Airways disease: phenotyping heterogeneity using measures of airway inflammation

Abstract

: Despite asthma and chronic obstructive pulmonary disease being widely regarded as heterogeneous diseases, a consensus for an accurate system of classification has not been agreed. Recent studies have suggested that the recognition of subphenotypes of airway disease based on the pattern of airway inflammation may be particularly useful in increasing our understanding of the disease. The use of non-invasive markers of airway inflammation has suggested the presence of four distinct phenotypes: eosinophilic, neutrophilic, mixed inflammatory and paucigranulocytic asthma. Recent studies suggest that these subgroups may differ in their etiology, immunopathology and response to treatment. Importantly, novel treatment approaches targeted at specific patterns of airway inflammation are emerging, making an appreciation of subphenotypes particularly relevant. New developments in phenotyping inflammation and other facets of airway disease mean that we are entering an era where careful phenotyping will lead to targeted therapy.

Figure 1

Sputum cytospins from different subjects with asthma illustrate the heterogeneity of the airway inflammation. In the upper left panel, the predominant cells are macrophages with a normal neutrophil and eosinophil count; this cytospin cannot be distinguished from a sample from a healthy control (paucigranulocytic asthma ×100 original magnification); the upper right panel shows combined neutrophilic and eosinophilic inflammation (×400 original magnification); the lower left panel shows neutrophilic inflammation (×400 original magnification); and the lower right panel shows eosinophilic inflammation (×400 original magnification). Adapted from Brightling [98]. (Romanowsky stain.)

Figure 2

Airway diseases are composed of a number of domains that can be assessed by several outcome measures. The combination of outcome measures allows for phenotyping the heterogeneity, which impacts on clinical management and research. AHR = airway hyperresponsiveness; BD = bronchodilator; BMI = body mass index; CRP = C-reactive protein; HRCT = high-resolution computed tomography, PEFR = peak flow reading; PFTs = pulmonary function tests.