Pathology of difficult asthma.

Severe asthma is poorly understood clinically, physiologically and pathologically. Although milder forms of asthma are generally easily treated, more severe forms remain refractory to the best current medical care. Both genetic and environmental elements are likely to play an important role in the development of severe disease. Physiologically, these patients often have air-trapping, airway collapsibility and loss of elastic recoil. The pathology demonstrates a heterogeneity of findings and is based mainly on adult studies. Some patients demonstrate continued eosinophilic inflammation despite the use of high doses of corticosteroids. At least one-third appear to have pathological changes inconsistent with classically described asthmatic pathology. Persistent inflammation can lead to structural changes involving the airways and perhaps the parenchyma as well. Finally, inflammation and structural changes appear to exist well into the lung periphery, out of reach of many inhaled medications. The importance of each of these factors in the development of severe disease probably varies from patient to patient. Understanding the commonalities of the pathology of severe asthma should, however, lead to the development of improved therapies.