• Neutrophils
• eosinophils
• severe asthma
• apoptosis
• induced sputum
• asthma
• eosinophil biology
• neutrophil biology

Patients with severe asthma make up a relatively small proportion of the total population of patients with asthma yet account for a disproportional amount of asthma-related morbidity and healthcare utilisation.1 2 These patients are usually highly symptomatic, difficult to treat and can be extremely refractory to current treatments. As a consequence, understanding the mechanisms underlying this particular form of asthma is of paramount importance.

Morphological examination of the asthmatic airway reveals epithelial desquamation, thickening of the reticular basement membrane, mucus gland hyperplasia, goblet cell differentiation, angiogenesis and smooth muscle hypertrophy.3 In addition to these structural changes, an inflammatory cell infiltrate is evident within the airways comprising eosinophils, mast cells, lymphocytes and neutrophils. While eosinophils are the most characteristic inflammatory cell type present in mild to moderate asthma, the neutrophil seems to take centre stage more often in patients with severe disease. In fact, the neutrophil is one of the earliest inflammatory cells recruited to the airways following allergen exposure and is particularly evident in bronchoalveolar lavage samples and bronchial and transbronchial biopsies from patients with corticosteroid-resistant asthma, occupational asthma and fatal asthma as well as those with acute exacerbations.4–6 Furthermore, measures of asthma severity such as forced expiratory volume in 1 s correlate directly with the number of neutrophils present in the sputum and bronchial wall.7 8 There is also evidence of neutrophil activation and impaired function in the asthmatic airway.9 10 Moreover, neutrophil elastase is recognised to be highly histotoxic and results in epithelial and eosinophil activation, increased vascular permeability and promotion of transforming growth factor β release which is linked to airways remodelling.

Given the propensity of neutrophils to die quite readily by ‘constitutive’ (ie, inbuilt time-dependent) apoptosis when studied in vitro,11 one major puzzle …