Biomedical subjects

Christophe Delclaux

Publications and source records attributed to Christophe Delclaux.

At least 19 recordsLinked to original sources

PubMed2007

Decrease in lung nitric oxide production after peritonitis in mice with sickle cell disease.

OBJECTIVE: Nitric oxide bioavailability may limit the occurrence or severity of acute vaso-occlusive episodes in patients with sickle cell disease. Because sepsis is frequently involved in the initiation of vaso-occlusive crisis and acute chest syndrome, we designed the present study in transgenic (SAD) sickle cell mice to investigate whether acute infectious peritonitis affects the enzymatic balance (nitric oxide synthases/arginases) that governs lung nitric oxide production. DESIGN: Controlled animal study. SETTING: Research laboratory of an academic institution. SUBJECTS: Transgenic Hbbsingle/single SAD1 (SAD) mice and nontransgenic wild-type littermates (C57/Black mice, control group). INTERVENTIONS: Cecal ligation and puncture-induced peritonitis. MEASUREMENTS AND MAIN RESULTS: We found that 24 hrs after peritonitis, control littermate mice showed an increase in inducible and endothelial nitric oxide synthase messenger RNA and proteins, together with an increase in exhaled nitric oxide (shift of the balance toward nitric oxide synthesis). In contrast, SAD mice, which showed elevated inducible and endothelial nitric oxide synthase protein expression at baseline, showed a marked decrease in nitric oxide synthase proteins, lung nitric oxide end-products, and exhaled nitric oxide after peritonitis, reflecting a shift of the enzymatic balance toward inhibition of nitric oxide synthesis. Peritonitis increased messenger RNA levels of arginase I and arginase II in controls and SAD mice but with a greater increase in arginase I in SAD than in control mice. Peritonitis was associated with a higher mortality rate at 24 hrs in SAD mice. Inhalation of nitric oxide (40 ppm in air) abolished the mortality rate induced by acute peritonitis in SAD mice. CONCLUSIONS: Acute peritonitis in SAD mice is associated with a defect in lung nitric oxide production and bioavailability that may participate in the acute systemic and lung vaso-occlusive complications of sickle cell disease.

Anemia, Sickle Cell↗

PubMed2006

Relationship between pressure-volume curve and markers for collagen turn-over in early acute respiratory distress syndrome.

OBJECTIVE: In acute respiratory distress syndrome, the relationships between changes in the elastic behavior of the respiratory system and biological markers of extra-cellular matrix or surfactant turn-over could give some insights into its pathophysiological determinants. DESIGN AND MEASUREMENTS: In 17 patients with acute respiratory distress syndrome, we assessed the relationship between chord compliance measured on pressure-volume curves obtained at two levels of positive end-expiratory pressure (0 and 10[Symbol: see text]cm[Symbol: see text]H(2)O) and biological markers of collagen turn-over or surfactant degradation in bronchoalveolar lavage fluid obtained simultaneously in the early phase of the disease (first 4 days). MAIN RESULTS: The compliance of the respiratory system obtained from the pressure-volume curves was significantly correlated with markers for collagen turn-over (type III procollagen peptide and matrix metalloproteinase 2) and with markers of surfactant degradation (type-IIA secretory phospholipase A2). The correlations were stronger when the curve was traced from positive end-expiratory pressure, suggesting that this condition may improve the assessment of tissue mechanics. A logarithmic relationship best described the correlation between compliance and type III procollagen peptide, in agreement with a collagen-dependent model of maximal distension. The marker for surfactant degradation was associated with ongoing alveolar inflammation (cellularity of bronchoalveolar lavage fluid and tumor necrosis factor-alpha concentration). Interleukin-10, an anti-inflammatory mediator, showed no correlation with compliance. CONCLUSION: These preliminary data suggest that a severe reduction in compliance in the early phase of acute respiratory distress syndrome is associated with both collagen deposition and surfactant degradation.

Adult↗

PubMed2006

Impairment of nitric oxide output of conducting airways in primary ciliary dyskinesia.

Nasal nitric oxide (NO) concentration is dramatically reduced in primary ciliary dyskinesia (PCD). The aims of this study were to apply a multiple-flow NO analysis to investigate whether NO output from the bronchial tree was affected in a similar way to nasal NO output, and to search for a relationship between flow-independent exchange parameters and airflow limitation. Multiple flow rate analysis of exhaled NO, allowing the calculation of maximum airway wall flux and alveolar NO concentration, was performed in 17 PCD patients (median age, 25-75th percentiles: 13.5, 12.1-17.6) with documented ultrastructural cilia abnormalities and 28 healthy subjects (16.0, 11.0-21.0). Median maximum airway wall flux and median alveolar NO concentration were significantly reduced in PCD patients compared to healthy subjects: 16.0, 7.5-29.5, vs. 25.0, 15.0-32.5 nl/min (P<0.05) and 2.5, 1.6-3.3, vs. 5.0, 3.6-6.5 ppb (P<0.01), respectively. Significant correlations between maximum airway wall flux and airflow limitation were found, i.e., resistance of respiratory system (rho=0.74, P<0.005), forced expiratory volume in one second (FEV(1))/VC (rho= -0.61, P<0.05), FEV(1) (rho=-0.52, P< 0.05), mid expiratory flow between 25 and 75% of forced vital capacity (MEF(25-75)) (rho=-0.54, P<0.05), and maximal instantaneous expiratory flow at 50% of the vital capacity (MEF(50)) (rho=-0.55, P<0.05). In conclusion, the impairment of NO output is less pronounced in the lower than in the upper (nasal) respiratory tract in PCD. A decrease in maximal NO output from conducting airways is associated with limited airflow impairment.

Adolescent↗

PubMed2006

Ventilator-associated pneumonia leading to acute lung injury after trauma: importance of Haemophilus influenzae.

BACKGROUND: Ventilator-associated pneumonia is a clear risk factor for acute lung injury which has been poorly described in trauma patients. This prospective study was undertaken to estimate the incidence of such ventilator-associated pneumonia leading to acute lung injury, the risk factors, and the associated morbidity and mortality in a group of multiple trauma patients. METHODS: Trauma patients who were mechanically ventilated and survived at least 24 h were included. Ventilator-associated pneumonia was confirmed by a bacterial culture of a blind protected telescoping catheter with at least 10 colony-forming units/ml of at least one pathogen. Episodes of acute lung injury were prospectively recorded. RESULTS: Ventilator-associated pneumonia was documented in 78 patients of the 175 included (44%) and led to the development of ventilator-associated pneumonia acute lung injury in 18 patients (23%). The sole independent risk factor for ventilator-associated pneumonia leading to acute lung injury was the presence of Haemophilus influenzae (hazard ratio, 8.8; 95% confidence interval, 2.7-28.6). Eleven (61%) of the 18 patients with ventilator-associated pneumonia leading to acute lung injury had development of a ventilator-associated pneumonia recurrence, as compared with 20 (33%) of the 60 patients with ventilator-associated pneumonia alone (P = 0.03). Seven (39%) of the 18 trauma patients with ventilator-associated pneumonia leading to acute lung injury died, as compared with 9 (15%) of the 60 trauma patients with ventilator-associated pneumonia alone (P = 0.04). CONCLUSION: Acute lung injury complicated the course of 15% of ventilator-associated pneumonia in trauma patients. H. influenzae seemed to be one of the most frequent bacteria involved and the sole risk factor identified. Occurrence of ventilator-associated pneumonia leading to acute lung injury modified the prognosis of trauma patients.

Adult↗

PubMed2005

Validity criteria and comparison of analytical methods of flow-independent exhaled NO parameters.

The objective was to assess both validity and comparability of multiple constant (MCF, mainly performed) and dynamically changing (DCF, new method) flow analyses calculating alveolar concentration (Calv(NO)), maximum conducting airway flux (J'aw(NO)) and airway diffusing capacity (Daw(NO)) of exhaled NO (FE(NO)). (Calv(NO), J'aw(NO))(R) where R is the correlation coefficient of the linear regression between NO output and expiratory flow rate (MCF) and (Calv(NO), J'aw(NO), Daw(NO))(Delta100) where Delta100 is the ratio ([observed-predicted FE(NO)]/observed FE(NO)) at 100 ml/s (DCF) were assessed in 18 healthy subjects (10 atopic). MCF demonstrated a linear relationship (R > or = 0.80) between NO output and expiratory flow in 15/18 subjects. DCF was valid (Delta100 < or = 30%) in 12/18 subjects. A good agreement between MCF and DCF was evidenced in the nine subjects with R > or = 0.80 and Delta100 < or = 30%. Failure of validity criteria was mainly observed in atopic subjects. In conclusion, when validity criteria are satisfied, the new DCF method similarly characterizes NO exchange parameters than MCF approach.

Adult↗

PubMed2005

Blood neutrophil bactericidal activity against methicillin-resistant and methicillin-sensitive Staphylococcus aureus during cardiac surgery.

Whether methicillin-resistant Staphylococcus aureus (MRSA) constitutes per se an independent risk factor for morbidity and mortality after surgery as compared with methicillin-sensitive Staphylococcus aureus (MSSA) remains a subject of debate. The aim of this study was to assess whether innate defenses against MRSA and MSSA strains are similarly impaired after cardiac surgery. Both intracellular (isolated neutrophil functions) and extracellular (plasma) defenses of 12 patients undergoing scheduled cardiac surgery were evaluated preoperatively (day 0) and postoperatively (day 3) against two MSSA strains with a low level of catalase secretion and two MRSA strains with a high level of catalase secretion, inasmuch as SA killing by neutrophils relies on oxygen-dependent mechanisms. After surgery, an increase in plasma concentration of IL-10, an anti-inflammatory cytokine able to inhibit reactive oxygen species secretion and bactericidal activity of neutrophils, was evidenced. Despite the fact that univariate analysis suggested a specific impairment of neutrophil functions against MRSA strains, two-way repeated-measures ANOVA failed to demonstrate that the effect of S. aureus phenotype was significant. On the other hand, an increase in type-II secretory phospholipase A2 activity, a circulating enzyme involved in SA lysis, was evidenced and was associated with an enhancement of extracellular defenses (bactericidal activity of plasma) against MRSA. Overall, cardiac surgery and S. aureus phenotype had a significant effect on plasma bactericidal activity. Cardiac surgery was characterized by enhanced antibacterial defenses of plasma, whereas neutrophil killing properties were reduced. The overall effect of S. aureus phenotype on neutrophil functions did not seem significant.

Aged↗

PubMed2005

Alveolar nitric oxide and effect of deep inspiration during methacholine challenge.

STUDY OBJECTIVES: To assess whether the dual anatomic origin of exhaled nitric oxide (NO), namely alveolar and bronchial, could explain the link between exhaled NO and airway responsiveness, and could participate in the bronchodilatory effect of deep inspiration (DI) that may be evidenced during methacholine challenge. DESIGN AND SETTING: Prospective study in a laboratory performing pulmonary function tests of an academic hospital. PATIENTS AND INTERVENTIONS: Patients underwent multiple flow analysis of exhaled NO, allowing calculation of total maximum airway NO flux (J'awno) and NO concentration of expansible compartment (CAno), and received a cumulative methacholine dose of 2,000 microg. DI effect was assessed by continuous measurement of the resistance of respiratory system using the forced oscillation technique before and after DI. RESULTS: In a first phase involving 23 patients, a positive correlation between log values of J'awno and CAno was demonstrated with the degree of airway responsiveness (percentage of FEV(1) decrease). In a second phase involving 38 patients, only log CAno was correlated with responsiveness, and no significant relationship was demonstrated between J'awno or CAno and the effect of DI. Patients with smaller airways and/or distal airflow limitation exhibited a constrictive response to DI. CONCLUSION: Airway responsiveness is mainly associated with an increase in distal origin of NO output, and no relationship between exhaled NO and the effect of DI was evidenced.

Adult↗

PubMed2005

Factors associated with dyspnea in adult patients with sickle cell disease.

OBJECTIVE: The aim of this prospective study was to determine the cardiorespiratory factors associated with dyspnea in patients with sickle cell SS-hemoglobin disease, with a specific interest in lung vascular involvement. MEASUREMENTS: Forty-nine patients (29 women and 20 men; mean [+/- SD] age: women, 29 +/- 6 years; men, 31 +/- 11 years) underwent direct evaluations (Borg scale evaluation during a 6-min walk test) and indirect evaluations (modified Medical Research Council [MRC]score) of their dyspnea, pulmonary function tests (PFTs) [spirometry, volumes, diffusing capacity of the lung for carbon monoxide (Dlco), diffusing capacity of the alveolar-capillary membrane, and pulmonary capillary blood volume measurements], echocardiography, and biological evaluation. RESULTS: Thirty-four patients complained of significant breathlessness (MRC score, > 1). Indirect and direct evaluations of dyspnea were correlated. PFT results depicted a very mild restrictive pattern (mean total pulmonary capacity, 86 +/- 11% predicted) and an impairment of Dlco (mean Dlco corrected for the degree of anemia, 69 +/- 13% predicted). The statistical analysis demonstrated that dyspnea and exercise performance were closely linked to indexes of Dlco but not with any echocardiographic or biological measure including anemia. Nevertheless, only approximately 25% of the variability was explained by these associations. Despite having a similar history of vasoocclusive crisis events, women had more severe anemia, dyspnea, decreases in Dlco (corrected for the degree of anemia), and a higher capillary blood volume (corrected for alveolar volume) than men. CONCLUSION: Lung vascular disease contributes to dyspnea and the exercise limitation of patients with sickle cell disease. A sequential assessment of Dlco would therefore constitute one of the objective functional end points for follow-up studies of these patients.

Adult↗

PubMed2004

Inspiratory flow in the nose: a model coupling flow and vasoerectile tissue distensibility.

We have developed a discrete multisegmental model describing the coupling between inspiratory flow and nasal wall distensibility. This model is composed of 14 individualized compliant elements, each with its own relationship between cross-sectional area and transmural pressure. Conceptually, this model is based on flow limitation induced by the narrowing of duct due to collapsing pressure. For a given inspiratory pressure and for a given compliance distribution, this model predicts the area profile and inspiratory flow. Acoustic rhinometry and posterior rhinomanometry were used to determine the initial geometric area and mechanical characteristics of each element. The proposed model, used under steady-state conditions, is able to simulate the pressure-flow relationship observed in vivo under normal conditions (4 subjects) and under pathological conditions (4 vasomotor rhinitis and 3 valve syndrome subjects). Our results suggest that nasal wall compliance is an essential parameter to understand the nasal inspiratory flow limitation phenomenon and the associated increase of resistance that is well known to physiologists. By predicting the functional pressure-flow relationship, this model could be a useful tool for the clinician to evaluate the potential effects of treatments.

Adult↗

PubMed2004

High bactericidal efficiency of type iia phospholipase A2 against Bacillus anthracis and inhibition of its secretion by the lethal toxin.

There is a considerable body of evidence supporting the role of secretory type II-A phospholipase A(2) (sPLA(2)-IIA) as an effector of the innate immune response. This enzyme also exhibits bactericidal activity especially toward Gram-positive bacteria. In this study we examined the ability of sPLA(2)-IIA to kill Bacillus anthracis, the etiological agent of anthrax. Our results show that both germinated B. anthracis spores and encapsulated bacilli were sensitive to the bactericidal activity of recombinant sPLA(2)-IIA in vitro. In contrast, nongerminated spores were resistant. This bactericidal effect was correlated to the ability of sPLA(2)-IIA to hydrolyze bacterial membrane phospholipids. Guinea pig alveolar macrophages, the major source of sPLA(2)-IIA in an experimental model of acute lung injury, released enough sPLA(2)-IIA to kill extracellular B. anthracis. The production of sPLA(2)-IIA was significantly inhibited by B. anthracis lethal toxin. Human bronchoalveolar lavage fluids from acute respiratory distress syndrome patients are known to contain sPLA(2)-IIA; bactericidal activity against B. anthracis was detected in a high percentage of these samples. This anthracidal activity was correlated to the levels of sPLA(2)-IIA and was abolished by an sPLA(2)-IIA inhibitor. These results suggest that sPLA(2)-IIA may play a role in innate host defense against B. anthracis infection and that lethal toxin may help the bacteria to escape from the bactericidal action of sPLA(2)-IIA by inhibiting the production of this enzyme.

Animals↗

PubMed2004

Decreased exhaled nitric oxide as a marker of postinsult immune paralysis.

Nitric oxide (NO) regulates neutrophil migration and alveolar macrophage functions such as cytokine synthesis and bacterial killing, both of which are impaired in immune paralysis associated with critical illness. The aim of this study was to determine whether NO is involved in immune paralysis and whether exhaled NO measurement could help to monitor pulmonary defenses. NO production (protein expression, enzyme activity, end products, and exhaled NO measurements) was assessed in rats after cecal ligation and puncture to induce a mild peritonitis (leading to approximately 20% mortality rate). An early and sustained decrease in exhaled NO was found after peritonitis (from 1 to 72 h) compared with healthy rats [median (25th-75th percentile), 1.5 parts per billion (ppb) (1.2-1.7) vs. 4.0 ppb (3.6-4.3), P < 0.05], despite increased NO synthase-2 and unchanged NO synthase-3 protein expression in lung tissue. NO synthase-2 activity was decreased in lung tissue. Nitrites and nitrates in supernatants of isolated alveolar macrophages decreased after peritonitis compared with healthy rats, and an inhibitory experiment suggested arginase overactivity in alveolar macrophages bypassing the NO substrate. Administration of the NO synthase-2 inhibitor aminoguanidine to healthy animals reproduced the decreased neutrophil migration toward alveolar spaces that was observed after peritonitis, but L-arginine administration after peritonitis failed to correct the defect of neutrophil emigration despite increasing exhaled NO compared with D-arginine administration [4.8 (3.9-5.7) vs. 1.6 (1.3-1.7) ppb, respectively, P < 0.05]. In conclusion, the decrease in exhaled NO observed after mild peritonitis could serve as a marker for lung immunodepression.

Animals↗

PubMed2004

Both inflammation and remodeling influence nitric oxide output in children with refractory asthma.

BACKGROUND: Exhaled nitric oxide can be used to monitor airway inflammation in asthma. We hypothesized that the strong link between nitric oxide and inflammation may obscure a weaker link with airway remodeling. OBJECTIVE: The aim of this study was to determine whether airway remodeling influenced exhaled nitric oxide in 28 asthmatic children (median age [25th-75th], 11 [10-14] years old) with refractory asthma defined as airflow limitation and/or exacerbations despite high-dose inhaled steroids. METHODS: Multiple-flow analysis of exhaled nitric oxide was used to correlate alveolar nitric oxide concentration and maximal conducting airway nitric oxide output to pulmonary function tests, bronchoalveolar lavage, and bronchial biopsy findings. RESULTS: Nitric oxide measurements were related to inflammation and T(H)1/T(H)2 balance, that is, subepithelial eosinophilic infiltration and eosinophilic cationic protein and IFN-gamma/IL-4 ratio in bronchoalveolar lavage fluids. Nitric oxide measurements were also correlated with several parameters of airway remodeling: alveolar nitric oxide concentration with TGF-beta in bronchoalveolar lavage fluid (r = 0.42, P =.03) and maximal conducting airway nitric oxide output with reticular basement membrane thickness (r = 0.61, P =.0007) and tissue inhibitor of matrix metalloproteinases 1/matrix metalloproteinase 9 ratio in bronchoalveolar lavage fluid (r = 0.43, P =.04). Moreover, alveolar nitric oxide concentration was correlated with MEF(25-75) (r = 0.60, P =.02). CONCLUSIONS: These findings suggest that both subacute inflammation and remodeling influence nitric oxide output in refractory asthma.

Adolescent↗

PubMed2004

Adenovirus-mediated fibroblast growth factor 1 expression in the lung induces epithelial cell proliferation: consequences to hyperoxic lung injury in rats.

High concentrations of oxygen can induce pulmonary toxicity and cause injury to alveolar epithelial and endothelial cells. The present study was performed to determine whether the potent epithelial and endothelial fibroblast growth factor 1 (FGF-1) protected against hyperoxia-induced lung injury. Recombinant adenovirus carrying the gene encoding human secreted FGF-1 (Ad. FGF1) increased the proliferation of lung epithelial cells in vitro. Ad.FGF1 or control vector with an empty expression cassette (Ad.V152) was administered intratracheally to Wistar rats. With Ad.FGF1 (10(9), 5 x 10(9), 10(10), or 5 x 10(10) viral particles [VP]), FGF-1 protein was found in bronchoalveolar lavage fluid 4 days postinfection at levels proportional to the viral dose and was detected in plasma after doses of 10(10) VP or more were administered. Histological examination of the lungs showed intense proliferation and apoptosis of alveolar and bronchial epithelial cells, with few inflammatory cells. The alveolar architecture returned to normal within 17 days. Rats pretreated with Ad.FGF1 (10(9) or 5 x 10(9) VP) 2 days before exposure to hyperoxia (95% O2) survived, whereas rats pretreated with Ad.V152 died within 3 days. In conclusion, adenovirus-mediated FGF-1 overexpression in the lungs causes epithelial cell proliferation and has beneficial effects in hyperoxic lung injury.

Adenoviridae↗

PubMed2004

Beneficial effect of an inhibitor of leukocyte elastase (EPI-hNE-4) in presence of repeated lung injuries.

Persistence of alveolar neutrophil influx and activation may enhance the fibrotic process after acute lung injury. On the other hand, elastase has an antimicrobial activity and could participate in neutrophil migration, both events being critically important in host defense, explaining the controversial issue of therapeutic elastase inhibition in the setting of acute lung injury. We assessed the effect of a neutrophil elastase inhibitor, EPI-hNE-4, in single (bleomycin, 1.2 mg/rat intratracheally) and repeated (bleomycin, 1.2 mg/rat plus endotoxin and 1 mg/kg intratracheally 24 h later) lung injuries to assess the role of neutrophil in fibrosis. Subsequently, the effect of EPI-hNE-4 on bacterial clearance was evaluated during Pseudomonas aeruginosa-induced pneumonia. In the single injury model, despite a dramatic reduction of alveolar neutrophil influx with EPI-hNE-4 treatment, no significant inhibition of the decrease in respiratory system compliance, an index of lung fibrosis, was demonstrated at day 14. In the repeated injury model, EPI-hNE-4 treatment afforded a significant protective effect on compliance and alveolar inflammation at day 14. During bacterial pneumonia, EPI-hNE4 did not modify alveolar neutrophil recruitment or bacterial clearance from bronchoalveolar lavage fluid and lung homogenate. In conclusion, EPI-hNE-4, a specific inhibitor of leukocyte elastase, afforded a partial protective effect on the respiratory system compliance during repeated lung injuries, and had no detrimental effect during a gram-negative bacterial pneumonia.

Animals↗

PubMed2004

Increase in alveolar nitric oxide in the presence of symptoms in childhood asthma.

STUDY OBJECTIVES: To determine respective contributions of alveolar and proximal airway compartments in exhaled nitric oxide (NO) output (QNO) in pediatric patients with asthma and to correlate their variations with mild symptoms or bronchial obstruction. PATIENTS AND DESIGN: In 15 asthmatic children with recent mild symptoms, 30 asymptomatic asthmatic children, and 15 healthy children, exhaled NO concentration was measured at multiple expiratory flow (V) rates allowing the calculation of alveolar and proximal airway contributions in QNO, using two approaches, ie, linear and nonlinear models. MEASUREMENTS AND RESULTS: Asymptomatic and recently symptomatic patients were not significantly different regarding FEV(1) and maximum V between 25% and 75% of FVC (MEF(25-75)): FEV(1), 93.3 +/- 13.4% vs 90 +/- 7.5%; MEF(25-75), 70 +/- 22% vs 68 +/- 28% of predicted values, respectively (mean +/- SD). Maximal airway QNO output was significantly higher in recently symptomatic vs asymptomatic patients (p < 0.0001), and in asymptomatic patients vs healthy children (p < 0.02): 134 +/- 7 nl/min, 55 +/- 43 nl/min, and 19 +/- 8 nl/min, respectively. In a multiple regression analysis, variables that influenced airway QNO output were symptoms (p < 0.0001) and distal airway obstruction as assessed by MEF(25-75) (p < 0.05). Alveolar NO concentration (FANO) was significantly (p < 0.03) higher in recently symptomatic than in patients without symptoms, whereas it was not significantly different between asymptomatic patients and healthy children: 7.2 +/- 2.4 parts per billion (ppb), 5.5 +/- 2.7 ppb, and 4.2 +/- 2.0 ppb, respectively. CONCLUSIONS: An increase in FANO was observed in the presence of symptoms, and proximal airway NO output was correlated with distal obstruction during asthma.

Asthma↗

PubMed2003

Is there a place for granulocyte colony-stimulating factor in non-neutropenic critically ill patients?

Immunoparalysis, characterised by impairments in neutrophil and monocyte/macrophage function, is common in critically ill patients. The theoretical ability of granulocyte colony-stimulating factor (G-CSF) to improve the functions of both neutrophils and monocytes/macrophages provides a rationale for G-CSF therapy in non-neutropenic critically ill patients with infection or a high risk of nosocomial infection. The expression of the receptors that mediate G-CSF effects in neutrophils and monocytes/macrophages is regulated by bacterial products, cytokines and endogenous G-CSF levels, accounting for the variables effects of G-CSF on the neutrophil functions of critically ill patients. This variability should be taken into account when designing studies on the use of G-CSF in ICU-patients. Studies are still needed to identify the subset of patients who may benefit from G-CSF therapy.

Adjuvants, Immunologic↗

PubMed2003

Effect of partial liquid ventilation on bacterial clearance during Pseudomonas aeruginosa-induced lung injury in rats.

OBJECTIVE: Partial liquid ventilation (PLV) has been shown to exhibit anti-inflammatory properties during non-infectious models of acute lung injury. The aim of this experimental study was to assess the effects of PLV on bacterial clearance during Pseudomonas aeruginosa-induced pneumonia in rats. DESIGN: The rats were assigned to four groups 4 h after bacterial challenge according to the kind of mechanical ventilation [gas ventilation (GV) or PLV, 6 ml/kg perflubron plus 2 ml/kg per h] and to the level of PEEP used (3 or 8 cm of water). Physiologic measures were recorded during anesthesia (arterial blood gases, airway and blood pressures) for 4 subsequent hours until sacrifice. RESULTS: No improvement of oxygenation was demonstrated in any group. The bacterial counts were higher in PLV-PEEP 8 rats compared to GV-PEEP 8 rats: median, 1.7.10(4) cfu (25th-75th percentiles, 1.2.10(4)-1.8.10(4)) versus 1.1.10(4) (8.7.10(3)-1.3.10(4))/ml of BAL fluid and 4.0.10(6) cfu (2.0.10(6)-5.5.10(6)) versus 1.7.10(6) cfu (9.7.10(5)-3.2.10(6))/ml of lung homogenate, respectively ( P<0.05, n=8/10 surviving rats per group). PEEP 8 was associated with a significant decrease in neutrophil recruitment in BAL fluid compared to PEEP 3 in both GV and PLV groups. Additional in vitro experiments demonstrated that perflubron induced a decrease in phagocytosis of P. aeruginosa by alveolar neutrophils. CONCLUSIONS: These results demonstrate that PLV is associated with an impaired bacterial clearance during early pneumonia in rats, which could have been favored by decreased bacterial phagocytosis by neutrophils.

Animals↗

PubMed2003

Efficacy and cost of home-initiated auto-nCPAP versus conventional nCPAP.

STUDY OBJECTIVES: To compare in a multicenter prospective study the efficacy and cost of conventional nasal continuous positive airway pressure (nCPAP) initiated at the sleep laboratory versus auto-nCPAP initiated at home. DESIGN: Patients with severe obstructive sleep apnea syndrome (OSAS) were randomized to treatment with either the REM+ auto device in constant mode at the effective pressure determined by titration at the sleep laboratory (n=17) or the REM+ auto device in automatic mode initiated at the patients home by a nurse (n=18). After 2 months, the efficacy and cost of nCPAP therapy and the time from diagnosis to nCPAP were evaluated. All values are reported as means +/- SD. PATIENTS: Thirty-five subjects with newly diagnosed OSAS (8 women and 27 men, mean age: 54.3 +/- 10.6 years, apnea-hypopnea index (AHI) 58.1 +/- 14.0 h(-1)). INTERVENTIONS: N/A. MEASUREMENTS AND RESULTS: Both treatments were used properly and induced similar decreases in the AHI (7.6 +/- 6.9 vs. 10.4 +/ -12.5 h(-1) for auto-nCPAP and conventional nCPAP, respectively; NS) and Epworth Sleepiness score (from 15.5 +/- 4.7 to 7.5 +/- 3.4 vs. 14.7 +/- 3.9 to 7.6 +/- 3.4 for auto-nCPAP and conventional nCPAP, respectively; NS). With auto-nCPAP initiated at home, the time from diagnosis to final adjustment of nCPAP was shorter (16.3 +/- 5.0 vs. 47.2 +/- 46.5 days with conventional nCPAP, P < 0.02) and the cost was lower (1,263 +/- 352 vs. 1720+/-455 E, respectively; P < 0.05). CONCLUSIONS: Treatment of OSAS with auto-nCPAP initiated at home is effective and reliable and reduces the time from diagnosis to therapy and the cost of treatment.

Body Mass Index↗