THEORETICAL REVIEWPotential mechanisms connecting asthma, esophageal reflux, and obesity/sleep apnea complex—A hypothetical review
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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Cited by (51)
Obstructive sleep apnea and asthma: Clinical implications
2021, Revue des Maladies RespiratoiresUpdate in Pediatric Asthma: Selected Issues
2020, Disease-a-MonthAn obstructive sleep apnea primer: What the practicing allergist needs to know
2017, Annals of Allergy, Asthma and ImmunologyCitation Excerpt :This definition is consistent with the Medicare criteria for the diagnosis of OSA (https://www.cms.gov/medicare-coverage-database/). The disorder is often associated with a plethora of cardiopulmonary complications, although the cause-effect relationship between sleep apnea and these sequelae is still unclear.3,4 During the 20th century, several patients with obesity, heart failure, respiratory acidosis, periodic breathing, and excessive daytime sleepiness were first described.
Healthcare burden of obstructive sleep apnea and obesity among asthma hospitalizations: Results from the U.S.-based Nationwide Inpatient Sample
2016, Respiratory MedicineCitation Excerpt :In addition, estimates note 56 billion dollars of both direct and indirect annual costs are attributable to asthma [2]. Studies have also highlighted both obesity and obstructive sleep apnea (OSA) as significant comorbidities of asthma [3]. For example, research has uncovered a significant association between increasing weight and higher severity of asthma [4], incidence of asthma [5], asthma hospitalizations [6], and poorer quality of life [7].
Obstructive sleep apnea and asthma: Associations and treatment implications
2014, Sleep Medicine ReviewsCitation Excerpt :Considering the current evidence-base, which is limited by the small sample size and the heterogeneity of the clinical populations studied, it remains difficult to draw firm conclusions or inform clinical practice regarding optimal management strategies in patients with OSA–asthma overlap. However, a careful evaluation for exacerbating co-morbidity,4 in addition to optimizing treatment of both OSA and asthma remains crucial in this population. Practice points
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The most important references are denoted by an asterisk.