Obstructive sleep apnoea and oral breathing in patients free of nasal obstruction.

Although there is an association between nasal obstruction, oral breathing and obstructive sleep apnoea syndrome (OSAS), it remains unknown whether increased oral breathing occurs in patients with OSAS who are free of nasal obstruction. The present study evaluated the relationship between breathing route and OSAS in patients without nasal obstruction. The breathing route of 41 snorers (25 male; aged 26-77 yrs) with normal nasal resistance was examined during overnight polysomnography using a nasal cannula/pressure transducer and an oral thermistor. In total, 28 patients had OSAS (apnoeics) and 13 patients were simple snorers. Apnoeics had a higher percentage of oral and oro-nasal breathing epochs. Oral and oro-nasal breathing epochs were positively related with apnoea/hypopnoea index (AHI) and duration of apnoeas/hypopnoeas and inversely related to oxygen saturation. Additionally, oro-nasal breathing epochs correlated with body mass index (BMI). In multiple linear regression analysis, oral breathing epochs were independently related only to AHI (r2 = 0.443), and oro-nasal breathing epochs were independently related to AHI (r2 = 0.736) and BMI (r2 = 0.036). In conclusion, apnoeics spent more time breathing orally and oro-nasally than simple snorers, and the apnoea/hypopnoea index is a major determinant of the time spent breathing orally and oro-nasally.     

Effects of rehabilitation on chest wall volume regulation during exercise in COPD patients.

In order to investigate underlying mechanisms, the present authors studied the effect of pulmonary rehabilitation on the regulation of total chest wall and compartmental (ribcage, abdominal) volumes during exercise in patients with chronic obstructive pulmonary disease. In total, 20 patients (forced expiratory volume in one second, mean +/- SEM 39 +/- 3% predicted) undertook high-intensity exercise 3 days x week(-1) for 12 weeks. Before and after rehabilitation, the changes in chest wall (cw) volumes at the end of expiration (EEV) and inspiration (EIV) were computed by optoelectronic plethysmography during incremental exercise to the limit of tolerance (W(peak)). Rehabilitation significantly improved W(peak) (57+/-7 versus 47+/-5 W). In the post-rehabilitation period and at identical work rates, significant reductions were observed in minute ventilation (35.1+/-2.7 versus 38.4+/-2.7 L x min(-1)), breathing frequency (26+/-1 versus 29+/-1 breaths x min(-1)) and EEV(cw) and EIV(cw) (by 182+/-79 and 136+/-37 mL, respectively). Inspiratory reserve volume was significantly increased (by 148+/-70 mL). Volume reductions were attributed to significant changes in abdominal EEV and EIV (by 163+/-59 and 125+/-27 mL, respectively). The improvement in W(peak) was similar in patients who progressively hyperinflated during exercise and those who did not (24 and 26%, respectively). In conclusion, pulmonary rehabilitation lowers chest wall volumes during exercise by decreasing the abdominal volumes. The improvement in exercise capacity following rehabilitation is independent of the pattern of exercise-induced dynamic hyperinflation.     

Evaluation of low dose prostaglandin E1 treatment for ductus dependent congenital heart disease

This study reports our experience with low-dose prostaglandin E₁ (PGE₁) treatment of 91 newborns with ductus dependent congenital heart disease (CHD). PGE₁ efficacy, side-effects as well as the cardiovascular and respiratory profile of the patients were analysed. PGE₁ doses > 0.02 g/kg per minute were used for only 5.3% of the total 23 656 h of treatment. The mean systolic blood pressures did not differ from the normal mean for patients with cyanotic CHD, while the diastolic values were lowered. Respiratory support was required only during 13.7% of the total treatment time. Apnoeas occurred in 21 (38%) of the 55 spontaneously breathing infants, who all had a cyanotic CHD. The incidence of apnoeas was lower during treatment with doses < 0.01 g/kg per minute.     

Erratum to: Depression,anxiety, and quality of life in a large cohort of patients with rheumatic diseases: common,yet undertreated

Clinical Rheumatology -     

Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators

OBJECTIVE: Angiopoietin (Ang)-2 is an endothelium-specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang-2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang-2 levels in critically-ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis-related inflammatory mediators on Ang-2 production by lung endothelium in vitro. DESIGN: Prospective clinical study followed by cell culture studies. SETTING: General intensive care unit and research laboratory of a university hospital. SUBJECTS: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13). INTERVENTIONS: Cells were exposed to lipopolysaccharide, tumor necrosis factor-alpha, and interleukin-6. MEASUREMENTS AND MAIN RESULTS: Patients' serum Ang-2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor-alpha (rs = 0.654, p < .001), serum interleukin-6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang-2 is mostly related to serum tumor necrosis factor-alpha and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration-dependent Ang-2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor-alpha increased Ang-2 release, and interleukin-6 reduced basal Ang-2 levels. CONCLUSIONS: First, patients' serum Ang-2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang-2 with serum tumor necrosis factor-alpha suggests that the latter may participate in the regulation of Ang-2 production in sepsis. Second, inflammatory mediators reduce Ang-2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang-2 in human sepsis.     

Increased Mobilization of Mesenchymal Stem Cells in Patients With Essential Hypertension: The Effect of Left Ventricular Hypertrophy

Stem cells have great clinical significance in many cardiovascular diseases. However, there are limited data regarding the involvement of mesenchymal stem cells (MSCs) in the pathophysiology of arterial hypertension. The aim of this study was to investigate the circulation of MSCs in patients with essential hypertension. The authors included 24 patients with untreated essential hypertension and 19 healthy individuals. Using flow cytometry, MSCs in peripheral blood, as a population of CD45−/CD34−/CD90+ cells and also as a population of CD45−/CD34−/CD105+ cells, were measured. The resulting counts were translated into the percentage of MSCs in the total cells. Hypertensive patients were shown to have increased circulating CD45−/CD34−/CD90+ compared with controls (0.0069%±0.012% compared with 0.00085%±0.0015%, respectively; P=.039). No significant difference in circulating CD45−/CD34−/CD105+ cells was found between hypertensive patients'' and normotensive patients'' peripheral blood (0.018%±0.013% compared with 0.015%±0.014%, respectively; P=.53). Notably, CD45−/CD34−/CD90+ circulating cells were positively correlated with left ventricular mass index (LVMI) (r=0.516, P<.001). Patients with essential hypertension have increased circulating MSCs compared with normotensive patients, and the number of MSCs is correlated with LVMI. These findings contribute to the understanding of the pathophysiology of hypertension and might suggest a future therapeutic target.

In recent years there has been growing interest in the role of adult stem cells in the pathophysiology of cardiovascular diseases. Although it used to be believed that mammalian cardiomyocytes cease replication soon after birth and that the subsequent growth of the heart was attributable only to cardiomyocyte hypertrophy, newer studies have demonstrated a small degree of cardiogenesis and cardiomyocyte turnover that occurs throughout life.¹, ² These findings led to further research into the contribution of stem cells to the pathophysiology of cardiovascular disorders that has raised the hope of developing new therapeutic approaches. Stem cells have the potential for self‐renewal and differentiation and are the origin cells of various mature cells.Mesenchymal stem cells (MSCs) are also known to have a highly plastic differentiation potential that includes not only adipogenesis, osteogenesis, and chondrogenesis, but also endothelial, cardiovascular,³ and neovascular differentiation.⁴, ⁵, ⁶ Although present in only very small numbers in peripheral blood, in recent years stem and progenitor cells have been implicated in ventricular remodeling and are thought to be of great clinical significance in the pathophysiology of heart failure and atheromatosis. Previous studies have indicated that MSCs derived from peripheral blood, apart from their multilineage potential, can also be used for cellular and gene therapies.⁷ Human MSCs isolated from adult bone marrow provide a model for the development of stem cell therapeutics and could find application in the cardiovascular system—although this is still under investigation.⁸ Under normal conditions, endogenous cardiac progenitor cells are responsible for homeostasis in the heart.⁹ However, it appears that under conditions of stress, this may change, with stem cells from extra‐cardiac sources also playing a role. An interesting experimental study has shown that an increase in preload results in the mobilization of progenitor cells from the bone marrow for use in neovascularization, which plays an important role in cardiac hypertrophy.¹⁰ There are indications that the recruitment of bone marrow–derived cells is involved in cardiac myocyte hypertrophy and maintenance of function in response to pressure overload.¹¹ A recent study from our department has shown increased expression of myocardin and GATA4 genes in the peripheral blood mononuclear cell fraction of hypertensive patients, implying the presence of mesenchymal progenitor cells in the peripheral blood that could possibly be intended to differentiate into cells of the cardiac series.¹² Interestingly, in the patients in that study, myocardin and GATA4 expression was associated with both blood pressure (BP) levels and left ventricular hypertrophy (LVH).To date, most published reports concerning the cardiovascular applications of stem cells have focused on their role in myocardial infarction and in heart failure. Very little work has been done on arterial hypertension, and most has concerned endothelial progenitor cells. The role and behavior of MSCs in patients with essential hypertension is unknown. In a recent animal study, it was shown that the degree to which angiotensin II increased neointima formation was statistically correlated with the increased incorporation of fluorescent bone marrow–derived smooth muscle cells, and that this was inhibited by angiotensin‐1 receptor antagonism.¹³ Based on the hypothesis that MSCs participate in pathophysiological processes that contribute to hypertension, and on the assumption that the behavior of MSCs is altered in hypertensive patients, we carried out the first flow cytometric analysis of CD45−/CD34−/CD90+ and CD45−/CD34−/CD105+ in the peripheral blood of those patients compared with healthy individuals.