Sleep Deprivation in Asthma - Part 2

Sleep and Stable Asthma

The quality of sleep is affected even in patients with clinically stable asthma. A study of 74 children, 40 of whom had well-controlled and stable asthma, found that in comparison to their controls, the children with asthma had poorer sleep quality. There was a significant correlation between peak flow readings and measures, both subjective and objective, of sleep. They had lower percentages of quiet sleep and increased activity levels during sleep. The authors suggested that the children with asthma were “at risk for developing neurobehavioural deficits associated with chronic sleep loss”.10

Vir11 studied 30 young, single, adult university students with clinically stable bronchial asthma with an equal number acting as a control group. The results showed that 93% of the patients with asthma experienced sleep disturbances compared with 33% in the control group. The statistically significant differences included

  • sleep disturbances
  • daytime sleepiness
  • tiredness
  • difficulty in maintaining sleep
  • early morning awakening
  • shorter duration of sleep

The consequence was impaired daytime performance. The researchers concluded that the differences were associated with the poor quality of sleep experienced by patients with clinically stable asthma.

Asthma Medications and Sleep

Many of the medications used in the treatment of asthma affect both the quality and quantity of sleep. These include beta-agonists, methylxanthines and systemic corticosteroids. The systemic corticosteroids are also known to cause nightmares in some individuals.

Theophylline, too, has an adverse effect on sleep. A crossover study of ten healthy, non-smoking adults between the ages of 23 and 35, given low doses of oral theophylline, found significant adverse effects due to theophylline on sleep quality, with a reduction in total sleep time and increased sleep disturbance resulting in more frequent awakenings during each hour of sleep.12

A recent case of a 9-year-old boy should act as a warning that any medication may have serious adverse effects. In this case, it was a combination of formoterol and budesonide. Within a month of starting this combination, the child developed suicidal thoughts, became agitated, and had problems with speech and insomnia. Within 48 hours of discontinuing the formoterol but continuing the budesonide, all the symptoms disappeared.13

Co-morbidites and Sleep

Sleep disturbance in patients with lung disease may occur due to oxygen deprivation, dyspnea or cough. Nocturnal asthma often causes problems ranging from difficulty falling asleep, to restless sleep, difficulty staying asleep, daytime sleepiness and resulting tiredness. Co-morbidities such as rhinitis, gastoesophageal reflux disease (GERD), sleep-disordered breathing and obesity may worsen symptoms and disrupt sleep. The poor quality of sleep may worsen the disease.

Allergic Rhinitis (AR)

Leger14 showed AR affected and impaired every dimension of sleep. In their DREAMS (Étude Descriptive des Rhinites Allergiques et des Modifications du Sommeil [Descriptive Study of Allergic Rhinitis and Sleep Impairment]) study of 591 individuals, patients with severe AR had significantly more impairment than patients with mild disease. AR was found to be independently related to14,15

  • daytime sleepiness with microsleeps occurring
  • increased difficulty in falling asleep
  • more somnolence
  • sleep disturbance
  • daytime fatigue
  • reduced cognitive and psychomotor capabilities
  • vitiated work performance
  • reduced productivity
  • impaired learning
  • reduced concentration
  • impaired memory, mood and sexuality
  • significantly increased consumption of alcohol and sedatives, and
  • reduced quality of life.

Allergic rhinitis can result in poor sleep quality and lead to sleep apnea16 and sleep-disordered breathing (SDB).17 Nocturnal asthma can lead to SDB – which is common in patients with asthma.

Obstructive Sleep Apnea (OSA)

OSA is also common in patients with asthma. Some possible reasons for this association include airway and systemic inflammation, recurrent upper airway collapse resulting in neuromechanical effects and the effect of asthma medications, particularly corticosteroids.18 Individuals with asthma are at greater risk(RR 1.39) of developing OSA than individuals without asthma. Further, the adjusted relative risk for OSA with habitual sleepiness was greater (RR 2.72) in patients with asthma than for those without asthma. It would appear that the asthma mediated by OSA increases sleepiness.19 Besides night time snoring and restlessness, OSA results in fatigue, poor concentration, cognitive dysfunction and daytime sleepiness. It also results in excessive daytime fatigue and has been shown to increase the risk of driving accidents.20

Guven and colleagues studied 47 patients with difficult-to-control asthma. They found that almost 75% (74.5%) had OSA. Of these, 31% had mild OSA while 65% had moderate-severe OSA.21 A study22 – to test the hypothesis that asthma promotes OSA – was conducted of 22 patients with difficult-to-control asthma who were receiving long-term oral (continuous or bursts) corticosteroid therapy in addition to standard therapy. It found a 95.5% prevalence of OSA, and the researchers theorized that protracted and continuous oral corticosteroid use tended to promote OSA.

Obesity

Obesity affects the treatment of asthma and the degree of asthma control. It can often present as asthma, displaying similar symptoms which often resolve once the individual loses weight. Dixon et al23 studied 488 subjects with asthma, almost half of whom were obese. Both obese and non-obese individuals had the same airflow limitation and bronchodilator response, but the obese individuals had more GERD and more sleep disturbance. Another study by Lumeng and colleagues looked at an equal number of male and female children (total 785). Using data from the National Institute of Child Health and Human Development Study of Early Child Care and Youth Development, they evaluated the relationship between sleep duration at the third grade and weight at grade six. After adjusting for all possible confounders, the researchers found that shorter sleep duration in the

  • third grade – independent of the child’s weight – was independently associated with being overweight in the sixth grade.
  • sixth grade was also independently associated with being overweight in the sixth grade.24

Sleep problems were not associated with being overweight. Long-term reductions in sleep may be a cause for weight gain since short sleep duration changes hormone levels, metabolism and glucose tolerance.

Gastroesophageal reflux disease (GERD)

GERD is a common comorbidity in patients with asthma. While its role in asthma is much like the chicken and the egg debate as to which came first, GERD is associated with asthma severity and GERD episodes are known to trigger bronchoconstriction in patients with asthma.25 The supine position makes GERD worse at night leading to increased asthma symptoms and fractured sleep.

Sleep is an essential restorative physiologic requirement such that impaired sleep has a significant and negative impact on health. It impacts cognition and job performance; is a cause of motor vehicle accidents, and increases health care use. In patients with asthma the effects are greatly increased. For children, nocturnal symptoms will impact school performance. All patients with asthma who have nocturnal symptoms will also have a reduced quality of life. Hence it behooves the health care professional to include questions on the quality of sleep when dealing with patients.

References

10.    Sadeh A, Horowitz I et al. Sleep and pulmonary function in children with well-controlled stable asthma. Sleep 1998; 21(4): 379-84
11.    Vir R, Bhagat R, Shah A. Sleep disturbances in clinically stable young asthmatic adults. Ann Allergy Asthma Immunol. 1997; 79(3): 251-5
12.    Kaplan J, Fredrickson PA et al. Theophylline effect on sleep in normal subjects. Chest 1993; 103(1): 193-5. Abstract.
13.    del Rosario MA, Bender BG, White CW. Suicidal ideation and thought disorder associated with the formoteral component of combined asthma medication. Pediatr Pulmonol 2013; 48(1): 102-3. doi: 10.1002/ppul.22563. Abstract.
14.    Léger D, Annesi-Maesano I, Carat F, et al. Allergic rhinitis and its consequences on quality of sleep: an unexplored area. Arch Intern Med 2006; 166(16): 1744-8
15.    Pratt EL, Craig TJ. Assessing outcomes from the sleep disturbance associated with rhinitis. Curr Opin Allergy Clin Immunol. 2007; 7(3):249-56
16.    Muliol J, Maurer M, Bosquet J. Sleep and allergic rhinitis. J Investig Allergol Clin Immunol 2008; 18(6):415-9
17.    Santos CB, Pratt EL et al. Allergic rhinitis and its effect on sleep, fatigue and daytime somnolence. Ann Allergy Asthma Immunol 2006; 97:579-87
18.    Prasad B, Nyenhuis Sm, Weaver TE. Obstructive sleep apnea and asthma: associations and treatment implications. Sleep Med Rev. 2014: 18(2): 165-71. doi: 10.1016/j.smrv.2013.04.004
19.    Teodorescu M, Barnet JH, Hagen EW, et al. Association between asthma and risk of developing obstructive sleep apnea. JAMA. 2015;313(2):156-164. doi:10.1001/jama.2014.17822.
20.    Smolendky, MH, Di Milia L et al. Sleep disorders, medical conditions, and road accident risk. Accid Anal Prev. 2011; 43(2):533-48. doi: 10.1016/j.aap.2009.12.004
21.    Guven SF, Dursun AB, et al. The prevalence of obstructive sleep apnea in patients with difficult-to-treat asthma. Asian Pac J Allergy Immunol. 2014 Jun;32(2):153-9. doi: 10.12932/AP0360.32.2.2013
22.    Yigla M, Tov N et al. Difficult-to-control asthma and obstructive sleep apnea. J Asthma. 2003; 40(8)” 865-71
23.    Dixon AD, Shade DM et al. Effect of obesity on clinical presentation and response to treatment in asthma. J Asthma 2006; 43(7):553-8
24.    Lumeng JC, Somashekar D, et al. Shorter sleep duration is associated with increased risk for being overweight at ages 9 to 12 years. Pediatrics. 2007 Nov;120(5):1020-9.
25.    Cibella F, Cuttitta G. Nocturnal asthma and gastroesophageal reflux.  Am J Med. 2001; 111 Suppl 8A: 31S - 36S