Can Asthma Incidence Be Reduced by Attention to Sleep Disorders?

Walter Alexander

April 13, 2023

Early detection and management of sleep disorders could reduce asthma incidence, according to a large-scale prospective study that included nearly half a million participants. The study was reported in BMJ Open Respiratory Research.

The population-attributable risk analysis indicated that 19% of asthma cases could be prevented through improving sleep traits. The investigators took into consideration polygenic risk scores (PRSs) for asthma and comprehensive sleep scores encompassing five sleep traits.

Sleep quality is generally recognized as a nongenetic driver of asthma. Poor sleep quality and obstructive sleep apnea have been reported particularly among those with severe disease. In addtion, asthma is known to adversely affect sleep duration, sleep quality, napping, and daytime sleepiness.

The researchers suggest that the relationship between sleep and asthma is bidirectional, given that sleep disorders (sleep of short duration, insomnia, evening chronotype ["night owl"], snoring, excessive daytime sleepiness) are associated with specific chronic inflammatory reactions. It has remained unclear, however, whether poor sleep reflects a higher risk of early asthma progression.

Genetic factors also contribute to asthma risk, but highly variable heritability suggests that the nongenetic exposures play an important role. "However, whether healthy non-genetic exposure could decrease the risk of asthma and mitigate the adverse effect of genetic risk remains largely unknown," the authors state. They hypothesize that healthier sleep could decrease future asthma risk and mitigate the hazards of genetic effects.

Using data from the UK Biobank, a national large, prospective cohort drawn from 22 UK assessment centers, they investigated the independent and combined effects of sleep pattern and PRSs on asthma incidence.

In the UK Biobank cohort (455,405 adults aged 38–73 years, who were enrolled from 2006 to 2010), 17,836 were diagnosed with asthma over 10 years of follow-up. PRSs were constructed for each participant on the basis of their having any of 17 single-nucleotide polymorphisms that are significantly associated with asthma. Participants were stratified into three groups: those at high genetic risk, those at intermediate genetic risk, and those at low genetic risk. Around 1 in 3 participants were classified as being at high genetic risk (150,429), and another third (151,970) were classified as being at intermediate risk. The remainder were classified as being at low risk. Some 7105 people at high genetic risk and 5748 at intermediate genetic risk were diagnosed with asthma during the monitoring period.

Comprehensive sleep scores, which ranged from 0 to 5, were constructed on the basis of self-reported sleep traits. Higher scores represented healthier sleep patterns. A healthy sleep pattern was defined as early chronotype; getting from 7–9 hours of sleep every night; never or rare insomnia; no snoring; and no frequent daytime sleepiness. On the basis of their responses, 73,223 people met the criteria for a healthy sleep pattern; 284,267, an intermediate sleep pattern; and 97,915, a poor sleep pattern.

"Compared with non-cases, asthma cases were more likely to have lower education levels, unhealthy sleep traits and patterns, obesity, higher PRS, more smoking, more alcohol consumption, hypertension, diabetes, depression, gastroesophageal reflux. and more air pollution exposure," the authors report. All five healthy sleep traits were independently associated with lower risk for asthma. Never/rare insomnia and sleep duration of 7–9 hours a night were seemingly the most influential; they were associated with risk reductions of 25% and 20%, respectively.

Analysis showed that compared with the low-risk group, the hazard ratios (HRs) and 95% confidence intervals for the highest PRS group and the poor sleep pattern group were 1.47 (95% CI, 1.41 – 1.52) and 1.55 (95% CI, 1.45 – 1.65), respectively.

Risk was twofold higher in the presence of a combination of poor sleep and high genetic susceptibility (HR, 2.22; 95% CI, 1.97 – 2.49; P < .001). Conversely, a healthy sleep pattern was associated with a lower risk of asthma in the low (HR, 0.56; 95% CI, 0.50 – 0.64), intermediate (HR, 0.59; 95% CI, 0.53 0.67), and high genetic susceptibility groups (HR, 0.63; 95% CI, 0.57 – 0.70). A population-attributable risk analysis indicated that improving these sleep traits would prevent 19% of asthma cases. Also, a subset analysis suggested that a healthy sleep pattern might reduce the risk of asthma among those at high genetic risk by 37%.

The study findings suggest that analysis of sleep patterns is warranted for all asthma patients, said co-author Qing Wang, PhD, Cheeloo College of Medicine, Shandong University, Jinan, People's Republic of China, in an interview. "In our results, the effects of sleep and genetics were independent. Therefore, what we learned about the effects of sleep on asthma could be applied to all the patients, including those with a high or low genetic predisposition. In addition, we believe that intervening among those with high genetic predisposition could be more beneficial since they are more likely to have asthma. However, because this study is observational, a large clinical trial is absolutely needed to provide causal evidence, especially before guidelines modifications can be considered."

Complex and Multifactorial

"Addressing relevant asthma comorbid conditions continues to be an integral part of asthma care," commented Diego J. Maselli, MD, associate professor of medicine and interim chief, Division of Pulmonary Diseases and Critical Care, UT Health, San Antonio, in an interview. "There is mounting evidence that sleep patterns and obstructive sleep apnea may influence asthma control. This association is complex and multifactorial. It is important to remember that obstructive sleep apnea may coexist with other conditions, such as obesity and gastroesophageal reflux disease, that in turn can also worsen asthma control and influence clinical outcomes.

"Yet, even after controlling for these factors, sleep disturbances have been associated with poor asthma outcomes. It is reasonable, particularly in patients with uncontrolled and/or severe asthma, to screen for sleep disturbances. There are multiple questionnaires and clinical tools that can be employed to screen for coexisting sleep apnea and other conditions. Although genetic testing has shown some promise in identifying individuals at risk, these assays are not widely available and are not ready yet for routine clinical practice. Therefore, sleep studies should be reserved for patients that have symptoms and test positive for screening questionnaires and other tools.

"The study by Xiang and colleagues adds to the field of study, but further evidence is required to change practice guidelines at this time. Fortunately, sleep studies are readily available now with more widespread use of home testing, so patients can be easily tested. The majority third-party payers have identified that diagnosing these disorders is cost-effective and are able to reimburse sleep studies," Maselli concluded

The research was funded by the Future Program for Young Scholars and National Key Research and Development Program. The study authors and Maselli have disclosed no relevant financial relationships.

BMJ Open Resp Res. 2023;Mar 10:e001535. Full text

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