Background:Pulmonary aspergillosis is a pulmonary infectious disease that is clinically difficult to diagnose and treat. When the lower respiratory tract is invaded by Aspergillus, the clinical manifestations and imaging features vary among patients with different immune states. The use of antifungal drugs and glucocorticoids are important, but some patients do not respond satisfactorily to treatment.Case presentation:A 59-year-old female had a long history of asthma and poor symptom control, with long-term use of long-acting inhaled glucocorticoids combined with a long-acting β2 receptor agonists (ICS + LABA) (salmeterol fluticasone inhalation powder). The ground glass shadow, tree-in-bud sign, and bronchiectasis in the middle lobe of the right lung and the lower lobe of both lungs were first detected by chest CT over 5 years ago. Atelectasis in the middle lobe of the right lung was detected over 3 years ago. Over 2 years ago, the patient was hospitalized and a repeat chest CT showed persistent atelectasis in the middle lobe of the right lung, and more lesions in bilateral lower lungs than before. Aspergillus fumigatus was detected in alveolar lavage fluid and sputum pathogenic culture, which confirmed the diagnosis of pulmonary aspergillosis. After treatment with voriconazole and amphotericin B, the middle lobe of the right lung partially reopened, but the lesions in bilateral lower lungs persisted. After 21 weeks of treatment, the antifungal drugs were stopped because the patient refused to use oral/intravenous glucocorticoids, and omalizumab was finally chosen for treatment. After 1 month of treatment, the patient’s clinical symptoms began to ease. After 1 year of treatment, imaging reexamination of lung showed that the lesions were completely cleared, accompanied by significant improvement in nutritional status and airway function.Conclusions:We reported the case of a patient with pulmonary Aspergillus infection who was treated with omalizumab and showed significant improvement in clinical symptoms and imaging abnormalities, which provides a new option for patients with pulmonary Aspergillus infection who show unsatisfactory response with first-line drugs.