Cigarette smoking is common among patients with schizophrenia, mood disorders, anxiety disorders,1-3 substance use disorders (SUDs),4 and other psychiatric disorders. Research suggests that compared with the general population, patients with SUDs consume more nicotine products and are more vulnerable to the effects of smoking.5 Despite the availability of effective treatments, many mental health professionals are reluctant to identify and treat tobacco use disorder,6-8 or they prioritize other disorders over tobacco use. Early detection and treatment of tobacco use disorder can improve patients’ health and reduce the incidence of acute and chronic illness.
Cotinine is a biomarker that can be used to detect tobacco use. It can be measured in routine clinical practice by collecting urinary, serum, or salivary specimens, and used to monitor psychiatric patients’ tobacco use. Monitoring cotinine levels is similar to using other biomarkers to assess medication adherence or identify illicit substance use. A growing body of evidence supports the utility of cotinine screening as a part of a comprehensive substance use disorder treatment plan,5,9,10 especially for:
- patients who have comorbid conditions that can be exacerbated by tobacco use, such as chronic obstructive pulmonary disease
- patients who are pregnant11,12
- patients who are less reliable in self-report or who require objective testing for validation.
Routine clinical screening of tobacco use is recommended for all patients and early detection may facilitate earlier treatment. Several FDA-approved medications are available for smoking cessation13; however, discussion of treatment options is beyond the scope of this review. In this article, we describe how cotinine is measured and analyzed, 3 case vignettes that illustrate its potential clinical utility, and limitations to its use as a biomarker of tobacco use.
Methods of measuring cotinine
Cigarette smoking is associated with the absorption of nicotine, which is mainly metabolized by cytochrome P450 (CYP) 2A6 to 6 primary metabolites: cotinine, hydroxycotinine, norcotinine, nornicotine, cotinine oxide, and nicotine oxide.14,15 Cotinine is the biomarker of choice for detecting use of tobacco/nicotine products due to its stability (it is not influenced by dietary or environmental factors), extended half-life (16 to 19 hours, compared with 2 hours for nicotine), and stable concentration throughout the day. Samples from saliva, urine, or blood can be analyzed through radioimmunoassay, enzyme-linked immunosorbent assay (ELISA), and gas/liquid chromatography.16 The specificity of cotinine for tobacco use is excellent, except for persons who are taking medications that contain nicotine.17
An advantage of cotinine over other biomarkers for smoking (such as carbon monoxide in expired air) is that the optimal cut-off points for cotinine are relatively uninfluenced by the prevalence of smoking in the population. The optimal cut-off levels used to detect current tobacco use may vary based on the sample or test used (saliva, urine, or plasma) and certain patient-specific factors (Box 111,16,18-21). However, for plasma or saliva cotinine, 16 ng/mL is the generally accepted cut-off level for detecting current tobacco use. A urinary cotinine cut-off level of 50 ng/mL is likely appropriate for most circumstances.17 Users of electronic nicotine delivery systems (electronic cigarettes) have been found to have cotinine levels similar to those of cigarette smokers.22
Box 1
Cotinine concentrations and cut-off levels
Daily smokers typically have a serum/plasma cotinine concentration of ≥100 ng/mL. Individuals with heavy exposure to secondhand smoking may have plasma cotinine concentrations up to 25 ng/mL, and urine samples tend to be much more specific.16 However, serum cotinine has a wide cut-off range due to diverse racial/ethnic, gender, and pregnancy-related variations; the wide range is also associated with genetic polymorphisms of cytochrome P450 2A6 alleles and nicotine’s numerous metabolic pathways.11,18
Traditionally a serum/plasma cut-off point of approximately 15 ng/mL has been accepted to detect current tobacco use; however, recent studies21 recommend an average optimal cut-off point for US adults of 3 ng/mL. This possibly reflects differences in national cigarette smoking patterns and exposure.21 One study suggested optimal cut-off differences for men (1.78 ng/mL) and women (4.47 ng/mL).19 The same study also suggested different optimal cut-off levels for non-Hispanic White men (6.79 ng/ mL), non-Hispanic Black men (13.3 ng/mL), and Mexican-American men (0.79 ng/mL).19 These researchers also suggested different optimal cut-off levels for non-Hispanic White women (4.73 ng/mL), non-Hispanic Black women (5.91 ng/mL), and Mexican-American women (0.84 ng/mL).19 Genetic factors may also play a role in the progression of nicotine dependence and pose challenges that impact smoking persistence.20
Assessment of cotinine levels in saliva may be considered for outpatient monitoring due to its noninvasive nature, tolerability, and the ability to collect multiple samples over a limited period.23 Saliva cotinine levels correlate closely with blood concentrations. Urine cotinine levels offer some advantage because concentrations are 6 times higher in urine than in blood or saliva. For this reason, urine cotinine is the most widely used biomarker in individuals who use tobacco due to its high sensitivity, specificity, reliability, and noninvasive collection.23 By using a lower urinary cut-off of ≥2.47 ng/mL, ELISA kits detect the highest sensitivity and specificity, which is useful for monitoring daily tobacco use.24 This cut-off value was associated with 100% sensitivity and specificity, and these numbers declined with increases in the cut-off threshold.23
Impact of cigarette smoking
The following 3 clinical vignettes illustrate the impact of tobacco use disorder on patients, and how cotinine might help with their treatment.
Continue to: Vignette 1