Progress in the Chronotherapy of Nocturnal Asthma
Bronchial asthma is a chronic airways disease. Symptoms include dyspnea, wheezy chest, cough, and fatigue. It is seldom a problem for those who suffer from the mild form of the disease. However, it is a significant and even life-threatening one for those
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Progress in the Chronotherapy of Nocturnal Asthma M.H. SMOLENSKY and G.E. D'ALONzo
A. Introduction Bronchial asthma is a chronic airways disease. Symptoms include dyspnea, wheezy chest, cough, and fatigue. It is seldom a problem for those who suffer from the mild form of the disease. However, it is a significant and even lifethreatening one for those prone to severe asthma. Asthma is characterized by persistent airways inflammation, airways hyperreactivity, and compromised pulmonary function (MARTIN 1993). All are reversible, at least to some extent, with medication and environmental control. Asthma severity varies between patients and even in the same patient over time. Most patients experience worsening of symptoms during the night; many experience symptoms only at night (DETHLEFSEN and REPGES 1985; TURNER-WARWICK 1988). Successful asthma management must address the major features of the disease - airways inflammation and hyperreactivity, compromised pulmonary function, and temporal patterning. This chapter addresses the chronotherapy (timed delivery of medication in proportion to biological need during the 24 h) of nighttime asthma. Since an understanding of the disease is central to discussing its chronotherapy with bronchodilator and anti-inflammatory medications, circadian rhythms in the epidemiology and physiology of the disease are first reviewed.
B. Day-Night Pattern of Acute Asthma The clock-time occurrence of acute asthma is not random during the 24 h, menstrual cycle, and year (DETHLEFSEN and REPGES 1985; 0RIE et al. 1964; TURNER-WARWICK 1988; WULFSOHN and POLITZER 1964). Several well-conducted epidemiologic and clinical investigations clearly establish the nighttime prevalence of the disease. Although historical accounts (ADAMS 1856; FLOYER 1698; SMITH 1860; TROUSSEAU 1865) described the nocturnal nature of the ailment, it was DETHLEFSEN and REPGES in Germany and TURNER-WARWICK in the United Kingdom who clearly established the nighttime occurrence of asthma. The German study involved more than 3,000 presumably diurnally active patients who maintained records of acute asthma during the washout phase of P. H. Redfern et al. (eds.), Physiology and Pharmacology of Biological Rhythms © Springer-Verlag Berlin Heidelberg 1997
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a medication trial. The clock time of the 1,631 recorded bouts of asthma was not random during the 24 h; asthma was several hundredfold more common during the nighttime sleep period than during the middle of the daytime activity span, when it was least common (Fig. 1). The epidemiologic study by TURNER-WARWICK focused on the extent to which asthma disrupted sleep in a large group of 7,729 noninstitutionalized patients, most of whom were under treatment with equal-interval, equal-dose bronchodilator and anti-inflammatory medications. Some 94% reported their sleep being disturbed by asthma at least one night per month, and 74% indicated that to be the case at least one night per week. Of great significance was the finding that sleep was compromised
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