Individual modeling of oxygen capture by the human lungs.

It has been proposed that oxygen capture by the human lungs depends on four determinants: ventilation, cardiac output, oxygen partial pressure in the inspired air and the venous blood. Indeed, the theoretical-numerical model proposed recently by Kang et al. was able to interpret the known empirical relation between the average of the determinants and the average oxygen capture called VO2. This method is tested here at the individual level in a group of 31 subjects submitted to standard pulmonary function testing and cardiopulmonary exercise testing. For this, an inverse method is used in which individual cardiac output is predicted from the clinical test data. Comparison to the cardiac output deduced from Fick principle confirms that the dynamic model is a "microscopic" justification of the "macroscopic" Fick principle. It shows that in addition to the four determinants, two secondary determinants, namely hemoglobin concentration and Bohr effect, expressed here through P50, play significant roles.

[Study about the prevalence of the obstructive sleep apnoea syndrome in Vietnam]. / Étude de la prévalence du syndrome d'apnées obstructives du sommeil au Vietnam.

INTRODUCTION: Epidemiological studies on obstructive sleep apnoea syndrome (OSAS) in Asia, South East Asia in particular, are few. The EPSASIE study aimed to determine the prevalence of OSAS in an adult Vietnamese population and to describe its characteristics. METHODS: This is a prospective, observational, multicenter study. Nocturnal ventilatory polygraphy (PV) or polysomnography (PSG) were performed in patients having symptoms evocative of the SAS syndrome and an index of respiratory events (IER)>10/h or>25 in one hour, measured by RU Sleeping. RESULTS: A total of 667/750 validated questionnaires were received. The mean age of the study population was 44±12 years with a mean body mass index of 21.6±5.2kg/m2. PV or PSG were performed on 93 subjects after positive screening by RU Sleeping. OSAS with an apnoea-hypopnoea index (AHI)>5 was found in 57 subjects (8.5%) and in 35 subjects with AHI>15 (5.2% of cases). CONCLUSION: The prevalence of OSAS is quite high in the Vietnamese population and comparable with current literature data.

Effects of growth and aging on the reference values of pulmonary nitric oxide dynamics in healthy subjects.

The lung just like all other organs is affected by age. The lung matures by the age of 20 and age-related changes start around middle age, at 40-50 years. Exhaled nitric oxide (FENO) has been shown to be age, height and gender dependent. We hypothesize that the nitric oxide (NO) parameters alveolar NO (CANO), airway flux (JawNO), airway diffusing capacity (DawNO) and airway wall content (CawNO) will also demonstrate this dependence. Data from healthy subjects were gathered by the current authors from their earlier publications in which healthy individuals were included as control subjects. Healthy subjects (n = 433) ranged in age from 7 to 78 years. Age-stratified reference values of the NO parameters were significantly different. Gender differences were only observed in the 20-49 age group. The results from the multiple regression models in subjects older than 20 years revealed that age, height and gender interaction together explained 6% of variation in FENO at 50 ml s-1 (FENO50), 4% in JawNO, 16% in CawNO, 8% in DawNO and 12% in CANO. In conclusion, in this study we have generated reference values for NO parameters from an extended NO analysis of healthy subjects. This is important in order to be able to use these parameters in clinical practice.

Cellular and molecular mechanisms in the pathophysiology of systemic sclerosis.

Fibrosis is characterized by disproportionate accumulation of collagens and other extracellular matrix substances, resulting in organ dysfunction and failure. In systemic sclerosis, cellular and molecular mechanisms involved in the pathophysiology of fibrosis are highly complex and yet barely understood. Anatomopathological findings showed the coexistence of patchy inflammatory cell infiltration, microvascular injuries, and fibrotic foci. One of the most commonly accepted hypotheses considers endothelial activation as the triggering phenomenon inducing inflammatory and autoimmunity activation. The resulting cytokines and autoantibodies production accelerates the proliferating rate of normal fibroblasts and their transformation into myofibroblasts, leading to diffuse fibrosis. This review aims to focus on cellular and molecular mechanisms implicated in the fibrogenesis of systemic sclerosis.

[Use of pulmonary function tests and biomarkers studies to diagnose and follow-up interstitial lung disease in systemic sclerosis]. / Intérêts des explorations fonctionnelles respiratoires et des études des biomarqueurs dans le diagnostic et le suivi évolutif de la pneumopathie interstitielle diffuse dans la sclérodermie systémique.

Interstitial lung disease (ILD) is becoming one of the main causes of death of patients with systemic sclerosis (SSc). The prevalence of ILD associated with SSc (SSc-ILD) varies from 33% to 100% according to diagnostic methods. Clinical features such as dyspnea on exertion, dry cough, and chest pains are not specific and usually late-appearing, implying more specific tests in the diagnostic, prognosis, and follow-up of ILD in patients with SSc. High resolution thoracic CT scanner (HRCT) is more sensitive than chest X-ray in the detection of SSc-ILD. Pulmonary function tests (PFT) are non-invasive and periodically used to assess the impacts of SSc on respiratory function. Diagnostic values of bronchoalveolar lavage and histological examination on lung biopsy are controversial. However, these techniques are essential for studying cellular and molecular mechanisms underlying the pathophysiology of SSc-ILD. Several biomarkers such as surfactant-A (SP-A), -D (SP-D), mucin-like high molecular weight glycoprotein (KL-6), and chemokine CCL-18 have been implicated in SSc-PID. Serum levels of these proteins are correlated with the severity of SSc-ILD, as assessed by HRCT and/or PFT. Finally, alveolar concentration of exhaled nitric oxide can be used to screen SSc patients with high risk of deterioration of respiratory function, in whom immunosuppressant treatment could be useful in preventing the evolution to irreversible lung fibrosis.

Early inhaled nitric oxide at high dose enhances rat lung development after birth.

RATIONAL: Inhaled nitric oxide (NO) is frequently administered to full term and preterm newborns in various clinical settings in order to alleviate pulmonary hypertension whilst improving oxygenation. However, the physiological effect of NO on early postnatal lung development has not yet been clearly described. We therefore investigated whether NO administered by inhalation affects lung development at early postnatal life. METHODS: Pregnant rats were placed in a chamber containing 5 ppm (iNO-5 ppm group) and 20 ppm NO (iNO-20 ppm group), started from the last day of their pregnancy in order to keep rat pups under ambient NO from birth to 7 days postnatal. Control animals were kept at room air and all rat pups were sacrificed at postnatal day 7 and day 14. RESULTS: Lung-to-body weight and wet-to-dry lung weight ratios did not significantly differ among 3 groups at postnatal day 7 and day 14. Vascular volume densities (Vv) in both NO groups (5 and 20 ppm) were higher than controls (P<0.05; P<0.001). Pulmonary vessel number was significantly increased in iNO-20 ppm group. Radial alveolar counts (RAC) and mean linear intercepts (MLI) markedly increased (consistent with increased alveolarization) in iNO-20 ppm group. This was associated with upregulation of VEGF/VEGFR-2, MT1-MMP/MMP2 and HO-1 protein expression in iNO-20 ppm group. CONCLUSIONS: We concluded that inhaled NO at 20 ppm enhanced lung development possibly through increased expression of HO-1, VEGF/VEGFR-2, and MMP2 at early stage of postnatal rat life.

[Pulmonary hypertension: from molecular pathophysiology to haemodynamic abnormalities]. / Hypertension pulmonaire: de la physiopathologie moléculaire aux anomalies hémodynamiques.

Pulmonary hypertension (PH) is a complex disorder resulting from many etiologies that cause disturbances of normal pulmonary haemodynamics. Recent breakthroughs have led to a better understanding of the pathophysiology of the disease. In PH, haemodynamic disturbances are closely linked to structural changes and excessive remodeling of pulmonary vessels, leading to progressive narrowing of the pulmonary vascular lumen. Imbalances between pulmonary vasoconstrictors and vasodilators on the one hand, and factors favoring cell proliferation and apoptosis on the other hand, probably account for most cases of PH. This review aims to update readers with the current knowledge on the molecular physiopathology of PH and how this can progress the therapeutic of this disorder.

Serum CC chemokine ligand-18 predicts lung disease worsening in systemic sclerosis.

Elevated serum CC chemokine ligand (CCL)18 reflects lung fibrosis activity in systemic sclerosis (SSc) and could be an early marker of lung function worsening. Therefore, we sought to evaluate whether serum CCL18 levels at baseline could predict worsening of lung disease in SSc. In this prospective study, 83 SSc patients were analysed longitudinally over a 4-yr observation period for the risk of occurrence of combined deleterious events, defined as a 10% decrease from baseline of total lung capacity or forced vital capacity % predicted, or death, according to serum CCL18 at inclusion. Receiver operating characteristic (ROC) curve analysis was performed for prediction of events during the first year after inclusion. The best cut-off level of serum CCL18 for prediction of a combined event within the follow-up period was 187 ng · mL(-1), with 53% sensitivity and 96% specificity (area under the ROC curve 0.86; p < 0.001). After a mean ± SD follow-up of 33.7 ± 10.8 months, a higher rate of disease progression occurred in the group with serum CCL18 levels >187 ng · mL(-1). The adjusted hazard ratio was 5.36 (95% CI 2.44-11.75; p < 0.001). In summary, serum CCL18 is an accurate predictive biomarker for the identification of patients with a higher risk of subsequent scleroderma lung disease worsening.

Increased Rho-kinase expression and activity and pulmonary endothelial dysfunction in smokers with normal lung function.

Endothelial dysfunction is one of the main consequences of the toxic effects of cigarette smoke on the vascular system. Increasing evidence suggests that the small G-protein RhoA and its downstream effectors, the Rho-kinases (ROCKs), are involved in systemic endothelial dysfunction induced by cigarette smoke. This study aimed to evaluate the role of the RhoA/ROCKs pathway in pulmonary artery endothelial function in current smokers with normal lung function. Lung tissues were obtained from nonsmokers and smokers who underwent lobectomy for lung carcinoma. Arterial relaxation in response to acetylcholine (ACh) was assessed in isolated pulmonary arterial rings. Protein expressions and activities of endothelial nitric oxide synthase (eNOS), ROCKs and the myosin phosphatase subunit 1 (MYPT-1) were sought. Relaxation in response to ACh was significantly lower in smokers as compared with nonsmokers (n = 8 in each group), consistent with reduced eNOS activity in the former compared with the latter. eNOS protein expression remained, however, the same in both groups. Expression of ROCKs, guanosine triphosphate-RhoA and phosphorylated MYPT-1 were significantly increased in smokers compared with controls. Pulmonary endothelial dysfunction is present in smokers whose lung function has not yet been impaired. Reduced activity of eNOS accounts at least in part for this endothelial dysfunction. Increased expression and activity of ROCKs accounts for another part through direct or indirect inhibition of the Rho-A/ROCKs pathway on nitric oxide synthesis and sustained pulmonary vasoconstriction through inhibition of myosin phosphatase.

[Early detection of smoking related chronic obstructive pulmonary disease in Vietnam]. / Détection précoce de la bronchopneumopathie chronique obstructive post-tabagique au Viet Nam.

INTRODUCTION: Epidemiological studies of chronic obstructive pulmonary disease (COPD) are rare in the developing countries, particularly in Viet Nam where the consumption of tobacco continues to increase. The aim of this study was to evaluate the feasibility of early screening of smokers for bronchial obstruction using the Piko-6 apparatus. MATERIALS AND METHODS: Smokers over 40 years of age who had smoked for more than 10 years were included. The subjects were classified into 3 groups according to the degree of bronchial obstruction measured by the Piko-6. (group 1: FEV1/FEV6>0.8; group 2: 0.7-0.8; group 3:<0.7). The smokers in group 3 and a sample of the smokers in groups 1 and 2 were recalled for full spirometric assessment. RESULTS: 2397 smokers were included, comprising 2130 active smokers and 267 ex-smokers. The mean age was 52 +/- 13 years. The mean smoking history was 24 +/- 13 pack years. 267 smokers from the 3 groups responded to the recall for full investigation. The prevalence of COPD detected by the Piko-6 in the study population was 13.5%. For the threshold FEV1/FEV6<0.7 and with the detected prevalence, the Piko-6 had a sensitivity of 97.8%, a specificity of 93.8%, a positive predictive value of 71% and a negative predictive value of 99.6% (confidence interval 95%). CONCLUSIONS: The Piko-6 is a useful tool for the early screening for COPD in smokers in a developing country where the prevalence of this disease appears to be under estimated.