Anti-IgE Therapy in Severe Aspirin-Exacerbated Respiratory Disease

Potential anti-IgE mechanisms for severe AERD examined
Potential anti-IgE mechanisms for severe AERD examined

ATLANTA, GA—At the 2017 AAAAI Annual Meeting, Masami Taniguchi, MD, PhD, from Sagamihara National Hospital, Japan, presented insight into the potential mechanisms of omalizumab as a treatment for severe aspirin-exacerbated respiratory disease (AERD).

In the oral session, Dr. Taniguchi aimed to describe the pathomechanism of induction of severe airway symptoms in AERD patients and described potential mechanisms of anti-IgE (omalizumab) as a treatment for AERD. He first described risk factors and protective factors for severe uncontrolled asthma in Japanese adult patients. Factors such as aspirin tolerance (odds ratio [OR] 3.0), obesity in females (OR 2.0), smoking (OR 1-2), older age (OR 1.5), long duration of asthma (OR 1.5), and nonatopy only in females (OR 1.5) were classified as risk factors. 

The specific features of AERD include aspirin hypersensitivity, severe asthma, nasal polyposis, and cysteinyl leukotriene (CysLT) overproduction, Dr. Taniguchi explained. The specific pathomechanisms in AERD patients vs. aspirin-tolerant asthma (ATA) patients include mast cell activation, platelet activation, and an investigation of possible basophil activation. In 1992, sodium cromoglycate (SCG) was found to have an acute bronchodilative effect only in patients with aspirin-intolerant asthma (AIA). Dr. Taniguchi reported that in a clinical study, 70% of stable AIA patients without inhaled corticosteroid (ICS) treatment saw significant improvement in pulmonary function "immediately after a single inhalation of SCG nebulized solution" whereas none of the ATA patients demonstrated bronchodilation after SCG inhalation. 

"These results suggest that airway mast cell activation is one of the most important pathomechanisms in AERD," he stated.

In describing the role of platelet activation in AERD, the percentages of platelet-adherent eosinophils, neutrophils, and monocytes in the blood of patients with AERD were much higher than ATA or control patients, according to a 2012 Laidlaw et al. study published in the journal Blood. The levels of all surface activation markers on platelets in AERD were significantly higher than those in patients with AT, chronic eosinophilic pneumonia or healthy controls (Mitsui C., Taniguchi M. et al. JACI 2016). "These results suggest that platelet activation may be the specific pathomechanism in AERD patients," Dr. Taniguchi added. Additional findings on the correlation of surface markers on platelet with urinary LTE4 concentration were presented, which supported the involvement of platelet activation in cysLT overproduction in AERD.

Basophils, however, were not found to be activated in AERD patients vs. ATA patients upon examining CD203c expression levels on basophils in peripheral blood of AERD and ATA patient populations. 

Dr. Taniguchi posed the following, "Why do AERD patients frequently show severe uncontrolled asthma? What is the mechanism of induction of severe airway symptoms in AERD patients?" Through multilogistic analysis, researchers determined that urinary LTE4 concentration was the most important risk factor for severe uncontrolled asthma in AERD.

There have been several AERD case reports on the clinical efficacy and tolerance to aspirin after treatment with omalizumab. Recently, a team of Spanish researchers reported in JACI that 5 of 6 AERD patients achieved complete tolerance to NSAIDs after 6 months of omalizumab. Its mechanism of action on AERD is still unclear, dr. Taniguchi reported. He conducted a study enrolling 21 adults with AERD who were started on omalizumab between July 2009 and September 2013. Patients had been treated with standard asthma therapy for at least 12 months prior to initiating omalizumab. Urinary biomarkers, asthma treatments, and symptoms pre- and post-omalizumab treatment were analyzed. 

"To the best of our knowledge, this is the first study demonstrating that omalizumab showed clinical effectiveness and inhibited mast cell activation and leukotriene overproduction in AERD," stated Dr. Taniguchi. The rate or response to omalizumab in patients with AERD was 86%. Omalizumab improved both upper and lower respiratory symptoms with significant reductions in urinary LTE4 and PGD2M.