Yves Berthiaume - Academia.edu (original) (raw)

Papers by Yves Berthiaume

Journal of Vascular and Interventional Radiology, 2006

Although bronchial artery embolization (BAE) is effective in the acute control of recurrent or ma... more Although bronchial artery embolization (BAE) is effective in the acute control of recurrent or major hemoptysis in adults with cystic fibrosis, outcomes after embolization are not well known. The objective of this retrospective study was to evaluate respiratory function, survival, and hemoptysis-free survival in adult patients with cystic fibrosis treated for hemoptysis with BAE. Of 297 patients with cystic fibrosis hospitalized from 1990 to 2004, 30 patients (mean age, 26.7+/-9.2 years) presented with major or persistent hemoptysis that required 42 BAE sessions. These patients were compared with a control group of 27 patients without hemoptysis requiring embolization who were matched for age, sex, and forced expiratory volume in 1 second (FEV1). Hemoptysis stopped within 24 hours after BAE in 96.6% of patients (n=29), and there were no major complications. The change in the slope of FEV1 after the BAE or matching date was significantly worse in the embolization group (P=.0007). At last follow-up, nine and one patients, respectively, had undergone lung transplantation in the BAE and control groups (P=.002). The 5-year survival rates without lung transplantation were 31% and 84%, respectively, in the BAE and control groups (hazard ratio, 5.95; P=.002). Sixty-two percent of patients were free of hemoptysis 5 years after BAE. The number of collateral arteries was the only factor associated with the risk of death or recurrent hemoptysis (P=.001). Despite the effectiveness of embolization in controlling recurrent or major hemoptysis, adults with cystic fibrosis who have undergone BAE for hemoptysis are at much higher risk of respiratory function aggravation, death, and the need for lung transplantation than those who have not undergone BAE for hemoptysis. They are more likely to die or to undergo lung transplantation than to present with recurrent major hemoptysis.

Diabetes, Jan 17, 2015

Cystic Fibrosis (CF) is due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulat... more Cystic Fibrosis (CF) is due to mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). Cystic Fibrosis-Related Diabetes affects 50% of adult CF patients. How CFTR deficiency predisposes to diabetes is unknown. Herein we examined the impact of the most frequent cftr mutation in humans, ΔF508, on glucose homeostasis in mice. We compared ΔF508 mutant mice to wild-type (WT) littermates. Twelve-week old male ΔF508 mutants had lower body weight, improved oral glucose tolerance and a trend towards higher insulin tolerance. Glucose-induced insulin secretion was slightly diminished in ΔF508 mutant islets, due to reduced insulin content, but ΔF508 mutant islets were not more sensitive to proinflammatory cytokines than WT islets. Hyperglycemic clamps confirmed an increase in insulin sensitivity with normal beta-cell function in 12- and 18-week old ΔF508 mutants. In contrast, 24-week old ΔF508 mutants exhibited insulin resistance and reduced beta-cell function. Beta-cell ma...

The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, Jan 7, 2015

Contemporary studies evaluating post-transplant survival are limited and often include data from ... more Contemporary studies evaluating post-transplant survival are limited and often include data from single centers or selected sub-groups. The purpose of this study was to evaluate overall transplant survival and to identify risk factors associated with death after transplant. The Canadian Cystic Fibrosis Registry, a population-based cohort, was used to describe survival after lung transplant. Pre-transplant factors associated with post-transplant survival were estimated using Cox proportional hazards models. Between 1988 and 2012, 580 patients received a lung transplant. In the entire cohort, post-lung transplant 1-year survival was 87.8%, 5-year survival was 66.7%, and 10-year survival was 50.2%. Median post-transplant survival was 3.3 years (95% confidence interval [CI] = 2.13-6.56) in patients infected with Burkholderia cepacia complex compared with 12.36 years (95% CI = 10.34-17.96) in patients without B cepacia infection (hazard ratio [HR] = 2.63, 95% CI = 2.0-3.44). After adjust...

Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society, Jan 26, 2015

CFRD is preceded and associated with a significantly increased morbidity and mortality. We aimed ... more CFRD is preceded and associated with a significantly increased morbidity and mortality. We aimed to characterize a large newly established glucose tolerance subgroup named INDET (indeterminate; 1-h oral glucose tolerance test (OGTT)>11.0 but 2h-OGTT<7.8mmol/L) in adult patients with cystic fibrosis (CF). All CF participants (n=252, ≥18yrs without CFRD) underwent a 2h-OGTT with glucose and insulin sample measurements every 30min. They were then classified as having either normal, impaired, or INDET glucose tolerance, or de novo CFRD. Other clinical characteristics were collected such as the BMI and pulmonary function. All groups were of similar age (P=0.629) and BMI (P=0.813). We found that the INDETs displayed decreased lung function comparable to de novo CFRD. OGTT-derived glucose or insulin secretion/sensitivity parameters cannot fully explain this observation. Prospective studies are required to establish if the INDET-CF group can identify clinically relevant outcomes.

PloS one, 2010

Abnormal fatty acid composition (FA) in plasma and tissue lipids frequently occurs in homozygous ... more Abnormal fatty acid composition (FA) in plasma and tissue lipids frequently occurs in homozygous and even in heterozygous carriers of cystic fibrosis transmembrane conductance regulator (CFTR) mutations. The mechanism(s) underlying these abnormalities remained, however, poorly understood despite the potentially CFTR contributing role. The aim of the present study was to investigate the impact of CFTR depletion on FA uptake, composition and metabolism using the intestinal Caco-2/15 cell line. shRNA-mediated cftr gene silencing induced qualitative and quantitative modifications in FA composition in differentiated enterocytes as determined by gas-liquid chromatography. With the cftr gene disruption, there was a 1,5 fold increase in the total FA amount, largely attributable to monounsaturated and saturated FA compared to controls. The activity of delta-7 desaturase, estimated by the 16:1(n-7)/16:0, was significantly higher in knockdown cells and consistent with the striking elevation of...

European Respiratory Journal, 2014

Previously established predictors of survival may no longer apply in the current era of cystic fi... more Previously established predictors of survival may no longer apply in the current era of cystic fibrosis (CF) care. Our objective was to identify risk factors associated with survival in a contemporary CF population. We used the Canadian CF Registry, a population-based cohort, to calculate median age of survival and summarise patient characteristics from 1990 to 2012. Clinical, demographic and geographical factors, and survival were estimated for a contemporary cohort (2000-2012) using Cox proportional hazards models. There were 5787 individuals in the registry between 1990 and 2012. Median survival age increased from 31.9 years (95% CI 28.3-35.2 years) in 1990 to 49.7 years (95% CI 46.1-52.2 years) in the most current 5-year window ending in 2012. Median forced expiratory volume in 1 s improved (p=0.04) and fewer subjects were malnourished (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.001) over time. Malnourished patients (hazard ratio (HR) 2.1, 95% CI 1.6-2.8), those with multiple exacerbations (HR 4.5, 95% CI 3.2-6.4) and women with CF-related diabetes (HR 1.8, 95% CI 1.2-2.7) were at increased risk of death. Life expectancy in Canadians with CF is increasing. Modifiable risk factors such as malnutrition and pulmonary exacerbations are associated with an increased risk of death. The sex gap in CF survival may be explained by an increased hazard for death in women with CF-related diabetes.

Journal of Trace Elements in Medicine and Biology, 2014

Background: Zinc status has been previously documented in cystic fibrosis (CF) infants, children ... more Background: Zinc status has been previously documented in cystic fibrosis (CF) infants, children and adolescents. However, despite the increasing life expectancy observed in CF populations, data regarding zinc status of CF adults are surprisingly lacking. The objectives of this study were to (1) characterize zinc status and (2) explore associations between zinc status and clinical outcomes of CF adult patients. Methods: A retrospective chart review was performed for patients who had their plasma zinc measured between 2009 and 2012. Data included demographics, clinical characteristics, biochemical parameters and co-morbid conditions. Results: A total of 304 CF patients were included in the study. These patients displayed a good nutritional status (mean BMI ± SD: 22.7 ± 3.5) and moderate lung disease (mean FEV 1 ± SD: 66.3 ± 22.2). Low plasma zinc concentration (<9.2 mol/L) was found in 68 out of 304 CF patients (22.4%). Compared to patients with normal zinc, those with low zinc had significantly lower forced vital capacity and forced expiratory volume in one second. 72% of CF adults with low zinc suffered from bone disease (vs 49% with normal zinc, p = 0.037) and 79% had impaired glycemic status (vs 58%, p = 0.016). Accordingly, negative correlations were found between plasma zinc and glucose (r = −0.139, p = 0.0001), HbA1c (r = −0.237, p = 0.0001) and fructosamine (r = −0.134, p = 0.034). In multiple linear regression, albumin and glycemic status were significant predictors of plasma zinc. Conclusion: Our data indicated that nearly one quarter of CF adults with good nutritional status and moderate lung disease had low plasma zinc concentration and that low zinc status was associated with worse clinical outcomes.

Journal of Cystic Fibrosis, 2007

Background: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF... more Background: Abnormal glucose tolerance is a frequent co-morbidity in cystic fibrosis patients (CF), and is associated with a worse prognosis. The objectives are to investigate (a) the relative contribution of insulinopenia and insulin resistance (IR) for glucose tolerance and (b) the association between various glucose parameters and CF clinical status. Methods: Oral glucose tolerance tests were performed in 114 consecutive CF patients not known to be diabetic as well as 14 controls similar for age and BMI. Results: Abnormal glucose tolerance was found in 40% of patients with CF: 28% had impaired glucose tolerance (IGT) and 12% had new cystic fibrosis related diabetes (CFRD). Compared to control subjects, all CF patients were characterized by an increased glucose excursion (AUC). While reduced early insulin release characterised CF, IGT and CFRD patients also present IR thus both mechanisms significantly contribute to glucose tolerance abnormalities. Increased glucose AUC and reduced early insulin release but not glucose tolerance categories were associated with a reduced pulmonary function (FEV 1 ). Conclusion: In CF, early insulin secretion defect but also IR contribute to glucose intolerance. Early in the course of the disease, increased glucose AUC and reduced early insulin secretion are more closely associated with a worse clinical status than conventional glucose tolerance categories.

Journal of Clinical Investigation, 1987

We did experiments to determine whether beta-adrenergic agonists increase lung liquid clearance i... more We did experiments to determine whether beta-adrenergic agonists increase lung liquid clearance in anesthetized ventilated adult sheep and, if so, whether the increase is mediated by beta receptors and what mechanism is involved. We instilled 100 ml of autologous serum either alone or with a beta-adrenergic agonist (terbutaline, 10(-5) M, or epinephrine, 5.5 X 10(-6) M) into one lower lobe. After 4 h both terbutaline and epinephrine increased lung liquid clearance. The increase in lung liquid clearance was inhibited when propranolol (a beta blocker) or amiloride (a sodium channel blocker) was added to the terbutaline. Increased clearance was not explained by changes in pulmonary hemodynamics, pulmonary blood flow, or lung lymph flow. We conclude that beta-adrenergic agonists increase lung liquid clearance in anesthetized intact adult sheep. This increase is mediated through beta receptors and probably depends on increased active transport of sodium across the alveolar barrier.

Journal of Aerosol Medicine, 1990

Page 1. JOURNAL OF AEROSOL MEDICINE Volume 3, Number 1, 1990 Mary Ann Liebert, Inc., Publishers P... more Page 1. JOURNAL OF AEROSOL MEDICINE Volume 3, Number 1, 1990 Mary Ann Liebert, Inc., Publishers Particle Retention in Airways by Surfactant P. GEHR,1 S. SCHÜRCH,2 Y. BERTHIAUME,2 V. IM HOF,3 and M. GEISER1 ...

IEEE Transactions on Biomedical Engineering, 1996

Electrical Impedance Tomography (EIT) uses surface electrical measurements to image changes in th... more Electrical Impedance Tomography (EIT) uses surface electrical measurements to image changes in the conductivity distribution within a medium. When used to measure lung ventilation, however, measurements depend both on conductivity changes in the thorax and on rib cage movement. Given that currently available reconstruction techniques assume that only conductivity changes are present, certain errors are introduced. A finite element model (FEM) is used to calculate the effect of chest expansion on the reconstructed conductivity images. Results indicate that thorax expansion accounts for up to 20% of the reconstructed image amplitude and introduces an artifact in the center of the image tending to "move" the reconstructed lungs closer together. Although this contribution varies depending on anatomical factors, it is relatively independent of inspiration depth. For certain applications in which one is only interested in changes in the level of physiological activity, the effect of the expansion can be neglected because it varies linearly with impedance changes. We conclude that chest expansion can contribute significantly to the conductivity images of lung ventilation and should be taken into account in the interpretation of these images.

Canadian Journal of Physiology and Pharmacology, 2005

Although the amiloride-sensitive epithelial sodium channel (ENaC) plays an important role in the ... more Although the amiloride-sensitive epithelial sodium channel (ENaC) plays an important role in the modulation of alveolar liquid clearance, the precise mechanism of its regulation in alveolar epithelial cells is still under investigation. Protein kinase C (PKC) has been shown to alter ENaC expression and activity in renal epithelial cells, but much less is known about its role in alveolar epithelial cells. The objective of this study was to determine whether PKC activation modulates ENaC expression and transepithelial Na+ transport in cultured rat alveolar epithelial cells. Alveolar type II cells were isolated and cultured for 3 to 4 d before they were stimulated with phorbol 12-myristate 13-acetate (PMA 100 nmol/L) for 4 to 24 h. PMA treatment significantly decreased alpha, beta, and gammaENaC expression in a time-dependent manner, whereas an inactive form of phorbol ester had no apparent effect. This inhibitory action was seen with only 5-min exposure to PMA, which suggested that PKC activation was very important for the reduction of alphaENaC expression. The PKC inhibitors bisindolylmaleimide at 2 micromol/L and Gö6976 at 2 micromol/L diminished the PMA-induced suppression of alphaENaC expression, while rottlerin at 1 micromol/L had no effect. PMA elicited a decrease in total and amiloride-sensitive current across alveolar epithelial cell monolayers. This decline in amiloride-sensitive current was not blocked by PKC inhibitors except for a partial inhibition with bisindolylmaleimide. PMA induced a decrease in rubidium uptake, indicating potential Na+-K+-ATPase inhibition. However, since ouabain-sensitive current in apically permeabilized epithelial cells was similar in PMA-treated and control cells, the inhibition was most probably related to reduced Na+ entry at the apical surface of the cells. We conclude that PKC activation modulates ENaC expression and probably ENaC activity in alveolar epithelial cells. Ca2+-dependent PKC is potentially involved in this response.

Canadian Journal of Diabetes, 2013

The Annals of Thoracic Surgery, 2008

Methods. Over a 6-year period, 153 consecutive patients underwent lung transplantation in our ins... more Methods. Over a 6-year period, 153 consecutive patients underwent lung transplantation in our institution. Group I consists of 65 patients who received lungs preserved with an antegrade flush of modified Euro-Collins solution. Group II includes 65 patients who received lungs preserved with an antegrade flush of low-potassium dextran (LPD) solution. Group III consists of 23 patients who received lungs preserved with an antegrade and a preimplantation retrograde flush of LPD solution. Endpoints evaluated were the following: acute lung injury (ALI) score, time to achieve a fraction of inspired oxygen (FiO 2 ) of 40% and a positive end-expiratory pressure (PEEP) of 5, length of ventilation, length of intensive care unit (ICU) stay, 90-day operative mortality, and patient survival rates.

Annals of Emergency Medicine, 1981

To study the delivery of oxygen to the cerebral tissue during metabolic acidosis and its therapy ... more To study the delivery of oxygen to the cerebral tissue during metabolic acidosis and its therapy with bicarbonate (NaHCO3), oxygen partial pressure of the cisternal fluid was measured in 12 experiments of HCl-induced acidemia and eight experiments of diabetic ketoacidosis in 16 unanesthetized dogs. Full correction of acidosis with bicarbonate caused a significant (P less than 0.05) decrease in Pcsf 2: in the HCl acidotic dogs, Pcsfo2 decreased from 53.9 +/- 2.2 torr to 45.9 +/- 2.3 torr within one hour; in the ketoacidotic dogs, Pcsfo2 decreased for 48.5 +/- 5.4 torr to 26.7 +/- 6.6 torr within six hours. In the ketoacidotic dogs not treated with bicarbonate, there was no significant change in Pcsfo2. An inverse relationship (P less than 0.01) between the cisternal lactic acid level and the cisternal PO2 was also observed. It is concluded that NaHCO3 therapy in diabetic ketoacidosis decreases the cerebral O2 availability and that cerebral hypoxia contributes to the brain dysfunction encountered after the initiation of such therapy in acidemia.

AJP: Lung Cellular and Molecular Physiology, 2006

In a recent study (Leroy C, Dagenais A, Berthiaume Y, and Brochiero E. Am J Physiol Lung Cell Mol... more In a recent study (Leroy C, Dagenais A, Berthiaume Y, and Brochiero E. Am J Physiol Lung Cell Mol Physiol 286: L1027-L1037, 2004), we identified an ATP-sensitive K(+) (K(ATP)) channel in alveolar epithelial cells, formed by inwardly rectifying K(+) channel Kir6.1/sulfonylurea receptor (SUR)2B subunits. We found that short applications of K(ATP), voltage-dependent K(+) channel KvLQT1, and calcium-activated K(+) (K(Ca)) channel modulators modified Na(+) and Cl(-) currents in alveolar monolayers. In addition, it was shown previously that a K(ATP) opener increased alveolar liquid clearance in human lungs by a mechanism possibly related to epithelial sodium channels (ENaC). We therefore hypothesized that prolonged treatment with K(+) channel modulators could induce a sustained regulation of ENaC activity and/or expression. Alveolar monolayers were treated for 24 h with inhibitors of K(ATP), KvLQT1, and K(Ca) channels identified by PCR. Glibenclamide and clofilium (K(ATP) and KvLQT1 inhibitors) strongly reduced basal transepithelial current, amiloride-sensitive Na(+) current, and forskolin-activated Cl(-) currents, whereas pinacidil, a K(ATP) activator, increased them. Interestingly, K(+) inhibitors or membrane depolarization (induced by valinomycin in high-K(+) medium) decreased alpha-, beta-, and gamma-ENaC and CFTR mRNA. alpha-ENaC and CFTR proteins also declined after glibenclamide or clofilium treatment. Conversely, pinacidil augmented ENaC and CFTR mRNAs and proteins. Since alveolar fluid transport was found to be driven, at least in part, by Na(+) transport through ENaC, we tested the impact of K(+) channel modulators on fluid absorption across alveolar monolayers. We found that glibenclamide and clofilium reduced fluid absorption to a level similar to that seen in the presence of amiloride, whereas pinacidil slightly enhanced it. Long-term regulation of ENaC and CFTR expression by K(+) channel activity could benefit patients with pulmonary diseases affecting ion transport and fluid clearance.

The American Journal of Medicine, 1983

Previous studies of lung function in asbestos workers have documented airflow limitation in many ... more Previous studies of lung function in asbestos workers have documented airflow limitation in many of the workers, but the specific influence of asbestos exposure could not be clearly differentiated from the effects of the cigarette smoking habit. In this study, airway function was evaluated in lifetime-nonsmoking, long-term workers of the mines and mills of Québec. The 17 asbestos workers in this study had worked for an average of 28 years in the mines and mills of the local asbestos industry and did not have any other respiratory industrial dust exposure. They did not have a history of previous pulmonary disease and did not meet the usual diagnostic criteria for chronic bronchitis, emphysema, or asthma. Seven of the workers met the diagnostic criteria for asbestosis and 10 workers did not. The latter group of workers did not differ from a matched control group except in terms of a higher isoflow volume (p less than 0.05). The workers with asbestosis, however, had a restrictive pattern of lung function, increased isoflow volume, and increased upstream resistance at low lung volumes (p less than 0.01). Lung biopsy in three of the patients with the disease demonstrated peribronchiolar alveolitis and fibrosis with obliteration and narrowing of the small airways. These data on lifetime-nonsmoking, long-term asbestos workers provide further evidence of small airway obstruction associated with asbestos exposure and independent of the smoking habit. This airflow limitation was observed predominantly in workers with a restrictive pattern of lung function associated with peribronchiolar alveolitis. The lifetime-nonsmoking asbestos workers without restrictive patterns of lung function had minimal dysfunction of the peripheral airways.

American Journal of Industrial Medicine, 1985

To analyze the clinical features of asbestos-induced alveolitis and stage its activity, we evalua... more To analyze the clinical features of asbestos-induced alveolitis and stage its activity, we evaluated 217 asbestos workers by the usual clinical, radiological, and functional parameters and computerized gallium 67(Ga) lung scan; we obtained bronchoalveolar lavage (BAL) in 33 and lung biopsy in 6. In addition, we scored the profusion of lung rales and correlated it with other parameters of severity of asbestosis. In the 55 workers without asbestosis and normal 67Ga scan, BAL analyses were comparable to those of controls. Of the 56 without asbestosis but increased 67Ga lung uptake, BAL analyses in 8 documented a predominantly macrophagic alveolitis (confirmed on lung biopsy in 3), with the highest levels of BAL fibronectin. In the 106 workers with asbestosis, 67Ga lung uptake was increased in 75; BAL in 17 demonstrated a macrophagic and neutrophilic alveolitis with elevated fibronectin levels. Lung biopsy in 3 of the latter workers documented peribronchiolar fibrosing alveolitis. Rale scores in all workers or in those without asbestosis did not correlate with 67Ga scores; they correlated fairly well with profusion of parenchymal opacities (Rs = 0.42) and rigidity of the lung pressure-volume curve (Rs = 0.39). Thus, 67Ga lung uptake is an early indicator of chronic macrophagic alveolitis in asbestos workers, which usually progresses to asbestosis. In the disease, profusion of lung rales constitutes a simple clinical mode of assessment of disease severity that correlates better with radiological and functional parameters than with parameters of alveolitis.

The American journal of physiology, 1993

Although active transport of sodium plays an important role in the resolution of pulmonary edema,... more Although active transport of sodium plays an important role in the resolution of pulmonary edema, the biochemical regulation of this process is still under investigation. The purpose of this study was to evaluate the activity of protein kinase C during the process of lung liquid clearance. Alveolar flooding was induced by instilling 5% bovine serum albumin solution, saline, or heterologous serum in the air spaces of rats. The activity of protein kinase C was measured in both the instilled and control lungs at 10 min and 1 and 4 h after fluid instillation. Four hours after instillation of 5% bovine serum albumin, the ratio of protein kinase C activity in the instilled lung compared with the control lung was 2.2 +/- 0.3. Similar results were obtained following instillation with heterologous serum or saline. Since we measured a clearance rate of 0.8 ml/h in anesthetized rats, we can postulate that the activation of protein kinase C occurred when > 40% of the liquid had been cleared ...