Sleep apnea is associated with bronchial inflammation and continuous positive airway pressure-induced airway hyperresponsiveness.

BACKGROUND: Obstructive sleep apnea syndrome (OSA) is associated with systemic and upper airway inflammation. Pharyngeal inflammation has a potential role in upper airway collapse, whereas systemic inflammation relates to cardiovascular morbidity. However, the presence of an inflammatory involvement of lower airway has been poorly investigated. OBJECTIVE: The aim of the study was to demonstrate an inflammatory process at the bronchial level in patients with OSA and to analyze effects of continuous positive airway pressure (CPAP) application and humidification on bronchial mucosa. METHODS: The study was conducted by using sequential induced sputum for cell analysis and IL-8 production, nitric oxide exhalation measurement, and methacholine challenge before and after CPAP. RESULTS: Bronchial neutrophilia and a high IL-8 concentration were observed in untreated OSA compared with controls (75% +/- 20% vs 43% +/- 12%, P < .05; and 25.02 +/- 9.43 ng/mL vs 8.6 +/- 3.7 ng/mL, P < .001, respectively). IL-8 in sputum supernatant was correlated to apnea hypopnea index (P < .01; r = 0.81). After 1 month of CPAP, this inflammatory pattern remained unchanged, and an increase in airway hyperresponsiveness (AHR) was observed (P < .001). CONCLUSION: Obstructive sleep apnea syndrome is associated with bronchial inflammation. Our data demonstrate CPAP effect on the development of AHR, possibly facilitated by the pre-existing inflammation. Both issues should be evaluated during long-term CPAP use. CLINICAL IMPLICATIONS: Results showing a spontaneous bronchial inflammation in OSA and the development of a CPAP-related AHR require a long-term follow-up to evaluate consequences on chronic bronchial obstruction.

Fructose-fed rat hearts are protected against ischemia-reperfusion injury.

High fructose-fed (HFF) rat model is known to develop the insulin-resistant syndrome with a very similar metabolic profile to the human X syndrome. Such metabolic modifications have been associated with a high incidence of cardiovascular disease. The role of free radical attack in diabetes mellitus and its cardiovascular complications have been abundantly documented. The present study examined the susceptibility to myocardial ischemic injury and the involvement of free radical attack and/or protection in the metabolic disorders of high FF rats. Rats were divided into two experimental groups that received diet for 4 weeks: a control group (C, n=28) receiving a standard diet and a HFF group (FF, n=28), in which 58% of the total carbohydrate was fructose. The euglycemic clamp technique was performed to assess insulin resistance. For the ischemia-reperfusion procedure, rat hearts were isolated and perfused at constant pressure before they were subjected to a 30-min occlusion of the left coronary artery followed by 120 mins of reperfusion. Hemodynamic parameters were measured throughout the protocol. Infarct-to-risk ratio (I/R) was assessed at the end of the protocol by 2,3,4-triphenyltetrazolium chloride staining and planimetric analysis. Lipid peroxidation, antioxidant enzyme activity, level of vitamin E, and trace element status were measured in blood samples from both groups. Rats of the FF group developed an insulin resistance indicated by the glucose infusion rate, which was decreased by 47%. Infarct size was significantly reduced in rats from the FF group (19.9% +/- 6.6%) compared to rats from the control group (34.6% +/- 4.9%), and cardiac functional recovery at reperfusion was improved in the FF group. Lipid peroxidation and oxidative stress were higher in the FF group, as indicated by higher malonedialdehyde level, whereas plasma vitamin E/triacylglycerol ratio was also enhanced in this group. This study indicates that fructose feeding affords protection against in vitro ischemia-reperfusion injury, potentially implicating vitamin E.

Bronchial hyperresponsiveness, airway inflammation, and airflow limitation in endurance athletes.

BACKGROUND: Whereas a high prevalence of bronchial abnormalities has been reported in endurance athletes, its underlying mechanisms and consequences during exercise are still unclear. STUDY OBJECTIVES: The purpose of this study was to assess the following: (1) bronchial responsiveness to methacholine and to exercise; (2) airway inflammation; and (3) airflow limitation during intense exercise in endurance athletes with respiratory symptoms. DESIGN: Cross-sectional observational study. SETTING: Lung function and exercise laboratory at a university hospital. PATIENTS AND MEASUREMENTS: Thirty-nine endurance athletes and 13 sedentary control subjects were explored for the following: (1) self-reported respiratory symptoms; (2) bronchial hyperresponsiveness (BHR) to methacholine and exercise; (3) airflow limitation during intense exercise; and (4) bronchial inflammation using induced sputum and nitric oxide (NO) exhalation. RESULTS: Fifteen athletes (38%) showed BHR to methacholine and/or exercise in association with bronchial eosinophilia (mean [+/- SD] eosinophil count, 4.1 +/- 8.5% vs 0.3 +/- 0.9% vs 0%, respectively), higher NO concentrations (19 +/- 10 vs 14 +/- 4 vs 13 +/- 4 parts per billion, respectively), a higher prevalence of atopy, and more exercise-induced symptoms compared with non-hyperresponsive athletes and control subjects (p < 0.05). Furthermore, airflow limitation during intense exercise was observed in eight athletes, among whom five had BHR. Athletes with airflow limitation reported more symptoms and had FEV1, FEV1/FVC ratio, and forced expiratory flow at midexpiratory phase values of 14%, 9%, and 29%, respectively, lower compared with those of nonlimited athletes (p < 0.05). CONCLUSION: BHR in endurance athletes was associated with the criteria of eosinophilic airway inflammation and atopy, whereas airflow limitation during exercise was primarily a consequence of decreased resting spirometric values. Both BHR and bronchial obstruction at rest with subsequent expiratory flow limitation during exercise may promote respiratory symptoms during exercise in athletes.

Night-time and diastolic hypertension are common and underestimated conditions in newly diagnosed apnoeic patients.

BACKGROUND: In newly diagnosed apnoeic patients without a history of hypertension, clinical hypertension is underdiagnosed in at least 40% of the cases. An increase in diastolic blood pressure is the most frequent pattern encountered. OBJECTIVE: To assess clinic and 24-h blood pressure, baroreflex sensitivity and left ventricular mass for identifying the prevalence, the type and the consequences of hypertension in newly diagnosed apnoeic patients. PATIENTS AND METHODS: Fifty-nine unselected patients (age = 48 +/- 12 years, body mass index = 28.1 +/- 4.5 kg/m2) referred to a university hospital sleep laboratory for symptoms suggesting obstructive sleep apnoea were included. Diagnosis of apnoea was accepted when respiratory disturbance index was > or = 15/h of sleep. Blood pressure was considered as normal by their general practitioner and all of them were free of any medication for hypertension. Echocardiography, 24-hour ambulatory blood pressure monitoring and assessment of the baroreflex sensitivity were performed. RESULTS: Forty-two percent of the apnoeic patients demonstrated a clinical hypertension, 34 subjects (58%) had a daytime hypertension, and 45 patients (76%) had a night-time hypertension, using 24-h monitoring. All the daytime hypertensives also had night-time hypertension. Forty-seven of the 59 patients (80%) were hypertensive either in the clinic or using 24-h recording. Diastolic and systolo-diastolic hypertension were the prominent types of hypertension observed both by clinic or ambulatory measurements. Respiratory disturbance index was significantly higher in apnoeic patients suffering isolated diastolic hypertension than in the normotensives (50.9 +/- 26.5/h versus 36.0 +/- 12.3/h, respectively; P = 0.02). The prevalence rate of left ventricular hypertrophy was high (between 15 and 20%) and occurred independently of associated hypertension. Baroreflex sensitivity was altered whatever the type of hypertension and decreased with the severity of obstructive sleep apnoea. CONCLUSION: Hypertension is hugely underdiagnosed in apnoeic patients unknown to be hypertensive. Use of 24-h blood pressure monitoring allowed the diagnosis of twice as much hypertension than did clinical measurement. Even at the beginning of their history of hypertension, apnoeic patients exhibited chronic adaptations of their cardiovascular system, as shown by early changes in baroreflex sensitivity and an increased prevalence of left ventricular hypertrophy.