Relationships between Obstructive Sleep Apnea Syndrome and cardiovascular risk in a naïve population of southern Italy.

BACKGROUND: Obstructive sleep apnea (OSA) is a worldwide increasing syndrome, which, by promoting endothelial dysfunction, contributes to extend the cardiovascular risk. We evaluated the cardiovascular risk in a group of OSA patients. METHODS: A total of 185 OSA subjects (19 normal weight, 57 overweight, 109 obese), who entered the Ambulatory of Sleep Disorders of the Institute of Respiratory Diseases of the University of Bari, during 1 year, were enrolled in the study. We assessed anthropometric features, polysomnographic findings, cardiovascular risk factors, smoking habit, Pulmonary Function Test, Arterial Blood Gas Analysis, Epworth Questionnaire, and Charlson Co-morbidities Index (CCI). Subjects were divided into three groups, according to their BMI: individuals with BMI ≥30 kg/m2 (Group 1 n = 109, mean age 61 ± 1; 74.3% men), individuals with BMI ranging from 25.0 to 29.9 kg/m2 defined as overweight subjects (Group 2 n = 57, mean age 58.8 ± 1.4; 77% men), and subjects with a BMI ranging from 18.5 to 24.9 kg/m2 defined as normal weight subjects (Group 3 n = 19, mean age 54.2 ± 2.3; 64,2% men). RESULTS: In the whole population, the percentage cardiovascular risk was weakly related with BMI (r = 0.33; P < .001), but not with AHI. The cardiovascular risk was strictly related to the obesity (P < .00002), while the Epworth Questionnaire score and the Charlson Co-morbidity Index were respectively statistically higher in the group of obese individuals (P = .004, P = .0002) than in the other two sub-groups. When AHI values were stratified in tertiles, the percentage cardiovascular risk did not vary with increasing AHI values (Figure 2). CONCLUSIONS: Further studies are required to investigate the pivotal role of inflammation resulting from obesity, and underlying increased cardiovascular risk in OSA patients.

Breathing Rhythm Variations during Wash-In Do Not Influence Exhaled Volatile Organic Compound Profile Analyzed by an Electronic Nose.

E-noses are innovative tools used for exhaled volatile organic compound (VOC) analysis, which have shown their potential in several diseases. Before obtaining a full validation of these instruments in clinical settings, a number of methodological issues still have to be established. We aimed to assess whether variations in breathing rhythm during wash-in with VOC-filtered air before exhaled air collection reflect changes in the exhaled VOC profile when analyzed by an e-nose (Cyranose 320). We enrolled 20 normal subjects and randomly collected their exhaled breath at three different breathing rhythms during wash-in: (a) normal rhythm (respiratory rate (RR) between 12 and 18/min), (b) fast rhythm (RR > 25/min) and (c) slow rhythm (RR < 10/min). Exhaled breath was collected by a previously validated method (Dragonieri et al., J. Bras. Pneumol. 2016) and analyzed by the e-nose. Using principal component analysis (PCA), no significant variations in the exhaled VOC profile were shown among the three breathing rhythms. Subsequent linear discriminant analysis (LDA) confirmed the above findings, with a cross-validated accuracy of 45% (p = ns). We concluded that the exhaled VOC profile, analyzed by an e-nose, is not influenced by variations in breathing rhythm during wash-in.

Covid-19 and ex-smokers: an underestimated prognostic factor?

Dear Editor, The recent and explosive worldwide outbreak of Covid-19 leads many scientists and clinicians to identify the most responsible triggering risk factors in individuals without comorbidities, as well as potential prognostic factors. A notable field of research has been conducted on the role of smoking, which has been initially hypothesized as being a protective factor for Covid-19....

Exhaled breath profiling by electronic nose enabled discrimination of allergic rhinitis and extrinsic asthma.

AIM: To assess whether an e-nose could discriminate between subjects affected by allergic rhinitis with and without concomitant extrinsic asthma, as well as from healthy controls, in terms of exhaled VOC-profile. METHODS: Fourteen patients with Extrinsic Asthma and Allergic Rhinitis (AAR), 14 patients with Allergic Rhinitis without asthma (AR) and 14 healthy controls (HC) participated in a cross-sectional study. Exhaled breath was collected by a standardized method and sampled by an e-nose (Cyranose 320). Raw data were reduced by Principal component analysis and analyzed by canonical discriminant analysis. Cross-validation accuracy (CVA) and Receiver Operating Characteristic(ROC)-curves were calculated. External validation in newly recruited patients (7 AAR, 7 AR and 7 HC) was tested using the previous training model. RESULTS: Breathprints of patients with AR clustered from those with AAR (CVA = 85.7%), as well as HC (CVA = 82.1%). Breathprints from AAR were also separated from those of HC (CVA = 75.0%). External validation confirmed the above findings. CONCLUSIONS: An e-nose can discriminate exhaled breath from subjects with allergic rhinitis with and without extrinsic asthma, which represent two different diseases with partly overlapping features. This supports the view of using breath profiling to diagnose asthma also in patients with allergic rhinitis.

In Vitro Identification of New Transcriptomic and miRNomic Profiles Associated with Pulmonary Fibrosis Induced by High Doses Everolimus: Looking for New Pathogenetic Markers and Therapeutic Targets.

The administration of Everolimus (EVE), a mTOR inhibitor used in transplantation and cancer, is often associated with adverse effects including pulmonary fibrosis. Although the underlying mechanism is not fully clarified, this condition could be in part caused by epithelial to mesenchymal transition (EMT) of airway cells. To improve our knowledge, primary bronchial epithelial cells (BE63/3) were treated with EVE (5 and 100 nM) for 24 h. EMT markers (α-SMA, vimentin, fibronectin) were measured by RT-PCR. Transepithelial resistance was measured by Millicell-ERS ohmmeter. mRNA and microRNA profiling were performed by Illumina and Agilent kit, respectively. Only high dose EVE increased EMT markers and reduced the transepithelial resistance of BE63/3. Bioinformatics showed 125 de-regulated genes that, according to enrichment analysis, were implicated in collagen synthesis/metabolism. Connective tissue growth factor (CTGF) was one of the higher up-regulated mRNA. Five nM EVE was ineffective on the pro-fibrotic machinery. Additionally, 3 miRNAs resulted hyper-expressed after 100 nM EVE and able to regulate 31 of the genes selected by the transcriptomic analysis (including CTGF). RT-PCR and western blot for MMP12 and CTGF validated high-throughput results. Our results revealed a complex biological network implicated in EVE-related pulmonary fibrosis and underlined new potential disease biomarkers and therapeutic targets.

Electronic Nose Technology in Respiratory Diseases.

Electronic noses (e-noses) are based on arrays of different sensor types that respond to specific features of an odorant molecule, mostly volatile organic compounds (VOCs). Differently from gas chromatography and mass spectrometry, e-noses can distinguish VOCs spectrum by pattern recognition. E-nose technology has successfully been used in commercial applications, including military, environmental, and food industry. Human-exhaled breath contains a mixture of over 3000 VOCs, which offers the postulate that e-nose technology can have medical applications. Based on the above hypothesis, an increasing number of studies have shown that breath profiling by e-nose could play a role in the diagnosis and/or screening of various respiratory and systemic diseases. The aim of the present study was to review the principal literature on the application of e-nose technology in respiratory diseases.

The Prognostic Role of Obstructive Sleep Apnea at the Onset of Amyotrophic Lateral Sclerosis.

BACKGROUND/OBJECTIVE: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by the progressive loss of central and peripheral motor neurons. Some studies have found discordant data in the presence of sleep apnea in ALS patients. An obstructive component also occurs with upper airways hypotonia and muscle weakness that may result in an excessive reduction of airway lumen, leading to obstructive sleep apnea (OSA). The aim of this study was to assess the role of obstructive apneic events at disease onset in the ALS prognosis. METHODS: A longitudinal retrospective study was conducted on 42 clinically diagnosed ALS patients. The study population was divided into 2 groups according to their obstructive apnea/hypopnea index (AHIo): group 1 consisted of 20 patients with an AHIo ≥5 and group 2 consisted of 22 patients with an AHIo <5. Both groups were compared with regard to demographic, polygraphic, and respiratory function parameters as well as ALS characteristics (bulbar onset, time between onset and first check-up, time between diagnosis and first check-up, time between first check-up and death or tracheostomy). RESULTS: The mean survival in ALS patients with an AHIo ≥5 was significantly shorter than in ALS without OSA (p = 0.0237). The sniff nasal inspiratory pressure test was significantly correlated with AHIo, time of oxyhemoglobin saturation below 90% and the oxyhemoglobin desaturation index (p < 0.0001). CONCLUSIONS: Our study highlights the importance of an early diagnosis of OSA in ALS patients, allowing the identification of ALS patients with an OSA phenotype (AHIo ≥5), who are characterized by a worse prognosis.

Evaluation of endothelial function and cardiovascular risk in non-obese patients with slight degree of obstructive sleep apnea syndrome.

Recently, it has been clearly described an independent relationship between obstructive sleep apnea syndrome (OSAS) and cardiovascular risk, with underlying mechanisms also including endothelial dysfunction. We enrolled 32 consecutive non-obese patients (mean age of 39.5±11.5 years), of which 16 with mild OSAS and 16 snoring without OSAS. Mild OSAS is defined by an AHI index between 5 and 15. We have investigated if whether there was a relationship between mild OSAS, endothelial function and carotid intima-media thickness (C-IMT). The population was divided into two groups: Group 1 (16 simple snorer patients with an average age of 39.4±12.1 years) and Group 2 (16 subjects with mild OSAS with an average age of 39.6±11.2 years). Each group underwent cardiovascular investigation including measurement of flow-mediated dilation (FMD) of the brachial artery and C-IMT. Both groups comprised non-obese subjects. Patients with mild OSAS had serum total cholesterol values statistically significantly higher than simple snores patients (178.6±24.9 vs 159.2±25.3; p=0.038). OSAS patients had also a trend towards higher values of maximum C-IMT compared to simple snorer patients (0.70±0.15 vs 0.65±0.16), although below the level of significance. Between the two groups, no difference was found for FMD values. The present results on mild OSAS strengthen the importance of a diagnosis of OSAS as soon as possible, in order to encourage all primary prevention interventions to correct risk factors responsible for disease progression and the occurrence of cardiovascular diseases, not excluding the use of therapies of non-invasive ventilation even in the early stages of the disease.

Echocardiographic findings and plasma endothelin-1 levels in obese patients with and without obstructive sleep apnea.

OBJECTIVE: Obstructive sleep apnea (OSA) and obesity are increasingly prevalent worldwide. Both promote endothelial dysfunction contributing to systemic and pulmonary hypertension over time. Endothelin-1 (ET-1) plays a pivotal role in the development of pulmonary hypertension (PH). The aim of the present study was to assess the association between plasma ET-1 and echocardiographic findings in obese individuals with and without OSA, as well as in non-obese patients with OSA. METHODS: Ninety-seven subjects (56 males) were enrolled in the study. All subjects underwent the following tests: venous endothelin-1 levels, pulmonary function testing, and arterial blood gas analysis. All patients except controls underwent transthoracic echocardiography and portable testing for sleep-disordered breathing. RESULTS: Plasma ET-1 levels were significantly higher in obese patients, both with and without OSA (respectively, n = 30 (mean value, 268.06 ± 49.56 pg/ml) and n = 32 (mean value, 263.12 ± 65.26 pg/ml)), compared with non-obese patients with OSA or to healthy controls (respectively, n = 20 (mean value, 149.8 ± 23.09 pg/ml) and n = 15 (mean value, 152.3 ± 27.64 pg/ml); p < 0.0001). Pulmonary artery pressure (PAPs) in obese patients with OSA were significantly higher than in obese patients without OSA (p < 0.0001), while there was no statistical difference between PAPs of obese patients without OSA, compared with the group of non-obese OSA patients. Plasma ET-1 levels significantly correlated with systolic PAPs in obese patients both with and without OSA (respectively, n = 30, r = 0.385, p = 0.03567; n = 32, r = 0.3497, p = 0.0497). CONCLUSIONS: Our study suggests that endothelin levels are more strongly associated with weight than the presence of sleep-disordered breathing, but pulmonary artery hypertension is associated with both weight and OSA.

Atrial flutter regression in HIV-associated pulmonary arterial hypertension after treatment with bosentan.

Pulmonary arterial hypertension (PAH) is a rare condition characterized by an increase in pulmonary arterial resistance leading to right heart failure and death. Arrhythmias are a growing problem in PAH; therefore, maintenance of sinus rhythm is considered to be an important treatment aim in these patients. We described the case of a 46-year-old woman with HIV-associated pulmonary arterial hypertension  who developed atrial flutter. After treatment with bosentan, it was observed a significant improvement in clinical and haemodynamic parameters. In addition, the AFL, which had previously persisted to both antiarrhythmic drug therapy and electrical stimulation, and had recurred after transthoracic electrical cardioversion, disappeared  in absence of any antiarrhythmic drug. Though the precise factors responsible for supraventricular arrhythmogenesis are still largely obscure, it is likely that initiation and maintenance of AFL may depend on all the conditions that can lead to increase in right atrial pressure, size, and wall stress, such as PAH. In our case, bosentan reduced both mean pulmonary artery pressure (mPAP) value and right heart chambers pressures. Therefore, it is conceivable that with the anatomical substrate needed for the maintenance of AFL being disappeared, sinus rhythm was restored.

Titration effectiveness of two autoadjustable continuous positive airway pressure devices driven by different algorithms in patients with obstructive sleep apnoea.

BACKGROUND AND OBJECTIVE: Nocturnal application of continuous positive airway pressure (CPAP) is the standard treatment for patients with obstructive sleep apnoea (OSA). Determination of the therapeutic pressure (CPAP titration) is usually performed by a technician in the sleep laboratory during attended polysomnography. One possible alternative to manual titration is automated titration. Indeed, during the last 15 years, devices have been developed that deliver autoadjustable CPAP (A-CPAP). The aim of the present study was to compare the titration effectiveness of two A-CPAP devices using different flow-based algorithms in patients with OSA. METHODS: This is a randomized study; 79 subjects underwent two consecutive unattended home A-CPAP titration nights with two different devices (Autoset Resmed; Remstar Auto Respironics); during the third and the fourth night, patients underwent portable monitoring in the sleep laboratory during fixed CPAP at the A-CPAP recommended pressure. RESULTS: Bland Altman plots showed good agreement between the recommended median and maximal pressure levels obtained with the two devices. A significant improvement was observed in all the sleep parameters by both A-CPAP machines to a similar degree. CONCLUSIONS: It was observed that the two A-CPAP devices using different algorithms are equally effective in initial titration of CPAP.

Exhaled volatile organic compounds for diagnosis and monitoring of asthma.

The asthmatic inflammatory process results in the generation of volatile organic compounds (VOCs), which are subsequently secreted by the airways. The study of these elements through gas chromatography-mass spectrometry (GC-MS), which can identify individual molecules with a discriminatory capacity of over 85%, and electronic-Nose (e-NOSE), which is able to perform a quick onboard pattern-recognition analysis of VOCs, has allowed new prospects for non-invasive analysis of the disease in an "omics" approach. In this review, we aim to collect and compare the progress made in VOCs analysis using the two methods and their instrumental characteristics. Studies have described the potential of GC-MS and e-NOSE in a multitude of relevant aspects of the disease in both children and adults, as well as differential diagnosis between asthma and other conditions such as wheezing, cystic fibrosis, COPD, allergic rhinitis and last but not least, the accuracy of these methods compared to other diagnostic tools such as lung function, FeNO and eosinophil count. Due to significant limitations of both methods, it is still necessary to improve and standardize techniques. Currently, e-NOSE appears to be the most promising aid in clinical practice, whereas GC-MS, as the gold standard for the structural analysis of molecules, remains an essential tool in terms of research for further studies on the pathophysiologic pathways of the asthmatic inflammatory process. In conclusion, the study of VOCs through GC-MS and e-NOSE appears to hold promise for the non-invasive diagnosis, assessment, and monitoring of asthma, as well as for further research studies on the disease.

Recurrent pulmonary embolism due to echinococcosis secondary to hepatic surgery for hydatid cysts.

We describe the case of a 53-year-old man with recurrent pulmonary embolism due to intra-arterial cysts from Echinococcus. Both the patient's medical history and the computed tomographic (CT) scan abnormalities led to the diagnosis. The CT scan, performed during hospitalization in our ward, showed cystic masses in the left main pulmonary artery and in the descending branch of the right pulmonary artery. Within cystic masses, thin septa were visible, giving a chambered appearance, which was suggestive of a group of daughter cysts. In the past, our patient underwent multiple operations for recurring echinococcal cysts of the liver. After the last intervention, 4 years earlier, his postoperative course was complicated by pulmonary embolism: a CT scan showed a filling defect in the descending branch of the right pulmonary artery, which was caused by the same cystic mass as 4 years later, although smaller. This mass, not properly treated, increased in diameter. Moreover, after 4 years, there has been a new episode of embolism, which involved the left main pulmonary artery. This is the first case in which there are repeated episodes of pulmonary embolism echinococcosis after hepatic surgery for removal of hydatid cysts.

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.

Short-Term Effect of Cigarette Smoke on Exhaled Volatile Organic Compounds Profile Analyzed by an Electronic Nose.

Breath analysis using an electronic nose (e-nose) is an innovative tool for exhaled volatile organic compound (VOC) analysis, which has shown potential in several respiratory and systemic diseases. It is still unclear whether cigarette smoking can be considered a confounder when analyzing the VOC-profile. We aimed to assess whether an e-nose can discriminate exhaled breath before and after smoking at different time periods. We enrolled 24 healthy smokers and collected their exhaled breath as follows: (a) before smoking, (b) within 5 min after smoking, (c) within 30 min after smoking, and (d) within 60 min after smoking. Exhaled breath was collected by a previously validated method and analyzed by an e-nose (Cyranose 320). By principal component analysis, significant variations in the exhaled VOC profile were shown for principal component 1 and 2 before and after smoking. Significance was higher 30 and 60 min after smoking than 5 min after (p < 0.01 and <0.05, respectively). Canonical discriminant analysis confirmed the above findings (cross-validated values: baseline vs. 5 min = 64.6%, AUC = 0.833; baseline vs. 30 min = 83.6%, AUC = 0.927; baseline vs. 60 min = 89.6%, AUC = 0.933). Thus, the exhaled VOC profile is influenced by very recent smoking. Interestingly, the effect seems to be more closely linked to post-cigarette inflammation than the tobacco-related odorants.