Voriconazole and Posaconazole Improve Asthma Severity in Allergic Bronchopulmonary Aspergillosis and Severe Asthma with Fungal Sensitization

Rationale and objectives. Severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA) are progressive allergic fungal lung diseases whose effective treatment remains to be established. Current treatment with itraconazole is associated with a 40% failure rate and adverse events (AEs). We assessed the effect of voriconazole or posaconazole as second- and third-line therapies. Methods. We conducted a retrospective review of adult asthmatic patients with either ABPA or SAFS receiving voriconazole or posaconazole. Clinical, radiological, and immunological evaluation was used to assess response. Results. There were 25 patients, ABPA (n = 20) or SAFS (n = 5), 10 males, median age = 58 years. All patients had failed itraconazole (n = 14) or developed AEs (n = 11). There were 33 courses of therapy analyzed, 24 with voriconazole and 9 with posaconazole. Clinical response to voriconazole was observed in 17/24 (70%) patients at 3 months, 15/20 (75%) at 6 months, and 12/16 (75%) at 12 months compared with 7/9 (78%) at 3, 6, and 12 months for posaconazole. Eighteen of 24 (75%) patients discontinued oral corticosteroids (OCS), 12 of them within 3 months of therapy. Asthma severity was downgraded from severe to moderate (n = 8) and moderate to mild (n = 1) asthma in 9 of 24 (38%) asthmatic patients. There was a marked reduction in OCS and short-acting beta-2 agonist use, health-care utilization due to asthma, and improvement in overall health status. Furthermore, there was a statistically significant reduction in immunological markers appearing at 9 months (p = .008) for total IgE and at 12 months for radioallergosorbent test IgE for Aspergillus fumigatus (p = .0056). Six of 23 (26%) patients on voriconazole had AEs requiring discontinuation before 6 months compared with none on posaconazole (p = .15). Four relapsed (57%), one at 3 months and three at 12 months after discontinuation. Conclusion. Both voriconazole and posaconazole are potentially effective alternative treatment options for SAFS and ABPA and may improve asthma control and reduce severity, though larger prospective studies are required to support these retrospective study findings.     

变态反应性支气管肺曲菌病的治疗:需要更多的循证依据

变态反应性支气管肺曲菌病(allergic bronchopulmonary aspergillosis,ABPA)是一个被临床忽视的疾病,常被误诊为哮喘和肺结核等疾病。有关ABPA自然病程和治疗的临床研究还比较缺乏,以往多以口服糖皮质激素治疗为主,目前普遍推荐口服糖皮质激素加抗真菌治疗的联合治疗方案,以达到控制机体对烟曲菌抗原的过敏反应、同时清除寄生于气道内的烟曲菌等。     

Successful Treatment of Mepolizumab- and Prednisolone-resistant Allergic Bronchopulmonary Aspergillosis with Dupilumab

A 45-year-old man with allergic bronchopulmonary aspergillosis (ABPA) was treated with oral prednisolone (PSL) (30 mg/day), inhaled corticosteroids, and long-acting beta2-agonists. After confirmation of a PSL-dependent status (8 mg/day), subcutaneous injection with anti-interleukin (IL)-5 antibody (mepolizumab, 100 mg/month) was performed, and the PSL dose was tapered to 5 mg/day. However, ABPA recurred and proved refractory to oral itraconazole (200 mg/day). Alternative subcutaneous injection therapy with dupilumab (induction dose of 600 mg followed by a maintenance dose of 300 mg/2 weeks) enabled the successful withdrawal of oral PSL without clinical deterioration. This case demonstrates the potential utility of dupilumab for steroid-dependent ABPA via the synergistic suppression of IL-4 and IL-13 compared to monotherapy with anti-IL-5 antibody.     

变应性支气管肺曲菌病1例并文献复习

目的:提高对变应性支气管肺曲菌病(ABPA)的认识并引起对该病的重视.方法:对1例ABPA患者临床资料进行分析,并结合文献进行复习.结果:ABPA是一种慢性、免疫介导的,对寄生繁殖的曲菌过敏导致的非感染性、炎症性肺部疾病,常发生在支气管哮喘的患者.结论:目前对该病的诊断应采取多种手段,包括纤支镜检查,痰培养及影像学、免疫学等;长期吸入糖皮质激素与口服伊曲康唑能达到较好治疗效果,且最大限度减少副作用.     

Clinical Manifestations of Allergic Bronchopulmonary Aspergillosis without Major Features of Asthma Diagnosed by the New Criteria in Japan

Allergic bronchopulmonary aspergillosis (ABPA) is a severe form of asthma in which structural airway destruction occurs due to a hypersensitivity reaction to fungi. A 25-year-old man without any major features of asthma had lung infiltration with dilatation of the central bronchus, high-attenuation mucus with histological eosinophilic invasion, fungi detected on cultures, and positive Aspergillus-specific immunoglobulin E (IgE) and precipitating antibody of Aspergillus, with a significant elevation of blood eosinophils and slightly increased total IgE. He recovered rapidly with systemic corticosteroid therapy without recurrence over 1-year follow-up and an increased forced expiratory volume in one second, which supported the possibility of ABPA without any major features of asthma.     

Successful Treatment with Benralizumab for Allergic Bronchopulmonary Aspergillosis That Developed after Disastrous Heavy Rainfall in Western Japan

We herein report a 56-year-old woman who developed allergic bronchopulmonary aspergillosis (ABPA) possibly due to fungal exposure after disastrous heavy rainfall in Western Japan in 2018. She was diagnosed with ABPA complicated with asthma, increased peripheral blood eosinophil count, elevation of specific immunoglobulin E for Aspergillus fumigatus, positive Aspergillus fumigatus precipitation antibody reaction test results, and notable chest computed tomography findings. After treatment with benralizumab, her symptoms, peripheral blood eosinophil count, radiological findings, and respiratory function dramatically improved. The administration of benralizumab appears to be an effective treatment strategy for ABPA.     

Evaluation of Allergic Bronchopulmonary Aspergillosis in Patients with and without Central Bronchiectasis

Allergic bronchopulmonary aspergillosis (ABPA) is a hypersensitivity disorder induced by Aspergillus species colonizing the bronchial tree. Thirty one patients fulfilling criteria of ABPA were evaluated in the present study. Eleven patients were diagnosed as ABPA-S (serological positive) and 20 patients as ABPA-CB (with central bronchiectasis). The two groups of patients were compared on the basis of clinical, serological, and radiographic observations. Serum anti Aspergillus fumigatus IgG was positive in 72% of cases of ABPA-S and 85% of ABPA-CB patients at the time of presentation. Specific IgE against A. fumigatus and total IgE were significantly lower in ABPA-S (specific IgE = 7.42 IU and total IgE = 1127 ng/mL) as compared to ABPA-CB (specific IgE = 44 IU and total IgE = 2874 ng/mL). The spirometric changes in ABPA-S (normal 80%, mild obstruction 10%, and severe obstruction 10%) were milder than in ABPA-CB (normal 40%, mild obstruction 10%, moderate obstruction 20%, and severe obstruction 30%). These patients were monitored closely for seasonal exacerbation with new pulmonary infiltrates which gave lower recordings in ABPA-S patients. No patient in the ABPA-S group progressed to end-stage lung disease. This may be due to early recognition and treatment. The present data suggest that ABPA-S represents the early stage of an apparently less aggressive form of ABPA than ABPA-CB.     

Distribution and Severity of Bronchiectasis in Allergic Bronchopulmonary Aspergillosis (ABPA)

The purpose of this paper was to quantitate the distribution and severity of computed tomography (CT) and radiographic findings in patients with allergic bronchopulmonary aspergillosis (ABPA), probable ABPA, and asthmatic controls. Chest radiographs and high-resolution CT images were evaluated in 19 patients with documented ABPA and 18 asthmatic controls. Ten patients with probable ABPA were also evaluated. On CT examination 17 patients (89%) with ABPA had central cystic or varicoid bronchiectasis in at least one lobe. One patient had no evidence for bronchiectasis. Three asthmatic patients (1 7%) had findings of cylindrical bronchiectasis. All 10 patients with probable ABPA had evidence of bronchiectasis on high-resolution CT (HRCT). The majority of patients with ABPA have diffuse disease at the time of diagnosis, manifested by central cystic and/or varicoid bronchiectasis in four or five lobes. Evaluation with HRCT can facilitate a diagnosis of ABPA and probable ABPA, allowing for earlier treatment which may prevent progression to fibrosis.     

Allergic bronchopulmonary aspergillosis: disease pattern in central Arabia

Despite a high prevalence of asthma in Saudi Arabia, allergic bronchopulmonary aspergillosis (ABPA) has not been reported. We reviewed the medical records in a large university hospital in Saudi Arabia where thousands of asthmatics are being followed up. Over a 9-year period starting January 1986, the diagnosis of ABPA was made in 10 patients only. Delay in diagnosis was common and in some patients the disease was confused with fungal pneumonia, tuberculosis or tumours. Aspergillus fumigatus was isolated from one patient only and different Aspergillus species were cultured from respiratory secretions of the others. Corticosteroids were uniformly effective in all patients with active disease. Low humidity may account for this apparent rarity of ABPA, although it is possible that some cases are overlooked. Further work is needed on the prevalent fungi in the Arabian environment and their potential health effects and particularly on the prevalence of allergic bronchopulmonary fungal disease.     

Severe Asthma with Fungal Sensitization: A Case Report and Review of Literature

There is a substantial body of evidence supporting an association between asthma severity and fungal exposure and sensitization. Fungal allergens are a recognized risk factor for severe asthma. We describe the case of a 44-year-old asthmatic whose asthma control deteriorated after moving to a new flat with walls covered in mould. Allergic bronchopulmonary aspergillosis was excluded. Although sensitization to Candida was demonstrated by a positive Candida-specific radioallergosorbent test, the patient did not entirely satisfy the criteria for a diagnosis of allergic bronchopulmonary candidiasis. The patient's asthma control improved after engaging in a monthly washing regimen of the walls. This case further demonstrates the association between fungal sensitization and asthma severity. The term severe asthma with fungal sensitization has been recently coined to describe this phenomenon.     

Allergic Bronchopulmonary Fungal Disease Caused by Saccharomyces cerevisiae

We describe a patient who presented with dry cough, low-grade fever, and focal patchy shadow of pulmonary infiltrates. Remarkably, the prospective etiological agent, Saccharomyces cerevisiae was purely and repeatedly cultured from her sputum. Allergic bronchopulmonary mycosis (ABPM) was diagnosed based on clinical, serological, and pathological criteria. Although the patient described here satisfied only three of the criteria, the conclusion that the allergic bronchopulmonary disease in our case was induced by S. cerevisiae was made based on the following evidence: 1) S. cerevisiae was repeatedly isolated from the patient's sputum, 2) anti-S. cerevisiae antibody was detected in her serum, and 3) bronchoprovocation test to S. cerevisiae antigen was positive. We present here a case of allergic bronchopulmonary fungal disease caused by S. cerevisiae antigen.     

Allergic Bronchopulmonary Fungal Disease Caused by Saccharomyces cerevisiae

We describe a patient who presented with dry cough, low‐grade fever, and focal patchy shadow of pulmonary infiltrates. Remarkably, the prospective etiological agent, Saccharomyces cerevisiae was purely and repeatedly cultured from her sputum. Allergic bronchopulmonary mycosis (ABPM) was diagnosed based on clinical, serological, and pathological criteria. Although the patient described here satisfied only three of the criteria, the conclusion that the allergic bronchopulmonary disease in our case was induced by S. cerevisiae was made based on the following evidence: 1) S. cerevisiae was repeatedly isolated from the patient's sputum, 2) anti‐S. cerevisiae antibody was detected in her serum, and 3) bronchoprovocation test to S. cerevisiae antigen was positive. We present here a case of allergic bronchopulmonary fungal disease caused by S. cerevisiae antigen.     

Allergic Bronchopulmonary Mycosis Complicated with Lung Adenocarcinoma

Chest computed tomography (CT) of a 76-year-old woman with bronchial asthma showed multiple lung nodules with high CT densities that were compatible with high-attenuation mucoid (HAM) impactions characteristic of allergic bronchopulmonary mycosis (ABPM). Follow-up chest CT revealed increased sizes of multiple lung nodules. However, a left upper lobe nodule showed lower CT density than the other HAM impactions. A transbronchial lung biopsy of that upper lobe nodule revealed lung adenocarcinoma. Measuring the CT density is important for the differential diagnosis of lung nodules when following ABPM patients. Our patient''s increased serum carcinoembryonic antigen levels were associated with peripheral blood eosinophilia. Mucoid impaction in the lung was positively stained with carcinoembryonic antigen and showed the distribution of eosinophilic granules.     

Allergic bronchopulmonary aspergillosis: new concepts of pathogenesis and treatment

Allergic bronchopulmonary aspergillosis (ABPA) is a condition that results from a hypersensitivity reaction to the fungus Aspergillus fumigatus. The purpose of the present review is to examine the pathogenesis of this condition and the evidence for treatments available. Allergic bronchopulmonary aspergillosis is characterized by an intense airway inflammation with eosinophils and the formation of mucus plugs. Clinically, there are periods of exacerbation and remission that may lead to proximal bronchiectasis and fibrotic lung disease. New evidence confirms the role of intense airway inflammation with eosinophils, but also suggests a role for interleukin (IL)-8/neutrophil-mediated inflammation in this process, and the potential deficiency of anti-inflammatory cytokines such as reduced IL-10. Treatment for ABPA has so far focused on corticosteroids to suppress eosinophilic airway inflammation. An expanding knowledge of the pathology of ABPA also suggests other therapies may be of potential benefit, particularly the use of azole antifungal agents. Allergic bronchopulmonary aspergillosis is itself an important complication of asthma and cystic fibrosis. A greater understanding of the condition is required to improve management and well-designed clinical trials need to be carried out to critically assess new and current treatments. In addition, the information gained from the studies of its pathogenesis has the potential to benefit our understanding of the disease processes in asthma and bronchiectasis.