Recognizing the impact of obstructive sleep apnea in patients with asthma

Obstructive sleep apnea (OSA) and asthma are both common medical problems.^1,2 It is estimated that up to 40 million persons in the United States have OSA, while 17 million have asthma.^1-4 Moreover, OSA and asthma may coexist,⁵ further complicating airway inflammatory pathology and the management of airway disease.

In this article, we will discuss the association between OSA and asthma and the role of certain comorbidities, such as obesity, gastroesophageal reflux disease (GERD), nasal obstruction, and rhinosinusitis, that may complicate either or both diseases.

Central sleep apnea is characterized by intermittent apnea or hypopnea that is secondary to cessation of respiratory effort. OSA is characterized by periodic or complete upper airway obstruction during sleep, resulting in intermittent cessation of breathing that may be complete (apnea) or partial (hypopnea) despite continued respiratory effort (Table 1).^2-4 The severity of a patient's OSA is determined by the number of apneic and/or hypopneic events occurring per hour, and OSA can be classified as mild, moderate, or severe.

Both forms of sleep apnea may coexist in a given patient. It has been estimated that sleep-disordered breathing may occur in as many as 24% of middle-aged men and 9% of middle-aged women, based on an apnea-hypopnea index (AHI) of more than 5 per hour.³ Up to 4% of men and 2% of women may have the full-blown OSA syndrome, including daytime hypersomnolence and apnea. OSA is not rare in children; the incidence may be as high as 1% to 3%.⁶ Despite the severe morbidity and mortality associated with OSA, it remains undiagnosed in most adults with this syndrome.⁶

The major risk factors for OSA include obesity, male sex, and a positive family history for the disease. A body mass index (BMI) of more than 30 kg/m² is a significant risk factor.

Some of the risk factors for OSA can also contribute to asthma (Table 2). In fact, several of these risk factors may coexist in a patient who has both OSA and asthma.

Snoring and apnea are common in patients with asthma and allergic rhinitis.⁷ In some instances, upper airway resistance syndrome and OSA may be mistaken for nocturnal asthma.⁸ Sleep deprivation, upper airway edema, and systemic inflammation associated with OSA can complicate the course of asthma.⁵

Many physiologic changes associated with sleep can promote nocturnal worsening of asthma. For example, sleep is routinely associated with an increase in parasympathetic tone relative to sympathetic activity, which could promote increased bronchomotor tone and bronchoconstriction.

Sleep has also been associated with reductions in lung volume in patients with asthma, who typically have hyperinflation during wakefulness.⁹ This reduction in lung volume clearly contributes to the increased lower airway resistance that has been measured during sleep. Fortunately, there is evidence that ventilatory responsiveness to induced bronchoconstriction is adequately maintained during sleep, even if there is excessive sleepiness after prolonged periods of sleep deprivation.¹⁰

Finally, there has been substantial interest in the potential association between OSA and asthma. Proposed mechanisms of contribution include a neurogenically mediated increase in bronchomotor tone resulting from snoring-associated vibration of the upper airway,¹¹ OSA-associated increase in systemic inflammation, and OSA-associated increase in pulmonary blood volume.¹²

As noted above, obesity is a risk factor for OSA. Moreover, an increased incidence of obesity has been observed in patients with asthma.^13-15

GERD is common in patients who have OSA, obesity, or asthma. It may occur in persons who have sleep-disordered breathing resulting from apnea or in association with obesity.¹⁶ GERD can also ex-acerbate asthma and airway inflammation.¹⁷ It can cause a va- riety of aerodigestive complications, including cough and laryngitis.^18,19 Reflux of gastric acid has been shown to worsen bronchial hyperresponsiveness.^16,18,19

Allergic and structural airway disease, such as allergic rhinitis, tonsillar enlargement, and micrognathia, may be contributory factors in some patients with OSA and/or asthma. Nasal obstruction can occur in patients with allergic asthma, vasomotor rhinitis, nonallergic rhinitis eosinophilic syndrome, nasal polyposis, or structural disease (deviated nasal septum, concha bullosa). Nasal obstruction of any cause can augment airway collapse and worsen OSA.^20-22

The coexistence of rhinitis, nasal polyposis, obesity, and GERD may contribute to the increasing frequency of the diagnosis of concurrent asthma and OSA. The acronym "CORE" describes the interactive disease states of OSA and asthma: Cough/asthma, Obesity/ OSA, Rhinosinusitis, and Esophageal reflux.²

OSA and other CORE components need to be considered in the evaluation of patients who have asthma that is refractory to therapy. The patient described below demonstrates a classic case of the CORE syndrome.

A 67-year-old man was evaluated for severe chronic asthma, rhinosinusitis, and hypertension. He complained of persistent wheezing, dyspnea, coughing, fatigue, daytime somnolence, headaches, and poorly controlled GERD. He had a 30-pack-year history of smoking but had quit smoking 4 years ago. His current medications included salmeterol(Drug information on salmeterol), ipratropium, inhaled triamcinolone(Drug information on triamcinolone), montelukast(Drug information on montelukast), and oral prednisone(Drug information on prednisone) (10 mg/d). He used nebulized ß-agonists almost every day.

Examination revealed an obese man who weighed 275 lb and had a BMI of 39.5 kg/m². He had a short, thick neck; bilateral expiratory wheezing; and peripheral edema. Pulmonary function tests revealed a forced expiratory volume in 1 second (FEV₁) of 2.09 L (69% of predicted) and a ratio of FEV₁ to forced vital capacity of 71%. Allergy skin test results were negative, and his total IgE level was normal.

Polysomnography (PSG) recorded 69 obstructive and 8 hypopneic events, and the patient's lowest oxygen saturation was 83% (Figure 1). Continuous positive airway pressure (CPAP) therapy reversed the abnormalities and improved the patient's nocturnal asthma and daytime wheezing.

Barium examination of the patient's upper GI tract indicated GERD and tertiary contractions (Figure 2). He was advised to lose weight, avoid sedatives and alcohol(Drug information on alcohol), and follow antireflux measures. His GERD and asthma were managed aggressively, and his symptoms improved.

Several endocrinopathies may play a role in the OSA-asthma relationship. Specifically, hypothyroidism needs to be evaluated and treated in OSA patients. C-reactive protein and inflammatory factors, such as cytokines and systemic inflammatory responses, elicited during apnea are also important to airway inflammation and remodeling (see "The role of inflammation in the relationship between asthma and obstructive sleep apnea").^1,2,14,23-26

Components of the diagnosis and management of OSA, asthma, and potential comorbidities are shown in Table 3.

As noted above, obesity is a predisposing factor for OSA, and the incidence of asthma is increased in obese persons.^13-15 The measurement of body fat and calculation of BMI assist in classification and diagnosis. The management of obesity involves counseling on diet and weight loss and, in some patients, pharmacologic therapy. Weight loss can reduce the severity of OSA.

Weight reduction has been widely recommended for patients with OSA, and at least 2 prospective controlled trials have indicated that losing weight by following a low-calorie diet can achieve significant improvement in sleep-disordered breathing.^27,28 Therefore, this would probably be helpful for obese patients who have OSA with concurrent asthma.