordance with the CARE reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-175/rc).
Case presentation
A 15-year-old boy was evaluated for having a cough, sputum, and asthma for three months. He had cough attacks with yellow white sputum and yellow plugs, exertional dyspnea and fatigue. Notably, he lacked fever, night sweats, or chest pain. Previous treatment for asthma and acute bronchitis at another facility had only temporary relief.
Clinical findings
Serology: significantly elevated total immunoglobulin E (IgE). Imaging of the chest computed tomography (CT) showed bronchiectasis localized centrally in the left upper lobe and basal segments of the left lower lobe along with bronchovascular bundle thickening (Figure 1).
Laboratory results
Key findings are summarized in the table below (Table 1).
Table 1
| Variable | Reference range, children† | On presentation, The First Affiliated Hospital of Guangxi Medical University |
|---|---|---|
| Hematology | ||
| Hemoglobin (g/dL) | 11.2–14.5 | 10.3 |
| Hematocrit (%) | 34.3–43.0 | 32.0 |
| Mean corpuscular volume (fL) | 78.3–87.7 | 71.4 |
| White-cell count (per mm3) | 4,000–10,000 | 9,720 |
| Neutrophils (per mm3) | 1,960–5,690 | 3,370 |
| Lymphocytes (per mm3) | 1,790–3,730 | 1,960 |
| Eosinophils (per mm3) | 50–410 | 450 |
| Platelet count (per mm3) | 205,000–376,000 | 467,000 |
| Blood chemistry | ||
| Albumin (g/dL) | 3.3–5.0 | 2.4 |
| Globulin (g/dL) | 1.9–4.1 | 4.3 |
| Erythrocyte sedimentation rate (mm/h) | 45–115 | >130 |
| C-reactive protein (mg/liter) | 0.0–8.0 | 40.1 |
| Ferritin (μg/liter) | Variable | 320 |
| Immunology & serology | ||
| Total IgE (IU/mL) | 0–200 | 2,359.0 |
| Aspergillus fumigatus-specific IgE (IU/mL) | <0.35 | 1.52 |
| Aspergillus fumigatus-specific IgG (AU/mL) | <11.405 (male) | 147.97 |
| Pulmonary function tests | ||
| FEV1 (L) | Age/height predicted | 4.2 |
| FEV1/FVC (%) | >80% | 68.67 |
| MEF25% (% predicted) | >60% | 32 |
| MEF50% (% predicted) | >60% | 50.7 |
†, Reference ranges for children follow the Chinese Pediatric Society’s expert consensus on ABPA and CF diagnosis. ABPA, allergic bronchopulmonary aspergillosis; AU, antibody unit; CF, cystic fibrosis; FEV1, forced expiratory volume in the first second; FVC, forced vital capacity; IgE, immunoglobulin E; IgG, immunoglobulin G; IU, international unit; MEF, maximum expiratory flow.
Pathogens & bronchoscopy: we found that there was purulent bronchial inflammation (Figure 2). Histology revealed chronic inflammation with lymphocytic infiltration, rare eosinophils and fungal hyphae (Figure 3). The metagenomic next-generation sequencing (mNGS) identified 97.28% fumigatus relative abundance (Figure 4).
The gene responsible for CF, CFTR is located on chromosome 7 (chr7:117188684). Whole-exome sequencing analysis of the patient showed disease-causing mutations in both alleles. The mutations NM_000492.4 (CFTR): c.1210-11delinsGTG (maternal) and NM_000492.4 (CFTR): c.1210 11T>G (paternal) confirm CF.
Diagnosis
CF-ABPA.
Management & outcome
Initially prescribed voriconazole, montelukast, and inhaled budesonide. After the CF-ABPA diagnosis, we changed the treatment to voriconazole and inhaled budesonide/formoterol. Clinical improvement was evident within 1 week. At the time of discharge (August 9, 2022) as well as at 1- and 3-month follow-ups, there were declining total IgE and eosinophil counts, improved forced expiratory volume in the first second/ forced vital capacity (FEV1/FVC), and a radiological resolution of sputum plugging (Figure 1B,1C), and a gradual reduction in both sputum plugs/purulent secretions and airway inflammation observed during subsequent bronchoscopies (Figure 2B,2C). There were no adverse effects as bronchoalveolar lavage fluid cultures were repeatedly negative.
All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the ethics board of The First Affiliated Hospital of Guangxi Medical University (No. 2024-E105-01). Written informed consent was obtained from the patient and his legal guardian for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Discussion
CF, an autosomal recessive disorder caused by mutations in the CFTR gene, has historically been underrecognized in China. Recent epidemiological studies challenge this perspective, estimating a carrier frequency of 1 in 127 and a potential disease prevalence of 1 in 64,000 in the Chinese population (2,6). The case of a 15-year-old boy with CF-ABPA illustrates this emerging pattern and demonstrates the complex diagnostic pathway typically initiated by respiratory symptoms. The clinical and genetic profile of Chinese CF patients exhibits distinct characteristics, including greater allelic heterogeneity compared to Caucasian populations (1,3,5). The patient’s presentation of chronic cough, bronchiectasis, and asthma-like symptoms that are refractory to conventional therapy represents a classic scenario that often masks underlying CF. High-resolution CT findings revealing bronchiectasis with bronchial wall thickening correspond with documented features in young CF patients (7). Diagnostic confirmation necessitated multiple approaches: markedly elevated total IgE prompted genetic testing, which revealed compound heterozygous CFTR mutations, while mNGS identified Aspergillus fumigatus. This case underscores the need to consider CF in adolescents presenting with bronchiectasis and ABPA, as misdiagnosis as asthma or bronchitis remains a significant concern. This study acknowledges the limitations of proband-only genetic analysis without familial segregation. Future family studies are essential to establish genotype-phenotype correlations and enhance genetic counseling for CF-ABPA patients.
ABPA, a complication of CF characterized by hypersensitivity to Aspergillus fumigatus, meets established international diagnostic criteria (3,8). While global prevalence estimates range from 7% to 9%, Chinese cohorts may demonstrate higher rates (8,9). The pathogenesis involves defective CFTR function and exaggerated immune responses to fungal antigens (10). The conclusive role of mNGS in diagnosing this case, despite negative microbiological tests, underscores the growing importance of molecular diagnostics in complex respiratory conditions. This study primarily focused on diagnosing ABPA as an allergic disease rather than an invasive Aspergillus infection. Consequently, mNGS was primarily utilized to confirm the presence of Aspergillus fumigatus as an allergen, acknowledging that the detection threshold has limited clinical significance in distinguishing colonization from infection in this specific context. This methodological approach highlights the emphasis on immune response rather than pathogen load in the diagnosis of ABPA.
The patient responded favorably to voriconazole combined with inhaled corticosteroids/bronchodilators, consistent with established treatments (11). However, this single case report has limitations, including the inability to definitively confirm parental inheritance patterns of CFTR variants without familial genetic analysis. Future multi-center studies with larger sample sizes should validate genotype-phenotype correlations in Chinese CF-ABPA patients. Further investigation is needed regarding CFTR modulators’ efficacy for variants common in China (e.g., p.G970D) (4), biologics for refractory cases (12), and long-term management strategies. For progressive lung failure, lung transplantation referral per international consensus may become necessary (13,14).
This case emphasizes CF-ABPA’s diagnostic challenges and the importance of multidisciplinary management in China, where both awareness and treatment options for CF continue to evolve.
Conclusions
In brief, this case demonstrates that CF, which was frequently excluded as a diagnosis, may also be relevant among Chinese patients with bronchiectasis and ABPA. That not just makes diagnosis easier but treatment as well. Nonetheless, because this is just a single case report, its generalizability has limitations. In addition, the long-term risk for relapse and antifungal toxicity remains uncertain. In the future, awareness should be increased, patients should be genetically and immunologically diagnosed as soon as possible, early diagnosis and the development of tailored management and treatment strategies should take place and larger studies should be conducted to define the natural history and optimal treatment of CF-ABPA in the Chinese and similar populations. To improve the quality of life and prognosis of these patients, collaboration of different disciplines is essential.
Acknowledgments
We appreciate The First Affiliated Hospital of Guangxi Medical University for its valuable contributions.
Footnote
Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-175/rc
Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-175/prf
Funding: This work was supported by
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-175/coif). Z.D. is a current employee of Guangxi King Med. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the Declaration of Helsinki and its subsequent amendments. This study was approved by the ethics board of The First Affiliated Hospital of Guangxi Medical University (No. 2024-E105-01). Written informed consent was obtained from the patient and his legal guardian for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
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Cite this article as: Dang Y, Deng Z, Wang K, Luo J, Wang C, Long F, Kong J. Cystic fibrosis complicated by allergic bronchopulmonary aspergillosis in a Chinese adolescent: a case report and literature review. AME Case Rep 2026;10:43.
