Omalizumab,as a biological agent targeting IgE,is a recombinant humanized monoclonal antibody and the first targeted drug approved for treating moderate-to-severe bronchial asthma.By reviewing one case of aspirin-induced asthma complicated with nasosinusitis and otitis media,we discussed the value of omalizumab in the treatment of asthma and its complications,aiming to provide a reference for clinical practice.
奥马珠单抗是一种重组人源化单克隆抗体,为抗IgE靶向生物制剂,是全球首个获批治疗中至重度支气管哮喘的靶向治疗药物。本文对1例阿司匹林哮喘伴分泌性中耳炎及鼻窦炎患者进行回顾性分析,探讨奥马珠单抗在治疗哮喘及其合并症中的价值,为临床实践提供依据。.

In the phase III SYNAPSE study, mepolizumab reduced nasal polyp (NP) size and nasal obstruction in chronic rhinosinusitis with NP.
We sought to assess the efficacy of mepolizumab in patients from SYNAPSE grouped by comorbid asthma, aspirin-exacerbated respiratory disease (AERD), and baseline blood eosinophil count (BEC).
SYNAPSE, a randomized, double-blind, 52-week study (NCT03085797), included patients with severe bilateral chronic rhinosinusitis with NP eligible for surgery despite intranasal corticosteroid treatment. Patients received 4-weekly subcutaneous mepolizumab 100 mg or placebo plus standard of care for 52 weeks. Coprimary end points were change in total endoscopic NP score (week 52) and nasal obstruction visual analog scale score (weeks 49-52). Subgroup analyses by comorbid asthma and AERD status, and post hoc by BEC, were exploratory.
Analyses included 407 patients (289 with asthma; 108 with AERD; 371 and 278 with BEC counts ≥150 or ≥300 cells/μL, respectively). The proportion of patients with greater than or equal to 1-point improvement from baseline in NP score was higher with mepolizumab versus placebo across comorbid diseases (asthma: 52.9% vs 29.5%; AERD: 51.1% vs 20.6%) and baseline BEC subgroups (<150 cells/μL: 55.0% vs 31.3%; ≥150 cells/μL: 49.5% vs 28.1%; <300 cells/μL: 50.7% vs 29.0%; ≥300 cells/μL: 50.4% vs 28.1%). A similar trend was observed in patients without comorbid asthma or AERD. More patients had more than 3-point improvement in nasal obstruction VAS score with mepolizumab versus placebo across comorbid subgroups.
Mepolizumab reduced polyp size and nasal obstruction in chronic rhinosinusitis with NP regardless of the presence of comorbid asthma or AERD.

阿司匹林加重呼吸道疾病（aspirin-exacerbated respiratory disease，AERD）是以慢性鼻窦炎、哮喘以及环氧化酶-1（cyclooxygenase 1，COX-1）抑制剂不耐受为临床特征的一种疾病。发病机制主要是花生四烯酸代谢紊乱，表现为半胱氨酸白三烯的过量产生和前列腺素E2的水平不足。AERD临床症状隐蔽，且病情复杂，治疗难度大。治疗方法有健康教育、药物治疗、手术干预、阿司匹林脱敏和单克隆抗体治疗等，其中阿司匹林脱敏治疗是其特异性疗法。本文主要就AERD的临床特征、诊断、激发试验、脱敏治疗及其他治疗方法作一综述。.

OBJECTIVE: To assess the safety and efficacy of Aspirin desensitization combined with long-term Aspirin therapy in patients with Aspirinexacerbated respiratory disease (AERD).
METHODS: We searched the PubMed, Ovid, Cochrane Library, and Google Scholar databases from inception to October 2018 for articles in English. We only included randomized controlled trials and parallel or cross-over studies in which adults with AERD were randomly assigned to undergo Aspirin desensitization and receive long-term Aspirin therapy or placebo.
RESULTS: A total of 869 citations were retrieved, and 6 studies met the criteria for analysis. All studies indicated that nasal symptoms, asthma symptoms, or both improved significantly after Aspirin desensitization. In addition, most studies reported a decline in corticosteroid dosage (oral and inhaled). The 4 studies that reported nasal polyps did not demonstrate a change in nasal polyps with Aspirin therapy compared with placebo. The dropout rates in all studies reviewed ranged from 5.8% to 55.7%, and the most common adverse events were gastrointestinal symptoms.
CONCLUSIONS: Clearly, Aspirin desensitization and treatment are beneficial for AERD patients, with relief of nasal symptoms, improvement in asthma control, decrease in daily corticosteroid use, and no fatal adverse events. However, the long-term adverse effects of Aspirin desensitization and optimal dosage of Aspirin merit further investigation.

Aspirin-exacerbated respiratory disease (AERD) differs from aspirin-tolerant disease in part because of eosinophilic tissue infiltration and overexpression of arachidonic acid metabolic pathway components that lead to enhanced secretion of cysteinyl leukotrienes and prostaglandin (PG) D2 observed constitutively and paradoxically in response to aspirin and other COX inhibitors. We have previously demonstrated the capacity of IFN-γ to drive cysteinyl leukotriene expression and response.
We investigated eosinophils as a source of PGD2 production in patients with AERD.
Eosinophils were enriched from tissue and peripheral blood obtained from control subjects, patients with aspirin-tolerant disease, and patients with AERD. mRNA was extracted and evaluated for expression of hematopoietic prostaglandin D synthase (hPGDS). Expression of hPGDS protein was confirmed with Western hybridization and immunofluorescence staining. Cells were stimulated with aspirin, and secretion of PGD2 was quantified. CD34+ progenitor cells were isolated and matured into eosinophils in the presence or absence of IFN-γ and hPGDS mRNA, and PGD2 release was measured.
Gene expression analysis revealed that eosinophils from tissue and blood of patients with AERD display increased levels of hPGDS compared with asthmatic and control samples. Western hybridization confirmed the increase in hPGDS mRNA translated to increased protein expression. Immunofluorescence confirmed mast cells and eosinophils from tissue of patients with AERD and asthma demonstrated hPGDS expression, with higher levels in eosinophils from patients with AERD. Incubation of eosinophils from blood and tissue with aspirin stimulated PGD2 release. IFN-γ-matured eosinophil progenitors showed enhanced hPGDS expression and increased levels of PGD2 release at baseline and after aspirin stimulation.
In addition to mast cells, eosinophils represent an important source of PGD2 in patients with AERD and identify a new target for therapeutic intervention.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) have recently been implicated in the pathogenesis of asthma, but their regulation in patients with aspirin-intolerant asthma (AIA) remains unclear.
OBJECTIVE: We sought to characterize MDSC accumulation and pathogenic functions in allergic airway inflammation mediated by COX-1 deficiency or aspirin treatment in mice.
METHODS: Allergic airway inflammation was induced in mice by means of ovalbumin challenge. The distribution and function of MDSCs in mice were analyzed by using flow cytometry and pharmacologic/gene manipulation approaches.
RESULTS: CD11b(+)Gr1(high)Ly6G(+)Ly6C(int) MDSCs (polymorphonuclear MDSCs [PMN-MDSCs]) recruited to the lungs are negatively correlated with airway inflammation in allergen-challenged mice. Aspirin-treated and COX-1 knockout (KO) mice showed significantly lower accumulation of PMN-MDSCs in the inflamed lung and immune organs accompanied by increased TH2 airway responses. The TH2-suppressive function of PMN-MDSCs was notably impaired by COX-1 deletion or inhibition, predominantly through downregulation of arginase-1. COX-1-derived prostaglandin E2 promoted PMN-MDSC generation in bone marrow through E prostanoid 2 and 4 receptors (EP2 and EP4), whereas the impaired arginase-1 expression in PMN-MDSCs in COX-1 KO mice was mediated by dysregulation of the prostaglandin E2/EP4/cyclic AMP/protein kinase A pathway. EP4 agonist administration alleviated allergy-induced airway hyperresponsiveness in COX-1 KO mice. Moreover, the immunosuppressive function of PMN-MDSCs from patients with AIA was dramatically decreased compared with that from patients with aspirin-tolerant asthma.
CONCLUSIONS: The immunosuppressive activity of PMN-MDSCs was diminished in both allergen-challenged COX-1 KO mice and patients with AIA, probably through an EP4-mediated signaling pathway, indicating that activation of PMN-MDSCs might be a promising therapeutic strategy for asthma, particularly AIA.

BACKGROUND: Although the prevalence of aspirin-exacerbated respiratory disease (AERD) in western populations is high, AERD is rather rare in China, and few related studies have been published to date.
METHODS: We performed a prospective cohort investigation on the incidence of AERD in patients with chronic rhinosinusitis (CRS) in southern China. A literature search of the China Academic Journal Network Publishing Database was conducted to obtain an overview of the incidence of AERD in the Chinese population, and previous studies on the incidence of AERD were reviewed.
RESULTS: We found 2 patients with aspirin hypersensitivity among 351 consecutive CRS (309 with nasal polyps [NPs]) patients, suggesting a rate of 0.57% in the CRS population. Forty-five articles about AERD were obtained by Chinese-language literature searches. In total, 346 cases of AERD were reported during the past 30 years.
CONCLUSIONS: Given the large population of NPs in China, the prevalence of AERD is very low, and this may be related to the reduced levels of nasal tissue eosinophilia and subsequent low asthma comorbidity.

BACKGROUND: Herein, we report a case of life-threatening status asthmaticus in a young male presented with nasal polyps but without any history of anaphylaxis or asthma.
CONCLUSIONS: The patient had normal results from preoperative respiratory systemic examinations. The postoperative asthma, which started after an infusion of nonsteroidal anti-inflammatory drugs (NSAIDs), was severe and difficult to manage. A relationship between the NSAID infusion and the asthma attack was indicated. Flurbiprofen axetil, a nonselective COX2 inhibitor, is most likely the causative agent in this case, although there are no prior reports of asthma caused by this agent.
CONCLUSIONS: We concluded that flurbiprofen axetil evoked severe bronchospasm in this case. Patients who are sensitive to flurbiprofen axetil will usually react to other NSAIDs; therefore, other ordinary NSAIDs should be used with caution in hypersensitive patients. An intranasal ketorolac challenge in individuals with nasal polyps, which is a novel and safe alternative to aspirin challenge, may be recommended to rule out aspirin-exacerbated respiratory disease, prior to the systemic administration of NSAIDs.