Allergic bronchopulmonary aspergillosis (ABPA) is a non-infectious, inflammatory lung disease characterized by a metabolic reaction of the body to Aspergillus fumigatus (Af) parasitic in the bronchi. I. Etiology, pathogenesis and pathology The pathogenic factor is mainly inhalation of Af spores. Due to the different immune status of patients, the response to Af varies widely, and can be manifested as invasive bronchopulmonary aspergillosis, pulmonary aspergilloma, ABPA, etc. The prominent pathological features of ABPA are: eosinophil-rich non-caseating granulomas and central bronchiectasis. Lung biopsies of patients with ABPA revealed that due to recurrent disease, it often results in cystic dilatation of the involved segment or subsegment bronchi with normal distal bronchi with central bronchial dilatation. The dilated bronchi are filled with mucus and fibers with Aspergillus filaments in the lumen, but no invasion of filaments into the airway wall and lung tissue. There can be infiltration of eosinophils and monocytes in bronchial and lung tissues, but the peripheral vasculitis is very mild, and there is no complement and immune complex deposition in the vessel wall. The main clinical manifestations and diagnostic points are Xue-mei Li, Department of Rheumatology and Immunology, Xuanwu Hospital, Capital Medical University. ABPA patients have a wide age of onset and are clinically more common between 20 and 40 years old, with no significant difference in gender. Most of these patients have atopic constitution and are allergic to a variety of foods and drugs. Clinically, relapses and remissions often alternate. Typical symptoms of attacks include wheezing, cough, coughing (sometimes with brown sputum clots), hemoptysis, fever, etc. During attacks, rales can be heard in both lungs, and fine wet? Sounds. Typical chest X-ray changes include: wandering infiltrative shadows, uniform solid shadows, limited pulmonary atelectasis and “toothpaste”-like or “fingertip”-like shadows (mostly suggestive of central bronchial dilatation). Laboratory tests often reveal elevated peripheral blood eosinophil counts, biphasic Af antigen intradermal tests, positive serum Af precipitating antibodies, elevated serum total IgE levels and IgE-Af and IgG-Af. Among them, the serum total IgE level is closely related to the disease activity. The natural course of ABPA is currently divided into five phases: Phase I: acute phase. Patients may show typical symptoms of exacerbation, with lung infiltrative shadow and elevated serum total IgE on secondary examination. Most of the patients’ asthma symptoms can be controlled by bronchodilators and inhaled glucocorticosteroids alone; Stage III: relapse and exacerbation. The symptoms of acute exacerbation may be manifested, but about 33% of the patients with relapse are asymptomatic, with only an exponential increase in total serum IgE or lung infiltrative shadow; Stage IV: hormone-dependent asthma stage. After patients enter this stage, asthma symptoms must be controlled by oral glucocorticoids, and it is difficult to stop the medication even if the symptoms are relieved; Stage V: interstitial lung fibrosis stage. Patients all develop irreversible lung damage and eventually die due to respiratory failure. If the patient’s expiratory volume per second is <0.8 liters, the prognosis is extremely poor, with most dying within 7 years. The common diagnostic criteria for ABPA are: (1) history of asthma; (2) positive immediate reaction to Af antigen intradermal test; (3) elevated serum total lgE level (>1,000 μg/L); (4) positive Af precipitating antibody; (5) lung infiltrative shadow on imaging; (6) elevated peripheral blood eosinophil count in the presence of lung infiltrative shadow; (7) elevated IgE-Af,IgG -Af levels are elevated; and (8) central bronchiectasis. Meeting seven of these diagnostic criteria (must include number 7) confirms the diagnosis of ABPA; meeting six of these diagnostic criteria makes the diagnosis of ABPA highly probable. ABPA-S meets diagnostic criteria 1 to 7, while ABPA-CB meets all 8 diagnostic criteria. The main goal of ABPA treatment is to protect the normal structure and function of the airway and lung tissue, including the control of acute symptoms, inhibition of the body’s metabolic response to Af antigen, and removal of Af before it settles in the airway. Currently, ABPA patients mainly rely on drug therapy. 1. Oral glucocorticoids It is currently the basic therapeutic measure for ABPA. Early studies found that the application of glucocorticoids can reduce pulmonary infiltration, control bronchospasm symptoms and reduce sputum volume. It can also play a role in reducing peripheral blood eosinophil counts and total serum lgE levels, but short-term application of glucocorticoids during exacerbations cannot stop the recurrence of this disease. The mechanism of action of oral glucocorticosteroids is not fully understood. The more common clinical regimen of oral glucocorticoid therapy is: (1) prednisone (0.5 mg kg-1 d-1) given orally for 2 weeks during the exacerbation period (sometimes a longer course is needed to completely eliminate the pulmonary infiltrate); (2) thereafter, the same dose is given orally every other day for 3 months; thereafter, prednisone is gradually reduced until it is discontinued, and the reduction process should be at least 3 months; (3) after imaging After the initial lung infiltrative shadow is confirmed to be cleared, the chest X-ray should be reviewed every 3 months and followed up for 2 years, and then changed to every 6 months and followed up for another 2 years. If there is no recurrence, it will be changed to once a year; (4) review serum total IgE once a month from the beginning of treatment, usually the serum total IgE level decreases at least 35% after 2 months of treatment, and reaches a plateau after 6 months of treatment (a significant increase in serum total IgE mostly indicates disease recurrence, and oral glucocorticoids should be added even if asymptomatic), and if there is no evidence of recurrence after 2 years of continuous observation, it can be changed to every 2 months 1 time; (5) review pulmonary function once a year and follow up for 2 years. Effective oral glucocorticoid therapy with close follow-up after early diagnosis of ABPA can indeed stop the progression of pulmonary lesions to end-stage in most patients with ABPA. However, oral glucocorticosteroid therapy has a long treatment cycle, so patients who receive it benefit from the above treatment while the incidence of glucocorticosteroid drug side effects gradually increases. Inhaled glucocorticoid therapy Scholars have tried to change the treatment strategy and apply inhaled glucocorticoids to control the inflammatory response in ABPA and to reduce the side effects of oral hormones. Early studies concluded that small doses of inhaled glucocorticoids (e.g., beclomethasone dipropionate 400 μg/d) were not sufficient to control ABPA. Recently, Balter et al. and Imbeault et al. treated three patients with ABPA with beclomethasone dipropionate 1,000-1,500 μg/d, respectively, and achieved the efficacy of discontinuing oral glucocorticoids and maintaining the disease without recurrence. Heinig et al [9] also achieved similar results with budesonide 1600 μg/d in one patient with ABPA. This suggests that inhaled medium to high doses of glucocorticoids may be effective in the treatment of ABPA, but this conclusion has yet to be confirmed by large-scale clinical studies. 3. Application of antifungal drugs Theoretically, antifungal drugs can reduce the antigenic load of the body by killing the fungi in the airway, thus reducing the metabolic reactions occurring in the body. Clinical attempts have been made to apply antifungal drugs such as mycobacterium, clotrimazole, dicloxacillin B and ketoconazole alone or in combination with glucocorticoids for the treatment of ABPA, but they have been abandoned either because of the inability to prove their definite efficacy or because of the serious side effects of the drugs themselves. A recent study found that the application of natamycin spray (natamycin) for the treatment of ABPA did not have beneficial effects relative to placebo. It is noteworthy that itraconazole has shown encouraging results in the treatment of ABPA in recent years. Itraconazole, a new highly lipid-soluble oral antifungal drug, has a significant fungicidal effect against Aspergillus in vivo and externally, while having minimal toxic effects relative to other antifungal drugs. The application of itraconazole in ABPA patients for more than 6 months can mostly reduce the dosage of oral glucocorticoids, reduce the serum total IgE level and improve pulmonary function and other efficacy. However, it is currently considered that itraconazole is indicated in combination with glucocorticoids to control ABPA episodes and its use should be limited to those patients who benefit from a reduction in glucocorticoid dosage. There is only one case report suggesting that itraconazole can be used alone for the treatment of ABPA, and it is analyzed that the good efficacy of itraconazole may be related to its significant fungicidal efficacy against Aspergillus, thus suggesting that highly effective antifungal drugs with low toxic side effects may have a promising application in the treatment of ABPA in the future. 4. Other treatments The application of disodium cromoglycate and other bronchodilators is limited to controlling asthma symptoms alone or in combination with glucocorticoids, which does not help to control disease recurrence. The application of Af desensitization therapy for ABPA is not only clinically observed to be ineffective, but also has the risk of directly inducing bronchospasm. There is a lack of accepted recommended treatment options for patients with cystic fibrosis combined with ABPA. Treatment monitoring The success of treatment and the corresponding reduction of drug side effects depend largely on whether effective treatment monitoring is performed. Total serum lgE levels, chest X-ray and pulmonary function tests are three important indicators for monitoring changes in ABPA. The serum total lgE level usually decreases after glucocorticoid treatment, and can still be higher than normal during the remission period of ABPA, but significantly increases before or during relapse. Therefore, regular monitoring of serum total lgE level allows clinicians to understand the bottom line serum total lgE level specific to different patients and adjust the glucocorticoid dosage accordingly. Regular chest X-rays are useful in detecting recurrences that present only as pulmonary infiltrates. By the time the lesion reaches the end stage, patients with ABPA have irreversible ventilation and diffusion dysfunction, so regular monitoring of pulmonary function is important to understand whether the ABPA lesion is progressing to the end stage. It is currently believed that early diagnosis, adequate oral glucocorticoids, regular serum total lgE levels, chest X-ray and pulmonary function tests can reduce the incidence of irreversible lung damage and minimize the side effects of oral glucocorticoids. Rigorous large-scale, prospective clinical studies are necessary in the future to further evaluate the role of inhaled glucocorticosteroids and antifungal drugs in the treatment of ABPA.