Randomised, placebo controlled trial of itraconazole in the treatment of fungal sensitised patients with severe asthma and without allergic bronchopulmonary aspergillosis (ABPA)

Tropical pulmonary eosinophilia (TPE) is characterized by lung tissue and peripheral blood eosinophilia. Serum total IgE is also markedly increased in TPE. However, an association with asthma or other hypersensitivity conditions has not been described. During the diagnostic workup of three patients eventually confirmed to have TPE, hypersensitivity to the fungus, Aspergillus Fumigatus was found. However, there was no evidence of diseases of aspergillus hypersensitivity such as severe asthma with fungal sensitization (SAFS) and allergic bronchopulmonary aspergillosis (ABPA). This association however raises the possibility of a future risk of these potentially serious allergic respiratory manifestations.RiassuntoL’eosinofilia polmonare tropicale (TPE) è caratterizzata da tessuto polmonare e eosinofilia nel sangue periferico. Anche il siero IgE totale è notevolmente aumentato in TPE. Tuttavia, un’associazione con asma o altre condizioni di ipersensibilità non è stata descritta. Durante l'iter diagnostico di tre pazienti, che alla fine si sono rivelati presentare TPE, ipersensibilità al fungo, è stato trovato l’Aspergillus fumigatus. Tuttavia, non vi era alcuna evidenza di malattie di Aspergillus ipersensibilità come l'asma grave con sensibilizzazione fungina (SAF) e aspergillosi broncopolmonare allergica (ABPA). Questa associazione pone tuttavia la possibilità di un rischio futuro di queste potenzialmente gravi manifestazioni allergiche respiratorie.

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A Phase 2a Randomized, Double-Blind, Placebo-Controlled Trial with Withdrawal Design of AZD1419, a Toll-9 Agonist in Adults with Eosinophilic, Moderate to Severe Asthma

10.1164/ajrccm-conference.2019.199.1_meetingabstracts.a7361 ◽

2019 ◽

Author(s):

I. Psallidas ◽

V. Backer ◽

P. Kuna ◽

L. Molnar ◽

M. Aurell ◽

...

Keyword(s):

Severe Asthma ◽

Controlled Trial ◽

Double Blind ◽

Double Blind Placebo ◽

Withdrawal Design

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Differential response to biologics in a patient with severe asthma and ABPA: a role for dupilumab?

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-020-00454-w ◽

2020 ◽

Vol 16 (1) ◽

Cited By ~ 2

Author(s):

Carlo Mümmler ◽

Bernd Kemmerich ◽

Jürgen Behr ◽

Nikolaus Kneidinger ◽

Katrin Milger

Keyword(s):

Lung Function ◽

Severe Asthma ◽

Allergic Bronchopulmonary Aspergillosis ◽

Oral Steroid ◽

Case Presentation ◽

Oral Steroids ◽

Treatment Responses ◽

Oral Steroid Therapy ◽

Switching Treatment ◽

Severe Hypersensitivity Reaction

Abstract Background Allergic bronchopulmonary aspergillosis (ABPA) is a severe hypersensitivity reaction to aspergillus species colonizing the airways of patients with asthma or cystic fibrosis. Biologics including anti-IgE and anti-IL5 antibodies have strongly changed the treatment of severe asthmatics and have partly been reported to be effective in the treatment of ABPA. Recently, dupilumab, an anti-IL4-Rα antibody which inhibits signaling by the Th2-cytokines IL4 and IL13, has been approved for the treatment of severe asthma. Case presentation Here, we report the case of a 49-year-old woman with severe asthma and ABPA, who was uncontrolled despite maximum inhalative therapy, anti-IL5-Rα antibody and continuous oral steroid therapy. Moreover, trials of itraconazole as well as omalizumab showed insufficient efficacy. Lung function revealed peripheral obstruction. FeNO and IgE were increased, eosinophils were suppressed under treatment while marked increases had been documented previously. Switching to dupilumab led to a complete resolution of pulmonary symptoms, resolution of exacerbations and complete withdrawal of oral steroids. A drastic improvement in lung function was noted, with an increase in FEV1 of almost 1 l. FeNO was normalized and IgE strongly reduced. Conclusion Our case highlights that a patient may exhibit differential treatment responses to the currently available asthma biologics and suggests switching treatment if outcome is insufficient. A potential role for dupilumab in the treatment of ABPA warrants future studies.

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