Treatment with systemic glucocorticoids results in moderate improvement in clinical outcomes among patients hospitalized for exacerbations of COPD. The maximal benefit is obtained during the first two weeks of therapy. Hyperglycemia of sufficient severity to warrant treatment is the most frequent complication.

FEV(1) is an objective measure of airflow obstruction used in clinical practice and in therapeutic trials. The precise relationship of FEV(1) to clinical outcomes is generally uncertain. As part of a randomized trial to assess systemic corticosteroid efficacy, we obtained serial FEV(1) measurements in patients hospitalized for exacerbations of chronic obstructive pulmonary disease (COPD). Over the first 14 Study Days at least one FEV(1) value was obtained in 261 subjects. Sixty-four of these subjects experienced treatment failure, defined as death, intubation, readmission for COPD, or intensification of drug therapy, by Study Day 30. After adjustment, both FEV(1) at entry into the study (odds ratio [OR] for a 100-ml increase, 0.87; 95% confidence interval [CI], 0.79 to 0.96) and change in FEV(1) over the first two Study Days (OR for a 100 ml increase, 0.80; 95% CI, 0.69 to 0.92) predicted treatment failure. We identified no baseline characteristic that was significantly related to FEV(1) at entry into the study. Assignment to the systemic corticosteroid treatment arm was associated with a significantly larger FEV(1) at Study Day two (p = 0.01). We conclude that FEV(1) measurements at admission and over the first several days of hospitalization are highly predictive of clinical outcomes during exacerbations of COPD.

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 15g 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-2H5]-Phenylalanine, L-[ring-2H2]-Tyrosine, L-[2H3]-3-Methylhistidine (given via continuous intravenous infusion), and L-[15N]-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.

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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 y, FEV1: 40 ± 2% of predicted) and 19 healthy age-matched subjects (age: 64 ± 2 y), 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. Trial registry ClinicalTrials.gov; Nos.: NCT01173354 and NCT01172314; URL: www.clinicaltrials.gov

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.

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Smokers were given 5 mg of aerosolized nicotine over a 5-min period on 3 separate days to determine if this mode of nicotine delivery could produce nicotine levels similar to those reported from cigarette smoking. Our subjects' mean nicotine level increased from a pretrial level of 12 +/- 2 ng/ml to a peak of 32 +/- 7 ng/ml at 2.5 min after completion of the inhalation. Cough was the most prominent side effect and seemed to be related to irritant effects of the aerosol. Seven of the 16 subjects dropped out of the study because of unpleasant side effects. Side effects did not seem to correlate with nicotine blood levels. We conclude that aerosolized nicotine can produce plasma nicotine levels analogous to cigarette smoking. Cough was a limiting side effect and was presumably due to an irritant effect of the aerosol on the upper airway.