Over the past two decades, increasing evidence has shown that, in patients with chronic airways disease, viral infection is the most common cause of exacerbation. This review will examine the evidence for viral-induced exacerbations of asthma and chronic obstructive lung disease and the potential mechanisms by which viruses cause exacerbations. Attention will be focused on rhinovirus, the most common cause of respiratory exacerbations. Exacerbations due to rhinovirus, which infects relatively few cells in the airway and does not cause the cytotoxicity of other viruses such as influenza or respiratory syncytial virus, are particularly poorly understood. While the innate immune response likely plays a role in rhinovirus-induced exacerbations, its precise role, either adaptive or maladaptive, is debated. Because current treatment strategies are only partially effective, further research examining the cellular and molecular mechanisms underlying viral-induced exacerbations of chronic airways diseases is warranted. 1. Introduction Readers of this paper who care for patients with asthma will be familiar with the following scenario. A patient with recurrent cough and wheeze presents to the clinic for evaluation. The patient states that the only time she has respiratory symptoms is fall, winter, and spring following “colds.” She has no symptoms in the summer, or between colds. She denies she has asthma and does not feel the need to take inhaled steroids even though she has been prescribed them in the past. My response to this patient, and the premise of this review, is that many patients have asthma which is only triggered by viral upper respiratory tract infections. Nevertheless, the role of viral infections in the exacerbation of asthma, chronic obstructive disease (COPD), and other chronic airways diseases was almost completely ignored until the late 1990s, when more sensitive methods of viral detection were developed. While the emphasis of allergic sensitization in the pathogenesis in asthma is strongly justified, serious exacerbations of this disease are more likely to relate to viral infection rather than allergen exposure (Table 1). Table 1: Causes of asthma exacerbation. Exacerbations constitute the major cause of morbidity and mortality in asthma and COPD, and therefore vigorous attention towards the problem of exacerbations is warranted. What is the evidence for viral-induced exacerbations of asthma and COPD, and why was the role of viral infection ignored for so long? It was once thought that rhinovirus and other cold viruses did not infect the lower
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