Clinical Analysis of 77 Patients with Allergic Bronchopulmonary Aspergillosis in Peking Union Medical College Hospital.
Zhang Mingqiang,Gao Jinming
Zhongguo yi xue ke xue yuan xue bao. Acta Academiae Medicinae Sinicae
Objective To summarize the clinical features of allergic bronchopulmonary aspergillosis(ABPA)to facilitate its early diagnosis and treatment. Methods We retrospectively analyzed the clinical data of 77 patients who had been admitted to Peking Union Medical College Hospital from January 1996 to July 2015 with ABPA. Results The average age of these 77 patients(38 men and 39 women)was(41.8±18.3)years. The co-morbidities included bronchial asthma(n=74,96%)and pulmonary cystic fibrosis(n=3,4%). The main symptoms and signs of ABPA were chronic cough(100%),sputum production(97%),wheeze(86%),sputum plugs(25%),blood-stained sputum(18%),hemoptysis(9%),chest pain(9%),fever(47%),weight loss(30%),and night sweat(12%). Laboratory tests revealed elevated levels of blood eosinophils absolute count(87%),anti-aspergillus antigen-specific IgE(89%)and specific IgG(57%)as well as a positive result of Aspergillus antigen skin test(88%). Pulmonary function testing showed that the incidences of obstructive ventilation and diffusion dysfunction were 66% and 65%,respectively;in addition,bronchodilatation test showed positive result in 60% of the patients. The most common CT findings were central bronchiectasis(81%),patchy infiltrations(79%),pleural thickening(49%),mediastinal adenopathy(35%),nodular opacities(25%),mucoid impaction(21%),and fleeting infiltrations(35%). In addition,44 cases(58%)were misdiagnosed as tuberculosis,pneumonia,lung abscess,and/or lung cancer autoimmune diseases. Conclusions ABPA can be easily misdiagnosed. ABPA should be carefully considered in patients with asthma or pulmonary cystic fibrosis who also suffer from wheeze,sputum plugs,elevated eosinophils central bronchiectasis,and fleeting infiltrations.
10.3881/j.issn.1000-503X.2017.03.009
Effectiveness and Safety of Omalizumab in Patients with Allergic Bronchopulmonary Aspergillosis Complicated by Chronic Bacterial Infection in the Airways.
Tomomatsu Katsuyoshi,Oguma Tsuyoshi,Baba Tomohisa,Toyoshima Mikio,Komase Yuko,Taniguchi Masami,Asano Koichiro,
International archives of allergy and immunology
BACKGROUND:Allergic bronchopulmonary aspergillosis (ABPA) develops in the presence of predisposing conditions such as asthma and cystic fibrosis. Even ABPA accompanied by asthma is often complicated by chronic Pseudomonas aeruginosa or nontuberculous mycobacterial infection of the lower respiratory tract, rendering treatment with corticosteroids difficult. There have been several reports on the effectiveness of omalizumab, an anti-IgE antibody, in patients with ABPA. We analyzed the effectiveness and adverse effects of omalizumab in ABPA patients with chronic respiratory infections. METHODS:Using our nationwide survey database and published case reports, we identified patients with severe asthma and ABPA who fulfilled the International Society for Human and Animal Mycology criteria and who had been treated with omalizumab. Exacerbation rates, control of symptoms, doses of oral corticosteroids, and pulmonary function were evaluated. RESULTS:Among 25 patients with ABPA treated with omalizumab (median age 62 years, range 33-83 years), 12 patients had a chronic bacterial infection of the lower airways attributable to P. aeruginosa (n = 6) or nontuberculous mycobacteria (n = 6) at the initiation of omaliz-umab. Treatment with omalizumab reduced the frequency of exacerbations and systemic corticosteroid doses and improved pulmonary function. There were no significant adverse events or worsening of infection during treatment with omalizumab, except for injection-site reactions. CONCLUSIONS:Treatment with omalizumab was effective and safe in patients with ABPA, regardless of comorbid chronic respiratory tract infections.
10.1159/000507216
Allergic Bronchopulmonary Aspergillosis: A Case Report.
Cureus
Allergic bronchopulmonary aspergillosis (ABPA) is an underdiagnosed lung condition in patients with asthma and cystic fibrosis. Its clinical and diagnostic manifestations result from an allergic response to multiple antigens expressed by , which colonize the bronchial mucus. This report presents the case of a 73-year-old female patient referred to our hospital for uncontrolled asthma for 35 years. The diagnosis of ABPA was made on the basis of clinical symptoms, peripheral blood eosinophilia, elevated total serum immunoglobulin E, positive aspergillus serology, and bronchiectasis with mucoid impaction. Systemic corticosteroids and antifungal therapy came up with satisfactory clinical results.
10.7759/cureus.38778
Beneficial effects of Omalizumab therapy in allergic bronchopulmonary aspergillosis: A synthesis review of published literature.
Li Jian-Xiong,Fan Li-Chao,Li Man-Hui,Cao Wei-Jun,Xu Jin-Fu
Respiratory medicine
Omalizumab, a humanized mAb that binds to IgE, has been an effective therapy for patients with severe allergic asthma; however, there are few clinical trials examining the efficacy of Omalizumab in patients with allergic bronchopulmonary aspergillosis (ABPA) except some case reports. To assess the clinical and immunological effects of Omalizumab in ABPA patients, we made a synthesis review of 102 cases from 30 published literature, analyzed the effects of Omalizumab therapy in ABPA and conducted subgroup analyses to determine factors that influenced the therapy endpoints. We found that Omalizumab treatment not only provided a clinically important reduction in serum IgE, exacerbation rates and steroid requirement, but also showed attenuated asthma symptoms and improved pulmonary function parameters in patients with ABPA. Moreover, further discussion was made when interpretating the results. Double-blind, randomized, placebo-controlled trials are necessary to establish the efficacy and safety of this novel therapeutic intervention for ABPA patients.
10.1016/j.rmed.2016.11.019
Review of current and future therapeutics in ABPA.
Therapeutic advances in chronic disease
Allergic bronchopulmonary aspergillosis is an allergic pulmonary condition caused by hypersensitivity to antigens of found most commonly in patients with underlying asthma or cystic fibrosis. Host factors which alter the innate and adaptive immune responses to this abundant airborne fungus contribute to the development of chronic airway inflammation, bronchiectasis, and fibrosis. Traditionally, treatment has focussed on reducing fungal burden and immune response to fungal antigens. However, a significant proportion of patients continue to suffer recurrent exacerbations with progressive lung damage, and the side effect burden of existing treatments is high. New treatments including novel antifungal agents, monoclonal antibodies against aspects of the adaptive immune response as well as targeted immunotherapies may be better tolerated and achieve improved outcomes but have not yet been studied in large-scale randomised control trials.
10.1177/20406223211047003
Allergic Bronchopulmonary Aspergillosis.
Clinics in chest medicine
Allergic bronchopulmonary aspergillosis (ABPA) is a complex allergic disorder caused by immune reactions against Aspergillus fumigatus. ABPA most commonly complicates the course of patients with poorly controlled asthma. Patients commonly present with uncontrolled asthma, fleeting pulmonary opacities, and bronchiectasis. Pathogenetically, ABPA is characterized by the persistence of A. fumigatus in the airways and an exaggerated type-2 immune response. The interest in ABPA stems from the fact that bronchiectasis in ABPA can be prevented if the disorder is diagnosed timely and treated appropriately. Herein, we summarize the current concepts in the epidemiology, pathogenesis, diagnosis, and treatment of ABPA.
10.1016/j.ccm.2021.12.002
Pattern recognition pathways leading to a Th2 cytokine bias in allergic bronchopulmonary aspergillosis patients.
Becker K L,Gresnigt M S,Smeekens S P,Jacobs C W,Magis-Escurra C,Jaeger M,Wang X,Lubbers R,Oosting M,Joosten L A B,Netea M G,Reijers M H,van de Veerdonk F L
Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology
BACKGROUND:Allergic bronchopulmonary aspergillosis (ABPA) is characterised by an exaggerated Th2 response to Aspergillus fumigatus, but the immunological pathways responsible for this effect are unknown. OBJECTIVE:The aim of this study was to decipher the pattern recognition receptors (PRRs) and cytokines involved in the Aspergillus-specific Th2 response and to study Aspergillus-induced responses in healthy controls and ABPA patients. METHODS:Peripheral blood mononuclear cells (PBMCs) were stimulated with heat-killed Aspergillus conidia, various other pathogens, or PRR ligands. PRRs and cytokine pathways were blocked with PRR-blocking reagents, anti-TNF (Etanercept or Adalimumab), IL-1Ra (Anakinra) or IFNγ (IFN-gamma). ELISA and FACS were used to analyse cytokine responses. RESULTS:Aspergillus was the only pathogen that stimulated the Th2 cytokines IL-5 and IL-13, while Gram-negative bacteria, Gram-positive bacteria, Candida albicans, chitin, β-glucan or Toll-like receptor (TLR) ligands did not. Depletion of CD4(+) cells abolished IL-13 production. Blocking complement receptor 3 (CR3) significantly reduced IL-5 and IL-13, while blocking TLR2, TLR4 or dectin-1 had no effect. ABPA patients displayed increased Aspergillus-induced IL-5 and IL-13 and decreased IFNγ production compared with healthy controls. All biological agents tested showed the capability to inhibit Th2 responses, but also decreased Aspergillus-induced IFNγ. CONCLUSIONS AND CLINICAL RELEVANCE:Aspergillus conidia are unique in triggering Th2 responses in human PBMCs, through a CR3-dependent pathway. ABPA patients display a significantly increased Aspergillus-induced Th2/Th1 ratio that can be modulated by biologicals. These data provide a rationale to explore IFNγ therapy in ABPA as a corticosteroid-sparing treatment option, by dampening Th2 responses and supplementing the IFNγ deficiency at the same time.
10.1111/cea.12354
Exploring the immunopathology of type 2 inflammatory airway diseases.
Frontiers in immunology
Significant advancements have been achieved in understanding the roles of different immune cells, as well as cytokines and chemokines, in the pathogenesis of eosinophilic airway conditions. This review examines the pathogenesis of Chronic Rhinosinusitis with Nasal Polyps (CRSwNP), marked by complex immune dysregulation, with major contributions from type 2 inflammation and dysfunctional airway epithelium. The presence of eosinophils and the role of T-cell subsets, particularly an imbalance between Treg and Th17 cells, are crucial to the disease's pathogenesis. The review also investigates the pathogenesis of eosinophilic asthma, a unique asthma subtype. It is characterized by inflammation and high eosinophil levels, with eosinophils playing a pivotal role in triggering type 2 inflammation. The immune response involves Th2 cells, eosinophils, and IgE, among others, all activated by genetic and environmental factors. The intricate interplay among these elements, chemokines, and innate lymphoid cells results in airway inflammation and hyper-responsiveness, contributing to the pathogenesis of eosinophilic asthma. Another scope of this review is the pathogenesis of Eosinophilic Granulomatosis with Polyangiitis (EGPA); a complex inflammatory disease that commonly affects the respiratory tract and small to medium-sized blood vessels. It is characterized by elevated eosinophil levels in blood and tissues. The pathogenesis involves the activation of adaptive immune responses by antigens leading to T and B cell activation and eosinophil stimulation, which causes tissue and vessel damage. On the other hand, Allergic Bronchopulmonary Aspergillosis (ABPA) is a hypersensitive response that occurs when the airways become colonized by aspergillus fungus, with the pathogenesis involving activation of Th2 immune responses, production of IgE antibodies, and eosinophilic action leading to bronchial inflammation and subsequent lung damage. This analysis scrutinizes how an imbalanced immune system contributes to these eosinophilic diseases. The understanding derived from this assessment can steer researchers toward designing new potential therapeutic targets for efficient control of these disorders.
10.3389/fimmu.2024.1285598