OSAHS患者呼出气冷凝液中MMP-9的变化

目的观察阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者呼出气冷凝液(EBC)中基质金属蛋白酶9(MMP-9)的变化。方法选取男性40例OSAHS患者为实验组,30例年龄、体重指数等均相匹配的健康查体者为对照组,用ELISA检测EBC中MMP-9水平。结果和对照组比较,OSAHS组EBC中MMP-9明显升高,有显著统计学意义(P0.05)。MMP-9与AHI呈正相关,与最低SaO2负相关(P均0.05)。结论OSAHS患者EBC中MMP-9水平可反映OSAHS病情的严重程度。     

阻塞性睡眠呼吸暂停综合征呼出气冷凝液中炎症因子检测的研究进展

阻塞性睡眠呼吸暂停综合征(OSAS)的发生机制与炎症和氧化应激有关,收集呼出气冷凝液(EBC)并检测其有关成分是一种新的无创检测技术.本文对OSAS患者EBC中炎症因子(白介素6、8-异前列烷和白三烯)的检测、变化规律和临床意义进行综述.     

The role of obstructive sleep apnea syndrome and obesity in determining leptin in the exhaled breath condensate

Leptin plays a key role in obstructive sleep apnea syndrome (OSAS). Leptin production in human airways has been previously evaluated by measuring leptin concentration in the exhaled breath condensate and in the induced sputum. The aim was to study leptin expression in the cells of induced sputum and in exhaled breath condensate of subjects with OSAS. Moreover, leptin concentrations in the blood were measured in the same groups of subjects. We enrolled four groups of patients: (1) obese patients with OSAS (OO); (2) non-obese patients with OSAS (NOO); (3) obese patients without OSAS (ONO); and (4) non-obese subjects without OSAS (C). Leptin expression was evaluated by immunocytochemistry in the sputum cells of the enrolled subjects. The concentrations of leptin in the exhaled breath condensate and plasma were measured by using a specific enzyme immunoassay. Leptin protein expression and the percentage of macrophages and neutrophils expressing leptin were higher in the induced sputum of OO, NOO and ONO patients than in C. Leptin concentrations in the exhaled breath condensate were significantly higher in OO patients (5.12 (3.8-6.6) ng ml(-1)) than in NOO (4.1 (3.9-5.2) ng ml(-1)) and ONO (4.2 (3.6-5.0) ng ml(-1)) patients. The concentration of leptin in plasma was significantly more elevated in OO (36 (24-65.9) ng ml(-1)) than in NOO (30.2 (12.4-51.4) ng ml(-1)), whereas it was not significantly different in ONO patients. This study showed that leptin in sputum and in the exhaled breath condensate is higher in obese patients with OSAS than in obese subjects without OSAS. Moreover, different mechanisms for determining leptin concentrations in the exhaled breath condensate and the blood are suggested.     

阻塞性睡眠呼吸暂停低通气综合征患者呼出气凝集液中过氧化氢浓度

目的测定阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者呼出气凝集液(EBC)中的过氧化氢(H2O2)浓度,观察其改变及与病情程度的相关性。方法收集EBC 42份,其中OSAHS患者32份(吸烟者18份,非吸烟者14份),非OSAHS对照组10份。荧光法测定睡前和晨起EBC中的H2O2浓度。结果OSAHS组患者睡前EBC中H2O2浓度与对照组比较差异无统计学意义(F= 0．01,P=0．99)。晨起EBC中H2O2浓度OSAHS不吸烟组和吸烟组分别为(1．82±1．12)、(1．65±0．89)μmol／L,较对照组(0．71±0．36)μmol／L明显增高(F=5．11,P=0．01)。其浓度亦分别较睡前[(0．87±0．45)、(0．88±0．36)μmol／L]升高(t分别为2．95、3．43,P均<0．01)。对照组睡前[(0．86±0．46)μmol／L]和晨起[(0．71±0．36)μmol／L]差异无统计学意义(t=0．81,P=0．43)。晨起EBC中H2O2浓度与夜间最低血氧饱和度(SpO2min)呈负相关(β=-0．36,P=0．02),晨起与睡前H2O2浓度变化的差值亦与SpO2min呈负相关(β=-0．38,P=0．01)。结论OSAHS患者由于夜间反复出现缺氧-再氧和,呼吸道局部氧应激反应在晨起增加。     

阻塞性睡眠呼吸暂停低通气综合征患者呼出气冷凝液中白细胞介素6的研究

目的探讨阻塞性睡眠呼吸暂停低通气综合征(OSAHS)患者是否存在夜间呼吸事件相关的呼吸道炎症反应。方法对31例OSAHS患者(分为OSAHS吸烟组15例和非吸烟组16例)和10名健康对照者(健康对照组)采用自行设计的呼出气冷凝液(EBC)收集器收集晨起即刻和睡前的EBC,应用酶联免疫技术测定EBC中白细胞介素6(IL6)的含量,并进行统计学分析。结果(1)睡前IL6水平OSAHS吸烟组[(2.5±1.0)ng/L]、非吸烟组[(2.3±0.8)ng/L]、健康对照组[(2.7±1.0)ng/L]比较差异无统计学意义(F=0.515,P>0.05)。晨起IL6水平OSAHS吸烟组[(3.7±1.9)ng/L]和非吸烟组[(3.1±1.2)ng/L]均高于健康对照组[(2.0±0.8)ng/L],差异有统计学意义(P<0.05);吸烟组和非吸烟组比较差异无统计学意义(P>0.05)。(2)晨起IL6水平OSAHS吸烟组和非吸烟组均较睡前显著增高(P<0.05);而健康对照组晨起IL6水平较睡前降低,差异有统计学意义(P<0.05)。(3)晨起IL6的浓度与呼吸暂停低通气指数(AHI)、氧减饱和指数(ODI4)呈正相关(r值分别为0.441、0.533,P均<0.05),与夜间最低血氧饱和度(LSaO2)呈负相关(r=-0.529,P<0.05)。结论EBC中IL6水平的高低与病情严重程度有关,故可作为OSAHS气道炎症反应的一项重要监测指标。     

阻塞性睡眠呼吸暂停低通气综合征呼出气冷凝液8-异前列烷的昼夜变化及其意义

目的 探讨阻塞性睡眠呼吸暂停低通气综合征(obstructive sleep apnea-hypopnea syndrome,OSAHS)患者呼出气冷凝液(exhaled breath condensate,EBC)8-异前列烷(8-isoprostane,8-isoPG)的昼夜变化及其意义.方法 采用德国JAEGER公司的呼出气收集器.收集40例OSAHS患者和30名正常对照者睡眠监测前后的EBC,同时采集睡眠监测后的血清,采用酶联免疫技术测定EBC及血清中8-isoPG的含量,并与睡眠监测指标进行相关性分析.结果 OSAHS组EBC中8-isoPG睡眠监测前为(13.08±1.42)ng/L、睡眠临测后为(14.93±1.39)ng/L(P<0.01).正常对照组EBC中8-isoPG睡眠监测前为(11.06±0.72)ng/L、睡眠监测后为(10.97±0.70)ng/L(P>0.05).OSAHS组睡眠监测后EBC及血清中8-isoPG比正常对照组升高,P<0.01.OSAHS患者睡眠监测后EBC 8-isoPG与血清8-isoPG呈正相关(r=0.685,P<0.01),与AHI呈正相关(r=0.650,P<0.05),与睡眠中最低血氧饱和度、基础血氧饱和度和平均血氧饱和度呈负相关(r=-0.406,-0.439,-0.454,P值均<0.05).结论 OSAHS患者存在夜间氧化应激反应增强,OSAHS患者早晨EBC中8-isoPG可以作为评价患者氧化应激状态和估计病情严重程度的较好指标.     

阻塞性睡眠呼吸暂停低通气综合征患者血清和呼出气冷凝液中基质金属蛋白酶-2的水平及意义

目的 探讨血清和呼出气冷凝液(EBC)中基质金属蛋白酶-2(MMP-2)的水平与阻塞性睡眠呼吸暂停低通气综合征(OSAHS)发病的关系.方法 利用酶联免疫吸附法对30例轻度OSAHS患者(轻度OSAHS组)、68例中重度OSAHS患者(中重度OSAHS组)和22名健康者(正常对照组)血清及EBC中MMP-2的水平进行检测,对其中40例中重度OSAHS患者在持续气道正压通气(CPAP)治疗1个月后进行复查.结果 与正常对照组相比,轻度、中重度OSAHS患者血清及EBC中MMP-2的水平依次增高,40例中重度OSAHS患者在CPAP治疗后明显下降,差异具有统计学意义(t=2.369、2.512,P值均＜0.05).结论 OSAHS患者血清及EBC中MMP-2水平升高,与OSAHS的发病可能相关.     

Inflammatory markers in exhaled breath condensate from patients with asthma

Background and objective:   Evaluation of airway inflammation is important for the diagnosis and treatment of asthma. Exhaled breath condensate (EBC) is a minimally invasive method for assessing inflammation and may be useful for monitoring airway inflammation in asthma. The aims of this study were to establish an EBC collection method, to assess biomarkers reflecting asthmatic airway inflammation, and to determine the relationship of these biomarkers with asthma severity and lung function.
Methods:   Fifty-eight non-smoking healthy subjects, seven asymptomatic smokers, nine subjects with common cold and 55 asthmatics with disease severity ranging from mild intermittent to severe persistent were studied. The efficacy of a pipette method was compared with that of a commercial collecting device. pH, CRP, albumin, hydrogen peroxide (H₂O₂) and nitrite/nitrate levels were measured in EBC.
Results:   Except for the quantity of EBC collected and albumin levels, there were no differences between the commercial method and the pipette method in levels of biomarkers measured. Levels of CRP, H₂O₂ and nitrite/nitrate were significantly higher in the asthma group than that in the control group. In terms of asthma severity, pH and levels of CRP, H₂O₂ and nitrate were significantly higher in the mild persistent group than that in the other groups. In addition, H₂O₂ levels in EBC correlated significantly with the level of nitrite/nitrate. FEV₁ and PEF showed significant negative correlations with H₂O₂ and nitrite/nitrate levels.
Conclusion:   Measurement of EBC biomarkers is a non-invasive and useful way to evaluate airway inflammation in patients with asthma.     

Increased 8-isoprostane and interleukin-6 in breath condensate of obstructive sleep apnea patients

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by repeated episodes of upper airways obstruction during sleep that result in episodes of hypoxia. An increase of systemic biomarkers of inflammation and oxidative stress has been found in patients with OSA and obesity. DESIGN: The aim of this study was to measure the levels of markers of inflammation (interleukin [IL]-6) and oxidative stress (8-isoprostane) in the exhaled breath condensate of OSA and obese patients. PATIENTS AND METHODS: Eighteen OSA patients (13 men; mean [+/- SEM] age, 44 +/- 7 years), 10 obese subjects (4 men; mean age, 39 +/- 8 years), and 15 healthy age-matched subjects (8 men; mean age, 42 +/- 4 years) were recruited. IL-6 and 8-isoprostane were measured in exhaled breath condensate by a specific enzyme immunoassay kit. Measurements and results: Higher concentrations of IL-6 were found in OSA patients (8.7 +/- 0.3 pg/mL) than in healthy control subjects (1.6 +/- 0.1 pg/mL; p < 0.0001). Obese subjects also had higher levels than healthy control subjects, but lower levels than OSA patients (2.1 +/- 0.2 pg/mL, p < 0.05 and p < 0.0001 respectively). Furthermore, 8-isoprostane levels were found to be higher in OSA patients (7.4 +/- 0.7 pg/mL) than in obese subjects (5 +/- 0.3 pg/mL; p = 0.4) and healthy subjects (4.5 +/- 0.5 pg/mL; p < 0.005). We found a positive correlation between these two markers and neck circumference and apnea/hypopnea index. CONCLUSIONS: These findings suggest that inflammation and oxidative stress are characteristic in the airways of OSA patients but not in obese subjects, and that their levels depend on the severity of the OSA. The measurement of IL-6 and 8-isoprostane levels may prove to be useful in screening and monitoring obese patients who have a high risk of developing OSA.     

Alveolar-derived exhaled nitric oxide is reduced in obstructive sleep apnea syndrome

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular diseases, in particular systemic arterial hypertension. We postulated that intermittent nocturnal hypoxia in OSAS may be associated to decreased fractional exhaled nitric oxide (FENO) levels from distal airspaces. METHODS: Multiple flow rate measurements have been used to fractionate nitric oxide (NO) from alveolar and bronchial sources in 34 patients with OSAS, in 29 healthy control subjects, and in 8 hypertensive non-OSAS patients. The effect of 2 days of treatment with nasal continuous positive airway pressure (nCPAP) on FENO was examined in 18 patients with severe OSAS. RESULTS: We found that the mean [+/- SE] concentrations of exhaled NO at a rate of 50 mL/s was 21.8 +/- 1.9 parts per billion (ppb) in patients with OSAS, 25.1 +/- 3.3 ppb in healthy control subjects, and 15.4 +/- 1.7 ppb in hypertensive control patients. The mean fractional alveolar NO concentration (CANO) in OSAS patients was significantly lower than that in control subjects (2.96 +/- 0.48 vs 5.35 +/- 0.83 ppb, respectively; p < 0.05). In addition, CANO values were significantly lower in OSAS patients with systemic hypertension compared to those in normotensive OSAS patients and hypertensive patients without OSAS. The mean values of CANO significantly improved after nCPAP therapy (2.67 +/- 0.41 to 4.69 +/- 0.74 nL/L, respectively; p = 0.01). CONCLUSIONS: These findings suggest that alveolar FENO, and not bronchial FENO, is impaired in patients with OSAS and that this impairment is associated with an increased risk of hypertension. NO production within the alveolar space is modified by treatment with nCPAP.     

Aldehydes in exhaled breath condensate of patients with chronic obstructive pulmonary disease

The aims of the present study were (1) to evaluate whether individual aldehydes resulting from lipid peroxidation can be measured in exhaled breath condensate, (2) to assess the influence of sampling procedures on aldehyde concentrations, and (3) to compare aldehyde levels of patients with stable, moderate to severe, chronic obstructive pulmonary disease with those of smoking and nonsmoking control subjects. Aldehydes (malondialdehyde, hexanal, heptanal, and nonanal) were measured by liquid chromatography-tandem mass spectrometry in all samples and overlapping results were obtained by different sampling procedures. Malondialdehyde (57.2 +/- 2.4 nmol/L), hexanal (63.5 +/- 4.4 nmol/L), and heptanal (26.6 +/- 3.9 nmol/L) were increased in patients as compared with nonsmoking control subjects (17.7 +/- 5.5 nmol/L, p < 0.0001; 14.2 +/- 3.5 nmol/L, p = 0.004; and 18.7 +/- 0.9 nmol/L, p = 0.002, respectively). Only malondialdehyde was increased in patients compared with smoking control subjects (35.6 +/- 4.0 nmol/L, p = 0.0007). In conclusion, different classes of aldehydes were identified in exhaled breath condensate of humans. Whereas all aldehydes but nonanal were lower in control subjects as compared with other groups, only malondialdehyde distinguished smoking control subjects from patients with chronic obstructive pulmonary disease and could be envisaged as a biomarker potentially useful to monitor the disease and its response to therapy.     

Adenotonsillectomy for obstructive sleep apnea in children with Prader-Willi syndrome

The aim of our study was to evaluate the efficacy of adenotonsillectomy for the treatment of obstructive sleep apnea syndrome (OSA) in pediatric patients with Prader-Willi syndrome (PWS), and to describe the postoperative complications. Five patients (4 males; median age, 4.4 years; range, 1.6-14.2 years) were studied. All patients underwent an overnight cardiorespiratory sleep study. All patients had adenotonsillar hypertrophy (ATH), and two were also obese. The preoperative obstructive apnea/hypopnea index (AHI; median and range) was 12.2 (9.0-19.9) events/hr; the mean oxygen saturation was 95 (79-96)%; the nadir oxygen saturation was 71 (58-78)%; and the oxygen desaturation index (ODI) was 15.8 (11.4-35.9) events/hr. Preoperatively, patients were classified as having moderate to severe OSA. A second sleep study, performed 16 (3-43) months after adenotonsillectomy, showed a significant decrease in AHI (P = 0.009) and ODI (P = 0.009). Mean and nadir oxygen saturation did not differ significantly postsurgery (P = 0.188, P = 0.073, respectively). Four out of five children showed at least one postoperative complication. Difficult awakening from anesthesia, hemorrhages, and respiratory complications requiring reintubation and/or supplemental oxygen administration were observed. In conclusion, patients with PWS and OSA who underwent adenotonsillectomy showed a significant decrease in AHI and number of oxygen desaturations.     

A review of 50 children with obstructive sleep apnea syndrome

Fifty children and adolescents with obstructive sleep apnea syndrome and related breathing disorders during sleep are reviewed. Subjects were subdivided according to whether their breathing irregularity was secondary to a medical problem (group I) or was the primary complaint (group II). The most common presenting complaint was excessive daytime somnolence; hyperactivity and antisocial behavior also were cited frequently. In 20% of cases, substantial personality changes were reported. Clinical symptoms included failure to thrive, abnormal weight for age, acute cardiac or cardiorespiratory failure, hypertension, and frequent upper airway infections. Continuous, heavy snoring was reported in all cases; disrupted nocturnal sleep, sleep walking, nightmares, and enuresis were common. All subjects, and 22 control patients, were monitored polygraphically during sleep for at least one night. Nocturnal sleep in the reported population was severely disrupted. A complete disappearance of stage 3 NREM sleep was noted in 86% of cases; REM sleep was decreased less. The management of these cases is reviewed. Eight patients received permanent tracheostomies. Thirty children had tonsillectomy and/or adenoidectomy (three later required tracheostomy). Non-surgical approaches also were used, particularly in group 1. Follow-up on these cases to date is presented.     

Aldehydes and glutathione in exhaled breath condensate of children with asthma exacerbation

Oxidative stress is implicated in the pathogenesis of asthma, and clinical studies show an imbalance in the level of oxidants to the level of antioxidants in subjects with asthma. Aldehydes and glutathione are examples of biomarkers of oxidant-induced damage and antioxidant status in asthma, respectively. In the study, we applied analytical techniques based on liquid chromatography for the assessment of aldehydes and glutathione in the exhaled breath condensate of children with asthma and in control subjects without asthma. Twelve subjects with asthma were evaluated at exacerbation and after 5 days of therapy with prednisone. At exacerbation, malondialdehyde levels were higher in patients with asthma (30.2 +/- 2.4 nM) than in control subjects (19.4 +/- 1.9 nM, p = 0.002) and were reduced after steroid therapy (18.5 +/- 1.6 nM, p = 0.001). At exacerbation, glutathione levels were lower in subjects with asthma (5.96 +/- 0.6 nM) than in control subjects (14.1 +/- 0.8 nM, p < 0.0001) and were increased after the therapy (8.44 +/- 1.2 nM, p = 0.04). Malondialdehyde and glutathione both in subjects with asthma and control subjects were negatively correlated (r = -0.5, p = 0.001). The study shows that aldehydes and glutathione are detectable in the exhaled breath condensate of children with asthma and healthy children and that their levels are modified during asthma exacerbation and after a 5-day course of therapy with oral prednisone.     

慢性阻塞性肺疾病呼出气冷凝液中生物标记物的研究进展

呼出气冷凝液(exhaled breath condensate,EBC)检测作为一种新的研究肺部疾病的方法,具有无创、简便易行、实时监测、重复性好、患者易耐受等优点.对慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者EBC中反映气道炎症、氧化应激状态的生物标...     

慢性阻塞性肺疾病呼出气冷凝液中的生物标记物及其意义

呼出气冷凝液(exhaled breath condensate,EBC)是一种无创研究气道内衬液成分的方法,也为评估肺部炎症提供可能.目前普遍认为,慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)是以气道、肺实质和肺血管的慢性炎症为特征的疾病.通过对COPD患者EBC的收集和检测,可实现对气道炎症的实时、无创、简单、重复的监测.     

Inflammatory markers in exhaled breath condensate following lung resection for bronchial carcinoma

Background and objective: Pulmonary resection may cause inflammatory changes with subsequent injury to the remaining lung and deterioration in respiratory function. This study investigated the pattern of serum inflammatory markers and exhaled breath condensate (EBC) in patients undergoing major lung resection due to bronchial carcinoma compared with minimally invasive thoracic surgery. Methods: The pro-inflammatory markers IL-1-β, IL-6, IL-8, tumor necrosis factor-α (TNF-α) and soluble intercellular adhesion molecule-1 (sICAM-1) were measured preoperatively (day −1) and on three postoperative days (day 1, 3, 7) in serum and EBC in patients after lobectomy or pneumonectomy due to bronchial carcinoma (test group) and in patients undergoing thoracoscopy with minimal wedge resection (control group). Results: All mediators were detectable in serum and all but IL-8 were detectable in EBC. No patient suffered postoperative respiratory failure. In the test group, serum IL-6 was significantly higher postoperatively compared with day −1 (P < 0.001). For EBC (test group), the postoperative values of IL-1-β were significantly higher compared with day −1 (P = 0.005). In EBC (test group), day −1 TNF-α and sICAM-1 were significantly higher compared with controls (P < 0.029 and P = 0.032, respectively). There was no correlation between the levels of mediators and the extent of resection. Conclusions: Pro-inflammatory markers are detected in EBC following pulmonary surgery. Mediators are detectable in both serum and EBC in patients with bronchial carcinoma undergoing pulmonary resection, but the levels are higher in EBC.