Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability.

Currently available nicotine replacement therapy (NRT) medications provide effective treatment for tobacco dependence, typically doubling success rates compared with placebo. A strategy for further improving the efficacy of NRT is to combine one medication that allows for passive nicotine delivery (e.g. transdermal patch) with another medication that permits ad libitum nicotine delivery (e.g. gum, nasal spray, inhaler). The rationale for combining NRT medications is that smokers may need both a slow delivery system to achieve a constant concentration of nicotine to relieve cravings and tobacco withdrawal symptoms, as well as a faster acting preparation that can be administered on demand for immediate relief of breakthrough cravings and withdrawal symptoms. This article reviews 5 published studies that have examined the effectiveness of combination NRT compared with monotherapy in providing withdrawal relief and smoking cessation, and examines other factors relevant to the promotion of combination NRT for treating tobacco dependence. The data show that there are conditions under which combinations of NRT products provide greater efficacy in relieving withdrawal and enabling cessation than monotherapy, but the findings are not robust and additional research is warranted to better understand the magnitude and generality of the benefits of combination therapy. There are also regulatory and commercial obstacles that must be considered. Nonetheless, combination NRT has the potential to provide effective treatment of tobacco dependence in persons whose dependence is refractory to currently available treatments.

Diaphragmatic electromyography using a multiple electrode array.

We have developed a new technique for diaphragmatic electromyography using an array of seven sequential electrode pairs at 1.0-cm spacing on an esophageal catheter. This array provides information about the spatial distribution of the electrical field generated by the diaphragm and reveals a sharply peaked variation of electrical potential with distance along the esophagus. The rectified and integrated information from each of the seven pairs is summed to give an approximation to the total electrical activity over the span of the array, providing a signal that is relatively insensitive to the position of the array over approximately 4 cm of catheter movement and removes the requirement for balloon stabilization of the catheter. With our array, we have confirmed the artifact in the evoked compound muscle action potential that seems to be related to diaphragmatic shape as reported by others who used supramaximal phrenic nerve stimulation, but the magnitude of this artifact (compared with the functional residual capacity level) was modest near functional residual capacity, averaging 12 +/- 14% (SD) for lung volumes 1.0 l above and -4 +/- 15% for lung volumes 1.0 l below functional residual capacity along the rib cage-abdomen relaxation line.

Comparison of clinical dyspnea ratings and psychophysical measurements of respiratory sensation in obstructive airway disease.

To investigate the hypothesis that clinical methods and psychophysical testing provide different information about breathlessness, we compared dyspnea ratings from a modified Medical Research Council (MRC) scale, the Oxygen-Cost Diagram (OCD), and the Baseline Dyspnea Index (BDI) with the perceived magnitude of added loads in 24 patients with obstructive airway disease (OAD) who experienced dyspnea on exertion. Age of the patients was 55.8 +/- 13.7 yr (mean +/- SD), FEV1 was 1.77 +/- 0.81 L, and FEV1/FVC ratio was 52.6 +/- 10.5%. Dyspnea ratings were obtained for each clinical method by 2 independent observers; estimates of the magnitude of 5 resistive loads (10 to 85 cm H2O/L/s) were obtained using the Borg category scale (0 to 10). For comparative purposes, 12 age-matched (48.9 +/- 13.5 yr) healthy subjects were also studied. Clinical ratings of dyspnea obtained in patients for MRC (range, 0 to 4), OCD (range, 23 to 98), and BDI (range, 0.5 to 12.0) were all highly interrelated (rs = 0.79, -0.83, and -0.71; p less than 0.001 for all comparisons). Exponents of the psychophysical power function for resistive breathing loads were similar for patients with OAD (0.57 +/- 0.27) and control subjects (0.63 +/- 0.18) (p = NS). Clinical dyspnea scores were significantly correlated with both FEV1 and FVC; however, neither dyspnea ratings nor lung function were significantly related to the exponent for added breathing loads in the patient group. These comparisons indicate that in patients with symptomatic OAD, clinical methods for rating dyspnea are interrelated and are correlated with lung function, but are independent of perception of resistive breathing loads.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of non-REM sleep upon respiratory drive and the respiratory pump in humans.

We observed that ventilation fell and end-tidal CO2 rose in the change from wakefulness to non-REM (NREM) sleep in 4 normal human subjects studied on two nights each. We hypothesized that the observed ventilatory depression was due to effects of sleep both upon the central respiratory neural output and upon the mechanical respiratory pump. Both the central controller response to CO2, as measured by diaphragmatic and intercostal EMG activity, and the ability of the respiratory pump in effecting ventilation in response to diaphragmatic or intercostal activation, as measured by the relationship between the EMG activities and minute ventilation, are reduced in NREM sleep. We describe a general method of apportioning the separate effects of sleep, or other factors, upon the central respiratory controller, the respiratory mechanical pump, and the metabolic rate, in determining the total observed increase in end-tidal CO2.