Chronobiology and chronotherapy of allergic rhinitis and bronchial asthma

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Abstract

Study of the chronobiology of allergic rhinitis (AR) and bronchial asthma (BA) and the chronopharmacology and chronotherapy of the medications used in their treatment began five decades ago. AR is an inflammatory disease of the upper airway tissue with hypersensitivity to specific environmental antigens, resulting in further local inflammation, vasomotor changes, and mucus hypersecretion. Symptoms include sneezing, nasal congestion, and runny and itchy nose. Approximately 25% of children and 40% of adults in USA are affected by AR during one or more seasons of the year. The manifestation and severity of AR symptoms exhibit prominent 24-h variation; in most persons they are worse overnight or early in the morning and often comprise nighttime sleep, resulting in poor daytime quality of life, compromised school and work performance, and irritability and moodiness. BA is also an inflammatory medical condition of the lower airways characterized by hypersensitivity to specific environmental antigens, resulting in greater local inflammation as well as bronchoconstriction, vasomotor change, and mucus hypersecretion. In USA an estimated 6.5 million children and 15.7 million adults have BA. The onset and worsening of BA are signaled by chest wheeze and/or croupy cough and difficult and labored breathing. Like AR, BA is primarily a nighttime medical condition. AR is treated with H1-antagonist, decongestant, and anti-inflammatory (glucocorticoid and leukotriene receptor antagonist and modifier) medications. Only H1-antagonist AR medications have been studied for their chronopharmacology and potential chronotherapy. BA is treated with some of the same medications and also theophylline and β2-agonists. The chronopharmacology and chronotherapy of many classes of BA medications have been explored. This article reviews the rather extensive knowledge of the chronobiology of AR and BA and the chronopharmacology and chronotherapy of the various medications used in their treatment.

Introduction

This article reviews the 24-h variation in the symptoms of allergic rhinitis (AR) and bronchial asthma (BR) and underlying chronobiologic mechanisms. It also reviews the findings relating to administration-time (i.e., circadian rhythm-determined) differences in the kinetics and effects of the various medications used in their treatment (i.e., chronopharmacology). The two medical conditions share a common core pathophysiology, that is, inflammation of the upper airways in AR and of the lower airways in BA. Moreover, both exhibit a remarkably similar temporal pattern in the occurrence and/or exacerbation of their respective symptoms. A relatively large number of studies have been devoted to the chronobiology of AR and BA and to the chronopharmacology of the several classes of therapeutic agents used to treat them. Due to the limited page budget, it is impossible to present a truly exhaustive review of the entire literature. Many circadian rhythm studies have been conducted on first-generation medications that are no longer considered front-line therapies for these conditions. Nonetheless, we have chosen to present illustrative examples of these therapies to demonstrate how the timing, with reference to circadian rhythms in drug handling and disease pathophysiology, can affect the evaluation of prescribed medications as well as the control of AR and BA symptoms. Moreover, given the current strong market for generic therapies, in developed and in developing nations, information on the chronopharmacology and chronotherapy of early-generation AR and BA medications could prove useful, through the application of new drug-delivery systems, in enhancing their safety and efficacy.

Section snippets

Allergic rhinitis (AR): introduction and history

AR is highly prevalent, affecting approximately 25% of adults and 40% of children in USA. The most common symptoms of AR are sneezing, nasal rhinorrhea (“runny nose”), nasal pruritus (“itching”), and nasal congestion. The nasal congestion and obstruction during the nighttime can be so severe that it often disrupts sleep, resulting in daytime fatigue, poor work and school performance, irritability, and altered or depressed mood. Although AR is not a life-threatening condition, it can profoundly

Chronopharmacology and chronotherapy of H1-receptor antagonist medication

Chronopharmacology is the study of biological rhythm influences, in relation to drug administration-time, on the pharmacokinetics and dynamics of medications and other chemical substances. Chronotherapy is either the delivery of medications in synchrony with endogenous biological rhythms in the pathophysiology of disease states to optimize treatment outcomes or the timed delivery of medications according to biological rhythm determinants to minimize or avoid troublesome and/or dose-limiting

Bronchial asthma (BA)

The second part of this article addresses the chronobiology and chronotherapy of BA. BA is characterized by airway inflammation, which results in hyperresponsivness of the lower respiratory tact to various environmental stimuli. The main symptom of BA is difficult breathing due to reduced airway caliber, bronchospam, and excessive secretion of mucus. BA is a reversible airways disease, since the abnormally low airflow rates can be partially of fully restored by prescription bronchodilator and

Chronopharmacology and chronotherapy of BA medications

The goals of BA therapy are: (a) prevention of acute and chronic symptoms of asthma during the day and night; (b) maintenance of normal or near normal pulmonary function, life style, activity, and sleep; and (c) avoidance of medication-induced adverse effects. Specific algorithms have been published by medical societies and governmental agencies [e.g., 89] to guide patient management and to achieve therapeutic goals, and both national and international guidelines now exist for the grading of

Discussion

This article addressed the chronobiology and chronotherapy of AR and BA. We chose to consider these two medical conditions together in a single article since they share common circadian rhythm dependencies, pathophysiologic mechanisms, and comparable day–night patterns in symptom manifestation and intensity. The symptoms of AR and BA both worsen overnight resulting in disturbed sleep and/or intense symptoms in the morning upon waking. The chronotherapy of AR and BA generally takes into

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    This review is part of the Advanced Drug Delivery Reviews issue on “Chronobiology, Drug Delivery, and Chronotherapeutics”.

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