Severe asthma: definition, diagnosis and treatment

Abstract

Background: A minority of patients with asthma have uncontrolled or partially controlled asthma despite intensive treatment. These patients present a special challenge because of the extensive diagnostic evaluation that they need, insufficient evidence regarding personalized treatments, and their high consumption of health-care resources.

Methods: The definition, diagnosis, and treatment of severe asthma are presented on the basis of a selective literature review and the authors' clinical experience.

Results: Severe asthma is present, by definition, when adequate control of asthma cannot be achieved by high-dose treatment with inhaled cortico - steroids and additional controllers (long-acting inhaled beta 2 agonists, montelukast, and/or theophylline) or by oral corticosteroid treatment (for at least six months per year), or is lost when the treatment is reduced. Before any further treatments are evaluated, differential diagnoses of asthma should be ruled out, comorbidities should be treated, persistent triggers should be eliminated, and patient adherence should be optimized. Moreover, pulmonary rehabilitation is recommended in order to stabilize asthma over the long term and reduce absences from school or work. The additional drugs that can be used include tiotropium, omalizumab (for IgE-mediated asthma), and azithromycin (for non-eosinophilic asthma). Antibodies against interleukin-5 or its receptor will probably be approved soon for the treatment of severe eosinophilic asthma.

Conclusion: The diagnosis and treatment of severe asthma is time consuming and requires special experience. There is a need for competent treatment centers, continuing medical education, and research on the prevalence of severe asthma.

Figure 1

Diagnosing and treating severe asthma ^*1Currently possible in Germany only within clinical trials ^*2In case of low eosinophil count (<0.2 × 10⁹/L during cessation of systemic corticosteroid therapy) and considering contraindications for macrolide therapy ICS, inhaled corticosteroid; LABA, long-acting beta 2 agonist; ABPA, allergic bronchopulmonary aspergillosis; CSS, Churg–Strauss syndrome; AERD, aspirin-exacerbated respiratory disease (ASA intolerance); IgE, immunoglobulin E; IL, interleukin

Figure 2

Neuronal control of airway tone and effect of bronchodilators (simplified). In parasympathetic ganglia in the airway wall, preganglionic parasympathetic nerve fibers (from the vagus nerve) synapse on postganglionic parasympathetic neurons that lead to bronchoconstriction by releasing acetylcholine (mediated in particular by the M3 receptor on the airway smooth muscle). Postganglionic sympathetic fibers do not innervate the human airway smooth muscle but affect airway tone indirectly (via innervation of the parasympathetic ganglia and control of vessel permeability and catecholamine release). Long-acting muscarinic antagonists (LAMAs) lead to bronchodilation by inhibiting muscarinic receptors (particularly the M3 receptor). Long-acting beta 2 agonists (LABAs) cause bronchodilation in particular by stimulating beta 2 receptors on the smooth muscle of the airways (27)