The concept that there may be heterogeneity of the underlying pathology of asthma has a long pedigree: 80 years ago, Rackemann¹ suggested that a subgroup of patients with intrinsic asthma had disease driven by bacterial infection of the upper and lower respiratory tract and the authors of an early postmortem study² were struck by the heterogeneity of lower airway inflammatory response in fatal asthma. However, since then the prevailing view, largely driven by bronchial biopsy studies of limited numbers of patients with relatively mild disease, has been that there are more similarities than differences in the pathology of subtypes of asthma. Thus, asthma is currently viewed as a condition characterised by TH2 cytokine-mediated eosinophilic airway mucosal inflammation.^3,4

The development of simple methods to assess airway inflammation non-invasively using induced sputum which are applicable to a wide variety of patients⁵ has renewed interest in investigation of the pathological heterogeneity of asthma. Using this technique, Turner et al⁶ unexpectedly found that just under half of 34 patients studied during a minor asthma exacerbation had no sputum eosinophilia. Fahy et al⁷ made a similar observation in patients studied during a more significant exacerbation; many patients had sputum evidence of neutrophilic airway inflammation. Subsequently non-eosinophilic asthma has been shown to be present in 25% of patients presenting to an adult respiratory clinic with symptomatic asthma,^8,9 in patients with occupational asthma¹⁰ and in up to 50% of patients with asthma treated with high doses of inhaled corticosteroids.¹¹ The concept that non-eosinophilic asthma represents a pathologically distinct form of the disease is supported by work by Wenzel et al¹² showing that a subgroup of patients with …