Page 41 - Comprehensive treatment of patients with glucocorticoid-dependent severe asthma

Late onset non-atopic, inflammation predominant phenotype with fixed airflow limitation
Late onset, non-atopic asthma has been regarded as a separate phenotype for many decades and was called “intrinsic asthma” by Rackemann in 1947 [110]. He described “intrinsic asthma” as a disease characterized by later onset in life, female predominance, higher degree of severity, and more frequent association with rhinosinusitis and nasal polyposis. Later it became clear that this phenotype was also frequently associated with aspirin sensitivity [111-113], distal airway inflammation [111;114;115] and persistent eosinophilia [116].
Chronic rhinosinusitis with nasal polyposis is strongly associated with asthma severity [117;118] and represents a risk factor for loss of asthma control [119] and frequent severe asthma exacerbations [120]. Very often patients with severe asthma who do not report nasal symptoms appear to have chronic rhinosinusitis on CT-scanning or after nasal endoscopy [121;122]. This implies that in patients with severe refractory asthma investigation of the sinuses should be part of the routine assessment
Treatment of chronic rhinosinusitis and nasal polyposis, either surgical or medical, has been shown to improve asthma control, airway inflammation and lung function [119;123]. In patients with nasal polyposis, medical treatment appeared to be superior to surgical treatment [123].
Chronic rhinosinusitis with nasal polyposis is often associated with aspirin sensitivity [112], but many patients with nasal polyposis have severe disease without exposure [111] or sensitivity to these drugs and in about half of the patients, adequate control of asthma can only be achieved with oral corticosteroids [124].
Proposed targeted therapies for patients with aspirin induced asthma include aspirin desensitization [125-127] and leukotriene modifiers [128;129]. Aspirin desensitization has been shown efficacious in several controlled and uncontrolled studies [125-127], although there are still unresolved questions with respect to optimal dosing and length of treatment. Leukotriene receptor antagonists [129] and synthesis inhibitors [130] have been demonstrated to improve control of asthma [129] and sinonasal symptoms [130] in aspirin sensitive patients with moderately severe asthma.
Current treatment of severe asthma
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