Elsevier

Sleep Medicine Reviews

Volume 11, Issue 1, February 2007, Pages 47-58
Sleep Medicine Reviews

THEORETICAL REVIEW
Potential mechanisms connecting asthma, esophageal reflux, and obesity/sleep apnea complex—A hypothetical review

https://doi.org/10.1016/j.smrv.2006.05.001Get rights and content

Summary

Obstructive sleep apnea (OSA) and asthma are potentially linked at several levels. The pathophysiology of these two conditions seems to overlap significantly, as airway obstruction, inflammation, obesity, and several other factors are implicated in the development of both diseases. Gastroesophageal reflux disease (GERD), cardiovascular complications, obesity itself, and the underlying inflammatory processes are all complex contributory factors that provide hypothetical links. Furthermore, a collateral rise in prevalence of both OSA and asthma has been noticed during the past few years, occurring in association with the emerging epidemic of obesity, a common risk factor for both conditions. OSA and asthma share many other risk factors as well. We propose a hypothetical OSA–asthma relationship that has implications on the diagnosis and management of patients presenting with either condition singly. Clinicians should be aware that OSA might complicate asthma management. Based on this hypothesis, we suggest that the treatment of the individual patient who experiences both asthma and OSA needs to be multidisciplinary and comprehensive. This hypothetical association of asthma and OSA, though described anecdotally, has not been systematically studied. In particular, the influence of continuous positive airway pressure therapy (for sleep apnea) on asthma outcomes (such as quality of life, steroid utilization, emergency room visits) and fatality needs to be studied further.

Introduction

There is circumstantial, possibly suggestive evidence of a close relationship between obstructive sleep apnea (OSA) and asthma. Both OSA and asthma involve airway obstruction as the cornerstone of their pathophysiology, being at different levels in each condition. Inflammation, a condition characteristic of asthma, was recently implicated in the progression and consequences of OSA, a traditionally all-mechanical problem. Recent studies have also found obesity, a significant risk factor in both OSA and asthma, to be associated with a systemic low-grade state of inflammation.

OSA and asthma are seemingly common conditions. Approximately 4% of middle-aged men and 2% of middle-aged women suffer from symptomatic OSA.1 The prevalence is higher (24% for men and 9% for women) when only an apnea–hypopnea index (AHI) of 5 or more is used as indicative of sleep-disordered breathing, regardless of coexistent daytime somnolence.1 The prevalence in elderly (age ⩾65 years) has been reported to be as high as 62%2. OSA is also being recognized by physicians more frequently. In the United States, there was a 12-fold increase in the annual number of patients diagnosed with OSA between 1990 and 1998, from 108,000 to over 1.3 million.3 Asthma prevalence varies in different age groups but has been reported to be as high as 5.3% in the United States in some reports. Furthermore, the prevalence of asthma appears to be increasing.4 Moreover, obesity rates are increasing rapidly in the United States. In 2000, approximately 20.1% of the adult population was obese.5 Because of their high prevalence, OSA and asthma may coexist in a large number of patients and recent studies have shown a strong link and coexistence. A study by Yigla et al.6 demonstrated a higher than expected prevalence of OSA in steroid-treated patients with asthma. Some clinicans, such as Thomas PS and Millman RP, suggest that OSA should be included in the differential diagnosis of difficult-to-control asthma.7, 8

Due to this close relationship between OSA and asthma, management of either condition may warrant treatment of the patient with the other disease. Based on the above discussion, a detailed evaluation of the OSA–asthma association is needed to further understand the correlation between the two diseases as well as other existing co-morbidities, and to possibly set forth further management goals and future areas of research.

Section snippets

Overview

OSA is characterized by repeated episodes of upper airway occlusion that result in brief periods of breathing cessation (apnea) or a marked reduction in tidal volume (hypopnea) during sleep (Table 1). This is followed by oxyhemoglobin desaturation, persistent inspiratory efforts against the occluded airway, and termination by arousal from sleep. These episodes are associated with excessive daytime sleepiness and abnormalities in cardiovascular, pulmonary, neurocognitive, and metabolic function.9

Why would asthma be a problem in a patient with OSA?

A large amount of data concerning the interaction between OSA and asthma has been accumulated in recent years. Studies have shown decreased quality of sleep defined as reduced sleep time, altered sleep quality, snoring, early morning awakening, difficulty in maintaining sleep, and daytime sleepiness in asthma,10 and as reviewed by Bonekat and Harding,11 OSA may coexist with asthma. Sleep deprivation, upper airway edema, and systemic inflammation associated with OSA could complicate the course

Hypothetical mechanisms linking obesity, asthma, and sleep apnea

We hypothesize on potential ways in which OSA can cause asthma or hyperreactive airway disease. Obesity, inflammation, cardiac disease, and esophageal reflux can all have effects on airway disease. Inflammation in turn could be triggered by either hypoxia, which can also induce reflex bronchoconstriction through stimulation of carotid bodies,24 or by other mechanisms. Bohadana et al.25 suggested that asthma can promote OSA. Proposed mechanisms include chronic disruption of sleep architecture,26

Diagnostic and management of the obesity–GERD–OSA–asthma complex

Details of the diagnosis and management of OSA and its complication are not within the scope of this study. The following is a brief discussion of the diagnostic and management approaches of OSA and its potential sequelae as summarized in Table 4.

Current state of knowledge and future reseach needs

OSA and asthma can coexist leading to enormous morbidity. Patho-physiologically, the two conditions seem to overlap significantly, as airway obstruction, inflammation, and obesity are pivotal aspects of both disorders. Complications, such as GERD, cardiovascular disease (especially ventricular dysfunction), obesity itself and the underlying inflammatory processes can compound the disease pathology seen in both conditions. The acronym “CORE” syndrome (Cough, Obstructive sleep apnea/Obesity, R

Acknowledgments

Funded by the National Institutes of Health Grants AI-43310 and HL-63070, RDC Grant of the East Tennessee State University and the Department of Medicine, East Tennessee State University.

Glossary

Obstructive sleep apnea
A disease characterized by repeated episodes of upper airway occlusion that result in brief periods of apnea hypopnea, associated with excessive daytime sleepiness and abnormalities in cardiovascular, pulmonary, neurocognitive and metabolic function.

Continuous positive airway pressure

Apnea
Cessation of airflow for more than 10 s.
Hypopnea
At least 30% reduction in airflow for 10 s associated with a 4% decrease in oxygen saturation.
Apnea–hypopnea index
the total number of apnea and hypopnea events per hour of

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