Here, we conducted a variety of questionnaires according to individual characteristics to assess the effectiveness of omalizumab on allergic asthmatics thoroughly and found that anti-IgE treatment could improve life quality of allergic asthmatics with diverse comorbidities. This study also suggested that changes in eosinophil may be important in the comprehensive assessment of the efficacy of omalizumab treatment.
In this study, a significant improvement was observed in FEV1/FVC%, FeNO, ACT, and mini-AQLQ scores, consistent with previous studies.23,24 Until now, most research merely stresses the importance of omalizumab in alleviating asthma symptoms, minimizing future risks of exacerbation, and improving the quality of daily life in allergic asthmatics.16,25 Patients with CVA are often not taken seriously, and few clinical studies of omalizumab on allergic asthma would spare an effort to evaluate its effectiveness on CVA. Epidemiology shows that CVA is the leading cause of chronic cough in China.26 In order to fill this gap, our study added LCQ as an indicator of the efficacy of omalizumab on CVA,27 and a significant improvement in LCQ was observed.
Allergic asthma is a complex disease often associated with diverse complications like AR, which play a detrimental role in controlling asthma symptoms and minimizing the future risk of exacerbation.6 AR is a common complication of allergic asthma and is considered to share similar physiological and pathological features with allergic asthma.28 There were 81.3% of allergic asthmatics implicated with AR in our study. omalizumab has been shown to be effective in suppressing allergic nasal inflammation, ameliorating nasal symptoms, and improving AR-specific quality of life.29,30 One study using data from the SOLAR trial indicated that response in asthma following omalizumab treatment for asthma is also significantly related to an increased probability of improvement in rhinitis.31 Consistently, patients with asthma and co-existing AR in our study benefiting from omalizumab therapy also experienced a significant improvement in rhinitis-specific quality of life.
Asthmatics with anxiety have enhanced perception of bronchoconstriction, and accurate perception, in turn, increases anxiety.32 One randomized controlled trial indicated that interventions reducing anxiety could improve asthmatic children’s health.33 In this study, we evaluated the effects of omalizumab on anxiety in allergic asthmatics using a SAS questionnaire and omalizumab was found to reduce anxiety feelings in allergic asthmatics. The combined results of these studies suggested that anxiety and asthma are not mutually exclusive, and managing anxiety may improve asthma management and vice versa. Additionally, such results that omalizumab improved anxiety alongside improvements in asthma were also found in chronic rhinosinusitis34 and chronic spontaneous urticaria35 treated with omalizumab.
Eosinophils are a type of granulated innate immune cells that are involved in diverse inflammatory responses. In asthma, eosinophils are typically recruited to tissues during type 2 inflammatory responses and play an essential role in airway inflammation.18 In 2006, Noga et al. found that omalizumab could induce eosinophils apoptosis.36 Likewise, one post hoc analysis analyzed data from 8 randomized trials of omalizumab and concluded that omalizumab treatment was associated with circulating eosinophil count reduction.37 Hanania et al. found that the subgroup with a peripheral blood eosinophil count of more than 260 cells/µL had lower exacerbation frequency after 48 weeks of omalizumab therapy.38 On the contrary, another prospective real-world study suggested that omalizumab initiation in asthmatics resulted in fewer exacerbations, fewer hospitalizations, and higher ACT scores regardless of blood eosinophil count.39 Therefore, we supposed that it was not a key issue that the number of circulating eosinophils change mattered, but rather their functions altered after omalizumab treatment.
Previously, it has been demonstrated that eosinophils could express major MHCⅡand co-stimulatory molecules CD40, CD80, and CD86, which are necessary for antigen uptake and process.40 One study had demonstrated that blockade of CD86 could inhibit the production of IgE and Th2 cytokines and inhibit recruitment of eosinophils to the lung in animal experiments.41 Our study showed that the expression of co-stimulatory molecules CD40, CD80, and CD86 on eosinophils reduced statistically after omalizumab treatment. In addition, the improvements in FEV1/FVC% predicted and MEF25% after omalizumab treatment were positively associated with the decline in CD80+ eosinophils. These findings suggested that the function of eosinophils as secondary APCs might have a subsidiary role in the mechanisms of anti-IgE treatment for asthma, and omalizumab may alter the ability of eosinophils in antigen-presenting. To the best of our knowledge, this is the first study demonstrating an association between surface expression of co-stimulatory molecules on eosinophil and anti-IgE treatment.
Eotaxin-1, a member of the C-C motif chemokine ligand(CCL) family, also called CCL11, was firstly discovered by Williams et al. in 1994 and demonstrated to play a crucial role in eosinophil accumulation in allergic airways in vivo.42 Subsequently, human eotaxin was cloned and found to be an effective and selective eosinophil chemoattractant through binding to and activating its high-affinity chemokine receptor CCR3 expressed on eosinophils.43,44 Afterward, it was demonstrated that the expression of eotaxin was higher in airways and the induced sputum in allergic asthmatics than in normal controls.45,46 Moreover, asthma patients with exacerbations presented significantly higher plasma eotaxin levels than stable asthmatics.47 Our study discovered that the serum eotaxin-1 levels decreased significantly in omalizumab responders after 16-week omalizumab treatment for the first time. These findings suggested that omalizumab may impair the ability of eosinophil recruitment to the lung. Taken together, the experimental results confirmed that the multifaceted function of eosinophils was altered with effective treatment with omalizumab.
There existed several limitations in our study. Firstly, the sample size was relatively small, and larger sample size is required to verify these findings. Secondly, as omalizumab has been applied to treat severe asthma clinically for many years and patients with a high degree of compliance with the indications tend to be treated very well, we didn’t recruit enough non-responders to omalizumab treatment as control group. Thirdly, detailed in vitro experiments need to be designed to further validate the effect of omalizumab on eosinophil chemotaxis and antigen-presenting function.