A method to study the effect of bronchodilators on smoke retention in COPD patients: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Chronic obstructive pulmonary disease (COPD) is a common disease, associated with cardiovascular disease. Many patients use (long-acting) bronchodilators, whilst they continue smoking alongside. We hypothesised an interaction between bronchodilators and smoking that enhances smoke exposure, and hence cardiovascular disease. In this paper, we report our study protocol that explores the fundamental interaction, i.e. smoke retention.</p> <p>Method</p> <p>The design consists of a double-blinded, placebo-controlled, randomised crossover trial, in which 40 COPD patients smoke cigarettes during both undilated and maximal bronchodilated conditions. Our primary outcome is the retention of cigarette smoke, expressed as tar and nicotine weight. The inhaled tar weights are calculated from the correlated extracted nicotine weights in cigarette filters, whereas the exhaled weights are collected on Cambridge filters. We established the inhaled weight calculations by a pilot study, that included paired measurements from several smoking regimes. Our study protocol is approved by the local accredited medical review ethics committee.</p> <p>Discussion</p> <p>Our study is currently in progress. The pilot study revealed valid equations for inhaled tar and nicotine, with an R²of 0.82 and 0.74 (p < 0.01), respectively. We developed a method to study pulmonary smoke retentions in COPD patients under the influence of bronchodilation which may affect smoking-related disease. This trial will provide fundamental knowledge about the (cardiovascular) safety of bronchodilators in patients with COPD who persist in their habit of cigarette smoking.</p> <p>Trial registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT00981851">NCT00981851</a></p

The pathophysiology of the vasovagal response

In Part I we found that the classic studies of vasovagal syncope, done on fit young subjects, over stated vasodilatation as the dominant hypotensive mechanism. Since 1980, blood pressure and cardiac output have been measured continuously using non-invasive methods during tilt, mainly in patients with recurrent syncope, including women and the elderly. This has allowed us to analyse in more detail the complex sequence of hemodynamic changes leading up to syncope in the laboratory. All tilt-sensitive patients appear to progress through 4 phases: 1 early stabilisation, 2 circulatory instability, 3 terminal hypotension and 4 recovery. The physiology responsible for each phase is discussed. Although the order of phases is consistent, the time spent in each phase may vary. In teenagers and young adults, progressive hypotension during phases 2 and 3 can be driven by vasodilatation or falling cardiac output. The fall in cardiac output is secondary to a progressive decrease in stroke volume because blood is pooled in the splanchnic veins. In adults a fall in CO is the dominant hypotensive mechanism because systemic vascular resistance always remains above baseline levels