Victor Pinto-plata | Harvard University (original) (raw)

Papers by Victor Pinto-plata

Research paper thumbnail of Emphysema and DLCO predict a clinically important difference for 6MWD decline in COPD

Respiratory Medicine, 2015

Exercise impairment is a central feature of chronic obstructive pulmonary disease (COPD), and a m... more Exercise impairment is a central feature of chronic obstructive pulmonary disease (COPD), and a minimal clinically important difference (MCID) for 6-min walk distance (6MWD) decline (>30 m) has been associated with increased mortality. The predictors of the MCID are not fully known. We hypothesize that physiological factors and radiographic measures predict the MCID. We assessed 121 COPD subjects during 2 years using clinical variables, computed tomographic (CT) measures of emphysema, and functional measures including diffusion lung capacity for carbon monoxide (DLCO). The association between an MCID for 6MWD and clinical, CT, and physiologic predictors was assessed using logistic analysis. The C-statistic was used to assess the predictive ability of the models. Forty seven (39%) subjects had an MCID. In an imaging-based model, log emphysema and age were the best predictors of MCID (emphysema Odds Ratio [OR] 2.47 95%CI [1.28-4.76]). In a physiologic model, DLCO, age, and male gender were selected the best predictors (DLCO OR 1.19 [1.08-1.31]). The C-statistic for the ability of these models to predict an MCID was 0.71 and 0.75, respectively. In COPD patients the burden of emphysema on CT scan and DLCO predict a clinically meaningful decline in exercise capacity.

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Research paper thumbnail of A randomised trial of lung sealant versus medical therapy for advanced emphysema

The European respiratory journal, Jan 2, 2015

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction usi... more Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved...

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Research paper thumbnail of Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD

Chest, 2007

Systemic inflammation in patients with COPD may worsen during exacerbations, but there is limited... more Systemic inflammation in patients with COPD may worsen during exacerbations, but there is limited information relating levels of systemic inflammatory markers with symptoms and physiologic changes during an exacerbation We measured dyspnea using the visual analog scale, pulmonary function tests, hemograms, and plasma levels for interleukin (IL)-6, IL-8, leukotriene B(4) (LTB4), tumor necrosis factor-alpha, and secretory leukocyte protease inhibitor (SLPI) in 20 patients on admission to a hospital for exacerbation of COPD (ECOPD), 48 h later (interim), and 8 weeks after hospital discharge (recovery). Dyspnea was present in all patients. Inspiratory capacity improved faster than FEV(1). Compared to recovery, there was a significant increase in the mean (+/- SD) hospital admission plasma levels of IL-6 (6.38 +/- 0.72 to 2.80 +/- 0.79 pg/mL; p = 0.0001), IL-8 (8.18 +/- 0.85 to 3.72 +/- 0.85 pg/mL; p = 0.002), and LTB4 (8,675 +/- 1,652 to 2,534 +/- 1,813 pg/mL; p = 0.003), and the percen...

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Research paper thumbnail of Protective role for club cell secretory protein-16 (CC16) in the development of chronic obstructive pulmonary disease

The European respiratory journal, Jan 19, 2015

Club cell secretory protein-16 (CC16) is the major secreted product of airway club cells, but its... more Club cell secretory protein-16 (CC16) is the major secreted product of airway club cells, but its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unclear. We measured CC16 airway expression in humans with and without COPD and CC16 function in a cigarette smoke (CS)-induced COPD murine model. Airway CC16 expression was measured in COPD patients, smokers without COPD and non-smokers. We exposed wild-type (WT) and CC16(-/-)mice to CS or air for up to 6 months, and measured airway CC16 expression, pulmonary inflammation, alveolar septal cell apoptosis, airspace enlargement, airway mucin 5AC (MUC5AC) expression, small airway remodelling and pulmonary function. Smokers and COPD patients had reduced airway CC16 immunostaining that decreased with increasing COPD severity. Exposing mice to CS reduced airway CC16 expression. CC16(-/-) mice had greater CS-induced emphysema, airway remodelling, pulmonary inflammation, alveolar cell apoptosis, airway MUC5AC expression...

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Research paper thumbnail of Decreased Air Trapping Improves Cardiac Function During Sub-maximal Cardio-pulmonary Exercise In Patients With COPD

C109. REVISITING EXERCISE FOR CHILDREN AND ADULTS, 2010

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Research paper thumbnail of Peripheral Muscle Weakness Is Associated With Impaired Cardiac Function At Rest And During Exercise In Patients With COPD

A27. ADVANCES IN PULMONARY REHABILITATION, 2010

Page 1. / Poster Discussion Session / Sunday, May 16/8:15 AM-10:45 AM / Room A27 ADVANCES IN PULM... more Page 1. / Poster Discussion Session / Sunday, May 16/8:15 AM-10:45 AM / Room A27 ADVANCES IN PULMONARY REHABILITATION 293-294 (Second Level), Morial Convention Center Peripheral Muscle Weakness Is Associated ...

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Research paper thumbnail of Profiling serum biomarkers in patients with COPD: associations with clinical parameters

Thorax, 2007

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Research paper thumbnail of Determinants of poor 6-min walking distance in patients with COPD: The ECLIPSE cohort

Respiratory Medicine, 2010

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Research paper thumbnail of A Novel Nonhuman Primate Model of Cigarette Smoke–Induced Airway Disease

The American Journal of Pathology, 2014

Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for ... more Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers for human COPD. These include a pulmonary anatomy that differs from humans, the limited airway pathologies and lymphoid aggregates that develop in smoke-exposed mice, and the challenges associated with serial biological sampling. Thus, we assessed the utility of cigarette smoke (CS)-exposed cynomolgus macaque as a nonhuman primate (NHP) large animal model of COPD. Twenty-eight NHPs were exposed to air or CS 5 days per week for up to 12 weeks. Bronchoalveolar lavage and pulmonary function tests were performed at intervals. After 12 weeks, we measured airway pathologies, pulmonary inflammation, and airspace enlargement. CS-exposed NHPs developed robust mucus metaplasia, submucosal gland hypertrophy and hyperplasia, airway inflammation, peribronchial fibrosis, and increases in bronchial lymphoid aggregates. Although CS-exposed NHPs did not develop emphysema over the study time, they exhibited pathologies that precede emphysema development, including increases in the following: i) matrix metalloproteinase-9 and proinflammatory mediator levels in bronchoalveolar lavage fluid, ii) lung parenchymal leukocyte counts and lymphoid aggregates, iii) lung oxidative stress levels, and iv) alveolar septal cell apoptosis. CS-exposed NHPs can be used as a model of airway disease occurring in COPD patients. Unlike rodents, NHPs can safely undergo longitudinal sampling, which could be useful for assessing novel biomarkers or therapeutics for COPD.

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Research paper thumbnail of Resting handgrip force and impaired cardiac function at rest and during exercise in COPD patients

Respiratory Medicine, 2011

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Research paper thumbnail of Comparison of arterial and venous blood biomarker levels in chronic obstructive pulmonary disease

F1000Research, 2013

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Research paper thumbnail of Prognostic evaluation of COPD patients: GOLD 2011 versus BODE and the COPD comorbidity index COTE

Thorax, 2014

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Research paper thumbnail of Gender Differences in Plasma Biomarker Levels in a Cohort of COPD Patients: A Pilot Study

PLOS One, 2011

RationaleLittle is known about gender differences in plasma biomarker levels in patients with chr... more RationaleLittle is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).HypothesisThere are differences in serum biomarker levels between women and men with COPD.ObjectiveExplore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.MethodsWe measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without

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Research paper thumbnail of Gene Expression Profiling of Human Lung Tissue from Smokers with Severe Emphysema

The mechanism by which inhaled smoke causes the anatomic lesions and physiologic impairment of ch... more The mechanism by which inhaled smoke causes the anatomic lesions and physiologic impairment of chronic obstructive pulmonary dis- ease remains unknown. We used high-density microarrays to mea- sure gene expression in severely emphysematous lung tissue re- moved from smokers at lung volume reduction surgery (LVRS) and normal or mildly emphysematous lung tissue from smokers under- going resection of pulmonary nodules. Class prediction algorithms identified 102 genes that accurately distinguished severe emphy- sema from non-/mildly emphysematous lung tissue. We also de- fined a number of genes whose expression levels correlated strongly with lung diffusion capacity for carbon monoxide and/or forced expiratory volume at 1 s. Genes related to oxidative stress, extracel- lular matrix synthesis, and inflammation were increased in severe emphysema, whereas expression of endothelium-related genes was decreased. To identify candidate genes that might be causally in- volved in the pathogenesis...

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Research paper thumbnail of Inflammatory and repair serum biomarker pattern. Association to clinical outcomes in COPD

Respiratory Research, 2012

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Research paper thumbnail of Gender Differences in Plasma Biomarker Levels in a Cohort of COPD Patients: A Pilot Study

PLoS ONE, 2011

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Research paper thumbnail of Disease progression in young patients with COPD: rethinking the Fletcher and Peto model

European Respiratory Journal, 2014

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Research paper thumbnail of CHANGES IN EXERCISE CAPACITY OF MEDICAL INTERNS OVER THEIR FIRST YEAR OF TRAINING

CHEST Journal, 2005

... DISTRESS SYNDROME (ARDS) SIGNIFICANTLY IMPROVES LUNG FUNCTION: RESULTS OF A RANDOMIZED CONTRO... more ... DISTRESS SYNDROME (ARDS) SIGNIFICANTLY IMPROVES LUNG FUNCTION: RESULTS OF A RANDOMIZED CONTROLLED TRIAL (RCT) Gianfranco U. Meduri MD* Emmel Golden MD Amado X. Freire MD Edwin Taylor MD Mohamad Zaman MD Stephanie J. Carson MD ...

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Research paper thumbnail of RESPIRATORY MECHANICS AND OXYGEN UPTAKE (VO2) DURING EXERCISE IN PATIENTS WITH COPD AND CONTROL POPULATION: CHANGES OVER TIME

CHEST Journal, 2006

PURPOSE: Exercise in patients with COPD can be limited by ventilatory and/or peripheral muscle dy... more PURPOSE: Exercise in patients with COPD can be limited by ventilatory and/or peripheral muscle dysfunction. Whether these limitations progress synchronously over time and how they compare to a control group is not known. METHODS: We evaluated 30 COPD ...

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Research paper thumbnail of EFFECTS OF STATIC AND DYNAMIC HYPERINFLATION DURING CARDIOPULMONARY EXERCISE ON O2 PULSE IN COPD PATIENTS IN GOLD STAGES 3 AND 4

CHEST Journal, 2007

Page 1. functional parameters which are related to the behaviour of small airways when expiratory... more Page 1. functional parameters which are related to the behaviour of small airways when expiratory flow-limitation is present. METHODS: We studied fifty-three patients selected at rest and during severe exercise (cardiopulmonary ...

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Research paper thumbnail of Emphysema and DLCO predict a clinically important difference for 6MWD decline in COPD

Respiratory Medicine, 2015

Exercise impairment is a central feature of chronic obstructive pulmonary disease (COPD), and a m... more Exercise impairment is a central feature of chronic obstructive pulmonary disease (COPD), and a minimal clinically important difference (MCID) for 6-min walk distance (6MWD) decline (>30 m) has been associated with increased mortality. The predictors of the MCID are not fully known. We hypothesize that physiological factors and radiographic measures predict the MCID. We assessed 121 COPD subjects during 2 years using clinical variables, computed tomographic (CT) measures of emphysema, and functional measures including diffusion lung capacity for carbon monoxide (DLCO). The association between an MCID for 6MWD and clinical, CT, and physiologic predictors was assessed using logistic analysis. The C-statistic was used to assess the predictive ability of the models. Forty seven (39%) subjects had an MCID. In an imaging-based model, log emphysema and age were the best predictors of MCID (emphysema Odds Ratio [OR] 2.47 95%CI [1.28-4.76]). In a physiologic model, DLCO, age, and male gender were selected the best predictors (DLCO OR 1.19 [1.08-1.31]). The C-statistic for the ability of these models to predict an MCID was 0.71 and 0.75, respectively. In COPD patients the burden of emphysema on CT scan and DLCO predict a clinically meaningful decline in exercise capacity.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A randomised trial of lung sealant versus medical therapy for advanced emphysema

The European respiratory journal, Jan 2, 2015

Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction usi... more Uncontrolled pilot studies demonstrated promising results of endoscopic lung volume reduction using emphysematous lung sealant (ELS) in patients with advanced, upper lobe predominant emphysema. We aimed to evaluate the safety and efficacy of ELS in a randomised controlled setting. Patients were randomised to ELS plus medical treatment or medical treatment alone. Despite early termination for business reasons and inability to assess the primary 12-month end-point, 95 out of 300 patients were successfully randomised, providing sufficient data for 3- and 6-month analysis. 57 patients (34 treatment and 23 control) had efficacy results at 3 months; 34 (21 treatment and 13 control) at 6 months. In the treatment group, 3-month lung function, dyspnoea, and quality of life improved significantly from baseline when compared to control. Improvements persisted at 6 months with >50% of treated patients experiencing clinically important improvements, including some whose lung function improved...

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Research paper thumbnail of Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD

Chest, 2007

Systemic inflammation in patients with COPD may worsen during exacerbations, but there is limited... more Systemic inflammation in patients with COPD may worsen during exacerbations, but there is limited information relating levels of systemic inflammatory markers with symptoms and physiologic changes during an exacerbation We measured dyspnea using the visual analog scale, pulmonary function tests, hemograms, and plasma levels for interleukin (IL)-6, IL-8, leukotriene B(4) (LTB4), tumor necrosis factor-alpha, and secretory leukocyte protease inhibitor (SLPI) in 20 patients on admission to a hospital for exacerbation of COPD (ECOPD), 48 h later (interim), and 8 weeks after hospital discharge (recovery). Dyspnea was present in all patients. Inspiratory capacity improved faster than FEV(1). Compared to recovery, there was a significant increase in the mean (+/- SD) hospital admission plasma levels of IL-6 (6.38 +/- 0.72 to 2.80 +/- 0.79 pg/mL; p = 0.0001), IL-8 (8.18 +/- 0.85 to 3.72 +/- 0.85 pg/mL; p = 0.002), and LTB4 (8,675 +/- 1,652 to 2,534 +/- 1,813 pg/mL; p = 0.003), and the percen...

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Research paper thumbnail of Protective role for club cell secretory protein-16 (CC16) in the development of chronic obstructive pulmonary disease

The European respiratory journal, Jan 19, 2015

Club cell secretory protein-16 (CC16) is the major secreted product of airway club cells, but its... more Club cell secretory protein-16 (CC16) is the major secreted product of airway club cells, but its role in the pathogenesis of chronic obstructive pulmonary disease (COPD) is unclear. We measured CC16 airway expression in humans with and without COPD and CC16 function in a cigarette smoke (CS)-induced COPD murine model. Airway CC16 expression was measured in COPD patients, smokers without COPD and non-smokers. We exposed wild-type (WT) and CC16(-/-)mice to CS or air for up to 6 months, and measured airway CC16 expression, pulmonary inflammation, alveolar septal cell apoptosis, airspace enlargement, airway mucin 5AC (MUC5AC) expression, small airway remodelling and pulmonary function. Smokers and COPD patients had reduced airway CC16 immunostaining that decreased with increasing COPD severity. Exposing mice to CS reduced airway CC16 expression. CC16(-/-) mice had greater CS-induced emphysema, airway remodelling, pulmonary inflammation, alveolar cell apoptosis, airway MUC5AC expression...

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Research paper thumbnail of Decreased Air Trapping Improves Cardiac Function During Sub-maximal Cardio-pulmonary Exercise In Patients With COPD

C109. REVISITING EXERCISE FOR CHILDREN AND ADULTS, 2010

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Peripheral Muscle Weakness Is Associated With Impaired Cardiac Function At Rest And During Exercise In Patients With COPD

A27. ADVANCES IN PULMONARY REHABILITATION, 2010

Page 1. / Poster Discussion Session / Sunday, May 16/8:15 AM-10:45 AM / Room A27 ADVANCES IN PULM... more Page 1. / Poster Discussion Session / Sunday, May 16/8:15 AM-10:45 AM / Room A27 ADVANCES IN PULMONARY REHABILITATION 293-294 (Second Level), Morial Convention Center Peripheral Muscle Weakness Is Associated ...

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Research paper thumbnail of Profiling serum biomarkers in patients with COPD: associations with clinical parameters

Thorax, 2007

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Determinants of poor 6-min walking distance in patients with COPD: The ECLIPSE cohort

Respiratory Medicine, 2010

Bookmarks Related papers MentionsView impact

Research paper thumbnail of A Novel Nonhuman Primate Model of Cigarette Smoke–Induced Airway Disease

The American Journal of Pathology, 2014

Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for ... more Small animal models of chronic obstructive pulmonary disease (COPD) have several limitations for identifying new therapeutic targets and biomarkers for human COPD. These include a pulmonary anatomy that differs from humans, the limited airway pathologies and lymphoid aggregates that develop in smoke-exposed mice, and the challenges associated with serial biological sampling. Thus, we assessed the utility of cigarette smoke (CS)-exposed cynomolgus macaque as a nonhuman primate (NHP) large animal model of COPD. Twenty-eight NHPs were exposed to air or CS 5 days per week for up to 12 weeks. Bronchoalveolar lavage and pulmonary function tests were performed at intervals. After 12 weeks, we measured airway pathologies, pulmonary inflammation, and airspace enlargement. CS-exposed NHPs developed robust mucus metaplasia, submucosal gland hypertrophy and hyperplasia, airway inflammation, peribronchial fibrosis, and increases in bronchial lymphoid aggregates. Although CS-exposed NHPs did not develop emphysema over the study time, they exhibited pathologies that precede emphysema development, including increases in the following: i) matrix metalloproteinase-9 and proinflammatory mediator levels in bronchoalveolar lavage fluid, ii) lung parenchymal leukocyte counts and lymphoid aggregates, iii) lung oxidative stress levels, and iv) alveolar septal cell apoptosis. CS-exposed NHPs can be used as a model of airway disease occurring in COPD patients. Unlike rodents, NHPs can safely undergo longitudinal sampling, which could be useful for assessing novel biomarkers or therapeutics for COPD.

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Resting handgrip force and impaired cardiac function at rest and during exercise in COPD patients

Respiratory Medicine, 2011

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Comparison of arterial and venous blood biomarker levels in chronic obstructive pulmonary disease

F1000Research, 2013

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Prognostic evaluation of COPD patients: GOLD 2011 versus BODE and the COPD comorbidity index COTE

Thorax, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Gender Differences in Plasma Biomarker Levels in a Cohort of COPD Patients: A Pilot Study

PLOS One, 2011

RationaleLittle is known about gender differences in plasma biomarker levels in patients with chr... more RationaleLittle is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD).HypothesisThere are differences in serum biomarker levels between women and men with COPD.ObjectiveExplore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD.MethodsWe measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Gene Expression Profiling of Human Lung Tissue from Smokers with Severe Emphysema

The mechanism by which inhaled smoke causes the anatomic lesions and physiologic impairment of ch... more The mechanism by which inhaled smoke causes the anatomic lesions and physiologic impairment of chronic obstructive pulmonary dis- ease remains unknown. We used high-density microarrays to mea- sure gene expression in severely emphysematous lung tissue re- moved from smokers at lung volume reduction surgery (LVRS) and normal or mildly emphysematous lung tissue from smokers under- going resection of pulmonary nodules. Class prediction algorithms identified 102 genes that accurately distinguished severe emphy- sema from non-/mildly emphysematous lung tissue. We also de- fined a number of genes whose expression levels correlated strongly with lung diffusion capacity for carbon monoxide and/or forced expiratory volume at 1 s. Genes related to oxidative stress, extracel- lular matrix synthesis, and inflammation were increased in severe emphysema, whereas expression of endothelium-related genes was decreased. To identify candidate genes that might be causally in- volved in the pathogenesis...

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Research paper thumbnail of Inflammatory and repair serum biomarker pattern. Association to clinical outcomes in COPD

Respiratory Research, 2012

Bookmarks Related papers MentionsView impact

Research paper thumbnail of Gender Differences in Plasma Biomarker Levels in a Cohort of COPD Patients: A Pilot Study

PLoS ONE, 2011

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Research paper thumbnail of Disease progression in young patients with COPD: rethinking the Fletcher and Peto model

European Respiratory Journal, 2014

Bookmarks Related papers MentionsView impact

Research paper thumbnail of CHANGES IN EXERCISE CAPACITY OF MEDICAL INTERNS OVER THEIR FIRST YEAR OF TRAINING

CHEST Journal, 2005

... DISTRESS SYNDROME (ARDS) SIGNIFICANTLY IMPROVES LUNG FUNCTION: RESULTS OF A RANDOMIZED CONTRO... more ... DISTRESS SYNDROME (ARDS) SIGNIFICANTLY IMPROVES LUNG FUNCTION: RESULTS OF A RANDOMIZED CONTROLLED TRIAL (RCT) Gianfranco U. Meduri MD* Emmel Golden MD Amado X. Freire MD Edwin Taylor MD Mohamad Zaman MD Stephanie J. Carson MD ...

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Research paper thumbnail of RESPIRATORY MECHANICS AND OXYGEN UPTAKE (VO2) DURING EXERCISE IN PATIENTS WITH COPD AND CONTROL POPULATION: CHANGES OVER TIME

CHEST Journal, 2006

PURPOSE: Exercise in patients with COPD can be limited by ventilatory and/or peripheral muscle dy... more PURPOSE: Exercise in patients with COPD can be limited by ventilatory and/or peripheral muscle dysfunction. Whether these limitations progress synchronously over time and how they compare to a control group is not known. METHODS: We evaluated 30 COPD ...

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Research paper thumbnail of EFFECTS OF STATIC AND DYNAMIC HYPERINFLATION DURING CARDIOPULMONARY EXERCISE ON O2 PULSE IN COPD PATIENTS IN GOLD STAGES 3 AND 4

CHEST Journal, 2007

Page 1. functional parameters which are related to the behaviour of small airways when expiratory... more Page 1. functional parameters which are related to the behaviour of small airways when expiratory flow-limitation is present. METHODS: We studied fifty-three patients selected at rest and during severe exercise (cardiopulmonary ...

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