Patients With Asthma Should Be Assessed for Obstructive Sleep Apnea

Becky McCall

December 10, 2010

December 10, 2010 (Dubai, United Arab Emirates) — Increasing evidence supports the hypothesis that sleep disturbances in patients with well-controlled asthma could be caused by obstructive sleep apnea (OSA).

Fulvio Braido, MD, from Allergy and Respiratory Diseases, Department of Internal Medicine, University of Genoa, Italy, made a presentation on the association between asthma and OSA here at the World Allergy Organization (WAO) 2010 International Scientific Conference.

His theory suggests that one disease causes the other or that they share a common cause. According to Dr. Braido, it is likely that asthma complicates the treatment of OSA, or vice versa.

He said that general sleep complaints in patients with asthma are fairly common and often relate to uncontrolled asthma. Nocturnal asthma is widely considered to be a signature feature of the disease. "There's a possibility that sleep apnea is a worsening factor for asthma. In fact, it is considered to be a symptom signifying disease severity or worsening," he told Medscape Medical News.

Dr. Braido presented evidence that suggests that nocturnal symptoms are related to the state of being asleep. The findings show that if an asthma patient is kept awake, there is a reduction in narrowing of the bronchi (Thorax. 1986;41:676-680). "This means that it is sleep itself that causes the narrowing of the airways, not the timing of sleep," explained Dr. Braido.

Several potential mechanisms could explain airway narrowing during sleep: cooling, the effect of being supine, allergy, gastroesophageal reflux (GERD), and OSA. Dr. Braido dismissed cooling by explaining that even when temperature remains constant, narrowing occurs. Similarly, if a patient remains supine for 24 hours, airway narrowing only occurs at night, during sleep. He suggested that GERD and OSA are the most likely causes.

Furthering his argument that asthma is linked to sleeping impairment, Dr. Braido discussed the relation between control of asthma and sleep disturbance. A study he and his colleagues conducted in 2009 showed that despite the fact that the majority of well-controlled patients had less sleep disturbance, 11% to 20% of those with well-controlled asthma reported sleep disturbances that increased the impact of their disease and affected their quality of life (Asian Pac J Allergy Immunol. 2009:27:27-33).

Given these findings — that even patients with well-controlled asthma experience sleep disturbances — Dr. Braido went on to discuss the association between OSA risk and asthma control, citing a recently published study (Chest. 2010: 138:543-550).

In that study, 472 patients with asthma completed questionnaires on their sleep disturbances and their asthma control. On analysis, the researchers found that uncontrolled asthmatics had a high risk for OSA, with an odds ratio of 3.60 (95% confidence interval [CI], 2.16 - 5.98; P = .0001). Other significant factors were obesity and GERD. After adjustment for confounding factors, patients with OSA maintained an odds ratio of 2.87 (95% CI, 1.54 - 5.32) for uncontrolled asthma.

Dr. Braido pointed out that these results supported a study published in the European Respiratory Journal (2005;26:812-818), which investigated risk factors for exacerbations in difficult-to-treat asthma. OSA was found to frequently coexist with difficult-to-treat asthma. But, "which mechanism is responsible for relating poorly controlled asthma to sleep apnea?" he asked.

The anticholinergic tiotropium bromide has recently been shown to be effective in relieving symptoms in uncontrolled asthma (N Engl J Med. 2010;363:1715-1726). In reference to this study (presented here at the WAO conference by lead author Stephen Peters, MD), Dr. Braido said that cholinergic mechanisms stimulated by inspiration against closed airways suggest the possibility of using anticholinergic drugs in these patients. "Rhinitis is a worsening factor for asthma and inflammation, and nasal congestion a risk factor for snoring. We know that snoring is strongly related to sleep apnea."

In addition, Dr. Braido pointed out that patients in Dr. Peters' study had a mean body mass index of 31.4 kg/m2 (±8.8). "Obesity is a predisposition for OSA development. The crucial question is how many of these patients suffered from sleep apnea. Anticholinergic treatments could be useful for patients with asthma and sleep apnea."

A diagnosis of OSA might be possible by monitoring levels of oral nitric oxide (NO), Dr. Braido advised. He referred to another recently published study (Respir Med. 2010;104:316-320), in which levels of NO, known as an indicator of airway inflammation, were measured, and NO exhaled through the oral cavity was compared with NO exhaled through the nose and airways.

The researchers found higher levels of oral NO expired by patients with OSA than by either healthy subjects or patients with asthma or chronic rhinosinusitis. In both the asthma and chronic rhinosinusitis groups, oral NO was similar to that of healthy control subjects. More exhaled NO and inflammatory metabolites were detected in the exhaled air of subjects with OSA than in healthy subjects.

"If we measure NO in the management of asthma, we need to consider that the production of NO is also seen in patients with concomitant sleep apnea, not just asthma. If we measure both the oral NO and the [exhaled air], we could distinguish the source and modify treatment to suit asthma or sleep apnea," explained Dr. Braido.

Commenting on the association between OSA and osteoporosis, Giovanni Viegi, MD, director of the Institute of Biomedicine and Molecular Immunology, Palermo, Italy, said that OSA is a field that has been neglected for too long. "My Institute has a long tradition of investigation into sleep apnea. It is increasing, yet it is poorly known by general practitioners and the general public, so everything that is done in the field is worth it."

Richard Lockey, MD, president of the WAO and director of the Division of Allergy and Immunology at James A. Haley Veterans' Hospital in Tampa, Florida, said in his opening address that OSA is a huge problem. "I always ask my asthma patients: 'Do you snore? If so, how loud do you snore?' Ask the bed partner too. I ask the patient if they are sleepy during the day and if they have loss of recent memory. I say: 'Do you ever sit up at night to catch your breath?' "

"You have to recognize it. You have to get the history, you have to suspect it, and you have to treat the underlying disorders, from upper airway disease to obesity. Use continuous positive airway pressure when indicated," he emphasized.

Dr. Braido, Dr. Viegi, and Dr. Lockey have disclosed no relevant financial relationships.

World Allergy Organization (WAO) 2010 International Scientific Conference. Presented December 6, 2010.

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