The pathophysiology of airway dysfunction

Abstract

Asthma and chronic obstructive pulmonary disease (COPD) are distinct inflammatory disorders with differing pathophysiologic mechanisms, different clinical courses, and, therefore, distinct treatment strategies. Whereas in asthma airflow limitation is typically episodic and reversible, airflow limitation in COPD is progressive and only partially reversible. In contrast to asthma, which is characterized by an elevated number of eosinophils in the blood and the accumulation of elevated numbers of activated eosinophils, mast cells, and CD4+ T(H)2-lymphocytes in the lungs, the primary inflammatory cells present in the lungs of patients with stable COPD are neutrophils, macrophages, and CD8+ lymphocytes. Bronchoconstriction in COPD is largely regulated by cholinergically mediated vagal tone, and the pathologic processes of COPD further reduce airway patency. Bronchodilators, most notably anticholinergics, are recommended as first-line pharmacologic therapy for COPD. Proper use of inhaled anticholinergic medications has been shown to lead to significant reversibility of acetylcholine-mediated bronchoconstriction during both stable disease and exacerbations of COPD. For patients with asthma, current guidelines recommend anti-inflammatory medications, specifically inhaled corticosteroids and leukotriene-modifiers, as first-line therapy, making these agents the mainstay of asthma therapy. In contrast, the current guidelines for COPD management recommend that inhaled anti-inflammatory agents be tried in patients with COPD only as second-line therapy for patients who have severe to very severe airflow obstruction with frequent exacerbations and who remain symptomatic despite maximized bronchodilation with multiple inhaled bronchodilators. Hence, it is extremely important to understand the differences between the underlying pathogenesis and pathophysiology of COPD and those of asthma, as these differences dictate the implementation of distinctly different treatment options for these 2 diseases.