Downregulation of exosomal let-7d and miR-16 in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic Pulmonary Fibrosis (IPF) is a degenerative interstitial lung disease with both a poor prognosis and quality of life once the diagnosis is made. In the last decade many features of the disease have been investigated to better understand the pathological steps that lead to the onset of the disease and, moreover, different types of biomarkers have been tested to find valid diagnostic, prognostic and therapy response predictive ones. In the complexity of IPF, microRNA (miRNAs) biomarker investigation seems to be promising. METHODS: We analysed the expression of five exosomal miRNAs supposed to have a role in the pathogenesis of the disease from serum of a group of IPF patients (n = 61) and we compared it with the expression of the same miRNAs in a group of healthy controls (n = 15). RESULTS: In the current study what emerged is let-7d down-regulation and, unexpectedly, miR-16 significant down-regulation. Moreover, through a cross-sectional analysis, a clustering of the expression of miR-16, miR-21 and miR-26a was found. CONCLUSIONS: These findings could help the individuation of previously unknown key players in the pathophysiology of IPF and, most interestingly, more specific targets for the development of effective medications.

Analysis of the fungal microbiome in exhaled breath condensate of patients with asthma.

BACKGROUND: The presence of virus and bacteria in the airways of subjects with asthma is common and seems to be associated with a deterioration due to the disease. The microbiologic study of airways in asthma is foreseen by guidelines with induced sputum that is often ineffective and contraindicated in severe asthma. AIM: To analyze the fungal microbiome in the exhaled breath condensate (EBC) of subjects with asthma by evaluating a possible correlation with anthropometric and asthma severity data. METHODS: We enrolled 47 consecutive subjects with asthma (28 with atopic asthma and 19 with nonatopic asthma) and 20 controls. Enrolled subjects underwent EBC and sputum collection. Fungal microbiome was assessed by culture on EBC and sputum samples by using Czapek yeast extract agar. RESULTS: A fungal colonization in the EBC of 70% of enrolled subjects with asthma was detected (none detected in the controls). An overlap of fungal microbiome in EBC and sputum was observed (100% of overlap). Fungal colonization was higher in subjects without atopic, obesity, and severe and uncontrolled asthma. CONCLUSION: When considering the high morbidity and mortality of patients with severe asthma in whom we found an important fungal airways colonization, we support the use of the analysis of exhaled fungal microbiome in these subjects.

Is the Exhaled Breath Temperature Sensitive to Cigarette Smoking?

The smoking habit is accompanied by an acute inflammatory response which follows tissue injury. It would be desirable to find a non-invasive inflammatory marker that would simplify the task of studying and monitoring smokers more simply and allow us to identify populations at risk of contracting Chronic Obstructive Pulmonary Disease (COPD). Today's expectations regarding research focus on issues ranging from inflammatory markers to those of exhaled breath temperature (EBT) are considerable. That said, although the EBT has been largely studied in asthma and COPD, there have not been any studies thus far that have analysed the effect of cigarette smoking on the EBT. Bearing this in mind, in this longitudinal study we aim to analyse the EBT in current smokers, monitor the effects both of cigarette smoking on EBT and of what happens after smoking cessation. Twenty-five (25) smokers (59.5 ± 3.1 yrs, 12 M) who participated in a multi-disciplinary smoking cessation programme and 25 healthy never-smokers (58.7 ± 2.9, 13 M) underwent EBT measurement. EBT values were higher in smokers before smoking (T0) than in never-smokers [34.6 (34.2-35) vs 33.2 (32.4-33.7)°C, p < 0.001. The smokers repeated measurement 5 minutes after smoking a cigarette (T1) and 2 hours after (T2). They repeated EBC measurement after 1 week (T3) and then after 3 months (T4) from smoking cessation. EBT is higher in smokers compared to controls. EBT increases after cigarette smoking and progressively decreases with the increase of time from when the last cigarette was smoked. Thus, we can conclude that EBT is increased in smokers and also sensitive to the acute effect of cigarette smoke.

Mitochondrial DNA alteration in obstructive sleep apnea.

BACKGROUND: Obstructive Sleep Apnea (OSAS) is a disease associated with the increase of cardiovascular risk and it is characterized by repeated episodes of Intermittent Hypoxia (IH) which inducing oxidative stress and systemic inflammation. Mitochondria are cell organelles involved in the respiratory that have their own DNA (MtDNA). The aim of this study was to investigate if the increase of oxidative stress in OSAS patients can induce also MtDNA alterations. METHODS: 46 OSAS patients (age 59.27 ± 11.38; BMI 30.84 ± 3.64; AHI 36.63 ± 24.18) were compared with 36 control subjects (age 54.42 ± 6.63; BMI 29.06 ± 4.7; AHI 3.8 ± 1.10). In blood cells Content of MtDNA and nuclear DNA (nDNA) was measured in OSAS patients by Real Time PCR. The ratio between MtDNA/nDNA was then calculated. Presence of oxidative stress was evaluated by levels of Reactive Oxygen Metabolites (ROMs), measured by diacron reactive oxygen metabolite test (d-ROM test). RESULTS: MtDNA/nDNA was higher in patients with OSAS than in the control group (150.94 ± 49.14 vs 128.96 ± 45.8; p = 0.04), the levels of ROMs were also higher in OSAS subjects (329.71 ± 70.17 vs 226 ± 36.76; p = 0.04) and they were positively correlated with MtDNA/nDNA (R = 0.5, p < 0.01). CONCLUSIONS: In OSAS patients there is a Mitochondrial DNA damage induced by the increase of oxidative stress. Intermittent hypoxia seems to be the main mechanism which leads to this process.

Aspergillus spp. colonization in exhaled breath condensate of lung cancer patients from Puglia Region of Italy.

BACKGROUND: Airways of lung cancer patients are often colonized by fungi. Some of these colonizing fungi, under particular conditions, produce cancerogenic mycotoxins. Given the recent interest in the infective origin of lung cancer, with this preliminary study we aim to give our small contribution to this field of research by analysing the fungal microbiome of the exhaled breath condensate of lung cancer patients from Puglia, a region of Italy. METHODS: We enrolled 43 lung cancer patients and 21 healthy subjects that underwent exhaled breath condensate and bronchial brushing collection. The fungal incidence and nature of sample collected were analysed by using a selected media for Aspergillus species. RESULTS: For the first time we were able to analyse the fungal microbioma of the exhaled breath condensate. 27.9% of lung cancer patients showed a presence of Aspergillus niger, or A. ochraceus or Penicillium ssp. while none of the healthy subjects did so. CONCLUSION: The results confirmed the high percentage of fungal colonization of the airways of lung cancer patients from Puglia, suggesting the need to conduct further analyses in this field in order to evaluate the exact pathogenetic role of these fungi in lung cancer as well as to propose efficient, empirical therapy.

Could exhaled ferritin and SOD be used as markers for lung cancer and prognosis prediction purposes?

BACKGROUND: Today an increasing interest is being generated by the study of lung cancer markers in the exhaled breath condensate (EBC), precisely because this sample seems to lend itself to lung cancer early screening and follow-up. Indeed, ferritin and superoxide dismutase (SOD) have recently been recognized to play a role in lung cancerogenesis and patients' survival. The aim of this study was to evaluate the clinical value and the prognostic power of exhaled ferritin and exhaled SOD in patients with lung cancer. MATERIAL AND METHODS: Forty patients with nonsmall cell lung cancer (NSCLC) and 15 controls were enrolled in the study. All subjects under study underwent EBC collection and analysis of ferritin and SOD. A total of 36 patients were either given a follow-up of at least 25.5 months or followed up until death. RESULTS: Exhaled ferritin and SOD resulted as being higher in NSCLC than in controls and as being influenced by the stage of cancer. A pronounced survival difference was found in the presence of exhaled ferritin 300 ng/mL and exhaled SOD > 13.5 U/µL. CONCLUSIONS: In conclusion, although the results need to be confirmed on a larger and homogeneous population, we hypothesized that the notion of using the measurement of ferritin and SOD in the EBC could, if deemed feasible, have clinical implications in the monitoring of lung cancer and as an outcome predictor.

Predictive equations for CPAP titration in OSAS patients.

BACKGROUND: Continuous positive airway pressure (CPAP) is the elective treatment of obstructive sleep apnea. The therapeutic level of CPAP is generally established by manual titration or an auto CPAP device, but an alternative way involves the use of predictive formulas. The aim of the present study was to test the difference between mathematical equations and CPAP or auto CPAP in terms of therapeutic pressure. METHODS: A retrospective analysis of 197 subjects with a diagnosis of obstructive sleep apnea needing a CPAP treatment was performed. The patients were divided into two groups: the first one included patients who had received CPAP after manual titration and the second one included patients who had received auto CPAP titration. The therapeutic CPAP pressure was then compared to the pressure calculated by three different equations: Eq. A by Stradling, Eq. B by Sériès, and Eq. C by Hoffstein. RESULTS: One hundred ninety-seven patients were included in the study, 110 were titrated by auto CPAP and 87 by manual titration. There was a positive correlation between the pressure defined by the three equations and both titration methods, but each equation usually gave a higher pressure with patients needing CPAP <8 and lower for patients needing CPAP >11. Equation C normally gave a lower result than the other two equations. CONCLUSIONS: Manual or auto CPAP titration remains the best way to define the appropriate CPAP. However, predictive formulas can be useful if used with caution and always after verifying the real efficacy, particularly for patients needing higher pressure.

Neutrophilic airways inflammation in lung cancer: the role of exhaled LTB-4 and IL-8.

BACKGROUND: Recent advances in lung cancer biology presuppose its inflammatory origin. In this regard, LTB-4 and IL-8 are recognized to play a crucial role in neutrophil recruitment into airways during lung cancer.Notwithstanding the intriguing hypothesis, the exact role of neutrophilic inflammation in tumour biology remains complex and not completely known.The aim of this study was to give our contribution in this field by investigating LTB-4 and IL-8 in the breath condensate of NSCLC patients and verifying their role in cancer development and progression. METHOD: We enrolled 50 NSCLC patients and 35 controls. LTB-4 and IL-8 concentrations were measured in the breath condensate and the blood of all the subjects under study using EIA kits. Thirty NSCLC patients and ten controls underwent induced sputum collection and analysis. RESULTS: LTB-4 and IL-8 resulted higher in breath condensate and the blood of NSCLC patients compared to controls. Significantly higher concentrations were found as the cancer stages progressed. A positive correlation was observed between exhaled IL-8 and LTB-4 and the percentage of neutrophils in the induced sputum. CONCLUSION: The high concentrations of exhaled LTB-4 and IL-8 showed the presence of a neutrophilic inflammation in the airways of NSCLC patients and gave a further support to the inflammatory signalling in lung cancer. These exhaled proteins could represent a suitable non-invasive marker in the diagnosis and monitoring of lung cancer.

Searching for Inflammatory and Oxidative Stress Markers Capable of Clustering Severe Asthma.

OBJECTIVE: Asthma inflammation may feature an imbalance between oxidative stress and antioxidant defenses. Oxidative stress induces propagation of airways inflammation and corticosteroid insensitivity contributing to poor asthma control, and frequent severe acute exacerbations. This study assessed inflammation and oxidative stress in severe asthmatic subjects and evaluated the possible correlations between inflammatory and oxidative stress markers investigated and asthma severity. MATERIAL AND METHOD: Fifty-three patients with severe asthma, 11 patients with mild-moderate asthma and 12 healthy subjects were enrolled and underwent fractional exhaled nitric oxide (FENO) analysis and blood and sputum count cell collection. The content of mitochondrial DNA (MtDNA) and nuclear DNA (nDNA) was measured in exhaled breath condensate (EBC) by Real Time PCR and the ratio between MtDNA/nDNA was calculated. We detected MtDNA/nDNA in the EBC of severe asthmatics. RESULTS: We found higher exhaled MtDNA/nDNA in severe asthmatics respectively compared to mild-moderate ones and to healthy controls (10.4±2.2 vs 7.9±2.5, p<0.05 and 10.4±2.2 vs 6.51±0.21, p<0.05). The level of exhaled MtDNA/nDNA was significantly higher in Non-T2 endotype severe asthmatics than T2 (14.07±10. 8 vs 6.5±5.5, p<0.05). CONCLUSION: Oxidative stress marker (MtDNA/nDNA) is increased significantly with asthma severity and may be useful for endotyping severe asthma.

Application of machine learning to predict obstructive sleep apnea syndrome severity.

INTRODUCTION: Obstructive sleep apnea syndrome has become an important public health concern. Polysomnography is traditionally considered an established and effective diagnostic tool providing information on the severity of obstructive sleep apnea syndrome and the degree of sleep fragmentation. However, the numerous steps in the polysomnography test to diagnose obstructive sleep apnea syndrome are costly and time consuming. This study aimed to test the efficacy and clinical applicability of different machine learning methods based on demographic information and questionnaire data to predict obstructive sleep apnea syndrome severity. MATERIALS AND METHODS: We collected data about demographic characteristics, spirometry values, gas exchange (PaO2, PaCO2) and symptoms (Epworth Sleepiness Scale, snoring, etc.) of 313 patients with previous diagnosis of obstructive sleep apnea syndrome. After principal component analysis, we selected 19 variables which were used for further preprocessing and to eventually train seven types of classification models and five types of regression models to evaluate the prediction ability of obstructive sleep apnea syndrome severity, represented either by class or by apnea-hypopnea index. All models are trained with an increasing number of features and the results are validated through stratified 10-fold cross validation. RESULTS: Comparative results show the superiority of support vector machine and random forest models for classification, while support vector machine and linear regression are better suited to predict apnea-hypopnea index. Also, a limited number of features are enough to achieve the maximum predictive accuracy. The best average classification accuracy on test sets is 44.7 percent, with the same average sensitivity (recall). In only 5.7 percent of cases, a severe obstructive sleep apnea syndrome (class 4) is misclassified as mild (class 2). Regression results show a minimum achieved root mean squared error of 22.17. CONCLUSION: The problem of predicting apnea-hypopnea index or severity classes for obstructive sleep apnea syndrome is very difficult when using only data collected prior to polysomnography test. The results achieved with the available data suggest the use of machine learning methods as tools for providing patients with a priority level for polysomnography test, but they still cannot be used for automated diagnosis.

Oral CorticoSteroid sparing with biologics in severe asthma: A remark of the Severe Asthma Network in Italy (SANI).

According to the data derived from several national and international registries, including SANI (Severe Asthma Network Italy), and considering the strong impact that frequent or regular use of oral corticosteroid has on quality of life (QoL) of severe asthmatics, as well as on the costs for managing corticosteroid-related diseases, oral corticosteroid sparing up to withdrawal should be considered a primary outcome in the management of severe asthma. New biologics have clearly demonstrated that this effect is possible, with concomitant reduction in the rate of exacerbations and in symptom control. Then, there is no reason for using so frequently oral corticosteroid before having explored all alternatives currently available for a large part of severe asthmatics.

IL-2, TNF-alpha, 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-alpha, 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-alpha, 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-alpha, 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-alpha and leptin were found in NSCLC patients than in controls (p < 0.0001). A statistically significant increase of IL-2, TNF-alpha, and leptin concentrations was observed in patients from stage I to stage III of NSCLC. These findings suggest that IL-2, TNF-alpha, 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.

Changes in sputum composition during 15 min of sputum induction in healthy subjects and patients with asthma and chronic obstructive pulmonary disease.

INTRODUCTION: The use of sputum induction by inhalation of hypertonic saline to study the cellular and biochemical composition of the airways allows noninvasive sampling of the airways content and identification of markers of airways inflammation. OBJECTIVE: The present study aimed to identify possible changes in the cellular composition of induced sputum between samples obtained sequentially (three periods of 5 min each) during one sputum induction. Moreover, difference between these samples and the mixed one (mixture of samples obtained after 5, 10 and 15 min of induction) was investigated. METHODS: Forty-six subjects (10 healthy volunteers, 12 patients with chronic obstructive pulmonary disease (COPD) and 24 patients with asthma) (mean age 53.0+/-14.0 yr, forced expiratory volume in one second (FEV(1)) 71.8+/-19.0% pred) produced sputum after three consecutive 5 min periods of hypertonic (4.5%) saline inhalation. Stained cytospins from the three periods separately and from the mixed sample were produced and analyzed. RESULTS: The mean percentage of neutrophils, eosinophils, lymphocytes and epithelial cells did not change significantly in samples obtained consecutively after 5, 10 and 15 min of the induction procedure. There was no significant difference in the cellular composition of samples obtained after 5, 10 and 15 min of induction and the cellular composition of the mixed sample (P=0.06). CONCLUSION: The separate analysis of induced sputum from three consecutive sampling and the mixed sample did not demonstrate significant changes in their cellular composition. Fifteen minutes induction procedure with the fixed concentration of hypertonic saline and processing of the mixed sample can be recommended for clinical settings and clinical trials.

Validation of the Exhaled Breath Temperature Measure: Reference Values in Healthy Subjects.

BACKGROUND: Exhaled breath temperature (EBT) is a new noninvasive method for the study of inflammatory respiratory diseases with a potential to reach clinical practice. However, few studies are available regarding the validation of this method, and they were mainly derived from small, pediatric populations; thus, the range of normal values is not well established. The aim of this study was to measure EBT values in an Italian population of 298 subjects (mean age, 45.2 ± 15.5 years; 143 male subjects; FEV1, 97.2% ± 5.8%; FVC, 98.4% ± 3.9%) selected from 867 adult volunteers to define reference values in healthy subjects and to analyze the influence of individual and external variables on this parameter. METHODS: EBT was measured with an X-halo PRO device to different ambient temperature ranging from 0°C to 38°C. RESULTS: We report reference values of EBT in healthy white subjects who had never smoked. EBT values were strongly influenced by the external temperature and to a lesser extent according to sex. CONCLUSIONS: In a large population of healthy subjects who never smoked, these data provide reference values for measuring EBT as a basis for future studies. Our results are contribute to the promotion of EBT from "bench" to "bedside."

New panel of microsatellite alterations detectable in the EBC for lung cancer prognosis.

Our research group demonstrated, in a precedent study, the prognostic power of the 3p microsatellites alterations (MAs) detectable in exhaled breath condensate (EBC) in NSCLC patients. The analysis of genetic markers in the EBC might have precious clinical and economic consequences when inserted in diagnostic and follow up programs for lung cancer. The aim of this study was to evaluate the prognostic value of a new panel of MAs in the EBC of patients with NSCLC. We enrolled 45 NSCLC patients during a period of 36 months and the follow-up period was 156 weeks. We analyzed MAs for eight markers in EBC samples: D3S2338, D3S1266, D3S1300, D3S1304, D3S1289, D5S2094, D3S1313, and AFMa305ye1. Our study showed that the presence of more than 2 simultaneous MAs reduces outcome in NSCLC patients. The new panel of eight microsatellites markers proposed in EBC samples could have a potential clinical role in assessing survival in lung cancer patients.

Exhaled markers in the monitoring of airways inflammation and its response to steroid's treatment in mild persistent asthma.

The measure of inflammatory cytokines in the exhaled breath condensate has been recently proposed for use in monitoring asthma and the therapeutic response to steroids. The aim of the present study was to investigate the usefulness of measuring exhaled IL-6, IL-4 and pH in mild persistent asthma. Furthermore the effects on these markers of inhaled steroids were assessed. The study enrolled 28 asthmatic (15 males, 38+/-12 years) and 15 healthy subjects (5 males, 35+/-6 years). IL-6, IL-4 and pH were measured in the exhaled breath condensate of the subjects studied. Significantly higher concentrations of IL-6 and IL-4 were observed in the breath condensate of asthmatic patients (7.1+/-1.1 and 64.4+/-8.3 pg/ml) compared to controls (2.7+/-0.6 and 31.7+/-3.5 pg/ml), p<0.001. Furthermore, exhaled IL-4 fell significantly after treatment with inhaled steroids for 6 months (47.9+/-3.2 pg/ml, p<0.001) while exhaled IL-6 did not (6.4+/-1.0 pg/ml, p=0.8). The exhaled pH turned out to be lower in asthmatic subjects than in controls (7.39+/-0.11 vs. 7.85+/-0.14; P<0.001) but trended towards control levels after steroid treatment (7.65+/-0.16, P<0.001). We conclude that the measurement of exhaled IL-4 and pH in mild asthmatic subjects could be a useful way of monitoring their airway inflammation as well as their response to the treatment.

Is the exhaled breath temperature in lung cancer influenced by airways neoangiogenesis or by inflammation?

Recently the exhaled breath temperature (EBT) was seen to increase in non-small cell lung cancer and was subsequently proposed as a possible non-invasive tool for its diagnosis. The need for further studies that confirm the previous findings and support the potential scope of this method underlies the main aim of this study that seeks to explore the pathogenic mechanisms determining the EBT in lung cancer. We enrolled 44 consecutive patients with a radiological suspicion of lung cancer and ten healthy non-smoker volunteers, after which their EBT was measured. On the same day, the subjects underwent breath condensate collection for the measurement of leukotriene (LTB)-4 and of the vascular endothelial growth factor (VEGF), the former being a marker of airways inflammation and the latter of neoangiogenesis. We confirmed the presence of a higher EBT in lung cancer patients compared to the controls. The multiple linear regression model showed that the exhaled VEGF was the only predictor of elevations of EBT. In conclusion, it can be stated that for the first time in this study, we have shown that EBT is higher in subjects with lung cancer and that the airways angiogenesis drives the increase in EBT in lung cancer. Moreover, the study suggests the potential for the use of EBT in monitoring the lung cancer progression, although the implementation of more in-depth studies to verify this result is recommended.

8-Isoprostane, a marker of oxidative stress, is increased in exhaled breath condensate of patients with obstructive sleep apnea after night and is reduced by continuous positive airway pressure therapy.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is characterized by recurrent apnea during sleep that may compromise oxidative balance. Oxidative stress is increased in the blood and in the airways of OSA patients. DESIGN: The aim of this study was to investigate whether oxidative stress is determined by nocturnal apneas and could be reduced by CPAP therapy, and whether there is a relation between local and systemic oxidative stress in these patients. PATIENTS AND METHODS: Eighteen patients with OSA (13 men; mean [+/- SD] age, 48 +/- 3 years) and 12 healthy age-matched and weight-matched subjects (8 men; mean age, 46 +/- 7 years) were recruited. 8-Isoprostane was measured in exhaled breath condensate and blood by a specific enzyme immunoassay. MEASUREMENTS AND RESULTS: Higher concentrations of 8-isoprostane were found in the morning exhaled condensate (9.5 +/- 1.9 pg/mL) and plasma (9.7 +/- 1.5 pg/mL) of OSA patients compared to healthy obese subjects (6.7 +/- 0.2 and 7.1 +/- 0.3 pg/mL, respectively; p < 0.0001). Elevated mean concentrations of exhaled 8-isoprostane were observed in the OSA patients at 8:00 AM (9.5 +/- 1.9 pg/mL) but not at 8:00 PM (7.6 +/- 0.8 pg/mL; p < 0.0005), and a significant reduction was seen after continuous positive airway pressure (CPAP) therapy (7.7 +/- 0.9 pg/mL; before treatment, 9.6 +/- 1.7 pg/mL; p < 0.005). A positive correlation was found between morning exhaled 8-isoprostane levels and the apnea-hypopnea index (r = 0.8; p < 0.0001), and 8-isoprostane levels and neck circumference (r = 0.6; p < 0.0001). CONCLUSIONS: These findings suggest that systemic and local oxidative stress are increased in OSA patients, and that they are higher after nocturnal apnea and reduced by CPAP therapy.

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.

Exhaled Interleukine-6 and 8-isoprostane in chronic obstructive pulmonary disease: effect of carbocysteine lysine salt monohydrate (SCMC-Lys).

Chronic obstructive pulmonary disease (COPD) is characterized by an airways inflammation and by an enhanced generation of reactive oxygen species. The aim of our study was to assess the inflammation and the oxidative stress in airways of COPD patients with acute exacerbation of disease and in stability. Furthermore, we investigated the anti-inflammatory and antioxidant effects of 6 months treatment with carbocysteine lysine salt monohydrate (SCMC-Lys) in COPD. We studied 30 mild acute COPD, 10 mild stable COPD and 15 healthy subjects. 8-isoprostane and Interleukine-6 were measured in their breath condensate through immunoassay. Significantly higher concentrations of exhaled 8-isoprostane and Interleukine-6 were found in acute COPD patients compared to stable COPD and healthy controls (21.8+/-5.1 vs. 13.2+/-2.0 vs. 4.7+/-1.8 pg/ml and 7.4+/-0.9 vs. 5.8+/-0.2 vs. 2.7+/-0.6 pg/ml, p<0.0001). COPD patients treated with SCMC-Lys showed a marked reduction of exhaled 8-isoprostane and Interleukine-6 (8.9+/-1.5 and 4.6+/-0.8 pg/ml, p<0.0001). These findings suggest that there is an increase of 8-isoprostane and Interleukine-6 concentrations in the breath condensate of COPD patients compared to healthy controls especially during acute exacerbations of the disease. Moreover, we showed an anti-inflammatory and antioxidant effect of short-term administration of SCMC-Lys in COPD, suggesting the importance of a further placebo-controlled study that should evaluate the effects of this drug.