Shorter interpuff interval is associated with higher nicotine intake in smokers with schizophrenia

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Abstract

Background

People with schizophrenia are frequent and heavy smokers.

Methods

The objective of this study was to measure serum nicotine levels and ad libitum smoking behavior for 24 + 2 h using the CReSS micro topography device in 75 smokers with schizophrenia (SCZ) and compare these to 86 control smokers (CON) without mental illness. Mean values of repeatedly measured topography variables were compared using three-level nested linear models to adjust for between subject differences and the double nested data.

Results

Smokers with SCZ smoked more cigarettes in the 24 h period and took an average of 2.8 more puffs per cigarette than CON (p < 0.001). The time between puffs, or interpuff interval (IPI), was shorter in SCZ by an average of 6.5 s (p < 0.001). The peak flow rate was higher in SCZ by an average of 4.9 ml/s (p < 0.05). Smokers with SCZ spent an average of 1.0 min less time smoking a single cigarette vs. CON (p < 0.001). Smokers with SCZ also had shorter IPI and more puffs per cigarette in an analysis of first cigarette of the day. For all subjects, a decrease in IPI by 1 s was associated with an increase in serum nicotine of 0.19 ng/ml and in cotinine of 5.01 ng/ml (both p < 0.05). After controlling for diagnosis group, higher craving scores on QSU Factor 2 (urgent desire to smoke) were associated with shorter IPI.

Discussion

Smokers with schizophrenia demonstrate more intense cigarette puffing that is associated with greater nicotine intake. This pattern may provide insight into other heavily dependent smokers.

Introduction

People with schizophrenia smoke at higher rates than the general population in both U.S. and international studies (Lasser et al., 2000, de Leon and Diaz, 2005). There is also evidence of high nicotine dependence in this group measured as heavy smoking (de Leon and Diaz, 2005), higher scores on structured nicotine dependence scales (Weinberger et al., 2007) or other indicators including higher carbon monoxide boost (Tidey et al., 2008) or waking at night to smoke (Prochaska et al., 2007). Not surprisingly, smoking-related diseases are common and individuals with schizophrenia suffer increased cardiovascular and respiratory diseases as well as reduced life expectancy (Curkendall et al., 2004, Brown et al., 2000, Capasso et al., 2008). Smoking cessation rates in this group are also lower compared to the general population (Lasser et al., 2000, Covey et al., 1994).

In addition to being heavy smokers, there is evidence that smokers with schizophrenia take in more nicotine per cigarette than smokers without this disorder as measured by levels of nicotine and cotinine, a nicotine metabolite (Olincy et al., 1997, Williams et al., 2005). Our prior work showed that smokers with schizophrenia have 1.3 times higher serum nicotine and cotinine levels compared to controls with no mental illness. Smokers with schizophrenia have no differences in rates of oxidative metabolism of nicotine based on a ratio of 3-hydoxycotinine (3HC) to cotinine (COT; Williams et al., 2005). 3HC/COT is a useful biomarker of CYP2A6 metabolic activity and measure of the rate of nicotine metabolism (Benowitz et al., 2003, Dempsey et al., 2004).

Higher nicotine intake from smoking a single cigarette (after a period of overnight abstinence) has been demonstrated in smokers with schizophrenia compared to controls (Williams et al., 2010). The increase in levels of blood nicotine that occur from smoking a single cigarette is referred to as “nicotine boost” which averages about 10 ng/ml per cigarette in non-psychiatrically ill smokers (Russell et al., 1981, Foulds et al., 1992, Patterson et al., 2003). Average levels of nicotine boost were 28 ng/ml in smokers with schizophrenia. Smokers with schizophrenia reached the nicotine peak earlier (4.8 min vs. 6.4 min) than control smokers and had a greater total nicotine intake (measured as area under the serum nicotine concentration–time curve) from a single cigarette (Williams et al., 2010).

Most studies of nicotine intake in schizophrenia have failed to include assessments of smoking topography to characterize differences in cigarette puffing behavior. Topography studies are important since the way in which cigarettes are smoked, rather than the physical characteristics of the cigarette, is the most important determinant of nicotine intake (Kozlowski et al., 2001). Smoking topography methodology is a valuable tool for assessing cigarette smoke self-administration and technological advances allow for these studies to be done in naturalistic settings, outside of the laboratory. A concern in interpreting prior laboratory-based topography studies has been that the setting and/or device might influence the smoking behavior (Scherer, 1999, Tobin and Sackner, 1982). Although all topography measurements are limited, at least to some degree, by the artificial act of smoking while using a device or smoking through a mouthpiece, these smaller portable devices are easy to use outside of the laboratory setting to capture more naturalistic smoking and allow for less intrusion from the research environment. The filter end of a cigarette is inserted into the topography instrument and smoke flows through the device into a sterilized mouthpiece from which the smoker inhales. A differential pressure flow sensor device measures the pressure differential generated by each puff on the mouthpiece. All of the other variables are derived from the basic measurements of flow and time (Hammond et al., 2005).

Tidey et al. (2005) published a study comparing topography measurements in 20 smokers with schizophrenia (SCZ) to 20 matched controls (CON) using a laboratory based topography device. Participants underwent two assessments of smoking topography taken during 90 min of ad libitum smoking on separate days. The study did not collect blood nicotine levels, but subjects did provide a saliva sample for cotinine level. SCZ subjects smoked significantly more total puffs, more puffs per cigarette, had larger total puff volume and had shorter inter-puff interval than CON. Test-retest reliabilities were good to excellent between smoking session and the authors concluded that smoking behavior in schizophrenia is reliable when assessed with topography. McKee et al. (2009) conducted a pilot study in 14 smokers that showed no difference in smoking topography measures between smokers with SCZ and controls.

The objective of this current study was to measure smoking topography and serum nicotine levels in smokers with schizophrenia and compare these to control smokers without mental illness. We were also interested in looking at puffing patterns for the first cigarette of the day smoked since it is a predictor of daily nicotine uptake, and nicotine dependence (Muscat et al., 2009).

By evaluating smoking puffing behavior and nicotine intake concurrently we hoped to examine associations between puff characteristics and nicotine levels measured in the same day. Identifying cigarette puffing parameters that determine nicotine intake is essential to understanding tobacco use in schizophrenia and can be used to develop better treatments and improve cessation outcomes for smokers with schizophrenia.

Section snippets

Subjects

This study was approved by the IRB at UMDNJ-Robert Wood Johnson Medical School. Subjects were recruited from the UMDNJ-University Behavioral Health Care System and other outpatient behavioral health care agencies. A community sample of healthy volunteer smokers without mental illness was recruited through advertisements to participate in the study. All subjects with schizophrenia were enrolled in mental health treatment, stable on antipsychotic medications and had their diagnosis confirmed with

Demographics

No differences were found between SCZ versus CON on cigarettes smoked per day (CPD), FTND total score, age of first smoking, number of past quit attempts, race/ethnicity and education (see Table 1). Smokers with SCZ had higher baseline expired CO (23.1 vs. 19.5; p < 0.05) and were older and more likely to be men compared to CON (both p < 0.01). CON were more likely to report waking up at night to smoke (89.5% vs. 77.3%; p < 0.05) although groups were not different in reporting time to first cigarette

Discussion

In this study, smokers with SCZ differed from smokers without this disorder in that they took more frequent puffs per cigarette and waited less time between puffs. Topography results from the 24 h smoking session were remarkably similar to the first cigarette of the day for measures of puff count and interpuff interval. Smoking more cigarettes before and during the study period could have biased the results towards the control group by reducing the impact of nicotine intake from a single

Conflict of interest

Jill Williams and Marc Steinberg have received research and grant support from Pfizer. Jill Williams is also a consultant of Pfizer.

Neal Benowitz has been a paid consultant to pharmaceutical companies that market or are developing smoking cessation medications, including Pfizer, GlaxoSmithKline, Novartis, Sanofi-Aventis, Accrux and Aradigm. Neal Benowitz has served as a paid expert witness in litigation against tobacco companies regarding tobacco addiction.

Kunal K. Gandhi, Supriya Kumar,

Acknowledgements

This work was supported by grants to JMW from the National Institute of Mental Health (MH076672-01A1 to JMW) and from the National Institute on Drug Abuse (DA12393, NLB).

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