Allergic Bronchopulmonary Aspergillosis Aided by Bronchoalveolar Lavage: A Case Report

Summary

This protocol outlines a stepwise diagnostic workflow for young, atypical patients with allergic bronchopulmonary aspergillosis (ABPA) unresponsive to antibacterial therapy. It includes bronchoscopy, analysis of bronchoalveolar lavage fluid (BALF), and targeted next-generation sequencing (tNGS) to detect Aspergillus fumigatus sequence reads, with informed consent and ethical approval.

Abstract

This protocol establishes a clear primary goal: to develop a structured, actionable diagnostic workflow that enables accurate differentiation of allergic bronchopulmonary aspergillosis (ABPA) from other chronic respiratory diseases with similar presentations in young patients with refractory respiratory symptoms. In this population, ABPA is frequently misdiagnosed due to non-classical clinical features, leading to avoidable delays in targeted therapy and persistent diagnostic uncertainty in routine clinical practice. The diagnostic workflow is designed as an integrated, multi-step approach incorporating comprehensive clinical assessment, high-resolution computed tomography (HRCT), bronchoscopy, and bronchoalveolar lavage fluid (BALF) analysis, including galactomannan assay, alongside targeted next-generation sequencing (tNGS) to detect Aspergillus fumigatus sequence reads. These components function as adjunctive tools within a holistic framework, guiding clinicians through the sequential evaluation of atypical ABPA cases. To demonstrate clinical applicability, the workflow was implemented in a 22-year-old male patient with a 10-year history of recurrent cough and sputum production, who had been initially misdiagnosed with infectious bronchiectasis and was unresponsive to antibacterial therapy. Application of the workflow enabled integration of serial HRCT findings, BALF testing, tNGS results for Aspergillus fumigatus sequence reads, and baseline serological data, ultimately leading to a definitive diagnosis of ABPA. This protocol highlights that a multimodal diagnostic strategy can enhance diagnostic confidence in young patients with refractory respiratory symptoms and elevated serum IgE levels, reducing diagnostic ambiguity and facilitating timely initiation of targeted anti-inflammatory and antifungal therapy to improve clinical outcomes.

Introduction

The primary goal of this case report is to illustrate a structured diagnostic workflow for identifying ABPA in young patients with atypical clinical presentations and a history of misdiagnosis.

ABPA is an allergic lung disease caused by Aspergillus spp., particularly Aspergillus fumigatus. Its clinical manifestations are complex and heterogeneous, primarily characterized by asthma-like episodes, recurrent infiltrative shadows on pulmonary imaging, and bronchiectasis. In 1952, British scholar Hinson first described this condition¹. As a progressive disease, ABPA presents with complex clinical feature....

Protocol

This study was approved by the Ethics Committee of Minhang Hospital, Fudan University (Approval No.: 2025-018-01K). Written informed consent was obtained from the patient prior to all clinical procedures, in compliance with the ethical principles of the Declaration of Helsinki. All patient data were anonymized, and no identifiable personal information was disclosed in this report. The reagents and equipment used are listed in the Table of Materials.

1. Pre-treatment evaluation and empirical therapy initiation

1. A detailed clinical history and symptom assessment were conducted. The following baseli....

Results

The patient’s clinical course demonstrated significant improvement following targeted therapy for ABPA, with systematic changes observed in diagnostic biomarkers, radiological findings, and clinical symptoms.

The patient was initiated on methylprednisolone (40 mg/day) and voriconazole (200 mg every 12 h). Within 10 days, marked improvement in cough, expectoration, and dyspnea was observed. Follow-up HRCT scans (Figure 3) demonstrated resolution of mucus plugs, red.......

Discussion

In China, bronchiectasis is a common chronic respiratory disease with a relatively high incidence. Among individuals aged 40 years or older, post-infectious bronchiectasis is more prevalent⁷. Although allergic bronchopulmonary aspergillosis (ABPA) is not uncommon in clinical practice, misdiagnosis and missed diagnosis remain frequent due to non-specific symptom descriptions, inconsistent diagnostic criteria, and other contributing factors⁸. Early and accurate diagnosis, alo.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Aspergillus-specific IgE Assay Kit	Thermo Fisher Scientific, USA	ELISA Aspergillus sIgE Kit	Enzyme-linked immunosorbent assay for Aspergillus-specific IgE detection; cutoff: >0.35 kUA/L; patient result: 2.8 kUA/L
Aspergillus Galactomannan Assay Kit	Bio-Rad Laboratories, USA	Platelia Aspergillus Ag EIA	Enzyme immunoassay (EIA) for Aspergillus galactomannan detection; serum result: 0.016 ODI, BALF result: 3.344 ODI; cutoff: >0.5 ODI
Aspergillus fumigatus-specific IgG Assay Kit	Thermo Fisher Scientific, USA	ELISA Aspergillus fumigatus IgG Kit	Enzyme-linked immunosorbent assay for Aspergillus fumigatus-specific IgG detection; cutoff: >1.0 AU/mL; patient result: 1.6 AU/mL
Acid-fast bacilli taining kit	Solarbio, China	AS-1010	Diagnostic Reagents/Tests
Ambroxol	Boehringer Ingelheim International GmbH, China	ABX-30	Therapeutic Drugs
Automated biochemical analyzer	Roche Diagnostics, Switzerland	cobas 8000	Serum IgE/eosinophil testing
BAL collection tubing kit	Medtronic plc, China	49445	Sample Collection Materials
BALF collection container	Corning, USA	352070	Sample Collection Materials
Bronchoscope	Olympus Corporation, Japan	BF-1TQ290	Lower respiratory tract sampling
Chest CT	Siemens, GER	Somatom Definition Force	High-resolution computed tomography (HRCT) scanner used for pulmonary
Drug sensitivity testing reagents	BD, USA	BD BBL Sensi-Disc	Diagnostic Reagents/Tests
Electronic medical record system	Cerner Corporation, USA	Millennium	Patient data management
Fungal (1,3)-β-D-Glucan Assay Kit	Associates of Cape Cod, China	Fungitell	Quantitative chromogenic assay for fungal (1,3)-β-D-glucan detection; normal range: <20 pg/mL; patient result: 25.1 pg/mL
Flexible Bronchoscope	Olympus, Japan	BF-1T260	Bronchoscope with 2.8 mm working channel; used for airway inspection and BALF collection from right upper lobe posterior segment
Fluconazole	Pfizer Inc, USA	FLC-200	Therapeutic Drugs
Hematology Analyzer	Sysmex	XN-9000	Automated hematology analyzer used for peripheral blood eosinophil count; patient pre-treatment result: 850 cells/μL
HRCT image analysis software	Siemens Healthineers, Germany	syngo.via	Pulmonary lesion quantification
Methylprednisolone	Pfizer Inc, USA	MP-40	Therapeutic Drugs
Microbial culture incubator	Thermo Fisher Scientific, USA	3110	BALF microbial culture
Piperacillin–tazobactam	Pfizer Inc, USA	TZP-4.5	Therapeutic Drugs
Prednisone	Pfizer Inc, USA	PDN-5	Therapeutic Drugs
Respiratory pathogen panel (SARS-CoV-2, EBV)	BGI Genomics, China	2019-nCoV/EBV-001	Diagnostic Reagents/Tests
Serum Total IgE Assay Kit	Beckman Coulter, China	Immage 800 IgE Kit	Quantitative ELISA kit for serum total IgE measurement; normal upper limit: 100 IU/mL; used to detect elevated IgE (1400 IU/mL) in the patient
Sputum culture media	Thermo Fisher Scientific,USA	TSA-100	Diagnostic Reagents/Tests
Sterile saline for lavage	Baxter, China	0.9% NaCl-500mL	Sample Collection Materials
Targeted Next-Generation Sequencing (tNGS) Platform	BGI Genomics, China	MGISEQ-2000	Metagenomic sequencing platform for BALF DNA analysis; detection threshold: ≥10 sequence reads; identified 55 Aspergillus fumigatus sequences
tNGS Library Preparation Kit	Illumina, USA	MGIEasy DNA Library Prep Kit	Library preparation kit for microbial DNA sequencing; used for BALF sample processing prior to tNGS
tNGS data analysis software	Illumina, USA	BaseSpace	Sequence read alignment/identification
tNGS sequencing platform	Illumina, USA	NextSeq 550	tNGS sequencing platform
Voriconazole	Pfizer Inc, USA	VRC-200	Therapeutic Drugs