ABSTRACT
BACKGROUND: Fat-free mass (FFM) depletion marks the imbalance between tissue protein synthesis and breakdown in chronic obstructive pulmonary disease (COPD). To date, the role of essential amino acid supplementation (EAAs) in FFM repletion has not been fully acknowledged. A pilot study was undertaken in patients attending pulmonary rehabilitation. METHODS: 28 COPD patients with dynamic weight loss > 5% over the last 6 months were randomized to receive EAAs embedded in a 12-week rehabilitation program (EAAs group n = 14), or to the same program without supplementation (C group n = 14). Primary outcome measures were changes in body weight and FFM, using dual X-ray absorptiometry (DEXA). RESULTS: At the 12th week, a body weight increment occurred in 92% and 15% of patients in the EAAs and C group, respectively, with an average increase of 3.8 +/- 2.6 kg (P = 0.0002) and -0.1 +/- 1.1 kg (P = 0.81), respectively. A FFM increment occurred in 69% and 15% of EAAs and C patients, respectively, with an average increase of 1.5 +/- 2.6 kg (P = 0.05) and -0.1 +/- 2.3 kg (P = 0.94), respectively. In the EAAs group, FFM change was significantly related to fasting insulin (r(2) 0.68, P < 0.0005), C-reactive protein (C-RP) (r(2) = 0.46, P < 0.01), and oxygen extraction tension (PaO(2x)) (r(2) = 0.46, P < 0.01) at end of treatment. These three variables were highly correlated in both groups (r > 0.7, P < 0.005 in all tests). CONCLUSIONS: Changes in FFM promoted by EAAs are related to cellular energy and tissue oxygen availability in depleted COPD. Insulin, C-RP, and PaO(2x) must be regarded as clinical markers of an amino acid-stimulated signaling to FFM accretion.
Subject(s)
Adipose Tissue , C-Reactive Protein/metabolism , Insulin/metabolism , Pulmonary Disease, Chronic Obstructive/diet therapy , Weight Loss/physiology , Absorptiometry, Photon , Adipose Tissue/anatomy & histology , Aged , Amino Acids, Essential/administration & dosage , Amino Acids, Essential/metabolism , Biomarkers , Body Mass Index , C-Reactive Protein/analysis , Female , Humans , Insulin/blood , Italy , Male , Pulmonary Disease, Chronic Obstructive/rehabilitationABSTRACT
BACKGROUND: Arterial oxygen tension, oxygen delivery to tissue, and systemic inflammation are recognized as pivotal factors in the progression of chronic obstructive pulmonary disease (COPD). However, interconnections between systemic inflammation and tissue oxygen availability are scantly investigated. Tissue oxygen availability depends on arterial PaO2, oxygen concentration, hemoglobin oxygen affinity (P50), and hemoglobin oxygen binding capacity (ceHb). As the integrated changes of those indices are summarized by oxygen extraction tension (PaO2x), the objective of this study was to explore the association between C-reactive protein (CRP) blood levels and either PaO2x or each of its determinants, in stable COPD. MATERIALS AND METHODS: Blood CRP and oxygen status of arterial blood were measured at rest while breathing room air in 44 moderate to severe stable COPD patients. PaO2x was calculated along the shape of oxygen binding curve as the oxygen tension resulting from removal of 2.3 mmol of oxygen per liter of blood. Multiple linear regression analysis was performed with PaO2, ceHb, and P50 as independent variables, and CRP as the dependent variable, adjusting for age and sex. The analysis was repeated using PaO2x as a sole independent variable. RESULTS: Multiple linear regression analysis indicated that ceHb, PaO2, and P50, were significant and independent predictors of CRP (R2 = 0.52, p < 0.0001). PaO2x alone was an even stronger predictor of CRP (R2 = 0.62, p < 0.0001). CONCLUSIONS: These findings indicate that physiological determinants of tissue oxygen availability are independently associated with CRP blood levels. Thus, improvement of tissue oxygen availability is a central therapeutic option to modulate the severity of systemic inflammatory processes in patients with COPD.
