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To assess the effect of isoproterenol on intrapulmonary gas mixing, simultaneous wash-out of He and SF was measured in five healthy subjects at rest (mean heart rate ≈ 73/min) and during infusion of isoproterenol (mean heart rate ≈ 118/min). Test gas segregation was characterized by use of a separation index, S.I., as proposed by Kawashiro et al. [7]. At both heart rates, wash-out of He was faster than that of SF (positive S.I.). However, during infusion of isoproterenol, S.I. decreased, indicating more similar wash-out kinetics of the test gases. About 20% of the separation effect could be attributed to the single breath dead space being larger for SF than for He. Mean dead space difference decreased significantly from 34 to 23 ml at the increased heart rate. With certain assumptions concerning the contribution of convection and diffusion to intrapulmonary gas mixing, the stratificational gas transfer conductance could be estimated. The stratificational conductance for O was estimated at 1 to 5 mmol · min · torr at rest, increasing on the average by more than 10% during infusion of isoproterenol. This increase can be most easily explained by enhanced gas mixing possibly due to the increased action of the heart during infusion of isoproterenol. [ABSTRACT FROM AUTHOR]

Purpose: A number of analyses have shown the immediate impact of COPD exacerbations on health status. However, none evaluated the long-term correlation between health status and the occurrence of exacerbations., Methods: DACCORD is an observational study in patients with COPD recruited across Germany following initiation or change in COPD maintenance medication. Data collected include COPD Assessment Test (CAT) total score on entry and after 1 and 2 years, and the occurrence of exacerbations. We analysed the correlation between change from baseline in CAT total score and exacerbations, after excluding patients who exacerbated during the quarter immediately prior to the CAT assessment of interest., Results: The initial correlation analysis was performed in 6075 patients, 28% with ≥ 1 exacerbation over the 2-year follow-up, and 58% with a clinically relevant CAT improvement. There was a significant correlation between exacerbations over 2 years and CAT change from baseline at Year 2 (p = 0.0041). The Spearman's correlation coefficient was 0.03711, indicating very weak correlation-potentially driven by the high proportion of non-exacerbating patients. In a subsequent logistic regression, the probability of experiencing frequent (≥ 2 per year) or severe exacerbations was higher in patients with worsening in CAT total score (p < 0.001). However, the probability of a patient exacerbating in Year 1 or Year 2 did not correlate with CAT change., Conclusions: In this population (initiating or changing maintenance COPD medication), patients with frequent or severe exacerbations had a long-term worsening in health status (beyond the acute effect of an exacerbation) compared with patients who do not exacerbate.

In severe asthma attacks beta 2-sympathomimetics lose part of their therapeutic efficiency. To elucidate this loss of efficiency in an experimental model we compared the relaxant potency of salbutamol (SAL), fenoterol (FEN), formoterol (FOR), and (-)-isoprenaline (ISO) in guinea pig tracheae partially and maximally precontracted by 0.1 and 60 mumol/L carbachol, respectively. In partially precontracted tracheae the beta 2-sympathomimetics exerted maximum relaxation in comparison with ISO and low EC50S (nmol/L) for relaxation (SAL, 20; FEN, 5.6; FOR, 0.28; and ISO, 2.5). In maximally precontracted tracheae, however, the beta 2-sympathomimetics were only partial agonists for relaxation with reduced intrinsic activities (%) in comparison to ISO (SAL, 59%; FEN, 61%; FOR, 76%) and significantly increased EC50S (nmol/L) for relaxation (SAL, 130; FEN, 57; FOR, 3.0; ISO, 37). To investigate if the high relaxant potency of FOR is correlated with a higher binding affinity and/or a higher intrinsic activity for adenylate cyclase stimulation than for FEN and SAL, we performed experiments in receptor membranes from guinea pig lung. Binding competition of SAL, FEN, and FOR with [3H]ICI 118,551 for lung beta 2-adrenoceptors yielded dissociation constants (KD) of 320 (SAL), 120 (FEN), and 7.6 (FOR) nmol/L, which exhibited the same ranking as EC50S for relaxation. Concentrations of SAL, FEN, and FOR equivalent to 100 KD of the respective dissociation constants stimulated beta 2-adrenoceptor-coupled adenylate cyclase with different intrinsic activities (%) incomparison to ISO (SAL, 61%; FEN, 63%; FOR, 89%) matching intrinsic activities for relaxation. From these experiments it may be concluded that FOR might improve drug therapy of severe asthma not only due to its long mode of action discovered in clinical studies but also due to its high intrinsic activity and receptor affinity.