Possible ABPA with persistent symptoms
Question:
6/10/2020
We have a 69 year-old Caucasian female patient with strong atopic predisposition with high level of sensitization to various environmental allergens particularly molds , allergic bronchopulmonary aspergillosis (positive Aspergillus IgE as well as Positive Aspergillus IgG, total IgE count is elevated at 403 and per history has had total IgE more than 800, as well as evidence of bronchiectasis.) CT scan from about a year ago had evidence of bronchiectasis. Currently on Tolsura two tabs bid for ABPA.
Despite being on multiple medications including Xolair, Singulair as well as Alvesco and Dulera, she suffers from frequent asthma exacerbations needing oral prednisone course. She had been on prednisone for many years at a dose of 30 mg before coming to our practice and we have been able to titrated down to 5 mg.
We have not started doing spirometry in the office because of COVID-19, but the last spirometry from about 6 months ago had an FEV1 of 61%. Still complains of daily shortness of breath, which she believes are triggered by environmental allergens. Wondering, would you consider her a candidate for allergen immunotherapy considering everything else has been tried?
Answer:
Persistent airway complaints, reduced lung function and need for systemic corticosteroids are criteria for severe persistent asthma, assuming that asthma is the diagnosis (1). The characteristics described support a Type 2 asthma with increased IgE and specific-IgE. Peripheral blood eosinophil count and exhaled FeNO would be helpful in confirming Type 2 airway disease. Bronchiectasis is not expected with asthma. Although allergic bronchopulmonary aspergillosis (ABPA) is suspected, I am skeptical of the diagnosis with total IgE at 403 kU/L, since typically the values would be >1000 kU/L. If the bronchiectasis is central and the IgG to aspergillus antigen is very positive (> 20-30 mg/L), the diagnosis of ABPA may indeed be correct (2). You may want to consider cystic fibrosis as well.
In summary, I would be less comfortable with allergen immunotherapy in a patient with severe, persistent, Type 2 asthma and FEV1 61%. Allergen immunotherapy is less effective in subjects with significant air flow limitation due to risk and evidence of benefit with treatment in the domains of symptoms and medication use rather than lung function improvement (3). The primary concern is the risk of severe adverse events with the allergen immunotherapy. I would consider other biologic treatment options, including anti-IL5, anti-IL5 receptor or anti-IL4 alpha chain receptor. If specific allergens are affecting her asthma, I would emphasize environmental control measures, recognizing the evidence of efficacy in application of individual efforts for environmental control are minimal (4).
1. Chung, Kian Fan, et al. "International ERS/ATS guidelines on definition, evaluation and treatment of severe asthma." European respiratory journal 43.2 (2014): 343-373.
2. Developments in the diagnosis and treatment of allergic bronchopulmonary aspergillosis
Agarwal R, Sehgal IS, Dhooria S, Aggarwal AN Expert Rev Respir Med. 2016;10(12):1317. Epub 2016 Nov 7.
INTRODUCTION Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder characterized by recurrent episodes of wheezing, fleeting pulmonary opacities and bronchiectasis. It is the most prevalent of the Aspergillus disorders with an estimated five million cases worldwide. Despite six decades of research, the pathogenesis, diagnosis and treatment of this condition remains controversial. The International Society for Human and Animal Mycology has formed a working group to resolve the controversies around this entity. In the year 2013, this group had proposed new criteria for diagnosis and staging, and suggested a treatment protocol for the management of this disorder. Since then, several pieces of new evidence have been published in the investigation and therapeutics of this condition. Areas covered: A non-systematic review of the available literature was performed. We summarize the current evidence in the evaluation and treatment of this enigmatic disorder. We suggest modifications to the existing criteria and propose a new scoring system for the diagnosis of ABPA. Expert commentary: All patients with asthma and cystic fibrosis should routinely be screened for ABPA using A. fumigatus-specific IgE levels. Glucocorticoids should be used as the first-line of therapy in ABPA, and itraconazole reserved in those with recurrent exacerbations and glucocorticoid-dependent disease.
3. Asamoah, Felix, et al. "Allergen immunotherapy for allergic asthma: a systematic overview of systematic reviews." Clinical and translational allergy 7.1 (2017): 25.
4. Leas, Brian F., et al. "Effectiveness of indoor allergen reduction in asthma management: a systematic review." Journal of Allergy and Clinical Immunology 141.5 (2018): 1854-1869.
I hope this information is of help to you and your practice.
All my best.
Dennis K. Ledford, MD, FAAAAI