Is atopy a risk indicator of chronic obstructive pulmonary disease in dairy farmers?

Allergic mechanisms related to environmental and occupational exposure have been suggested to contribute to the development of chronic obstructive pulmonary disease (COPD). OBJECTIVES: To investigate the relationships between atopy markers, persistent airflow limitation (PAL) and occupational exposure in dairy farmers. METHODS: Clinical and biological (total IgE and 21 allergen specific IgE) markers of atopy were assessed in 101 dairy farmers with PAL (DF-PAL), 85 non-farmers with PAL (NF-PAL) (both groups were prospectively included from a screening program performed between 2011 and 2015), and matched controls, i.e. 98 farmers without PAL (DF-controls) and 89 non-farming subjects without PAL (NF-controls). Occupational exposure in farmers was estimated using a validated questionnaire. RESULTS: Prevalence of allergy history was significantly higher in DF-PAL and in NF-PAL than in controls. Polysensitization, and sensitization to seasonal and food allergens were more frequent in DF-PAL than in DF-controls, respectively: 13.8% vs 1% (adjusted odds ratio (aOR): 17.5 (2.2-134), 11.9% vs 3.1% (aOR: 4.4 (1.2-7.2) and 16.8% vs 4.1% (aOR: 5.2 (1.7-7.2)). The prevalence of atopy markers was similar between NF-PAL patients and NF-controls. CONCLUSIONS: PAL in farmers is associated with a high rate of markers of atopy, supporting atopy as a risk indicator. Clinical trial registered with ClinicalTrials.gov (NCT02540408).

Circulating levels of 3-hydroxymyristate, a direct quantification of endotoxaemia in noninfected cirrhotic patients.

BACKGROUND & AIMS: The quantification of lipopolysaccharide (LPS) in biological fluids is challenging. We aimed to measure plasma LPS concentration using a new method of direct quantification of 3-hydroxymyristate (3-HM), a lipid component of LPS, and to evaluate correlations between 3-HM and markers of liver function, endothelial activation, portal hypertension and enterocyte damage. METHODS: Plasma from 90 noninfected cirrhotic patients (30 Child-Pugh [CP]-A, 30 CP-B, 30 CP-C) was prospectively collected. The concentration of 3-HM was determined by high-performance liquid chromatography coupled with mass spectrometry. RESULTS: 3-HM levels were higher in CP-C patients (CP-A/CP-B/CP-C: 68/70/103 ng/mL, P = 0.005). Patients with severe acute alcoholic hepatitis (n = 16; 113 vs 74 ng/mL, P = 0.012), diabetic patients (n = 22; 99 vs 70 ng/mL, P = 0.028) and those not receiving beta blockers (n = 44; 98 vs 72 ng/mL, P = 0.034) had higher levels of 3-HM. We observed a trend towards higher baseline levels of 3-HM in patients with hepatic encephalopathy (n = 7; 144 vs 76 ng/mL, P = 0.45) or SIRS (n = 10; 106 vs 75 ng/mL, P = 0.114). In multivariate analysis, high levels of 3-HM were associated with CP (OR = 4.39; 95%CI = 1.79-10.76) or MELD (OR = 8.24; 95%CI = 3.19-21.32) scores. Patients dying from liver insufficiency (n = 6) during a 12-month follow-up had higher baseline levels of 3-HM (106 vs 75 ng/mL, P = 0.089). CONCLUSIONS: In noninfected cirrhotic patients, 3-HM arises more frequently with impairment of liver function, heavy alcohol consumption, diabetic status, nonuse of beta blockers and a trend towards poorer outcome is also observed. The direct mass measurement of LPS using 3-HM appears reliable to detect transient endotoxaemia and promising to manage the follow-up of cirrhotic patients.

Enterocyte damage in critically ill patients is associated with shock condition and 28-day mortality.

OBJECTIVES: Small bowel dysfunction in critically ill patients is frequent, underdiagnosed, and associated with poor prognosis. Intestinal fatty acid-binding protein is a marker of enterocyte damage, and plasma citrulline concentration is a marker of functional enterocyte mass. Primary objective was to identify factors associated with intestinal fatty acid-binding protein in critically ill patients. Secondary objectives were to study factors associated with plasma citrulline concentration and its correlation with intestinal fatty acid-binding protein. DESIGN: Prospective observational study. SETTING: ICU in a University Hospital PATIENTS: Critically ill patients 18 years old or older with an expected length of ICU stay 48 hours or more, without pregnancy, chronic small bowel disease, or chronic renal failure. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Plasma intestinal fatty acid-binding protein and citrulline concentrations, and variables relating to prognosis and treatment, were measured at admission to the ICU. One hundred and three patients were included. Intestinal fatty acid-binding protein elevation at admission to the ICU was associated with catecholamine support, higher lactate concentration, higher Sequential Organ Failure Assessment score, and higher international normalized ratio (all p≤0.001). Plasma citrulline concentration less than or equal to 10 µmol/L at admission to the ICU was associated with higher intra-abdominal pressure, higher plasma C reactive protein concentration, and more frequent antibiotic use (all p≤0.005). There was no correlation between plasma levels of intestinal fatty acid-binding protein and citrulline. At ICU admission, Sequential Organ Failure Assessment score≥12, plasma citrulline≤12.2 µmol/L, and plasma intestinal fatty acid-binding protein concentration≥355 pg/mL were all independently associated with 28-day mortality (odds ratio, 4.39 [1.48-13.03]; odds ratio, 5.17 [1.59-16.86]; and odds ratio, 4.46 [1.35-14.74], respectively). CONCLUSIONS: In critically ill patients, enterocyte damage is frequent, and it is significantly associated with shock and 28-day mortality. The link between intestinal fatty acid-binding protein and plasma citrulline concentrations in critically ill patients needs to be further evaluated.

Small Annexin V-Positive Platelet-Derived Microvesicles Affect Prognosis in Cirrhosis: A Longitudinal Study.

INTRODUCTION: Microvesicles (MVs) with procoagulant properties may favor liver parenchymal extinction, then cirrhosis-related complications and mortality. In a longitudinal cohort of cirrhotic patients, we measured plasma levels of platelet-derived MVs (PMVs), endothelial-derived MVs, and red blood cell-derived MVs, expressing phosphatidylserine (annexin V-positive [AV+]) or not, and evaluated their impact on Model for End-Stage Liver Disease (MELD) score and transplant-free survival. METHODS: MVs were quantified using flow cytometry in plasma from 90 noninfected cirrhotic patients and 10 healthy volunteers matched for age and sex. Impact of plasma microvesicle levels on 6-month transplant-free survival was assessed using log-rank tests and logistic regression. RESULTS: Microvesicle levels, mostly platelet-derived, were 2.5-fold higher in healthy volunteers compared with cirrhotic patients. Circulating small AV+ PMV levels were lower in cirrhotic patients (P = 0.014) and inversely correlated with MELD scores (R = -0.28; P = 0.0065). During 1-year follow-up, 8 patients died and 7 underwent liver transplantation. In the remaining patients, circulating microvesicle levels did not change significantly. Six-month transplant-free survival was lower in patients with low baseline small AV+ PMV levels (72.6% vs 96.2%; P = 0.0007). In multivariate analyses adjusted for age, ascites, esophageal varices, encephalopathy, clinical decompensation, total platelet counts, MELD score, and/or Child-Pugh C stage, patients with lower small AV+ PMV levels had a significant 5- to 8-fold higher risk of 6-month death or liver transplant. Other PMV levels did not impact on survival. DISCUSSION: Decreased circulating small AV+ PMV levels are associated with significantly lower transplant-free survival in cirrhotic patients independently of MELD score and platelet counts.

[Performance criteria for the verification of IgE and tryptase assay methods: recommendations from the AllergoBioNet network]. / Critères de performance pour la vérification des méthodes de dosages des IgE et de la tryptase : recommandations du réseau AllergoBioNet.

Accreditation of an in vitro diagnostic assay according to the NF/EN/ISO 15189 standard requires to analyze its technical performance before implementation for routine use, and annually when reviewing effectiveness of quality controls. Performance is evaluated through repeatability, intermediate fidelity, accuracy and uncertainty of measurement. The coefficients of variation (CV) of the intra-assay and inter-assay precision tests must be compared with those of "peers" (results from laboratories employing the same method) and also with those obtained with "all methods", i.e., results from all laboratories performing the same assay, irrespective of the method. To our best knowledge, there is currently no French or international recommendation on what the acceptable limits of performance for specific IgE and tryptase assays should be. Therefore, the AllergoBioNet network of hospital allergy laboratories set out to characterize the performance of their current methods as a basis for the development of recommendations. The results provided by 24 centers were analyzed and led to consensus recommendations for specific IgE, total IgE and tryptase assays.

Impact of the route of nutrition on gut mucosa in ventilated adults with shock: an ancillary of the NUTRIREA-2 trial.

PURPOSE: The effects of the route of nutrition on the gut mucosa of patients with shock are unclear. Plasma citrulline concentration is a marker of enterocyte mass, and plasma intestinal fatty acid binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to study the effect of the route of nutrition on plasma citrulline concentration measured at day 3 of nutrition. MATERIALS AND METHODS: Ancillary study of the NUTRIREA-2 trial. Ventilated adults with shock were randomly assigned to receive enteral or parenteral nutrition. Enterocyte biomarkers were measured at baseline, day 3, and day 8 of nutrition. RESULT: A total of 165 patients from 13 French ICUs were included in the study: 85 patients in the enteral group and 80 patients in the parenteral group. At baseline, plasma citrulline was low without difference between groups (12.2 µmol L-1 vs 13.3 µmol L-1). At day 3, plasma citrulline concentration was higher in the enteral group than in the parenteral group (18.7 µmol L-1 vs 15.3 µmol L-1, p = 0.01). Plasma I-FABP concentration was increased at baseline, without difference between groups (245 pg mL-1 vs 244 pg mL-1). Plasma I-FABP concentration was higher in the enteral group than in the parenteral group at day 3 and day 8 (158 pg mL-1 vs 50 pg mL-1, p = 0.005 and 225 pg mL-1 vs 50 pg mL-1, p = 0.03). CONCLUSION: Plasma citrulline concentration was higher after 3 days of enteral nutrition than after 3 days of parenteral nutrition. This result raises the question of the possibility that enteral nutrition is associated with a more rapid restoration of enterocyte mass than parenteral nutrition.

Enterocyte Damage: A Piece in the Puzzle of Post-Cardiac Arrest Syndrome.

Cardiac arrest is considered to be a cause of small bowel ischemia, but the consequences of cardiac arrest on the human small bowel have been rarely studied. Plasma citrulline concentration is a marker of functional enterocyte mass, and plasma intestinal fatty acid-binding protein (I-FABP) concentration is a marker of enterocyte damage. We aimed to measure enterocyte biomarkers after cardiac arrest and to study the prognostic value of biomarker abnormalities. This is a prospective, observational, single-center study of patients admitted to the intensive care unit (ICU) for cardiac arrest, evaluating plasma citrulline and I-FABP concentrations at admission and after 24  h and variables according to the Utstein criteria. Variables according to 28-day Cerebral Performance Category score of 1 to 2 (good neurological outcome) versus 3 to 5 (poor neurological outcome) were compared. Sixty-nine patients with cardiac arrest of both cardiac and hypoxic origin were included. At ICU admission, plasma citrulline concentration was low in 65% and plasma I-FABP was elevated in 82% of the patients. After 24  h, plasma citrulline was low in 82% and I-FABP was normal in 60% of the patients. Patients with a poor neurological outcome had a lower plasma citrulline concentration and a higher I-FABP concentration at ICU admission. By multivariate analysis, plasma citrulline levels of 13.1  µmol L or less and I-FABP more than 260  pg mL were independently associated with a poor neurological outcome (odds ratio, 21.9 [2.2-215], and odds ratio, 13.6 [1.4-129], respectively). Cardiac arrest resuscitation is associated with evidence of small bowel mucosal damage in most patients, with a short and intense I-FABP elevation at admission and a decrease in citrulline concentration during the first day. In this study, low plasma citrulline and high I-FABP concentrations at ICU admission were predictive of a poor neurological outcome. This study confirms that cardiac arrest is a model of small bowel mucosal ischemia and suggests that enterocyte damage is a piece in the puzzle of post-cardiac arrest syndrome.

Catecholamine use is associated with enterocyte damage in critically ill patients.

Small bowel damage is frequent but underdiagnosed among critically ill patients with shock. High catecholamine doses may have a deleterious effect on mesenteric blood flow. Plasma intestinal fatty acid-binding protein (I-FABP) concentration is a marker of enterocyte damage, whereas plasma citrulline concentration is a marker of functional enterocyte mass. We hypothesized that high doses of catecholamines in critically ill patients may be associated with enterocyte damage. This study aimed to determine the link between catecholamine use and dose with enterocyte damage. This is a prospective observational study performed in a large regional university teaching hospital. Critically ill patients requiring epinephrine and/or norepinephrine at admission to a medical intensive care unit (ICU) were included, as well as controls not receiving catecholamines. We evaluated at admission plasma I-FABP and citrulline concentrations, abdominal perfusion pressure (APP), and variables relating to prognosis and treatment. Patients were categorized according to the quartiles of catecholamine dose at ICU admission. Sixty critically ill patients receiving catecholamines and 27 not receiving catecholamines were included. Plasma I-FABP was higher among patients receiving catecholamine than in controls. Among patients receiving catecholamines, a dose of 0.48 γ kg min or more at ICU admission was associated with a higher I-FABP concentration. A Sepsis-related Organ Failure Assessment score higher than 11 and plasma I-FABP more than 524 pg mL at ICU admission were independently associated with 28-day mortality (odds ratio, 4.0 [1.24-12.95] and odds ratio, 4.90 [1.44-16.6], respectively). Catecholamine use is associated with I-FABP elevation in critically ill patients. Critically ill patients receiving more than 0.48 γ kg min of epinephrine and/or norepinephrine at ICU admission have high I-FABP concentrations. This suggests that enterocyte damage reflects the severity of shock, and an adverse effect of catecholamines per se is possible.

Acute intestinal failure in critically ill patients: is plasma citrulline the right marker?

INTRODUCTION: Small bowel functions are more complex than colon functions, and short bowel conditions are associated with increased mortality. Gastrointestinal dysfunction in critically ill patients is common, probably underestimated, and associated with a poor prognosis. However, a validated definition of acute intestinal failure is lacking, in absence of a marker to measure it. Consequently, small bowel dysfunction is not clearly integrated into the overall approach used to treat ICU patients. MATERIALS AND METHODS: Review of the literature on gastrointestinal dysfunction in critically ill patients, and proposition of a definition of acute intestinal failure. CONCLUSION: On the one hand, small bowel ischemia is related to acute reduction of enterocyte mass and loss of gut barrier function by epithelial lifting of villi. On the other hand, systemic inflammatory response syndrome (SIRS) and sepsis could be linked to an acute dysfunction of enterocytes without enterocyte reduction. Citrulline is an amino acid mainly synthesized by small bowel enterocytes. Various contexts of chronic and acute reduction of enterocyte mass have been correlated with low plasma citrulline concentration. Critically ill patients with shock have an acute reduction of enterocyte mass and reduced gut citrulline synthesis, leading to a low plasma citrulline concentration. Acute intestinal failure could be defined as an acute reduction of enterocyte mass and/or acute dysfunction of enterocytes, associated or not with loss of gut barrier function. The influence of SIRS and acute renal failure on plasma citrulline concentration and the value of this concentration as an indicator of acute intestinal failure in critically ill patients must be further evaluated.

Plasma citrulline kinetics and prognostic value in critically ill patients.

PURPOSE: Multiple organ failure is a leading cause of death in critically ill patients and could be secondary to early gut ischemia. Plasma citrulline is a biomarker of enterocyte mass, and critically ill patients may have enterocyte mass reduction. The objectives of this study were to assess plasma citrulline kinetics and its prognostic value in critically ill patients. METHODS: This prospective observational study included adults without small bowel disease and without chronic renal failure consecutively admitted to a single intensive care unit. Prognostic variables as well as plasma citrulline concentrations were studied at admission, 12, 24, 48 h, and the 7th day after admission. Univariate and multivariate analyses including plasma citrulline (0-10, 11-20, and >20 micromol l(-1)) and other variables were performed. RESULTS: Sixty-seven patients were included, and the 28-day mortality was 34%. During the 1st day mean plasma citrulline decreased from 18.8 to 13.5 micromol l(-1). Low plasma citrulline at 24 h was associated with low plasma glutamine and arginine (p = 0.01 and 0.04), and high plasma CRP concentration, nosocomial infection rate, and 28-day mortality (p = 0.008, 0.03, and 0.02, respectively). In multivariate analysis plasma citrulline < or = 10 micromol l(-1) at 24 h and SOFA score > or =8 at 24 h were associated with 28-day mortality(odds ratios 8.70 and 15.08). CONCLUSIONS: In critically ill patients, low plasma citrulline at 24 h is an independent factor of mortality and could be a marker of acute intestinal failure.