IL13 May Play an Important Role in Developing Eosinophilic Chronic Rhinosinusitis and Eosinophilic Otitis Media with Severe Asthma

Abstract

A woman in her 50s was a super responder to benralizumab administered for the treatment of severe bronchial asthma (BA) with eosinophilic chronic rhinosinusitis with nasal polyp (ECRS) and eosinophilic otitis media (EOM). She exhibited the gradual exacerbation of ECRS/EOM despite good control of BA approximately 1 year after benralizumab initiation. Therefore, the treatment was switched to dupilumab, and the condition of the paranasal sinuses and middle ear greatly improved with the best control of her asthma. The patient reported that her physical condition was the best of her life. However, she developed a pulmonary opacity on chest computed tomography after 6 months. Histological examination of the lung parenchyma and cell differentiation of the bronchoalveolar lavage fluid indicated atypical chronic eosinophilic pneumonia, and treatment was switched to mepolizumab. Similarly to the period of benralizumab treatment, exacerbation of ECRS/EOM reduced her quality of life approximately 10 months after the administration of mepolizumab. Dupilumab was again introduced as a replacement for mepolizumab. The clinical course and consideration of the interaction between inflammatory cells led us to speculate that interleukin-13 could play a key role in the development of ECRS/EOM with severe BA.

Efficacy of Biologics on Refractory Eosinophilic Otitis Media Associated with Bronchial Asthma or Severe Uncontrolled CRSwNP

“…Since multiple cytokines, including IL-4, IL-13, and IL-5, are involved in the eosinophilic type-2 inflammation, various molecular targeted drugs have been used in the treatment of patients with allergic or eosinophilic diseases and were introduced as a treatment modality for type-2 refractory disorders [12,13,27]. In this scenario, the success in targeting specific immunologic mediators in asthma with biological drugs has led to an interest in the use of a similar therapeutic approach as an adjunct treatment for CRSwNP [28].…”

“…In this scenario, the success in targeting specific immunologic mediators in asthma with biological drugs has led to an interest in the use of a similar therapeutic approach as an adjunct treatment for CRSwNP [28]. So, monoclonal antibodies, such as anti-IgE (Omalizumab), anti-IL-5 (Mepolizumab, Benralizumab, Reslizumab), and anti-IL-4 and IL-13 (Dupilumab), have emerged as effective treatments for type-2-inflammation-related diseases [26], including EOM, a condition often resistant to conventional treatments (leukotriene receptor antagonist (LTRA), mucoregulator, macrolide antibiotics, topical application of corticosteroids, thus requiring oral corticosteroids (OCS)), with frequent recurrence in the case of treatment suspension [13]. Furthermore, previous works suggest that the improvement of EOM could be reached by optimizing asthma treatment, including corticosteroids; nevertheless, it is well known that long term use of the last one may lead to higher risk of serious adverse effects [29].…”

“…In fact, the accumulation of highly viscous effusion and granulation with eosinophil infiltration in the middle ear causes bulging of the eardrum and frequently results in its perforation. Therefore, a combination of hearing disturbance with CRSwNP and SEA worsens considerably the quality of life (QoL) [13].…”

“…Although EOM in association with ECRS received the attention of the scientific community in the 1990s as new disease entities [13,14], diagnostic criteria were set later in 2011 and implemented with a severity classification [1,2,12]. According to Iino et al [1], a major criterion (otitis media with effusion or chronic otitis media with eosinophil-dominant effusion) and two or more minor criteria (highly viscous middle ear effusion; resistance to conventional treatment for otitis media; association with bronchial asthma; association with nasal polyposis) are needed to assess the proper diagnosis of EOM.…”

“…EOM is considered a type-2 (Th2) inflammatory disease, as it contains numerous eosinophils and high concentrations of biomarkers of the type-2 inflammation, such as immunoglobulin (Ig)-E, eosinophil cationic protein (ECP), and interleukin (IL)-5 [1,2]. Since current medical treatment, including local and systemic corticosteroids, is notoriously challenging and surgery is often ineffective [13], new therapeutic strategies are required. Biologic drugs, such as anti-IgE and anti-IL-5, anti-IL-4/IL-13 monoclonal antibodies, are currently being used with clinical success in patients with type-2 diseases, such as asthma and CRSwNP [2], and only recently some authors [12] suggested their efficacy also in the treatment of comorbid EOM.…”