Nocturnal Asthma: Mechanisms and Therapy
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© Springer-Verlag New York Inc. 1997
Nocturnal Asthma: Mechanisms and Therapy A. Di Stefano, M. Lusuardi, A. Braghiroli, and C. F. Donner Salvatore Maugeri Foundation, IRCCS, Medical Center of Rehabilitation, Division of Pulmonary Disease, 28010 Veruno (NO), Italy
Abstract. Nocturnal worsening of symptoms affects a large number of patients suffering from asthma. Recent studies show that airway inflammation underlies nocturnal awakenings and increased airway hyperreactivity. These studies, however, yield conflicting results concerning the pathogenesis of the disease, making it difficult to understand the mechanisms involved in sustaining nocturnal asthma. This article reviews the principal pathogenetic mechanisms of nocturnal asthma, showing that worsening of symptoms at night may be the result of a more severe disease as well as of increased inflammation at night and higher susceptibility. We also review the pharmacologic treatment of nocturnal asthma which is mainly based on antiinflammatory treatment with inhaled or oral steroids or combined therapies with theophylline and b2 agonists. The activity of antileukotrine compounds in asthma is also summarized. Key words: Asthma—Biopsy—Bronchoalveolar lavage—Inflammation— Circadian rhythm. Introduction Nocturnal asthma is characterized by worsening at night of symptoms such as wheezing, chest tightness, breathlessness, cough, increased nocturnal awakenings between 3 and 5 in the morning and, from a pathophysiologic point of view, by increased bronchial reactivity and reduction of pulmonary function. Nocturnal awakenings are a common feature of asthma, despite current treatment. More than one third of patients wake nightly, and about three fourths wake at least once a week [56]. Furthermore, nocturnal worsening of symptoms and the related awakening constitute events at risk for patients, as shown by the higher frequency of deaths in the hospital between 12 p.m. and 8 a.m. in patients with asthma [13]. Offprint requests to: Antonnio Di Stefano, Salvatore Maugeri Foundation, IRCCS, Medical Center of Rehabilitation, Division of Pulmonary Disease, Via Revislate 13, 28010 Veruno (NO), Italy
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Postmortem studies on the pathology of asthma show that lumen occlusion by mucous plugs, epithelial shedding, thickening of the basement membrane, edema, infiltration of eosinophils in the submucosa, hyperplasia of mucous glands, and hypertrophy of bronchial smooth muscle are characteristic features of asthma deaths [18, 19, 48]. More recently, studies performed on bronchial biopsies and bronchoalveolar lavage (BAL) of patients with mild symptomatic asthma have confirmed the increased numbers of inflammatory cells and structural alterations, supporting the view that the inflammatory process plays a key role in sustaining symptoms of asthma [7, 17]. The analysis of bronchial inflammation has only recently been extended to nocturnal asthma, and the findings show that the characteristic inflammatory picture seen in severe and mild asthma is also true for patients
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