American journal of respiratory and critical care medicine
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Am. J. Respir. Crit. Care Med. · Jun 2020
Randomized Controlled TrialOmalizumab for Aspirin-Hypersensitivity and Leukotriene Overproduction in Aspirin-Exacerbated Respiratory Disease: A Randomized Trial.
Rationale: Aspirin-exacerbated respiratory disease is characterized by severe asthma, nonsteroidal antiinflammatory drug hypersensitivity, nasal polyposis, and leukotriene overproduction. Systemic corticosteroid therapy does not completely suppress lifelong aspirin hypersensitivity. Omalizumab efficacy against aspirin-exacerbated respiratory disease has not been investigated in a randomized manner. ⋯ The area under the logarithm level of urinary leukotriene E4 concentration versus time curve during an oral aspirin challenge was significantly lower in the omalizumab phase (median [interquartile range], 51.1 [44.5-59.8]) than in the placebo phase (80.8 [interquartile range, 65.4-87.8]) (P < 0.001). Ten of 16 patients (62.5%) developed oral aspirin tolerance up to cumulative doses of 930 mg in the omalizumab phase (P < 0.001). Conclusions: Omalizumab treatment inhibited urinary leukotriene E4 overproduction and upper/lower respiratory tract symptoms during an oral aspirin challenge, resulting in aspirin tolerance in 62.5% of the patients with aspirin-exacerbated respiratory disease.
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The stepwise approach to pharmacological treatment in adult asthma mandates that asthma treatment is progressively stepped up to achieve symptom control and reduce the risk of exacerbations and stepped down after a period of prolonged control. This review proposes that in adults without good asthma control, well-controlled asthma can only be achieved in approximately 70% of patients across the strata of severity, and only if there is a progressive increase in inhaled corticosteroid/long-acting β2 agonist therapy to a maintenance inhaled corticosteroid dose that causes the same magnitude of systemic side effects as oral prednisone at a 5-mg daily dose. ⋯ Finally, it is widely assumed that asthma symptom control equates to elimination of risk of asthma attacks, an assumption that may not apply to many patients, particularly those with more severe asthma. We propose that further research be undertaken to determine the optimal levels of asthma control and the potential value of different treatment targets, such as control of type-2 airway inflammation, that can be achieved with currently available treatment, based on efficacy, side effects, and cost.