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Utility of Continuous Positive Airway Pressure Therapy for Treating Chronic Coughs in Patients with Obstructive Sleep Apnea

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Utility of Continuous Positive Airway Pressure Therapy for Treating Chronic Coughs in Patients with Obstructive Sleep Apnea □ CASE REPORT □ Utility of Continuous Positive Airway Pressure Therapy for Treating Chronic Coughs in Patients with Obstructive Sleep Apnea Naoko Yokohori, Mizue Hasegawa, Akitoshi Sato and Hideki Katsura Abstract We experienced two patients with chronic coughs whose symptoms persisted after initial treatment under a diagnosis of suspected upper airway cough syndrome or cough variant asthma. Neither patient exhibited day- time somnolence, although both were subsequently found to have severe obstructive sleep apnea. Following the administration of nocturnal continuous positive airway pressure therapy, the cough symptoms rapidly im- proved in both cases. These cases represent the first reports of obstructive sleep apnea-induced chronic cough in Japan. Key words: chronic cough, obstructive sleep apnea, continuous positive airway pressure therapy (Intern Med 53: 1079-1082, 2014) (DOI: 10.2169/internalmedicine.53.1855) ports of OSA-induced chronic cough in Japan. Introduction Case Reports The most common causes of chronic coughs in non- smokers with normal chest radiography and pulmonary Case 1 function test findings include cough variant asthma (CVA), gastroesophageal reflux disease (GERD), upper airway A 63-year-old non-smoking woman presented to her pri- cough syndrome (UACS), post-nasal drip syndrome (PNDS), mary care physician due to a dry cough that had persisted chronic bronchitis and the use of angiotensin-converting en- for several years. The primary care physician prescribed zyme (ACE) inhibitors (1, 2). Although the current diagnos- treatment with an inhaled corticosteroid (ciclesonide), two tic and treatment guidelines for chronic cough attempt to different long-acting β2-agonist/inhaled corticosteroid com- rule out such conditions, a significant proportion of chronic binations (salmeterol/fluticasone and formoterol/budesonide), coughs remain unexplained (3, 4). In recently reported cases theophylline, a leukotriene receptor antagonist (pranlukast) of chronic cough in which obstructive sleep apnea (OSA) and a long-acting anticholinergic (tiotropium); however, was concomitantly diagnosed, the administration of continu- none of these treatments improved the patient’s condition. ous positive airway pressure (CPAP) therapy resolved the Therefore, she was referred to our hospital. The cough oc- cough symptoms (5-9). Although the current treatment curred throughout the day and night without any specific guidelines for chronic cough do not incorporate tests for triggers. The patient did not exhibit any symptoms of dysp- OSA, OSA is increasingly being recognized as a cause of nea or wheezing, nor did she complain of any symptoms chronic cough. We herein report the cases of two patients suggestive of GERD. In addition, the Frequency Scale for with unexplained chronic coughs whose conditions im- the Symptoms of GERD (FSSG) score was only 2 points. A proved with CPAP therapy for OSA. Neither patient exhib- previous study recommended that an FSSG score of !8 ited daytime somnolence, although sleep studies confirmed points be used to diagnose GERD (10). The patient’s medi- severe OSA in both cases. These cases represent the first re- cal history included hypertension and diabetes. She had not Division of Respiratory Medicine, Tokyo Women’s Medical University Yachiyo Medical Center, Japan Received for publication October 7, 2013; Accepted for publication December 5, 2013 Correspondence to Dr. Naoko Yokohori, [email protected] 1079 Intern Med 53: 1079-1082, 2014 DOI: 10.2169/internalmedicine.53.1855 Table. Laboratory Findings in Cases 1 and 2 tive results for house dust, tick, Japanese cedar and cat dan- der antigens (Table). We treated the patient with an antihis- tamine (epinastine hydrochloride), leukotriene receptor an- tagonist (montelukast) and long-acting β2-agonist/inhaled corticosteroid combination (formoterol/budesonide) for three months under a diagnosis of suspected severe CVA; how- ever, the patient’s cough worsened. Therefore, she was as- sessed by an otolaryngologist to rule out PNDS, which re- sulted in a diagnosis of chronic rhinitis. Clarithromycin (CAM) and carbocisteine were added to the treatment regi- men. However, the PND worsened the following day, and the CAM and carbocisteine were immediately discontinued. The patient did not exhibit daytime somnolence (Epworth sleepiness scale (ESS) score: 3). On the other hand, she was Figure. Improvements in cough in the present cases accord- obese (body mass index (BMI): 33.2) and had a narrow ing to the visual analogue scale scores before and after CPAP pharynx and history of snoring. A polysomnographic (PSG) therapy. Each subject was asked to indicate the intensity of examination was subsequently performed, which indicated a their cough by writing an X at the appropriate point on a 100- diagnosis of severe OSA (apnea-hypopnea index (AHI): mm line, where 0 mm represented no cough and 100 mm rep- 90.2). Nocturnal nasal CPAP therapy was commenced, and resented maximal cough. The scores were obtained by measur- the patient noticed an immediate improvement in her cough ing the distance from the left end of the scale to the examinee’s (Figure). A sleep study indicated that the CPAP therapy had mark in millimeters. completely resolved the patient’s OSA (AHI: 1.1). The pa- tient’s cough disappeared within one month, and she was previously received ACE inhibitors. able to stop taking the leukotriene receptor antagonist and Chest radiography, high-resolution computed tomography long-acting β2-agonist/inhaled corticosteroid combination. and pulmonary function tests, including a test for airway re- Case 2 versibility involving the use of a short-acting β2-agonist, demonstrated normal results. An allergy test revealed a A 66-year-old non-smoking woman presented with a dry slightly elevated immunoglobulin E (IgE) level, and an IgE cough and dyspnea on effort that had lasted for five months. multiple antigen simultaneous test (MAST) produced posi- She had been suffering from sick sinus syndrome; however, 1080 Intern Med 53: 1079-1082, 2014 DOI: 10.2169/internalmedicine.53.1855 her primary care physician did not detect any abnormalities toms 12 months later (5). Subsequently, Sundar et al. re- during clinical or electrocardiographic examinations. An up- ported the cases of two patients with chronic coughs that per gastrointestinal endoscopic examination was performed, dramatically improved following the administration of CPAP which indicated a diagnosis of GERD. Accordingly, the pa- therapy for OSA (6). These chronic cough patients displayed tient was treated with a proton-pump inhibitor (PPI: lanso- normal chest radiography and pulmonary function test find- prazole); however, her chronic cough persisted. After three ings, as did the present patients. In addition, although the months of observation by her primary care physician, the coughs were resistant to antihistamines, leukotriene receptor patient was referred to our hospital. She also complained of antagonists, long-acting β2-agonists, inhaled corticosteroids mild dyspnea on effort, although she did not exhibit wheez- and PPIs, the patients’ conditions rapidly improved after ing. She had previously undergone pacemaker implantation treatment with CPAP. due to sick sinus syndrome and had suffered from depres- The etiology of chronic coughs in patients with OSA is sion and hypertension; however, she had never taken ACE unclear and may be multifactorial. OSA patients with inhibitors. She did not complain of any symptoms sugges- chronic coughs are likely to have upper airway injury and tive of PNDS or GERD, and her FSSG score was only 2 inflammation resulting from snoring and frequent episodes points. The findings of chest X-rays were normal (except for of airway obstruction, which can cause epithelial damage the presence of the pacemaker), as were the findings of pul- and inflammation in the airway (11). Patients with OSA ex- monary function tests. The IgE level was not elevated, al- hibit increased concentrations of inflammatory mediators, though a MAST test detected an elevated anti-Japanese ce- such as interleukin (IL)-6, interferon (INF)-γ and regulated dar antibody titer (Table). Since the patient complained of and normal T cell expressed and secreted (RANTES), as upper airway irritability, she was treated with an antihista- well as higher levels of exhaled nitric oxide in the upper air- mine (epinastine hydrochloride) for two months under a di- ways, which may increase the sensitivity of cough recep- agnosis of suspected UACS; however, this did not produce tors (12, 13). any improvements in her condition. She was subsequently Second, it is possible that CPAP therapy is effective in re- treated with an inhaled steroid (ciclesonide) followed by a ducing the frequency of nocturnal GERD and hence any as- long-acting β2-agonist/inhaled corticosteroid combination sociated cough. Patients with OSA exhibit a higher inci- (salmeterol/fluticasone); however, these treatments had only dence of GERD, and CPAP therapy has been shown to re- a temporary effect. Although the patient did not exhibit day- duce the frequency of GERD episodes (14, 15). time somnolence (ESS score: 3), she was mildly obese Another possibility is that such coughs have a mechanical (BMI: 26.1) and had a narrow pharynx and history of snor- cause, as the chronic coughs observed in the present study ing. A PSG examination was arranged, which indicated a di- remained resistant to therapy for one year, while CPAP ther- agnosis of severe OSA (AHI: 47). The patient’s
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