Laszlo Kunos

Exhaled biomarker pattern is altered in children with obstructive sleep apnoea syndrome

OBJECTIVES Obstructive sleep apnoea syndrome (OSAS) is a common disorder in children, which is associated with enhanced inflammatory status. Inflammation-associated changes could be monitored by the assessment of exhaled biomarker profile. This study aimed to compare the exhaled biomarker profile in children with OSAS and habitual snorers. METHODS Eighteen children with OSAS (8 ± 2 years, mean ± SD) and ten non-OSAS subjects with habitual snoring (9 ± 2 years) were recruited. Exhaled breath was collected from the lower airways, processed using an electronic nose (E-nose) and analyzed off-line using principal component analysis, followed by discrimination analysis and logistic regression to build a receiver operating characteristic (ROC) curve. RESULTS Exhaled biomarker pattern of OSAS patients was discriminated from that of control subjects (p = 0.03, cross-validation accuracy: 64%), ROC curve analysis (area: 0.83) showed 78% sensitivity and 70% specificity. CONCLUSIONS The altered exhaled biomarker pattern in OSAS might reflect accelerated airway and/or systemic inflammation in diseased state. Breath pattern analysis by an E-nose can serve as a new tool to monitor inflammation in children with OSAS.

Gene expression profiling of experimental asthma reveals a possible role of paraoxonase-1 in the disease

In this study, we aimed to identify novel genes involved in experimental and human asthma, importance of which has not yet been recognized. In an ovalbumin-induced murine model of asthma, we applied microarray gene expression analysis at different time points after allergen challenges. Advanced statistical methods were used to relate gene expression changes to cellular processes and to integrate our results into multiple levels of information available in public databases. At 4 h after the first allergen challenge, gene expression pattern reflected mainly an acute, but non-atopic, inflammatory response and strong chemotactic activity. At 24 h after the third allergen challenge, gene set enrichment analysis revealed significant over-representation of gene sets corresponding to T(h)2-type inflammation models. Among the top down-regulated transcripts, an anti-oxidant enzyme, paraoxonase-1 (PON1), was identified. In human asthmatic patients, we found that serum PON1 activity was reduced at exacerbation, but increased parallel with improving asthma symptoms. PON1 gene polymorphisms did not influence the susceptibility to the disease. Our observations suggest that an altered PON1 activity might be involved in the pathogenesis of asthma, and serum PON1 level might be used for following up the effect of therapy.

Exhaled breath analysis, a simple tool to study the pathophysiology of obstructive sleep apnoea

Accelerated airway inflammation may play a crucial role in the pathophysiology of obstructive sleep apnoea (OSA); however this phenomenon has been investigated only in a limited number of studies. The analysis of exhaled breath represents a promising, non-invasive tool to evaluate airway inflammation in this context. The knowledge on exhaled biomarkers in OSA has been growing with an emerging number of methodological studies which help to interpret exhaled breath data. This article not only summarises the results of studies on exhaled breath condensate (EBC) biomarkers, exhaled volatile compounds and exhaled monoxides in OSA, but also aims to critically review methodological limitations and provide some guideline for further research.

Plasma VEGF levels and their relation to right ventricular function in pulmonary hypertension

Abstract A protective role of vascular endothelial growth factor (VEGF) on right heart function has been reported only in animal studies of pulmonary hypertension. Twenty patients with idiopathic pulmonary hypertension and fifteen healthy volunteers were involved. Plasma VEGF levels were compared to right heart parameters. Plasma VEGF levels tended to be higher in patients (82/0–345/pg/ml) than in controls (48/0–141/pg/ml, p = 0.08) with a significant correlation between VEGF concentration and tricuspid annular plane systolic excursion (TAPSE; p = 0.03, r = 0.48). This is the first study to report a positive association between elevated plasma VEGF levels and right heart function in humans.

Complement system activation in obstructive sleep apnea

The complement system may play a role in the systemic inflammation characterising obstructive sleep apnea; however, this has not been investigated before. We aimed to study the involvement of effector complement elements in obstructive sleep apnea, namely C3a, C5a and SC5b‐9. Venous blood was collected in 50 patients with obstructive sleep apnea and 26 control subjects in the evening and the following morning. Plasma complement proteins were analysed with ELISA. Complement factor levels were compared between the two groups and correlated with clinical variables. Plasma C3a concentration was elevated in obstructive sleep apnea both in the evening (84.1 [0–338.5] ng ml−1) and in the morning (85.5 [0–247.8] ng ml−1) compared with controls (30.3 [0–176.8] ng ml−1 and 36.3 [0–167.1] ng ml−1, evening and morning, respectively, both p < 0.05). On the contrary, C5a and SC5b‐9 levels were comparable between patients and controls at each time point (p > 0.05). There was no change in complement factors from evening to morning in either group (p > 0.05), except for C5a that decreased from evening to morning in obstructive sleep apnea (from 11.6 [1.6–47.4] ng ml−1 to 9.3 [0–46.4] ng ml−1, p = 0.01). Elevated C3a levels were directly related to obstructive sleep apnea severity, and were significantly associated with male gender, weight, body mass index, hypertension, high C‐reactive protein and low high‐density lipoprotein cholesterol (p < 0.05). The complement system is activated in obstructive sleep apnea, which is correlated with disease severity. Our findings highlight the potential role of complement system in the pathophysiology of obstructive sleep apnea, thus facilitating further research.

Role of lung volume and airway inflammation in obstructive sleep apnea

Obstructive sleep apnea (OSA) is a prevalent disorder that affects not only the upper airways but also the intrathoracic airways. In this review, we summarize the results of studies on lung function and airway inflammation. We provide evidence that the alterations in intrathoracic airways observed in OSA are not purely consequences of mechanical trauma and oxidative stress during apneic events but have a causal role in the structural changes associated with OSA and increasing severity of this disorder.

[Simultaneous occurrence of chronic obstructive pulmonary disease and obstructive sleep apnea: the overlap syndrome].

Obstructive sleep apnea syndrome is a common disorder in adults associated with several cardiovascular diseases and impaired quality of life. Chronic obstructive pulmonary disease is also a common clinical condition in middle-aged adults. The combination of these two conditions can eventuate a severe combined sleep-related breathing disorder. It is important to recognize coexisting sleep apnea in patients with chronic obstructive pulmonary disease in time and to treat it appropriately.