The prevalence of sleep disturbance among asthmatic patients in a tertiary care center

Sleep disturbances are commonly reported by patients with asthma. However, the prevalence of sleep disturbance and its association with the level of asthma control is unknown. The primary objective was to determine the prevalence of sleep disturbance among Saudi adult asthmatic patients attending pulmonary clinics at King Abdulaziz Medical City (KAMC). The study also aimed to compare sleep quality between controlled and uncontrolled asthma patients. The study was carried out in the outpatient pulmonary clinics at KAMC and utilized a cross-sectional survey. The survey included five different questionnaires: asthma control test and questionnaires related to the quality of sleep (Pittsburgh sleep quality index [PSQI], Epworth sleepiness scale [ESS], Berlin questionnaire [a measure of obstructive sleep apnea risk], and insomnia severity index [ISI]). Among the 200 asthma patients, 66% suffered from poor sleep quality (PSQI > 5), 43% were at high risk for obstructive sleep apnea, 25% had excessive daytime sleepiness (ESS > 10), and 46.5% had significant clinical insomnia (ISI ≥ 10). Poor sleep quality was less common in patients with well-controlled asthma (37%) compared to those with partially controlled asthma (78%) and uncontrolled asthma (82%) (p < 0.001). Poor sleep quality was common among patients with asthma, particularly those with suboptimal levels of asthma control. Further studies are needed to better understand the interaction between these two conditions.

Statistical analysis. All analyses were conducted using Statistical Package for Social Sciences (SPSS; v. 25.0). Continuous variables are summarized as means ± standard deviations (SD) or medians and interquartile range (IQR) for normal and non-normal distributions, respectively. Categorical data are described by frequencies and percentages. The one-way analysis of variance test was used to compare the means of continuous variables, and the chi-square test was used to compare the proportion of sleep disturbance between patients with different levels of asthma control. Potential risk factors causing poor sleep quality in asthma patients, including age, body mass index (BMI), gender, GERD, and risk of sleep apnea, were analyzed using univariate and multivariate analyses. To identify factors that were strongly associated with poor sleep quality, logistic regression analysis was used. A p value < 0.05 was considered statistically significant.
Ethics approval and consent to participate. The study was approved by the institutional review board of King Abdullah International Medical Research Center (KAIMRC) in Riyadh, Saudi Arabia. All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments .Written informed consent was obtained from individual or guardian participants, and from the parent for patient who are less than 16 years old.

Results
The study was conducted from August 2018 to April 2019. A total of 200 asthma patients participated in the study and filled out the questionnaires, with a response rate of 90%. Baseline patient characteristics included a mean age of 50.6 ± 17 years and female predominance (67%). According to the ACT, 67 (33.5%) patients had well-controlled asthma, 55 (27.5%) had partially controlled asthma, and 78 (39%) had uncontrolled asthma. Comorbid conditions were present in almost half of the patients (Table 1).
When comparing the mean BMI among different levels of asthma control, patients with well-controlled asthma had lower BMI (28.9 ± 7.4 kg/m 2 ) compared to the partially controlled group (32.7 ± 6.8 kg/m 2 ) and uncontrolled group (32.1 ± 7.4 kg/m 2 ) (p = 0.008). Sleep quality and asthma control levels. There was a strong association between sleep quality and asthma control. Poor sleep quality was less common in patients with well-controlled asthma (37%), compared to those with partially controlled asthma (78%) and uncontrolled asthma (82%) (p ≤ 0.001) (Fig. 1). Furthermore, patients with well-controlled asthma had less excessive daytime sleepiness, a lower risk of OSA, and lower clinical insomnia compared to the partially controlled and uncontrolled asthma patients (p = 0.002, 0.003, and ≤ 0.001, respectively) ( Table 2). PSQI domains. The mean global PSQI score was lower in the well-controlled group (5.12 ± 3.2) than in the partially controlled (9.07 ± 3.9) and uncontrolled (9.69 ± 3.9) groups (p ≤ 0.001). In addition, the mean score of all PSQI domains was lower in the well-controlled group compared to the partially controlled and uncontrolled groups, with the exception of sleep duration and use of sleep medication, which were only different between well-controlled and uncontrolled groups (Table 3).

Multivariable analysis.
Multivariable analysis was performed to identify factors that were strongly associated with poor sleep quality. The following factors were significantly associated with sleep disturbance: high risk for OSA ( Another important finding of this study was that asthma control had an inverse relationship with sleep disturbance. In comparison to patients with partially controlled or uncontrolled asthma, patients with well-controlled asthma were less likely to report poor sleep quality. Similarly, previous studies from different countries have shown that patients with better asthma control have less sleep disturbance 4,5,14,16,31,33 . Our study also demonstrated sleep disturbances in patients with well-controlled asthma (37%). Braido et al. reported that 10-20% of totally controlled asthma patients still have poor sleep quality 4 . Luyster et al. reported mean PSQI scores > 5 in both severe and non-severe asthma patients 16 .
There was no association between gender or age and sleep disturbance. In contrast, Janson et al. reported that the percentage of asthma patients with difficulties maintaining sleep was higher in females (55%) compared to males (31%). The same study showed that age was associated with a decline in estimated sleep duration 34 .
Asthma patients have a higher prevalence of snoring and OSA compared to the general population, and asthma is an established risk factor for OSA 5,35 . In addition, patients with asthma and OSA are seven times more likely to develop severe asthma 36 . Some factors that might play a role in the interaction between asthma and OSA include local inflammation in the upper airway, allergic rhinitis, systemic inflammation, circulating leptin, neuromechanical reflex bronchoconstriction, intermittent hypoxia, GERD, obesity, and asthma therapy 37 . Julien et al. used overnight home polysomnography to investigate the prevalence and severity of OSA in patients with different levels of asthma. The frequency of OSA-hypopnea events was higher in severe asthmatics compared to moderate asthmatics or non-asthmatics 14 . In the current study, 43% of the asthmatics demonstrated high risk for OSA. Similarly, Lu et al. utilized the STOP-Bang questionnaire to show that 44% of the asthmatics in their cohort were at high risk for OSA 35 . When adjusting for other covariates, our results show that a high risk for OSA was significantly associated with poor sleep quality.
Using multi-regression analysis, the current study shows that having rhino-sinusitis did not increase the chance of having sleep disturbance in asthmatics. This is similar to findings reported in previous studies 4, 16 . Nevertheless, Janson et al. reported that allergic rhinitis is associated with difficulty inducing sleep, daytime tiredness, and daytime sleepiness 5 . In our study, patients with co-morbid GERD did not experience increased sleep disturbance compared to those without GERD. Similarly, Luyster et al. reported that the majority of patients with asthma had poor sleep quality regardless of the presence of GERD 16 .
Excessive daytime sleepiness as a result of sleep disturbance has been previously reported among asthma patients 5,7,18,33 . Our study reveals that 27-36% of patients with uncontrolled or partially controlled asthma had excessive daytime sleepiness, whereas only 10% of well-controlled asthma patients had excessive daytime sleepiness. Campos et al. reported significantly increased daytime sleepiness with worse asthma control among 123 women with asthma 33 . Teodorescu et al. also reported a significantly higher percentage of excessive daytime sleepiness in patients with severe asthma (31%), compared to those with non-severe asthma (19%) 18 .
The current study also looked at the relationship between insomnia and asthma control. Insomnia was identified in 68% of patients with uncontrolled asthma, 49% with partially controlled asthma, and 19% with well-controlled asthma. Luyster et al. reported 37% of patients suffering from insomnia among 714 patients with physician-diagnosed asthma, and insomnia was significantly associated with worse asthma control, worse quality of life, and increased depression 17 . Another study showed that the prevalence of insomnia symptoms was common among patients with asthma and asthma-chronic obstructive pulmonary disease overlap (ACO), in comparison to patients without airway diseases 38 .
The current study had several limitations. First, the sample size was small, and it was predominantly female. Second, the study was performed in a single tertiary referral center, which may have introduced referral bias and may not accurately represent the prevalence of the sleep disturbance among asthma patients in the community or in other geographical areas. Third, the cross-sectional design prevented against inferences regarding the directionality of the relationship between sleep quality and asthma control. Lastly, accurate measurements of sleep disturbance, such as sleep studies for OSA and sleep diaries, were not performed.

Conclusions
Poor sleep quality was common among patients with asthma, especially those with suboptimal levels of asthma control. In addition, patients with uncontrolled asthma had a higher risk for OSA and were more likely to report insomnia and excessive daytime sleepiness. Further studies are needed to better understand the interaction between asthma and sleep.

Data availability
The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request.