The Bidirectional Nature of Asthma and Obstructive Sleep Apnea

Although researchers have begun to elucidate the various phenotypes and endotypes of asthma in recent years, there has been little change in asthma-related morbidity and mortality. This lack of progress points to the need to address basic knowledge gaps, such as clarifying the relationship between asthma and obstructive sleep apnea (OSA).

A range of study findings indicates that the prevalence of OSA in patients with asthma is up to 2 to 3 times higher compared with the general population.¹ A cross-sectional analysis based on a national survey showed a substantially increased odds of asthma diagnosis in patients with OSA (adjusted odds ratio [aOR], 2.7; 95% CI, 1.6-4.6; P <.001).² Similarly, in a 2015 study using polysomnography (PSG), patients with asthma demonstrated an increased 4-year incidence of OSA (relative risk [RR], 1.58; 95% CI, 1.08-2.31) and symptomatic OSA (RR, 2.72; 95% CI, 1.26-5.89) compared with individuals without asthma.³

The same investigation found that the risk of incident OSA increased in a dose-dependent manner with asthma duration, such that each 5-year increment in the duration of asthma was linked to a greater risk for both incident OSA (RR, 1.07; 95% CI, 1.02-1.13; P =.01) and incident OSA with habitual sleepiness (RR, 1.18; 95% CI, 1.07-1.31; P =.02).³

Bidirectional Relationship

“The occurrence of OSA in [patients with] asthma appears to be inversely related to the degree of therapeutic control of the patient’s asthma,” said Clete A. Kushida, MD, PhD, neurologist and professor of psychiatry and behavioral sciences at Stanford University Medical Center, division chief and medical director of Stanford Sleep Medicine, and director of the Stanford Center for Human Sleep Research in California. Studies have reported a dose-dependent increase in OSA prevalence in association with asthma severity, and PSG-diagnosed OSA has been noted in 88% to 95% of difficult-to-control asthma cases.¹

The common comorbidity of asthma and OSA has been partially attributed to the high prevalence of both diseases, as well as shared risk factors including rhinitis, obesity, and gastroesophageal reflux. In addition, a bidirectional relationship has been observed in which the severity of each disease affects that of the other.¹

“Emerging evidence implicates airway and systemic inflammation, neuroimmune interactions, as well as effects of asthma-controlling medications (corticosteroids) as factors predisposing patients with asthma to OSA,” wrote the authors of a review published in December 2019 in the American Journal of Respiratory and Critical Care Medicine.¹ “Conversely, undiagnosed or inadequately treated OSA adversely affects asthma control, partly via effects of intermittent hypoxia on airway inflammation and tissue remodeling.”

Effect of OSA on Asthma Outcomes

In research highlighting the potential effect of OSA on asthma outcomes, various findings have shown that OSA diagnosis was positively associated with the use of inhaled corticosteroids and the frequency of emergency department visits in patients with asthma,⁴ as well as worse outcomes (including increased costs, longer lengths of stay, and the need for invasive respiratory therapy) in patients hospitalized because of asthma exacerbations.^1,5

In other research, an elevated risk or diagnosis of OSA in patients with asthma was associated with worse asthma symptoms, increased exacerbations, increased bronchodilator use, reduced forced expiratory volume in 1 second (FEV₁), and lower quality of life.¹ In addition, poor “quality and frequent sleep disruption are already present in many patients with asthma, and comorbid OSA results in even poorer sleep quality and quantity, with resultant daytime sleepiness,” Dr Kushida noted.

Evidence suggests that the effects of comorbid asthma and OSA may have a more substantial effect on women, with one study demonstrating worse outcomes in women vs men with asthma and OSA who were hospitalized for asthma exacerbations.⁵ The factors driving these disparities are not yet clear.

Screening and Treatment Considerations

The review authors recommended that clinicians screen patients with asthma for OSA, especially individuals with poorly controlled disease and/or longer disease duration, as well as those receiving higher doses of inhaled corticosteroids. The authors noted that sleep studies using respiratory polygraphy (which lacks electroencephalography) may underestimate OSA severity in this population compared with PSG.¹

“Patients with both conditions should strive for optimal control of asthma, which in turn can improve their OSA,” Dr Kushida stated. “Treatment of OSA, particularly with [continuous positive airway pressure (CPAP)], in patients with asthma has been shown to improve asthma-specific quality of life.”⁶ Several studies have shown that CPAP treatment reduced the risk for worse asthma outcomes and decline in FEV₁, especially in older patients.¹

Research published in 2013, for example, found that the likelihood of severe asthma was nearly 7 times higher in older adults with OSA (OR, 6.67), and CPAP use reduced the likelihood of severe asthma by 91% (P =.005) in this group.⁷ Other research has demonstrated improvements in asthma symptoms, peak expiratory flow rates, and rescue bronchodilator use in patients with asthma treated with CPAP for OSA.⁶

However, there have been “mixed and generally negative results with respect to wakefulness physiologic measures of lung function (FEV₁)” after CPAP, according to the review.¹ These discrepancies “may be due to irreversible airway remodeling that could occur with delayed OSA recognition, focus on wakefulness (instead of nocturnal) airway measures known to be more affected during sleep, lack of uniformity in regards to asthma treatment regimens within each study, and variable duration of CPAP therapy and nightly adherence….”¹

Future Directions

“More work needs to be established in exploring this overlap syndrome of asthma and OSA, and that of comorbid asthma, COPD, and OSA,” said Dr Kushida. Among many remaining gaps in these areas, there is a need for more rigorous experiments with well-defined populations to clarify the effects of CPAP effects on physiologic measures of airway function.¹ Future research should also further explore sex differences in outcomes of patients with comorbid OSA and asthma.

References

1. Prasad B, Nyenhuis SM, Imayama I, Siddiqi A, Teodorescu M. Asthma and obstructive sleep apnea overlap: what has the evidence taught us? [published online December 16, 2019]. Am J Respir Crit Care Med. doi:10.1164/rccm.201810-1838TR

2. Bhattacharyya N, Kepnes LJ. Ambulatory office visits and medical comorbidities associated with obstructive sleep apnea. Otolaryngol Head Neck Surg. 2012;147(6):1154-1157.

3. Teodorescu M, Barnet JH, Hagen EW, Palta M, Young TB, Peppard PE. Association between asthma and risk of developing obstructive sleep apnea. JAMA. 2015;313(2):156-164.

4. Shen TC, Lin CL, Wei CC, et al. Risk of obstructive sleep apnea in adult patients with asthma: a population-based cohort study in Taiwan. PLoS One. 2015;10(6):e0128461.

5. Becerra MB, Becerra BJ, Teodorescu M. Healthcare burden of obstructive sleep apnea and obesity among asthma hospitalizations: Results from the U.S.-based Nationwide Inpatient Sample. Respir Med. 2016;117:230-236.

6. Teodorescu M, Polomis DA, Teodorescu MC, et al. Association of obstructive sleep apnea risk or diagnosis with daytime asthma in adults. J Asthma. 2012;49(6):620-628.

7. Teodorescu M, Polomis DA, Gangnon RE, et al. Asthma control and its relationship with obstructive sleep apnea (OSA) in older adults. Sleep Disord. 2013;2013:251567.