Circulating apelin, IL22RA2 and VEGF in pre-capillary pulmonary hypertension.

Cytokines can modulate vascular remodelling and the adaptation of the right ventricle in pre-capillary pulmonary hypertension (PH). However, detailed data on the circulating levels of cytokines in patients are limited. We measured blood cytokine concentration in 39 treatment-naïve patients (pulmonary arterial hypertension: N = 16, chronic thromboembolic PH: N = 15, PH due to lung disease: N = 8) and 12 control subjects using enzyme-linked immunoassays. Apelin concentration >1,261 ng/mL identified patients with PH (66% sensitivity and 82% specificity), and in patients it was related to systolic pulmonary arterial pressure (PAP) (r = 0.33, P = 0.04), right atrial pressure (r = 0.38, P = 0.02), cardiac index (r = -0.34, P = 0.04), and right ventricular stroke work index (r = -0.47, P = 0.003). IL22RA2 concentration correlated with mean PAP (r = -0.32, P = 0.04) and serum N-terminal pro B-type natriuretic peptide level (r = -0.42, P = 0.01). VEGF concentration increased in patients upon clinical improvement (N = 16, P = 0.02). Circulating apelin is a novel biomarker of pre-capillary PH. Apelin and IL22RA2 levels are related to right ventricular function upon diagnosis of PH.

Analysis of possible risk factors for the severity of paediatric obstructive sleep apnoea syndrome.

PURPOSE: This study aimed to determine the effect of body mass index (BMI) percentile, asthma, sex, and age on the paediatric obstructive sleep apnoea (OSA) severity. Furthermore, to determine the possible predictive role of the BMI percentile and age in severe OSA. METHODS: This retrospective study included 921 children aged 2-18 years diagnosed with OSA by polysomnography. Analysis of Covariance (ANCOVA), Spearman's correlation, Receiver Operating Characteristics (ROC) analyses were performed and area under the curve (AUC) was determined. RESULTS: We observed a significant association between a higher BMI percentile and the severity of OSA (p < 0.001, ρ = 0.15). The correlation also was significant under (p = 0.007, ρ = 0.11) and over 7 (p = 0.0002, ρ = 0.23) years of age. There was no association between the severity of OSA and the presence of asthma (p = 0.9) or sex (p = 0.891), respectively. Age was significantly related to OSA severity (p = 0.01, ρ = 0.08). Although both the BMI percentile (0.59 AUC [0.54-0.65]) and age (0.58 AUC [0.52-0.63]) predicted severe OSA, according to the sensitivity and specificity values of the ROC curve, the association presents a slight clinical relevance. CONCLUSIONS: OSA severity is determined by the BMI percentile and age in children; however, these factors are unsuitable for predicting severe OSA in clinical practice. Based on our results, obesity is also a significant risk factor for OSA in younger children. Our study highlights that older, overweight, and obese children have a higher risk for severe OSA.

Combined Pulmonary Fibrosis and Emphysema: Comparative Evidence on a Complex Condition.

Combined pulmonary fibrosis and emphysema (CPFE) is a clinical syndrome characterized by upper lobe emphysema and lower lobe fibrosis manifested by exercise hypoxemia, normal lung volumes, and severe reduction of diffusion capacity of carbon monoxide. It has varying prevalence worldwide with a male predominance, and with smoking history of more than 40 pack-years being a common risk factor. The unique imaging features of CPFE emphasize its distinct entity, aiding in the timely detection of pulmonary hypertension and lung cancer, both of which are common complications. High-resolution computed tomography (HRCT) is an important diagnostic and prognostic tool, while lung cancer is an independent factor that alters the prognosis in CPFE patients. Treatment options for CPFE are limited, but smoking cessation, usual treatments of pulmonary fibrosis and emphysema, and avoidance of environmental exposures are encouraged.

Postoperative respiratory complications in children with obstructive sleep apnoea syndrome.

Objective: We aimed to prospectively assess the effect of comorbidities on the occurrence of postoperative respiratory complications (PoRCs) after adenotonsillectomy in children with obstructive sleep apnoea syndrome (OSA) and whether otherwise healthy children need a higher level of postoperative monitoring. Methods: 577 children who had OSA and underwent adenotonsillectomy were enrolled. The effects of demographics, comorbidities and OSA on PoRCs were investigated with logistic regression analysis. Results: The PoRC rate was 4.3%. Postoperative oxygen desaturations were more marked in patients with comorbidities (p = 0.005). The presence of comorbidity increased the risk of PoRCs (odds ratio 4.234/3.226-5.241, 95% confidence intervals, p < 0.001). There was no difference in apnoea-hypopnoea index (AHI) values between comorbid patients with and without PoRCs [8.2 (3.8-50.2) vs 14.3 (11.7-23.3)]. (p = 0.37). In the group of patients without comorbidities, PoRCs were associated with a higher AHI [14.7 (3.4-51.3) vs 3.9 (2.0- 8.0), p < 0.001]. Conclusions: Comorbidities are more closely linked with PoRCs than OSA severity. In patients without comorbidity, PoRCs are associated with OSA severity and usually occur within the first 2 hours after the intervention.

Circulating Survivin Protein Levels in Lung Cancer Patients Treated With Platinum-Based Chemotherapy.

The survivin protein contributes to the development and progression of tumors. Protein expression and mRNA levels correlate with clinicopathological parameters and survival of cancer patients. Our purpose was to evaluate whether circulating survivin levels have any diagnostic or predictive value in lung cancer. 118 patients with advanced stage lung cancer participated in our study. 53 suffered from adenocarcinoma (ADC), 33 from squamous cell carcinoma (SqCC), and 32 from small cell lung cancer (SCLC). We also enrolled 21 control subjects. Blood samples were collected before and after two cycles of chemotherapy. We measured survivin concentrations with ELISA. Non-parametric tests were used for analysis. We did not find significant difference in survivin levels between patients and control subjects (17.19/0-829.74/vs. 49.13/0-165.92/pg/ml; p = 0.07). We found lower survivin concentrations in patients with SqCC (0/0-171.24/pg/ml) than in those with ADC (24.94/0-626.46 pg/ml) and SCLC (45.51/0-829.74/pg/ml) (ADC vs. SqCC p < 0.0001, ADC vs. SCLC p = 0.0405, SqCC vs. SCLC p < 0.0001). Survivin levels were higher in stage IV patients than in patients without distant metastases (p = 0.0061), and concentrations were progressively higher with increasing number of metastatic organ sites (p = 0.04). We observed a decrease in survivin levels in ADC patients after platinum plus pemetrexed chemotherapy (26.22/0-626.46/pg/ml before vs. 0/0-114.36/pg/ml after; p = 0.01). Neither progression-free nor overall survival correlated with survivin levels at baseline. Our data imply that survivin may be involved in the development of metastases and it might be used as a biomarker of disease progression. However, circulating survivin concentrations do not predict survival of patients with lung cancer.

The Role of Soluble Low-Density Lipoprotein Receptor-Related Protein-1 in Obstructive Sleep Apnoea.

Intermittent hypoxia in obstructive sleep apnoea (OSA) is related to inflammation and metabolic abnormalities. Soluble low-density lipoprotein receptor-related protein-1 (sLRP-1) is involved in anti-inflammatory and metabolic processes. However, its ligand, calreticulin (CALR) promotes pro-inflammatory responses and apoptosis. Our aim was to analyse the levels of these biomarkers in OSA. We recruited 46 patients with OSA and 30 control subjects. Inpatient sleep study was performed and fasting plasma samples were collected. Triglyceride glucose index (TyG) and atherogenic index of plasma (AIP) were calculated. Plasma sLRP-1 levels were significantly lower in the OSA group compared to the controls (1.67 (0.90-2.11) mg/L vs. 1.99 (1.53-3.51) mg/L; p = 0.04) after adjustment for age, gender, BMI and lipid profile. Plasma sLRP-1 concentrations were inversely related to age (r = -0.29), BMI (r = -0.35), cigarette pack years (r = -0.31), LDL-C (r = -0.34) and triglyceride levels (r = -0.27), TyG (r = -0.37) and AIP (r = -0.27) as well as to the oxygen desaturation index (ODI, r = -0.24; all p < 0.05). BMI (p = 0.01) and ODI (p = 0.04) were independent predictors for low sLRP-1 levels. CALR did not differ significantly between the two groups (0.23 (0.17-0.34) ng/mL vs. 0.24 (0.20-0.36) ng/mL p = 0.76). We detected lower sLRP-1 levels in subjects with OSA which could contribute to metabolic abnormalities associated with this disease.

The role of hyaluronic acid and hyaluronidase-1 in obstructive sleep apnoea.

Biological functions of hyaluronic acid (HA) depend on its molecular size. High-molecular weight HA (HMW-HA) is an important component of the endothelial wall and has anti-inflammatory and antioxidant properties. Under inflammation or hypoxia, HMW-HA is degraded by hyaluronidases, such as HYAL-1 resulting in pro-inflammatory low-molecular weight fragments. Obstructive sleep apnoea (OSA) is characterised by intermittent hypoxia and systemic inflammation. Our aim was to evaluate circulating HMW-HA and HYAL-1 in OSA. We recruited 68 patients with OSA and 40 control volunteers. After full-night sleep study blood samples were taken for HMW-HA and HYAL-1 measurements. HYAL-1 levels were significantly higher in patients with OSA compared to controls (0.59/0.31-0.88/ng/mL vs. 0.31/0.31-0.58/ng/mL; p = 0.005) after adjustment for gender, age, BMI and smoking. There was a trend for reduced HMW-HA concentrations in OSA (31.63/18.11-59.25/ng/mL vs. 46.83/25.41-89.95/ng/mL; p = 0.068). Significant correlation was detected between circulating HMW-HA and apnoea-hypopnoea-index (r = - 0.195, p = 0.043), HYAL-1 and apnoea-hypopnoea-index (r = 0.30, p < 0.01) as well as oxygen desaturation index (r = 0.26, p < 0.01). Our results suggest that chronic hypoxia is associated with increased plasma HYAL-1 concentration and accelerated HMW-HA degradation. Altered hyaluronan metabolism may be involved in the inflammatory cascade potentially leading to endothelial dysfunction in OSA.

Impact of Clinical Factors on Generic and Disease-Specific Quality of Life in COPD and Asthma-COPD Overlap with Exacerbations.

PURPOSE: The health-related quality of life (HRQL) in chronic obstructive pulmonary disease (COPD) is worsened by frequent exacerbations, and it can be affected by the concomitant presence of bronchial asthma (asthma-COPD overlap (ACO)). The impacts of clinical factors associated with HRQL have not been compared in patients with COPD and ACO experiencing exacerbations. Patients and Methods. Patients with COPD (N =705) and ACO (N =148) belonging to C and D groups according to GOLD 2017 were recruited in stable condition. Demographic and clinical data were collected, spirometry was performed, and patients rated the intensity of respiratory symptoms during the previous week. The COPD Assessment Test (CAT) and the EQ-5D 3 level version (dimensions and visual analogue scale (VAS)) were used to assess disease-specific and generic HRQL, respectively. Fisher's exact test, χ 2 test, ANOVA, and Pearson correlation were used for analysis (mean ± SD). Multiple linear regression was applied to identify variables related to CAT and EQ-5D VAS scores. RESULTS: The CAT and EQ-5D VAS scores showed similarly low HRQL in COPD and ACO (20.7 ± 6.7 vs. 21.1 ± 6.3 (p = 0.52) and 56.2 ± 17.8 vs. 53.7 ± 18.2 (p = 0.11)). There was a weak correlation between CAT and EQ-5D VAS scores (COPD: r = -0.345, p < 0.001; ACO: r = -0.245, p = 0.003). More patients with COPD had problems related to anxiety/depression in EQ-5D (63.7% vs. 55.4%, p = 0.06). Pack-years exerted a negative effect on HRQL measures both in ACO and COPD. Low HRQL in COPD was associated with female gender, dyspnea, cough, gastroesophageal reflux disease, and arrhythmia, while in ACO, it was related to arrhythmia, hypertension, and cough, but less to dyspnea. CONCLUSIONS: Patients with COPD and ACO experiencing exacerbations have low quality of life, which is influenced by smoking history, symptoms, and comorbidities. These findings have important implications for the development of therapeutic strategies to improve the health status of patients with these conditions.

Exhaled carbon monoxide levels in obstructive sleep apnoea.

BACKGROUND: Obstructive sleep apnoea (OSA) is characterised by chronic intermittent hypoxia, which enhances airway inflammation and oxidative stress. Exhaled carbon monoxide (eCO), a marker for oxidative stress, has been investigated in OSA. However, previous studies could be biased as they did not differentiate patients with OSA based on smoking history, a known factor influencing eCO levels. The aim of this study to investigate eCO levels in patients with OSA and non-OSA controls and compare evening to morning results. METHODS: Exhaled carbon monoxide concentration was measured in the evening and in the morning following an in-hospital cardiorespiratory polygraphy in 60 never-smoker OSA patients, 14 ex-smoker OSA patients, 39 current-smoker OSA patients, 10 never-smoker asthmatic patients with OSA, 16 COPD patients with OSA and 20 never-smoker non-OSA controls. OSA was diagnosed based on the apnoea-hypopnoea index (AHI > 5/h). RESULTS: There was no difference between the never-smoker controls and never-smoker patients with OSA either in the evening (1.98 ± 1.00 ppm versus 1.95 ± 1.28 ppm, p = 0.57, OSA versus controls, respectively) or morning (1.95 ± 0.96 ppm versus 1.80 ± 0.95 ppm, p = 0.42), however there was a weak correlation between eCO and AHI in the evening (r = 0.31, p = 0.01). Accordingly, patients with severe OSA had higher eCO levels in the evening (2.43 ± 1.12 ppm) compared to mild OSA patients (1.57 ± 0.87 ppm, p < 0.01). Ex-smoker (3.07 ± 2.23 ppm), current-smoker (13.13 ± 11.35 ppm), asthmatic (2.70 ± 1.16 ppm) and COPD (18.25 ± 18.60 ppm) patients with OSA had higher levels of eCO compared to the non-smoker OSA group. CONCLUSION: Exhaled carbon monoxide is elevated only in severe never-smoker OSA suggesting accelerated oxidative stress. Previous smoking history is a major influencing factor which may explain differences between our findings and those of previous studies. Although our results show some impact of OSA on eCO measurements, the bias is small, and it does not significantly affect the clinical utility of eCO to monitor smoking cessation.

Central and peripheral airway nitric oxide in patients with stable and exacerbated chronic obstructive pulmonary disease.

Nitrative stress pathways are involved in airway inflammation characterizing chronic obstructive pulmonary disease (COPD). Extended nitric oxide (NO) analysis allows the partitioned measurement of nitrative stress in the conducting bronchi and peripheral airways/alveolar spaces. However, pulmonary NO production at these two sites has not been systemically studied in stable and exacerbated COPD. Twenty-eight patients with stable COPD, 34 patients during an exacerbation, and 15 smoking controls were recruited. Exhaled NO was measured at constant flow rates of 50 ml s-1 (for FENO50) and 100-150-200-250 ml s-1 (for the extended NO analysis). Clinical variables, including lung function, white blood cell count, C-reactive protein concentration, blood gas values and symptom score (COPD assessment test) were collected. The measurements were repeated in 26 patients with an exacerbation during convalescence. The exhaled NO parameters were analysed with non-parametric tests. The alveolar NO (CANO) was higher in stable COPD (median (interquartile range), 4.24 (2.35-6.09) ppb, p < 0.01) and in patients with an exacerbation (3.83 (2.31-6.62) ppb, p < 0.05) than in the controls (2.05 (1.77-2.80) ppb), but no difference was found between the stable and exacerbated disease (p > 0.05). The CANO correlated with the blood eosinophil percentage in all COPD patients (r = 0.29, p = 0.02). The total flux of bronchial NO (JawNO) increased in an exacerbation (exacerbated: 1.01 (0.45-2.44) nl s-1 versus stable: 0.47 (0.16-0.81) nl s-1, p < 0.01; exacerbated versus control: 0.38 (0.27-0.80) nl s-1, p < 0.05), and it was reduced in convalescence after therapy (0.50 (0.31-0.96) nl s-1, p = 0.01). Neither CANO and JawNO or their change were related to the clinical variables or the length of hospital stay in COPD. JawNO correlated with FENO50 during exacerbation (r = 0.80, p < 0.001). Extended NO analysis is a feasible method to monitor nitrative stress at different anatomical sites within the airways in stable and exacerbated COPD patients. Our results suggest that nitrative stress is constantly elevated in the small airways in COPD and increases in the conducting airways during an exacerbation.

NTPDase1/CD39 and aberrant purinergic signalling in the pathogenesis of COPD.

Purinergic receptor activation via extracellular ATP is involved in the pathogenesis of chronic obstructive pulmonary disease (COPD). Nucleoside triphosphate diphosphohydrolase-1/CD39 hydrolyses extracellular ATP and modulates P2 receptor signalling.We aimed to investigate the expression and function of CD39 in the pathogenesis of cigarette smoke-induced lung inflammation in patients and preclinical mouse models. CD39 expression and soluble ATPase activity were quantified in sputum and bronchoalveolar lavage fluid (BALF) cells in nonsmokers, smokers and COPD patients or mice with cigarette smoke-induced lung inflammation. In mice, pulmonary ATP and cytokine concentrations, inflammation and emphysema were analysed in the presence or absence of CD39.Following acute cigarette smoke exposure CD39 was upregulated in BALF cells in smokers with further increases in COPD patients. Acute cigarette smoke exposure induced CD39 upregulation in murine lungs and BALF cells, and ATP degradation was accelerated in airway fluids. CD39 inhibition and deficiency led to augmented lung inflammation; treatment with ATPase during cigarette smoke exposure prevented emphysema.Pulmonary CD39 expression and activity are increased in COPD. CD39 deficiency leads to enhanced emphysema in mice, while external administration of a functional CD39 analogue partially rescues the phenotype. The compensatory upregulation of pulmonary CD39 might serve as a protective mechanism in cigarette smoke-induced lung damage.

Altered purinergic signaling in the tumor associated immunologic microenvironment in metastasized non-small-cell lung cancer.

OBJECTIVES: Purines are well-known as intracellular sources for energy but they also act as extracellular signaling molecules. In the recent years, there has been a growing interest in the therapeutic potential of purinergic signaling for cancer treatment. This is the first study to analyze lung purine levels and purinergic receptors in non-small-cell lung cancer (NSCLC) patients. MATERIALS AND METHODS: In this prospective clinical trial we enrolled 26 patients with NSCLC and 21 patients with chronic obstructive pulmonary disease (COPD) without signs of malignancy. The purine concentrations were analyzed in bronchoalveolar lavage fluid (BALF) using fluorescent/luminescent assays. Expression of purinergic receptors and ectonucleotidases were analyzed using real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: Patients with NSCLC have significantly lower ATP and ADP concentrations in BALF than patients with COPD (p=0.006 and p=0.009). Expression of the ectonucleotidase CD39 is significantly higher in BAL cells from cancer patients compared to COPD (p=0.001) as well as in metastasized tumors compared to non-metastasized tumors (p=0.009). Receptor-analysis revealed a higher expression of P2X4 (p=0.03), P2X7 (p=0.001) and P2Y1 (p=0.003) in BAL cells of tumors with distant metastasis. CONCLUSION: Our data suggests a role for CD39 in lung cancer tumor microenvironment, influencing tumor invasiveness and metastasization. Potentially the increased degradation of ATP and ADP leads to a subversion of their anti-neoplastic effects. Furthermore P2Y1, P2X4 and P2X7 receptors are upregulated in BAL cells in metastatic disease. Our findings might facilitate the identification of new therapeutic targets for cancer immunotherapy.

Exhaled Breath Condensate pH in Lung Cancer, the Impact of Clinical Factors.

PURPOSE: Lung cancer may be associated with airway acidification due to enhanced airway inflammation and oxidative stress. Exhaled breath condensate (EBC) pH is a non-invasive indicator of airway acidity; however, it is still unclear how EBC pH changes in lung cancer. The aim of the study was to investigate EBC pH in lung cancer together with clinical variables. METHODS: Thirty-five patients with lung cancer and 37 control subjects (21 patients with stable COPD and 16 non-COPD smokers) were enrolled. EBC was collected for pH, which was determined with the argon-purging method, compared among the groups and correlated with clinical variables of patients with lung cancer. RESULTS: No difference was found in EBC pH between patients with lung cancer and control subjects. However, endobronchial tumour localisation, squamous-cell carcinoma subtype and gastro-oesophageal reflux were associated with low EBC pH values. No relationship was observed between EBC pH and the presence of COPD, lung function variables or smoking history. CONCLUSIONS: Although, EBC pH is unchanged in lung cancer, lower EBC pH values are associated with distinct phenotypes. Our findings could facilitate further research on airway acidity in lung cancer.

Modest genetic influence on bronchodilator response: a study in healthy twins.

AIM: To determine the reasons for large standard deviation of bronchodilator response (BDR) and establish whether there is a potential heritable component in healthy subjects. METHODS: 67 monozygotic and 42 dizygotic adult twin pairs were assessed for bronchodilator response (% change in FEV1 after inhaling 400 µg salbutamol). Univariate quantitative genetic modeling was performed. RESULTS: Multiple regression modeling showed a significant association between BDR and sex and baseline FEV1 (P<0.05), while no association was found with smoking habits, body mass index, or age. Within pair correlation in monozygotic twins was modest (0.332), but higher than in dizygotic twins (0.258). Age-, sex-, and baseline FEV1-adjusted genetic effect accounted for 14.9% (95% confidence interval, CI 0%-53.1%) of the variance of BDR, shared environmental effect for 18.4% (95% CI 0%-46.8%), and unshared environmental effect for 66.8% (95% CI 46.8%-88.7%). CONCLUSION: Our twin study showed that individual differences in BDR can be mostly explained by unshared environmental effects. In addition, it is the first study to show low, insignificant hereditary influences, independently from sex, age, and baseline FEV1.

Ceramide-1-phosphate inhibits cigarette smoke-induced airway inflammation.

Sphingolipids are involved in the pathogenesis of inflammatory diseases. The central molecule is ceramide, which can be converted into ceramide-1-phosphate (C1P). Although C1P can exert anti- and pro-inflammatory effects, its influence on cigarette smoke (CS)-induced lung inflammation is unknown. We aimed to clarify the role of C1P in the pathogenesis of CS-triggered pulmonary inflammation and emphysema in humans and mice. The effects of C1P were addressed on CS-induced lung inflammation in C57BL/6 mice, CS extract-triggered activation of human airway epithelial cells (AECs) and neutrophils from patients with chronic obstructive pulmonary disease. Differential cell counts in bronchoalveolar lavage fluid were determined by flow cytometry and pro-inflammatory cytokines were measured by ELISA. Expression and DNA binding of nuclear factor (NF)-κB and neutral sphingomyelinase (nSMase) were quantified by PCR, electrophoretic mobility shift and fluorometric assays. C1P reduced CS-induced acute and chronic lung inflammation and development of emphysema in mice, which was associated with a reduction in nSMase and NF-κB activity in the lungs. nSMase activity in human serum correlated negatively with forced expiratory volume in 1 s % predicted. In human AECs and neutrophils, C1P inhibited CS-induced activation of NF-κB and nSMase, and reduced pro-inflammatory cytokine release. Our results suggest that C1P is a potential target for anti-inflammatory treatment in CS-induced lung inflammation.

Evening and morning exhaled volatile compound patterns are different in obstructive sleep apnoea assessed with electronic nose.

PURPOSE: Electronic noses represent a technique for the measurement of exhaled breath volatile compound pattern which can discriminate patients with obstructive sleep apnoea (OSA) from control subjects. Although overnight changes in circulating biomarkers were reported, this effect on the exhaled volatile compound pattern has not been studied before. We aimed to compare breath patterns in the evening and in the morning in patients with OSA and to study the ability of the electronic nose to distinguish patients from controls based on these exhaled volatile patterns. METHODS: Exhaled breath volatile compound pattern was measured before and after night in 26 patients with suspected sleep-disordered breathing (53 ± 15 years) who underwent polysomnography and in ten control subjects (37 ± 15 years), by whom sleep-disordered breathing was excluded with a home apnoea screening device. Breath measurements were also performed in the morning in 26 healthy, non-smoking age-matched controls (48 ± 10 years) with no complaints about disturbed sleep. Exhaled volatile compound pattern was processed with a Cyranose 320 electronic nose, and principal component analysis was used for statistical analysis. RESULTS: Exhaled volatile compound patterns recorded in the evening and in the morning were different in patients with OSA (p = 0.01) but not in non-OSA habitual snorers (p = 0.49) or in control subjects (p = 0.23). The electronic nose distinguished patients with OSA from control subjects based on the breath samples collected in the morning (p < 0.001, classification accuracy 77 %) but not in the evening (p > 0.05). CONCLUSIONS: Evening and morning exhaled volatile compound patterns are different in OSA. This might affect the ability of electronic noses to identify this disorder. Overnight alterations in volatile substances need to be taken into account during exhaled breath measurements in OSA.

Transmission of second-hand smoke sensitivity and smoking attitude in a family.

INTRODUCTION AND OBJECTIVE: The role of genetic factors in nicotine dependence is well understood, but no information is available on the inheritability of second-hand smoke (SHS) exposure sensitivity and their co-variance. MATERIALS AND METHODS: 186 adult same-gender pairs of twin (146 monozygotic, 40 dizygotic; 44±17 years±SD) completed a questionnaire. RESULTS: The model showed a significant role of unshared environmental factors influencing the co-variance between smoking habit and SHS sensitivity (re=-0.191, 95% CI, -0.316 to -0.056, or the total phenotypic correlation of rph=-0.406, p<0.001) without evidence for genetic covariation. Age, gender and country-adjusted analysis indicated 51.5% heritability for smoking habit (95% confidence interval/CI/, 6.2 to 89.8%), 49.7% for SHS sensitivity (95%CI, 19.1-72.0%), 35.5% for general opinions on SHS exposure in restaurants/cafés (95%CI, 10.7-58.6%), and 16.9% in pubs/bars (95%CI, 0.0-49.0%). CONCLUSIONS: The co-variance between SHS sensitivity and smoking habits is driven mainly by the unshared environment. SHS sensitivity is moderately inheritable. The considerable influence of environmental factors on general opinions on SHS exposure in designated indoor public venues emphasizes the importance of smoking bans and health behaviour interventions at the individual level in developing an anti-smoking attitude.

Exhaled breath temperature in patients with stable and exacerbated COPD.

The measurement of the peak exhaled breath temperature (EBT) during multiple tidal breaths offers an easy, non-invasive tool for monitoring airway inflammation. Chronic obstructive pulmonary disease (COPD) is linked to airway inflammation, which is further aggravated by exacerbations of the disease. However, the peak EBT has not been studied in patients with COPD. The breath temperature was measured (X-halo, Delmedica Investments) in 19 control non-smoking subjects (age: 28 ± 11 years, mean ± standard deviation), 19 control smoking/ex-smoking subjects (53 ± 9 years), 20 patients with stable COPD (66 ± 8 years), and 17 patients with COPD at onset and also after recovery from an acute exacerbation (AECOPD; 65 ± 10 years). Spontaneous sputa were collected in AECOPD. The intra-class correlation coefficient of the repeated EBT measurements in non-smokers was 0.87 (95% confidence interval: 0.70-0.95). The peak EBT was different between the subject groups (Kruskal-Wallis test, p = 0.02), with lower values in the patients with stable COPD (34.00/33.35-34.34/°C; median /interquartile range/) than in the smoking/ex-smoking control subjects (34.51/34.20-34.68/°C, p < 0.05). The EBT was higher at the onset of AECOPD (34.58/34.12-34.99/°C, p < 0.05) compared to in a stable condition, and positively correlated with the sputum leukocyte count (p = 0.049, r2 = 0.30; Spearman test) and neutrophil percentage (p = 0.03, r(2) = 0.36). The breath temperature decreased after recovery from AECOPD (34.10/33.72-34.43/°C, p = 0.008; Wilcoxon test). The peak exhaled breath temperature, recorded during multiple tidal breaths, increases with an acute exacerbation of COPD, and may be related to accelerated airway inflammation. The application of exhaled breath temperature measurements when monitoring the activity of COPD should be further assessed in longitudinal studies.

Lack of heritability of exhaled volatile compound pattern: an electronic nose twin study.

Electronic noses can distinguish various disorders by analyzing exhaled volatile organic compound (VOC) pattern; however it is unclear how hereditary and environmental backgrounds affect the exhaled VOC pattern. A twin study enrolling monozygotic (MZ) and dizygotic (DZ) twins is an ideal tool to separate the influence of these factors on the exhaled breath pattern. Exhaled breath samples were collected in duplicates from 28 never smoking twin pairs (in total 112 samples) without lung diseases and processed with an electronic nose (Cyranose 320). Univariate quantitative hereditary modeling (ACE analysis) adjusted for age and gender was performed to decompose the phenotypic variance of the exhaled volatile compound pattern (assessing principal components (PCs) derived from electronic nose data) into hereditary (A), shared (C), and unshared (E) environmental effects. Exhaled VOC pattern showed good intra-subject reproducibility as assessed with the Bland-Altman plot. Significant correlations were found between exhaled VOC patterns of both MZ and DZ twins. The hereditary background did not influence the VOC pattern. The shared environmental effect on PC 1, 2 and 3 was estimated to be 93%, 94% and 54%, respectively. The unshared (unique) environmental influence explained a smaller variance (7%, 6% and 46%). For the first time using the twin design, we have shown that the environmental background largely affects the exhaled volatile compound pattern in never smoking volunteers without respiratory disorders. Further studies should identify these environmental factors and also assess their influence on exhaled breath patterns in patients with lung diseases.

Genetic and environmental factors on the relation of lung function and arterial stiffness.

BACKGROUND: An association between reduced lung function and increased cardiovascular risk has been reported, but the underlying mechanisms are unknown. The aim of this study was to assess the heritability of lung function and to estimate its genetic association with arterial stiffness. METHODS: 150 monozygotic and 42 dizygotic healthy Hungarian and American Caucasian twin pairs (age 43 ± 17 years) underwent spirometry (forced vital capacity/FVC/, forced expiratory volume in 1 s/FEV1/; MIR Minispir, USA); and their brachial and central augmentation indices (AIx), and aortic pulse wave velocity (PWV) were measured by oscillometric Arteriograph (TensioMed Ltd, Budapest, Hungary). Phenotypic correlations and bivariate Cholesky decomposition models were applied. RESULTS: Age-, sex-, country- and smoking-adjusted heritability of FEV1, percent predicted FEV1, FVC and percent predicted FVC were 73% (95% confidence interval /CI/: 45-85%), 28% (95% CI: 0-67%), 68% (95% CI: 20-81%) and 45% (95% CI: 0-66%), respectively. Measured and percent predicted FVC and FEV1 values showed no significant phenotypic correlations with AIx or aortic PWV, except for phenotypic twin correlations between measured FEV1, FVC with brachial or aortic augmentation indices which ranged between -0.12 and -0.17. No genetic covariance between lung function and arterial stiffness was found. CONCLUSIONS: Lung function is heritable and the measured FVC and FEV are phenotypically, but not genetically, associated with augmentation index, a measure of wave reflection. This relationship may in turn reveal further associations leading to a better mechanistic understanding of vascular changes in various airway diseases.