Systematic review and meta-analysis investigating nicotine, cotinine and carbon monoxide exposures in people who both smoke and use nicotine replacement therapy

Aims: To determine effects of concurrent smoking and nicotine replacement therapy (NRT) use on reported heaviness of smoking, nicotine (cotinine) body fluid and exhaled air carbon monoxide (CO) concentrations. Methods: Systematic review and meta-analysis of RCTs, which test interventions permitting concurrent NRT use and smoking and comparing, within participants, outcomes when smoking with those when smoking and using NRT concurrently. Measurements included reported number of cigarettes smoked per day (CPD), body fluid cotinine and expired air CO concentrations. Results: Twenty-nine studies were included in the review. Meta-analysis of nine showed that, compared with when solely smoking, fewer cigarettes were smoked daily when NRT was used (mean difference during concurrent smoking and NRT use, −2.06 CPD [95% CI = −3.06 to −1.07, P < 0.0001]). Meta-analysis of seven studies revealed a non-significant reduction in exhaled CO during concurrent smoking and NRT use (mean difference, −0.58 ppm [95% CI = −2.18 to 1.03, P = 0.48]), but in the three studies that tested NRT used in the lead-up to quitting (i.e. as preloading), a similar reduction in exhaled CO was statistically significant (mean difference, −2.54 ppm CO [95% CI = −4.14 to −0.95, P = 0.002]). Eleven studies reported cotinine concentrations, but meta-analysis was not possible because of data reporting heterogeneity; of these, seven reported lower cotinine concentrations with concurrent NRT use and smoking, four reported no differences, and none reported higher concentrations. Conclusions: People who smoke and also use nicotine replacement therapy report smoking less heavily than people who solely smoke. When nicotine replacement therapy is used in the lead-up to quitting (preloading), this reported smoking reduction has been biochemically confirmed. There is no evidence that concurrent smoking and nicotine replacement therapy use result in greater nicotine exposure than solely smoking.