New Insights Into the Understanding of Asthma* Robert J. Davies, MD; Jiahua Wang, MD; Muntasir M. Abdelaziz; Moises A. Calderon, MD; Omer Khair, MSc; Jagdish L. Devalia, MSc, PhD; and Csaba Rusznak, MD The prevalence of asthma is increasing, despite better understanding of its pathogenesis and improved treatments. During the past 10 years, the perception of asthma has shifted from a disease primarily characterized by altered smooth muscle function to one mainly characterized by chronic inflammation. This article reviews the evidence supporting the relationship of inflammation in both the upper and lower airways, focusing on intermittent seasonal disease as well as on the more chronic and severe forms of asthma, including that associated with aspirin intolerance. It also presents evidence to support a pivotal role for the epithelial cell, together with the mast cell and the eosinophil, in initiating and maintaining inflammation in the upper and lower airways. (CHEST 1997; 111:2S-10S) Key words: airway inflammation; asthma; eosinophil; epithelial cell; granulocyte-macrophage colony-stimulating factor; interleukin; leukotriene; mast cell; rhinitis; tumor necrosis factor A sthma is one of the few chronic diseases in the developed world that is increasing in prevalence, despite better understanding of its pathogenesis and improved treatments. This paradox necessitates con- tinuing efforts both to review current knowledge and to search for new insights into the causes of this complex disorder. The past decade has seen a major shift in the perception of asthma. It has gone from being considered a disease primarily characterized by altered smooth muscle function to one whose main abnormality is chronic inflammation. The recent report of the Global Initiative for Asthma 1 succinctly defines asthma as a chronic inflammatory disorder of the airways in which many cells play a role; in particular, mast cells, eosinophils, and T lymphocytes. In susceptible persons, this inflammation causes recurrent episodes of wheezing, breathlessness, chest tightness, and cough, particu- larly at night and in the early morning. These symptoms are usually associated with widespread but variable airflow limitation that is at least partly reversible, either spontaneously or with treatment. Two patterns of asthma are discussed in this report: an intermittent form, involving exacerbations of symptoms separated by weeks or months of normal lung function without symptoms, and a persistent form of varying severity. On the basis of biopsy and lavage studies of the mucosa of both the nose and the airways of the lung, indexes of inflammation can be compared between normal persons and patients who have rhinitis and asthma of varying severity. Similar studies also make it possible to analyze the effects of treatment with anti-inflammatory drugs and bronchodilators 2,3 on airway inflammation. These studies not only allow a review of current therapy, they also indicate the direction new drug development should take and establish the criteria on which their efficacy should be judged. This article reviews the evidence for inflammation in both the upper and lower airways, focusing on intermittent seasonal disease and on the more chronic and severe forms of asthma, including that associated with aspirin intolerance. It also presents evidence to support a pivotal role for epithelial cells, together with mast cells and eosinophils, in the initiation and persistence of airway inflammation. Forms of Asthma Seasonal Rhinitis and Intermittent Asthma Evidence for the central role of the mast cell and the eosinophil in seasonal and intermittent disease of *From the Academic Department of Respiratory Medicine, St. Bartholomew’s and the Royal London School of Medicine and Dentistry, The London Chest Hospital, London, United King- dom. Reprint requests: Dr. Davies, Academic Department of Respira- tory Medicine, St. Bartholemew’s and the Royal London School of Medicine and Dentistry, The London Chest Hospital, Bonner Road, London E2 9JX, United Kingdom 2S Asthma Management: Perspectives and Paradigms in a Changing Environment