Omalizumab in Asthma with Fixed Airway Obstruction: Post Hoc Analysis of EXTRA.

BACKGROUND: Although asthma is typically characterized by bronchodilator responsiveness (BDR), fixed airflow obstruction (FAO) occurs in ∼50% of patients with severe asthma. OBJECTIVE: Do FAO/BDR associate with efficacy of omalizumab, a monoclonal antibody that targets IgE? METHODS: In EXTRA, patients aged 12-75 years with inadequately controlled severe allergic asthma despite high-dose inhaled corticosteroids plus long-acting ß2-agonists were randomized to omalizumab (n = 427) or placebo (n = 423) for 48 weeks of treatment. In this post hoc analysis, high/low BDR were defined as ≥12%/<12% increases in baseline forced expiratory volume in 1 second (FEV1) after bronchodilator administration, respectively. FAO presence (+)/absence (-) were defined as baseline postbronchodilator FEV1/forced vital capacity <70%/≥70%, respectively. Poisson regression/analysis of covariance models were used to estimate exacerbation relative rate reductions (RRRs)/least-squares mean changes in FEV1, respectively. RESULTS: In patients with high BDR, omalizumab reduced exacerbations more than placebo over the 48-week treatment period regardless of FAO status (RRR [95% confidence interval (CI)]: FAO+, 59.8% [17.7-80.4%]; FAO-, 44.3% [16.6-62.8%]). Omalizumab improved FEV1 compared with placebo in the FAO-, high BDR subgroup (FEV1 change from baseline [95% CI] for omalizumab vs placebo, 0.065 L [-0.071 to 0.201 L] to 0.236 L [0.112-0.359 L]) across 48 weeks. This was not observed in patients with low BDR, irrespective of FAO. CONCLUSION: Omalizumab was more efficacious than placebo at reducing exacerbations in patients with high, but not low, BDR, regardless of the presence of FAO. Lung function improvement primarily occurred in FAO-, high BDR patients, suggesting that asthma with low BDR may represent a difficult-to-treat phenotype.

Angioedema with severe acute abdominal pain: Think of hereditary angioedema.

Angioedema can be either mast cell-(histamine-)mediated or bradykinin-mediated. Treatment approaches for the two types are very different, making differential diagnosis critical. Severe acute abdominal pain caused by intestinal angioedema is commonly misdiagnosed, especially when associated with bradykinin-mediated angioedema. After describing a typical clinical scenario and diagnostic journey of a patient with recurrent, undiagnosed abdominal pain due to hereditary angioedema (HAE), a rare variant of bradykinin-mediated angioedema, we delve into the classification and differential diagnosis of the various types of angioedema and provide an overview of appropriate management with an emphasis on the bradykinin-mediated types. Bradykinin-induced angioedema may be inherited or acquired and is infrequent compared to mast cell-mediated angioedema. HAE is a rare disease characterized by recurrent attacks of non-urticarial, nonpruritic edema usually affecting the face, respiratory tract, extremities, gastrointestinal tract, and genitalia. Unlike mast cell-mediated angioedema, painful abdominal symptoms are prevalent in bradykinin-mediated angioedema and are sometimes the only manifestation of an attack, increasing the likelihood of initial misdiagnosis as appendicitis or other forms of acute abdomen. It is important for gastroenterologists to be vigilant for the possibility of angioedema pathology in patients presenting with undiagnosed, recurrent, abdominal symptoms to facilitate accurate diagnosis and effective treatment.