Maarten A.M. Jansen

In contrast to methacholine, a stimulus that induces airway constriction mainly by "direct" stimulation of airway smooth muscle cells, AMP airway responsiveness reflects "indirectly" induced airway narrowing via inflammatory or neural reflex mechanisms. In order to determine inflammatory contribution to airway narrowing in COPD, we performed AMP and methacholine inhalation provocation tests in nonatopic subjects with COPD and compared the results with those obtained from atopic nonsmoking asthmatics and from healthy smoking volunteers. AMP caused airway narrowing in all but two subjects with COPD and in only three of the 12 healthy smoking subjects. Patients with COPD were significantly more responsive to AMP and methacholine than were healthy smoking volunteers. Geometric mean PC20 AMP was significantly lower in the smokers with COPD (7.2 mg/ml) than in the nonsmokers with COPD (58.5 mg/ml), whereas PC20 methacholine values and baseline FEV1 were comparable. In the nonatopic nonsmoking subjects with COPD, PC20 AMP was significantly higher than in the atopic nonsmoking asthmatics (3.8 mg/ml), whereas they responded similar to methacholine provocation. These results indicate that most subjects with COPD respond to AMP provocation and that smoking determines the degree of airway responsiveness to AMP in COPD. We suggest that increased susceptibility to mediator release by mast cells or neural reflex mechanisms are involved in AMP-induced airway constriction in asthma and in COPD.

OBJECTIVE: To assess health-related quality of life (QL) in a group of Dutch predialysis end-stage renal disease (ESRD) patients prior to the initiation of dialysis, and to compare QL between patients with different intended initial dialysis treatments. DESIGN: In a prospective cohort study, demographic, clinical, and QL data were obtained from Dutch adult patients who were consecutively enrolled from 27 different centers 0 - 4 weeks prior to the beginning of their chronic dialysis treatment. PATIENTS: Of the 301 patients who completed the QL questionnaires (of a possible 337 enrolled patients), 152 intended to start with hemodialysis (pre-HD) and 149 patients with peritoneal dialysis (pre-PD). MAIN OUTCOME MEASURE: Perceived QL of pre-HD and pre-PD patients. Quality of life was assessed with two generic health assessment instruments: the SF-36 and the EuroQol. RESULTS: After correction for group differences, pre-HD patients scored consistently, but not significantly, lower for all separate dimensions of the SF-36 and the overall health score of the EuroQol compared to pre-PD patients. However, analyzing the dimensions of the SF-36 together, adjusted for case-mix, pre-HD patients scored significantly lower than pre-PD patients. Mean difference was 6.5 points (p = 0.04). CONCLUSION: Multivariate adjustment for known case-mix differences at the start of dialysis therapy was not sufficient to adjust for all patient selection effects on QL. Consequently, published QL comparisons between HD and PD in nonrandomized cohort studies should be interpreted with caution. Assessment of QL just before start of dialysis therapy and subsequent adjustment for baseline values may be the only valid alternative for randomized studies.