Right Heart Function in COPD

MacNee, William

doi:10.1055/s-0030-1254070

Cited by 29 publications

(23 citation statements)

References 90 publications

(145 reference statements)

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“…Our data show that repeated LPS challenge also induces right ventricular hypertrophy, a feature of pulmonary hypertension, a known comorbidity of COPD (MacNee, 2010). The LPS-induced right ventricular hypertrophy was prevented by ABH.…”

Section: Discussionsupporting

confidence: 54%

“…Therefore, our data suggest that repeated LPS challenge results in pulmonary hypertension via induction of arginase. Pulmonary hypertension and associated right ventricular hypertrophy may result from (a combination of) vascular remodeling and functional changes in the vessel wall, both leading to increased resistance in the pulmonary vasculature (MacNee, 2010). In our model, we did not observe changes in pulmonary vessel dimensions after repeated LPS instillation or by treatment with inhaled ABH, suggesting that increased resistance in the pulmonary vessels and subsequent right ventricular hypertrophy occur through exaggerated constriction of the vessels rather than remodeling of the vessel wall.…”

Section: Discussioncontrasting

confidence: 46%

“…Airway remodeling in COPD is predominantly characterized by mucus cell hyperplasia and peribronchiolar fibrosis (Pauwels et al, 2001). In addition, pulmonary hypertension, a comorbidity present in a large proportion of COPD patients, may lead to right ventricular hypertrophy and pulmonary vascular remodeling (Wright et al, 1983;Peinado et al, 1999;MacNee, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Arginase Inhibition Prevents Inflammation and Remodeling in a Guinea Pig Model of Chronic Obstructive Pulmonary Disease

Pera

Zuidhof

Smit

et al. 2014

J Pharmacol Exp Ther

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Airway inflammation and remodeling are major features of chronic obstructive pulmonary disease (COPD), whereas pulmonary hypertension is a common comorbidity associated with a poor disease prognosis. Recent studies in animal models have indicated that increased arginase activity contributes to features of asthma, including allergeninduced airway eosinophilia and mucus hypersecretion. Although cigarette smoke and lipopolysaccharide (LPS), major risk factors for COPD, may increase arginase expression, the role of arginase in COPD is unknown. This study aimed to investigate the role of arginase in pulmonary inflammation and remodeling using an animal model of COPD. Guinea pigs were instilled intranasally with LPS or saline twice weekly for 12 weeks and pretreated by inhalation of the arginase inhibitor 2(S)-amino-6-boronohexanoic acid (ABH) or vehicle. Repeated LPS exposure increased lung arginase activity, resulting in increased L-ornithine/L-arginine and L-ornithine/L-citrulline ratios. Both ratios were reversed by ABH. ABH inhibited the LPS-induced increases in pulmonary IL-8, neutrophils, and goblet cells as well as airway fibrosis. Remarkably, LPS-induced right ventricular hypertrophy, indicative of pulmonary hypertension, was prevented by ABH. Strong correlations were found between arginase activity and inflammation, airway remodeling, and right ventricular hypertrophy. Increased arginase activity contributes to pulmonary inflammation, airway remodeling, and right ventricular hypertrophy in a guinea pig model of COPD, indicating therapeutic potential for arginase inhibitors in this disease.

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Section: Discussionsupporting

confidence: 54%

Section: Discussioncontrasting

confidence: 46%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Arginase Inhibition Prevents Inflammation and Remodeling in a Guinea Pig Model of Chronic Obstructive Pulmonary Disease

Pera

Zuidhof

Smit

et al. 2014

J Pharmacol Exp Ther

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“…[6][7][8][9] Low red cell mass impairs pulmonary hemodynamics, oxygen delivery, and gas exchange, 6 which seems particularly relevant for COPD patients presenting with chronic respiratory failure. Conversely, polycythemia can contribute to pulmonary hypertension, reduced cerebral blood flow, and increased risk of venous thromboembolic disease, 26,27 and thus may also negatively influence the prognosis. On the other hand, a higher red cell mass may indicate that an adequate physiologic response to hypoxemia is still present, which may be particularly relevant in a systemic inflammatory disease such as COPD.…”

Section: Discussionmentioning

confidence: 99%

“…Our data point out that cutoff values must be adapted to their purpose and that patients with Hb values above anemia levels can also be at risk. Possibly, a higher Hb level in the presence of chronic hypoxemia prior to treatment reflects adequate bone marrow function 35 and response to inflammation and/or hypoxia 26,31 and therefore indicates patients with a better prognosis.…”

Section: Discussionmentioning

confidence: 99%

Hemoglobin Levels Above Anemia Thresholds Are Maximally Predictive for Long-Term Survival in COPD With Chronic Respiratory Failure

et al. 2012

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BACKGROUND: In patients with COPD, chronic anemia is known as an unfavorable prognostic factor. Whether the association between hemoglobin (Hb) levels and long-term survival is restricted to anemia or extends to higher Hb levels has not yet been systematically assessed. METHODS: We determined Hb levels in 309 subjects with COPD and chronic respiratory failure prior to initiation of noninvasive ventilation, accounting for confounders that might affect Hb. Subjects were categorized as anemic (Hb < 12 g/dL in females, Hb < 13 g/dL in males), polycythemic (Hb > 15 g/dL in females, Hb > 17 g/dL in males), or normocythemic. In addition, percentiles of Hb values were analyzed with regard to mortality from any cause. RESULTS: Two-hundred seven subjects (67.0%) showed normal Hb levels, 46 (14.9%) had anemia, and 56 (18.1%) had polycythemia. Polycythemic subjects showed a higher survival rate than anemic (P ‫؍‬ .01) and normocythemic subjects (P ‫؍‬ .043). In a univariate Cox hazards model, Hb was associated with long-term survival (hazard ratio 0.855; 95% CI 0.783-0.934, P < .001). The 58th percentiles of Hb (14.3 g/dL in females, 15.1 g/dL in males) yielded the highest discriminative value for predicting survival (hazard ratio 0.463, 95% CI 0.324 -0.660, P < .001). In the multivariate analysis this cutoff was an independent predictor for survival (hazard ratio 0.627, 95% CI 0.414 -0.949, P ‫؍‬ .03), in addition to age and body mass index. CONCLUSIONS: In subjects with COPD and chronic respiratory failure undergoing treatment with noninvasive ventilation and LTOT, high Hb levels are associated with better long-term survival. The optimal cutoff level for prediction was above the established threshold defining anemia. Thus, predicting survival only on the basis of anemia does not fully utilize the prognostic potential of Hb values in COPD.

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Role of CA‐125 in Identification of Right Ventricular Failure in Chronic Obstructive Pulmonary Disease

Yilmaz¹,

Zorlu²,

Doǧan

et al. 2011

Clinical Cardiology

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Background: Chronic obstructive pulmonary disease (COPD) is a progressive and debilitating disease. Cor pulmonale, characterized by right ventricular (RV) failure, can severely influence prognosis in these patients. Hence, early recognition might be important for tailoring therapy. An old biomarker, CA-125, seems to be associated with the right heart. We aimed to show the relationship between CA-125 levels and RV failure in patients with COPD. Hypothesis: CA-125 might be a useful biomarker in identification of RV failure in patients with COPD. Methods: Forty patients with recent exacerbation of COPD were enrolled into the study. Another 40 age-and sex-matched individuals were enrolled for comparison. Levels of CA-125 were measured in the patients during the hospital stay. The COPD patients underwent echocardiographic study on the same day. Right-ventricular parameters were evaluated, and RV failure was identified via transthoracic echocardiography. Results: Patients with COPD had significantly higher CA-125 levels compared with controls (median 33.94 U/mL vs 9.76 U/mL, respectively; P < 0.001). Levels of CA-125 were correlated with systolic pulmonary artery pressure (r = 0.550, P < 0.001), tricuspid annular plane systolic excursion (r = −0.496, P = 0.001), and tricuspid lateral annulus S velocity (r = −0.549, P = 0.002). High CA-125 levels, obtained in hospitalized patients with COPD before echocardiography, enabled identification of RV failure with a sensitivity of 89.5% and specificity of 85.7%. Conclusions:The CA-125 biomarker can be used to identify COPD patients with RV failure.

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Right Heart Function in COPD

Cited by 29 publications

References 90 publications

Arginase Inhibition Prevents Inflammation and Remodeling in a Guinea Pig Model of Chronic Obstructive Pulmonary Disease

Arginase Inhibition Prevents Inflammation and Remodeling in a Guinea Pig Model of Chronic Obstructive Pulmonary Disease

Hemoglobin Levels Above Anemia Thresholds Are Maximally Predictive for Long-Term Survival in COPD With Chronic Respiratory Failure

Role of CA‐125 in Identification of Right Ventricular Failure in Chronic Obstructive Pulmonary Disease

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