Marcia L. Erbland

Chronic obstructive pulmonary disease: an update on diagnosis and management issues in older adults.

Chronic obstructive pulmonary disease (COPD) is a debilitating disease of the elderly that causes significant morbidity and mortality. Despite being a treatable and preventable disease, the prevalence continues to rise because of the worldwide epidemic of smoking. COPD is associated with enormous healthcare costs. It has systemic effects, and common co-morbid conditions such as cardiovascular disease, muscle wasting and osteoporosis may all be linked through a common systemic inflammatory cascade. Depression, anxiety and malnutrition are also common in elderly COPD patients. These factors not only affect quality of life (QOL) but also compliance with therapy. Malnutrition is an independent predictor of mortality and poor outcome. Spirometry is essential for the diagnosis of COPD, but the criteria defining airflow limitation are not clear cut for elderly patients and could result in over-diagnosis. However, older patients perceive their symptoms differently, and COPD could also be under-diagnosed in this population. Acute exacerbations result in worsening symptoms that necessitate additional treatment, and may cause a more rapid decline in lung function and QOL. The management of elderly patients with COPD should encompass a multidisciplinary approach. An evaluation of patients’ nutritional status and mental health should be undertaken, in addition to assessing their lung function and functional impairment. Significant underlying co-morbidities should be evaluated and treated to derive the maximal benefit of therapy. Specific therapy for COPD should start with cessation of exposure to the most important risk factor, tobacco smoke. Smoking cessation rates in the elderly have not declined, and this may reflect an underlying reluctance by physicians to counsel and offer smoking cessation therapies to the elderly. Unlike oxygen therapy in hypoxaemic patients, bronchodilators and corticosteroids do not decrease mortality in COPD patients and they are primarily directed towards symptom relief. However, they do have a positive effect on QOL and exacerbation rates. The choice of delivery devices for inhaled medications is important in the elderly, and patients’ inhaler technique and manual dexterity should be frequently assessed. Pulmonary rehabilitation and nutritional supplementation are other important components of care. End-of-life issues should be adequately addressed in the elderly with COPD, and an approach integrating curative and palliative interventions is recommended.

Hydrolyzed casein and whey protein meals comparably stimulate net whole-body protein synthesis in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion

BACKGROUND & AIMS Muscle wasting commonly occurs in COPD, negatively affecting outcome. The aim was to examine the net whole-body protein synthesis response to two milk protein meals with comparable absorption rates (hydrolyzed casein (hCAS) vs. hydrolyzed whey (hWHEY)) and the effects of co-ingesting leucine. METHODS Twelve COPD patients (GOLD stage II-IV) with nutritional depletion, were studied following intake of a 15 g hCAS or hWHEY protein meal with or without leucine-co-ingestion, according to a double-blind randomized cross-over design. The isotopic tracers L-[ring-(2)H5]-Phenylalanine, L-[ring-(2)H2]-Tyrosine, L-[(2)H3]-3-Methylhistidine (given via continuous intravenous infusion), and L-[(15)N]-Phenylalanine (added to the protein meals) were used to measure endogenous whole-body protein breakdown (WbPB), whole-body protein synthesis (WbPS), net protein synthesis (NetPS), splanchnic extraction and myofibrillar protein breakdown (MPB). Analyses were done in arterialized-venous plasma by LC/MS/MS. RESULTS WbPS was greater after intake of the hCAS protein meal (P < 0.05) whereas the hWHEY protein meal reduced WbPB more (P < 0.01). NetPS was stimulated comparably, with a protein conversion rate greater than 70%. Addition of leucine did not modify the insulin, WbPB, WbPS or MPB response. CONCLUSIONS Hydrolyzed casein and whey protein meals comparably and efficiently stimulate whole-body protein anabolism in COPD patients with nutritional depletion without an additional effect of leucine co-ingestion. This trial was registered at clinicaltrials.gov as NCT01154400.

Effectiveness of essential amino acid supplementation in stimulating whole body net protein anabolism is comparable between COPD patients and healthy older adults

BACKGROUND The development of effective nutritional strategies in support of muscle growth for patients with chronic obstructive pulmonary disease (COPD) remains challenging. Dietary essential amino acids (EAAs) are the main driver of postprandial net protein anabolism. In agreement, EAA supplements in healthy older adults are more effective than supplements with the composition of complete proteins. In patients with COPD it is still unknown whether complete protein supplements can be substituted with only EAAs, and whether they are as effective as in healthy older adults. METHODS According to a double-blind randomized crossover design, we examined in 23 patients with moderate to very severe COPD (age: 65±2 years, FEV1: 40±2% of predicted) and 19 healthy age-matched subjects (age: 64±2 years), whether a free EAA mixture with a high proportion (40%) of leucine (EAA mixture) stimulated whole body net protein gain more than a similar mixture of balanced free EAAs and non-EAAs as present in whey protein (TAA mixture). Whole body net protein gain and splanchnic extraction of phenylalanine (PHE) were assessed by continuous IV infusion of L-[ring-2H5]-PHE and L-[ring-2H2]-tyrosine, and enteral intake of L-[15N]-PHE (added to the mixtures). RESULTS Besides an excellent positive linear relationship between PHE intake and net protein gain in both groups (r=0.84-0.91, P<0.001), net protein gain was 42% higher in healthy controls and 49% higher in COPD patients after intake of the EAA mixture compared to the TAA mixture (P<0.0001). These findings could not be attributed to the high LEU content, as in both groups net protein gain per gram EAA intake was lower for the EAA mixture (P<0.0001). Net protein gain was higher in COPD patients for both mixtures due to a 40% lower splanchnic extraction (P<0.0001), but was similarly related to dietary PHE (i.e. EAA) plasma appearance. CONCLUSIONS In COPD patients, similarly to healthy older adults, free EAA supplements stimulate whole body protein anabolism more than free amino acid supplements with the composition of complete proteins. Therefore, free EAA supplements may aid in the prevention and treatment of muscle wasting in this patient population.

Alterations in whole-body arginine metabolism in chronic obstructive pulmonary disease

BACKGROUND Chronic obstructive pulmonary disease (COPD) is a condition characterized by systemic low-grade inflammation that could increase the production of nitric oxide (NO), of which arginine is the sole precursor. Arginine is derived from the breakdown of protein and through the conversion of citrulline to arginine (de novo arginine production). OBJECTIVE Our objective was to study whole-body arginine and citrulline and related metabolism in stable COPD patients. DESIGN With the use of stable isotope methodology, we studied whole-body arginine and citrulline rates of appearance, de novo arginine (citrulline-to-arginine flux) and NO (arginine-to-citrulline flux) production, protein synthesis and breakdown rates, and plasma amino acid concentrations in a heterogeneous group of patients with moderate-to-severe COPD [n = 23, mean ± SE age: 65 ± 2 y, forced expiratory volume in 1 s (FEV1): 40% ± 2% of predicted], and a group of healthy older adults (n = 19, mean ± SE age: 64 ± 2 y, FEV1: 95% ± 4% of predicted). RESULTS Although plasma arginine and citrulline concentrations were comparable between COPD patients and controls, whole-body arginine (P = 0.015) and citrulline (P = 0.026) rates of appearance were higher in COPD patients and related to a 57% greater de novo arginine production (P < 0.0001). Despite a higher whole-body arginine clearance in COPD patients (P < 0.0001), we found no difference in NO production. CONCLUSION In stable patients with moderate-to-severe COPD, endogenous arginine production is upregulated to support a higher arginine utilization that is unrelated to whole-body NO production. This trial was registered at clinicaltrials.gov as NCT01173354 and NCT01172314.

Successful Management of Neobladder Variceal Bleeding

Hematuria from a neobladder can occur due to a variety of pathologies including tumors, stones, and fistulas. Variceal bleeding in a neobladder is a very rare condition with only one case reported in literature. We present a case of a patient with cirrhosis and portal hypertension and an ileocolic orthotopic neobladder presenting with hematuria. Computed tomographic angiography showed dilated varices around the neobladder which were successfully embolized. To the best of our knowledge, this is the first report case of variceal bleeding in a neobladder successfully managed with the combination of TIPS (transjugular intrahepatic portosystemic shunt) procedure and embolization.