Onofrio Resta

Sleep-related breathing disorders, loud snoring and excessive daytime sleepiness in obese subjects.

OBJECTIVE: To investigate the prevalence of sleep breathing disorders, loud snoring and excessive daytime sleepiness in a group of obese subjects, and to identify the predictors of obstructive sleep apnea (OSA) severity in these patients.SUBJECTS: A total of 161 consecutive obese patients (body mass index (BMI)≥30.0 kg/m2), ranging between 30.0 and 67.3, represented by 57 men and 104 women, aged 16–75 y. Forty (15 men and 25 women) age-matched (20–70 y) nonobese (BMI<27 kg/m2) volunteers were also recruited for the study.MEASUREMENTS: Respiratory function parameters, nocturnal sleep quality (evaluated by a specific questionnaire), nocturnal hypoventilation and OSA (evaluated by night polysomnography) were examined in all subjects. Anthropometric parameters (neck circumference, waist circumference, waist-to-hip ratio) were also investigated.RESULTS: Eighty-three obese patients (51.5% of the obese group) had a respiratory disturbance index (RDI)≥10, corresponding to a moderate or severe sleep apnea. In particular, 24.8% (40/161), ie a quarter of all obese patients, were affected by severe OSA and this alteration was present in 42.1% of obese men (24/57) and in 15.4% (16/104) of obese women. When a stepwise multiple regression analysis was performed, neck circumference in men and BMI in women were shown to be the strongest predictors of sleep apnea. Twenty-nine percent of all obese subjects (40.3% of men and 23.1% of women) showed nocturnal hypoventilation; however, it was present as a unique breathing alteration in only 5% of the obese population. The percentage of patients having excessive daytime sleepiness was significantly higher than in nonobese subjects, even when only nonapneic obese patients were considered (P<0.001).CONCLUSION: This study shows that OSA is present in more than 50% of a population of obese patients with a mean BMI higher than 40.0, this percentage being much higher than that commonly reported in previous studies, particularly in women. Neck circumference in men and BMI in women seem to be the strongest predictors of the severity of OSA in obese patients. Nocturnal hypoventilation seems to be present in more than 29% of a severe obese population. Moreover, this study indicates that morbid obesity can be associated with excessive daytime sleepiness even in the absence of sleep apnea.

An electronic nose in the discrimination of patients with non-small cell lung cancer and COPD

BACKGROUND Exhaled breath contains thousands of gaseous volatile organic compounds (VOCs) that may be used as non-invasive markers of lung disease. The electronic nose analyzes VOCs by composite nano-sensor arrays with learning algorithms. It has been shown that an electronic nose can distinguish the VOCs pattern in exhaled breath of lung cancer patients from healthy controls. We hypothesized that an electronic nose can discriminate patients with lung cancer from COPD patients and healthy controls by analyzing the VOC-profile in exhaled breath. METHODS 30 subjects participated in a cross-sectional study: 10 patients with non-small cell lung cancer (NSCLC, [age 66.4+/-9.0, FEV(1) 86.3+/-20.7]), 10 patients with COPD (age 61.4+/-5.5, FEV(1) 70.0+/-14.8) and 10 healthy controls (age 58.3+/-8.1, FEV(1) 108.9+/-14.6). After 5 min tidal breathing through a non-rebreathing valve with inspiratory VOC-filter, subjects performed a single vital capacity maneuver to collect dried exhaled air into a Tedlar bag. The bag was connected to the electronic nose (Cyranose 320) within 10 min, with VOC-filtered room air as baseline. The smellprints were analyzed by onboard statistical software. RESULTS Smellprints from NSCLC patients clustered distinctly from those of COPD subjects (cross validation value [CVV]: 85%; M-distance: 3.73). NSCLC patients could also be discriminated from healthy controls in duplicate measurements (CVV: 90% and 80%, respectively; M-distance: 2.96 and 2.26). CONCLUSION VOC-patterns of exhaled breath discriminates patients with lung cancer from COPD patients as well as healthy controls. The electronic nose may qualify as a non-invasive diagnostic tool for lung cancer in the future.

Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome

Abstract.  Resta O, Foschino‐Barbaro MP, Bonfitto P, Giliberti T, Depalo A, Pannacciulli N, De Pergola G (Respiratory Pathophysiology, University of Bari, School of Medicine, Bari, Italy; University of Foggia, School of Medicine, Foggia, Italy; and Internal Medicine, Endocrinology, and Metabolic Diseases, University of Bari, Bari, Italy). Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome. J Intern Med 2003; 253: 536–543.

Increased inflammatory markers in the exhaled breath condensate of cigarette smokers

Cigarette smoking induces an inflammatory response in the airways that may play a key role in the pathogenesis of chronic obstructive pulmonary disease. Noninvasive markers of inflammation may, therefore, be useful in monitoring the airways of smokers as well as in the screening of subjects at high risk of developing airway obstruction. The aim of the present study was to determine whether the concentrations of the pro-inflammatory cytokine, interleukin (IL)-6, is increased in the exhaled breath condensate of smokers and whether the number of cigarettes smoked has any influence on the exhaled concentrations. The possibility that exhaled IL-6 levels are related to exhaled carbon monoxide (CO) and lung function has also been explored. Another inflammatory marker, leukotriene (LT), was also measured. Twenty-one smokers (39±7 yrs, 13 male) and 14 nonsmokers (45±6 yrs, eight male) were recruited. IL-6 and LTB4 levels in the breath condensate were measured with an immunoassay kit and exhaled CO examined by means of a modified electrochemical sensor. Higher IL-6 and exhaled CO concentrations were found in current smokers (5.6±1.4 pg·mL−1 and 16.7±5.5 parts per million (ppm)) than in nonsmokers (2.6±0.2 pg·mL−1 and 2.1±0.6 ppm). Elevated concentrations of LTB4 were also observed in smokers compared to nonsmokers (9.4±0.4 pg·mL−1 versus 6.1±0.3 pg·mL−1). In addition, there was a correlation between IL-6 concentrations, the number of cigarettes smoked per day, exhaled CO, LTB4 and lung function. Exhaled interleukin-6 and leukotriene B4 levels may be useful noninvasive markers of airway inflammation in cigarette smokers.

Supplementary oxygen in healthy subjects and those with COPD increases oxidative stress and airway inflammation.

Background: Hyperoxia increases oxidative stress through the generation of reactive oxygen species and may therefore enhance inflammation in the lungs. The aim of this study was to investigate whether short term supplementary oxygen (28%) increases oxidative stress and inflammation in the airways by measuring 8-isoprostane and interleukin 6 (IL-6) concentrations in exhaled breath condensate. Methods: Twenty three healthy subjects (12 men, mean (SD) age 48 (7) years) and 23 patients with chronic obstructive pulmonary disease (COPD; 15 men, mean (SD) age 56 (5) years) were studied. 8-isoprostane and IL-6 concentrations were measured by immunoassay. Results: Increased concentrations of 8-isoprostane and IL-6 were found in all subjects after breathing 28% oxygen for 1 hour. In healthy subjects the concentrations of 8-isoprostane and IL-6 were 10.9 (2.9) pg/ml and 4.9 (0.8) pg/ml, respectively, compared with baseline concentrations of 6.1 (1.3) pg/ml and 2.9 (0.6) pg/ml, and in patients with COPD the concentrations were 27.9 (3.1) pg/ml and 8.3 (1.2) pg/ml), respectively, compared with baseline concentrations of 18.9 (3.6) pg/ml and 6.3 (0.6) pg/ml. By contrast, breathing air through the same face mask for 1 hour had no significant effects on 8-isoprostane or IL-6 concentrations in normal subjects or those with COPD. Conclusions: These findings suggest that short term supplementary oxygen may enhance oxidative stress and inflammation in the airways. Whether this happens with long term oxygen therapy needs to be determined.

Gender, age and menopause effects on the prevalence and the characteristics of obstructive sleep apnea in obesity

Background  In the 1970s and 80s it was believed that obstructive sleep apnea (OSA) was primarily a disease of men. The present study was addressed to evaluate the effect of gender and menopause on the prevalence and the characteristics of OSA and on anthropometric, clinical, respiratory and polysomnographic data in a population of obese individuals.

An electronic nose distinguishes exhaled breath of patients with Malignant Pleural Mesothelioma from controls

BACKGROUND Malignant Pleural Mesothelioma (MPM) is a tumour of the surface cells of the pleura that is highly aggressive and mainly caused by asbestos exposure. Electronic noses capture the spectrum of exhaled volatile organic compounds (VOCs) providing a composite biomarker profile (breathprint). OBJECTIVE We tested the hypothesis that an electronic nose can discriminate exhaled air of patients with MPM from subjects with a similar long-term professional exposure to asbestos without MPM and from healthy controls. METHODS 13 patients with a histology confirmed diagnosis of MPM (age 60.9±12.2 year), 13 subjects with certified, long-term professional asbestos exposure (age 67.2±9.8), and 13 healthy subjects without asbestos exposure (age 52.2±16.2) participated in a cross-sectional study. Exhaled breath was collected by a previously described method and sampled by an electronic nose (Cyranose 320). Breathprints were analyzed by canonical discriminant analysis on principal component reduction. Cross-validated accuracy (CVA) was calculated. RESULTS Breathprints from patients with MPM were separated from subjects with asbestos exposure (CVA: 80.8%, sensitivity 92.3%, specificity 85.7%). MPM was also distinguished from healthy controls (CVA: 84.6%). Repeated measurements confirmed these results. CONCLUSIONS Molecular pattern recognition of exhaled breath can correctly distinguish patients with MPM from subjects with similar occupational asbestos exposure without MPM and from healthy controls. This suggests that breathprints obtained by electronic nose have diagnostic potential for MPM.

Prescription of nCPAP and nBIPAP in obstructive sleep apnoea syndrome: Italian experience in 105 subjects. A prospective two centre study

Nasal continuous positive airway pressure (nCPAP) is the current treatment of obstructive sleep apnoea syndrome (OSAS). The indications of bilevel pressure support ventilation (BIPAP PSV) in OSAS patients remain controversial. The purpose of this investigation was to verify the frequency of prescription of BIPAP PSV in a group of OSAS patients when CPAP was ineffective or not tolerated during titration. The study included 286 consecutive patients > or = 18 years of age referred to two Sleep laboratories for sleep related breathing disorders (SRBD) between December 1994 and November 1995. Of these, 130 patients were enrolled and 105 (88 males, 77 females) with moderate to severe OSAS completed the study and were finally analysed. After a full night diagnostic polysomnography (PSGD), patients had a second full night PSG under nCPAP (PSGT). If nCPAP was not tolerated, or failed to correct breathing abnormalities during sleep, a second PSGT was performed, using a BIPAP PSV. Our study shows that nCPAP (mean 8.5 +/- 2.0 cmH20) was considered a satisfactory therapy in 81 patients (77%). Twenty four (23%) required BIPAP PSV (mean IPAP 13.9 +/- 2.9 cmH20). We found the highest prevalence of BIPAP in patients with OSAS associated to obesity hypoventilation syndrome (OHS) (11 of 17) and in OSAS associated to chronic obstructive pulmonary disease (COPD) (nine of 16). Patients treated with BIPAP PSV were more obese and had a higher PaCO2 and sleep-related desaturations and a lower FEV1, FVC, FEV1/FVC and PaO2. In conclusion our study shows that CPAP therapy in the effective therapeutic option in the majority of patients with OSAS. There is a subset of patients with OSAS associated to COPD or to OHS in whom BIPAP PSV may be a better treatment modality.

IL-2, TNF-α, and Leptin: Local Versus Systemic Concentrations in NSCLC Patients

One recent line of cancer research shows increasing interest for biological factor such as IL-2, TNF-α, and leptin, which have been found to participate in the development and progression of non-small cell lung cancer (NSCLC). The aim of this study was to measure IL-2, TNF-α, and leptin concentrations in the airways and in the systemic circle of patients with NSCLC, investigating the role of these factors in the lung tumors. We enrolled 32 patients (17 men, 71 ± 7 years) with a histological diagnosis of NSCLC and 20 healthy ex-smoker controls, negative for computed tomography of the chest (14 men, 69 ± 8 years). IL-2, TNF-α, and leptin levels were measured in the serum, the urine, the bronchoalveolar lavage, the induced sputum, and exhaled breath condensate (EBC) of patients enrolled by means of a specific enzyme immunoassay kit. Higher concentrations of IL-2, TNF-α and leptin were found in NSCLC patients than in controls (p < 0.0001). A statistically significant increase of IL-2, TNF-α, and leptin concentrations was observed in patients from stage I to stage III of NSCLC. These findings suggest that IL-2, TNF-α, and the leptin play an important role in the cancerogenesis of NSCLC. Their measure in the EBC could be proposed as noninvasive markers for an early detection of NSCLC and in the follow-up of this tumor.

Correlation between Inflammatory Markers of Atherosclerosis and Carotid Intima-Media Thickness in Obstructive Sleep Apnea

Obstructive Sleep Apnea (OSA) is a sleep-related breathing disorder associated with the development of cardiovascular diseases and atherosclerosis. Systemic inflammation plays an important role in the development of cardiovascular complications in OSA patients. The aim of the study was to evaluate the relationship between carotid intima-media thickness (cIMT) and inflammatory markers plasma levels in OSA patients. We enrolled 80 OSA patients and 40 controls matched for age and body mass index (BMI). The presence and severity of sleep apnea was determined by in-laboratory portable monitoring (PM). Demographic data, blood pressure, heart rate, and cIMT were measured. High-sensitive C-Reactive Protein (hsCRP), interleukin (IL)-6, tumor necrosis factor (TNF)-α and pentraxin (PTX)-3 serum concentrations were detected. cIMT was higher in OSA patients than controls (0.89 ± 0.13 mm vs. 0.65 ± 0.1 mm, p < 0.01). Moderate-severe OSA patients (0.95 ± 0.09 mm) had significantly increased cIMT than mild OSA (0.76 ± 0.1 mm; p < 0.01) and control (0.65 ± 0.1 mm; p < 0.01). hsCRP, IL-6, TNF-α, and PTX-3 in patients with OSA (1.67 ± 0.66 mg/L, 2.86 ± 1.39 pg/mL, 20.09 ± 5.39 pg/mL, 2.1 ± 0.59 ng/mL, respectively) were significantly higher than in controls (1.08 ± 0.53 mg/L, p < 0.01; 1.5 ± 0.67 pg/mL, p < 0.01; 12.53 ± 3.48 pg/mL, p < 0.01; 1.45 ± 0.41 ng/mL, p < 0.01, respectively). Carotid IMT was significantly correlated to CRP (r = 0.44; p < 0.01), IL-6 (r = 0.42; p < 0.01), TNF-α (r = 0.53; p < 0.01), and PTX-3 (r = 0.49; p < 0.01). OSA patients showed increased cIMT, CRP, IL-6, TNF-α, and PTX-3 levels. Inflammatory markers levels are correlated to cIMT in OSA patients.