Predictors of oxygen desaturation during submaximal exercise in 8,000 patients.

STUDY OBJECTIVES: To determine predictors of oxygen desaturation during submaximal exercise in patients with various lung diseases. DESIGN AND SETTING: This retrospective case series used pulmonary function laboratory results from all patients referred to a major tertiary-care center. PATIENTS AND MEASUREMENTS: All patients > or = 35 years old who underwent spirometry, diffusing capacity of the lung for carbon monoxide (DLCO), lung volumes, and pulse oximetry during 3-min submaximal step-test exercise during 1996 were included (4,545 men and 3,472 women). Logistic regression models, correcting for gender, age, and weight, determined the odds ratios (ORs) for oxygen desaturation of > or = 4% during exercise for each category of lung function abnormality (compared to those with entirely normal lung function). RESULTS: Approximately 74% of the patients had airways obstruction, while only 5.6% had restriction of lung volumes. One third of those with obstruction had a low DLCO, compared to 56% with restriction, while 2.7% had a low DLCO without obstruction or restriction. The risk of oxygen desaturation during submaximal exercise was very high (OR, 34) in patients with restriction and low DLCO (as in interstitial lung disease) and in patients with obstruction and low DLCO (as in COPD; OR, 18), intermediate (OR, 9) in patients with only a low DLCO, and lowest in those with a normal DLCO (OR, 4 if restricted; OR, 2 if obstructed). A cut point of DLCO < 62% predicted resulted in 75% sensitivity and specificity for exercise desaturation. No untoward cardiac events occurred in any patients during or following the submaximal exercise tests. CONCLUSIONS: The risk of oxygen desaturation during submaximal exercise is very high in patients with a low DLCO. Submaximal exercise tests are safe, even in elderly patients with heart and lung diseases.

The cannabinoid agonist WIN55,212-2 suppresses opioid-induced emesis in ferrets.

BACKGROUND: Cannabinoid receptor agonists reverse nausea and vomiting produced by chemotherapy and radiation therapy in animals and humans but have not been tested against opioid-induced emesis. This study tests the hypothesis that cannabinoid receptor agonists will prevent opioid-induced vomiting. METHODS: Twelve male ferrets were used. They weighed 1.2-1.6 kg at the beginning and 1.8-2.3 kg at the end of the experiments. All drugs were injected subcutaneously. WIN55,212-2, a mixed CB1-CB2 cannabinoid receptor agonist, was administered 25 min before morphine. Retches and vomits were counted at 5-min intervals for 30 min after morphine injection. RESULTS: Retching and vomiting responses increased with increasing morphine doses up to 1.0 mg/kg, above which the responses decreased. Previous administration of naloxone prevented morphine-induced retching and vomiting. WIN55,212-2 dose-dependently reduced retching and vomiting. The ED50 was 0.05 mg/kg for retches and 0.03 mg/kg for vomits. At 0.13 mg/kg, retching decreased by 76% and vomiting by 92%. AM251, a CB1 receptor-selective antagonist, blocked the antiemetic actions of WIN55,212-2, but AM630, a CB2 receptor-selective antagonist, did not. CONCLUSIONS: These results demonstrate that WIN55,212-2 prevents opioid-induced vomiting and suggest that the antiemetic activity of WIN55,212-2 occurs at CB1 receptors. This is consistent with findings that CB1 receptors are the predominant cannabinoid receptors in the central nervous system and that antiemetic effects of cannabinoids appear to be centrally mediated.

Predictors of loss of lung function in the elderly: the Cardiovascular Health Study.

Pulmonary function, as measured by spirometry (FEV1 or FVC), is an important independent predictor of morbidity and mortality in elderly persons. In this study we examined the predictors of longitudinal decline in lung function for participants of the Cardiovascular Health Study (CHS). The CHS was started in 1990 as a population-based observational study of cardiovascular disease in elderly persons. Spirometry testing was conducted at baseline, 4 and 7 yr later. The data were analyzed using a random effects model (REM) including an AR(1) error structure. There were 5,242 subjects (57.6% female, mean age 73 yr, 87.5% white and 12.5% African-American) with eligible FEV1 measures representing 89% of the baseline cohort. The REM results showed that African-Americans had significantly lower spirometry levels than whites but that their rate of decline with age was significantly less. Subjects reporting congestive heart failure (CHF), high systolic blood pressure (> 160 mm Hg), or taking beta-blockers had significantly lower spirometry levels; however, the effects of high blood pressure and taking beta-blockers diminished with increasing age. Chronic bronchitis, pneumonia, emphysema, and asthma were associated with reduced spirometry levels. The most notable finding of these analyses was that current smoking (especially for men) was associated with more rapid rates of decline in FVC and FEV1. African-Americans (especially women) had slower rates of decline in FEV1 than did whites. Although participants with current asthma had a mean 0.5 L lower FEV1 at their baseline examination, they did not subsequently experience more rapid declines in FEV1.