嚴重阻塞性睡眠呼吸中止症患者其運動誘發支氣管收縮現象之探討

Abstract

研究背景及目的：阻塞性睡眠呼吸中止症之病徵為睡眠時週期性重覆發生的上呼吸道阻塞。近年來研究證據顯示此類患者的呼吸道有局部發炎現象。呼吸道處於慢性發炎的狀態會增加運動誘發支氣管收縮的機會。本研究主要目的為探討嚴重阻塞性睡眠呼吸中止症患者是否會在運動激發測試中發生運動誘發支氣管收縮現象。另外研究也將追蹤為期三個月的持續性正壓呼吸治療對阻塞性睡眠呼吸中止症患者在運動激發測試中氣道反應的影響。方法：於睡眠門診徵召22位患有嚴重阻塞性睡眠呼吸中止症之患者為實驗組，9位依性別、年齡、身體質量指數配對之受試者為對照組。所有受試者皆需至實驗室兩次。第一次進行基線肺功能的測量與誘發痰液以分析呼吸道基線發炎狀況；第二次為進行一標準化之運動激發測試並於運動結束後第2.5、5、10、15、20及30分鐘分別測量第一秒用力吐氣量（forced expiratory volume in one second, FEV1），以評估運動誘發支氣管收縮發生與否及程度。實驗組受試者在接受為期3個月之持續性正壓呼吸治療後，再次進行上述所有測試。結果：實驗組受試者FEV1與用力吐氣肺容量（forced vital capacity, FVC）之比值（FEV1/FVC）（p＜0.01）及用力吐氣中段流速（25%-75% forced expiratory flow, FEF25-75）（p=0.03）均較對照組低。運動激發測試後實驗組無受試者出現運動誘發支氣管收縮的現象。基線及運動後實驗組痰液中之巨噬細胞比例均顯著低於對照組（p=0.03）。與基線相比，兩組受試者運動後誘發痰液中支氣管上皮細胞所佔比例均會升高。基線之嗜中性球比例與運動後FEV1之改變間具顯著低度負相關。結論：嚴重阻塞性睡眠呼吸中止症患者其呼吸道存在發炎。雖然本研究之OSAS患者均未達臨床判定具運動誘發支氣管收縮現象，但其氣道發炎程度仍會影響氣道在運動時的反應。

Background and purpose: Obstructive sleep apnea syndrome (OSAS) is characterized by repeated episodes of upper airway obstruction during sleep. Recent studies have found evidence of airway inflammation in patients with OSAS. Individuals with chronic airway inflammation are at higher risk for exercise-induced bronchoconstriction (EIB) during exercise. The main purpose of this study was to evaluate EIB during exercise challenge test in patients with severe OSAS. The effect of a 3-month continuous positive airway pressure (CPAP) therapy on EIB was also explored. Methods: Twenty-two patients with severe OSAS and 9 control subjects matched for age, gender, and body mass index (BMI) were recruited from sleep clinic. All participants came to the laboratory on 2 separate days. On the 1st visit, baseline pulmonary function test (PFT) and airway inflammation assessed by induced sputum were performed. On the 2nd visit, an exercise challenge was performed using standard testing protocol and post-exercise forced expiratory volume in one second (FEV1) were measured at 2.5, 5, 10, 15, 20, and 30 minutes. For patients with severe OSAS, all measurements were repeated after a 3-month CPAP therapy. Results: The FEV1/FVC ratio (p＜0.01) and FEF25-75 (p=0.03) were significantly lower in the OSAS group than those in the control group. None of the subjects in the OSAS group demonstrated EIB attack after exercise challenge test. The percentages of macrophage in the induced sputum were significantly lower in the OSAS group both at baseline and post-exercise (p=0.03). Compared with baseline, the percentages of bronchial epithelial cells were significantly higher after exercise challenge test in both groups. The percentage of neutrophil at baseline was negatively correlated with the maximal FEV1 drop post exercise challenge test. Conclusions: The study confirmed airway inflammation exists in patients with severe OSAS. Although no EIB attack was found in patients with OSAS in this study, the correlation between airway inflammation and FEV1 changes post exercise challenge test suggests that the degree of airway inflammation plays a role in how airways would respond to exercise.