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The Food and Drug Administration has the authority to reduce the nicotine content of cigarettes. In this randomized trial, participants assigned to reduced-nicotine cigarettes smoked fewer cigarettes than those assigned to standard-nicotine cigarettes. Twenty years ago, Benowitz and Henningfield published a landmark commentary that coincided with initial attempts by the Food and Drug Administration (FDA) to regulate tobacco products. 1 They reasoned that if the nicotine content of cigarettes were limited to approximately 0.5 mg per cigarette (approximately 0.7 mg per gram of tobacco), cigarettes would be rendered nonaddictive. Although a reduction in nicotine content was endorsed by representatives of the medical community, 2 in 2000, the FDA lost its initial argument to regulate cigarettes in a hearing before the Supreme Court, and the proposal ultimately languished. 3 In the past 8 years, the prospect of . . .

In this trial involving pregnant women in low- and middle-income countries, cooking with LPG instead of biomass did not lead to a lower incidence of severe infant pneumonia, despite lower levels of household air pollutants.

Abstract Introduction This study examined changes in biomarkers of exposure (BoE) after 5 days of nicotine-salt pod system (NSPS) use, compared with continuation of usual-cigarette smoking and cigarette abstinence, among adult combustible cigarette smokers. Aims and Methods A randomized, open-label, parallel-cohort, confinement study of healthy adult smokers, naive to NSPS use, was conducted. Participants (N = 90) were randomized to six cohorts (n = 15 each): exclusive ad libitum use of NSPS (four flavors: Virginia Tobacco, Mint, Mango, Creme), continuation of usual-brand cigarette smoking, or cigarette abstinence. Total nicotine equivalents and BoE (NNN, NNAL, 3-HPMA, MHBMA, S-PMA, HMPMA, CEMA, 1-OHP, and COHb) were measured. Results Eight non-nicotine BoEs, measured in urine, were reduced by an aggregate of 85.0% in the pooled NSPS cohort; increased by 14.4% in the cigarette cohort (p < .001 for pooled NSPS vs. cigarette); and reduced by 85.3% in the abstinence cohort (p > .05; 99.6% relative reduction between pooled NSPS vs. abstinence). Similar changes in individual BoEs were also observed (p < .001 for each BoE between pooled NSPS vs. cigarettes; and abstinence vs. pooled NSPS; p > .05 for each BoE between pooled NSPS vs. abstinence). Blood COHb decreased by 71.8% in the pooled NSPS cohort and 69.1% in the abstinence cohort (p > .05) and increased by 13.3% in the cigarette cohort (p < .001). Mean total urine nicotine equivalents increased in the pooled NSPS and cigarette cohorts by 9% and 26%, respectively, and did not significantly differ (p > .05). Conclusion Complete switching from cigarettes to NSPS produced significant reductions in key non-nicotine BoEs associated with cigarette smoking. Implications The results of this study concorded with evidence that complete switching from combustible cigarettes to tobacco and nontobacco-flavored vapor products may reduce exposure to key carcinogens and other toxicants known to be associated with tobacco-related diseases. Future research is needed to assess the long-term health effects of NSPS use. These results should not be interpreted to mean that the use of NSPS is without any risk, particularly for nonusers of tobacco products.

IntroductionFlavourants and humectants in waterpipe tobacco (WT) increase product appeal. Removal of these constituents, however, is associated with increased intensity of WT puffing, likely due to reduced nicotine delivery efficiency. To clarify the potential public health outcomes of restrictions on flavourants or humectants in WT, we evaluated the effects of these constituents on puffing behaviours, biomarkers of exposure and subjective effects among adults with high versus low WT dependence.MethodsN=39 high dependence and N=49 low dependence WT smokers (Lebanese Waterpipe Dependence Scale scores >10 = high dependence) completed four smoking sessions in a cross-over experiment. Conditions were preferred flavour with humectant (+F+H), preferred flavour without humectant (+F-H), unflavoured with humectant (−F+H) and unflavoured without humectant (−F−H). Measures of puff topography, plasma nicotine and expired carbon monoxide (eCO) boost, and subjective effects were assessed.ResultsLevel of WT dependence modified the effect of WT condition on average flow rate, average puff volume and eCO boost. Although, overall, participants puffed the +F+H WT least intensely and −F−H WT most intensely, this association was strongest among WT smokers with high dependence. Participants preferred smoking the +F+H WT and achieved the largest plasma nicotine boost in that condition.DiscussionFindings underscore the complexity of setting product standards related to flavourants and humectants in WT. Future research evaluating whether WT smokers with high dependence would quit or reduce their WT smoking in response to removal of flavourants or humectants from WT is necessary to appreciate the full public health effects of such policies.

BackgroundPictorial health warning label (PHWL) is an effective risk communication measure among cigarette smokers. However, there is a lack of knowledge regarding the effect of PHWL on low- and high-frequency waterpipe (WP) smokers. This study examined the effects of PHWL on puffing behavior, subjective experiences, and toxicant exposures among low- and high-frequency WP smokers in the United States (US).MethodsSixty current (past-month) WP smokers (low-frequency; n = 30 and high-frequency; n = 30) completed two 45-min ad libitum WP smoking sessions in a cross-over design study (WP with no-PHWL vs. WP with PHWL). We compared the mean differences of puff topography, expired carbon monoxide (eCO), plasma nicotine concentration, and subjective experiences between the two smoking groups.ResultsMean age of low-frequency smokers was 21.5 years and high-frequency smokers was 21.3 years. Compared to high-frequency, low-frequency smokers had significant reduction in average total smoking time [mean difference (SD) =  −7.6 (10.2) min vs. −2.6 (6.7) min, p = 0.03] and number of puffs [mean difference (SD) =  −33.37 (70.7) vs. −0.70 (29.2), p = 0.02] following exposure to PHWL compared to no-PHWL condition. Post-session subjective experiences were lower among high-frequency smokers compared to low-frequency smokers following smoking WP with PHWL compared to the no-PHWL session (puff liking −1.2 vs. −0.5; puff satisfaction −1.0 vs. −0.3; craving reduction −0.5 vs. 1.2) (p < 0.05 for all).ConclusionOur findings indicate that placing PHWL on the WP device may be a promising strategy with differential effectiveness among WP smokers: low-frequency (reduce puffing behaviors) and high-frequency (reduce smoking experience).

Background Exposure to diesel exhaust causes inflammatory responses. Previous controlled exposure studies at a concentration of 300 μg/m 3 of diesel exhaust particles mainly lasted for 1 h. We prolonged the exposure period and investigated how quickly diesel exhaust can induce respiratory and systemic effects. Methods Eighteen healthy volunteers were exposed twice to diluted diesel exhaust (PM 1 ~300 μg/m 3 ) and twice to filtered air (PM 1 ~2 μg/m 3 ) for 3 h, seated, in a chamber with a double-blind set-up. Immediately before and after exposure, we performed a medical examination, spirometry, rhinometry, nasal lavage and blood sampling. Nasal lavage and blood samples were collected again 20 h post-exposure. Symptom scores and peak expiratory flow (PEF) were assessed before exposure, and at 15, 75, and 135 min of exposure. Results Self-rated throat irritation was higher during diesel exhaust than filtered air exposure. Clinical signs of irritation in the upper airways were also significantly more common after diesel exhaust exposure (odds ratio=3.2, p<0.01). PEF increased during filtered air, but decreased during diesel exhaust exposure, with a statistically significant difference at 75 min (+4 L/min vs. -10 L/min, p=0.005). Monocyte and total leukocyte counts in peripheral blood were higher after exposure to diesel exhaust than filtered air 20 h post-exposure, and a trend (p=0.07) towards increased serum IL-6 concentrations was also observed 20 h post-exposure. Conclusions Diesel exhaust induced acute adverse effects such as symptoms and signs of irritation, decreased PEF, inflammatory markers in healthy volunteers. The effects were first seen at 75 min of exposure.

Background Exposure to particulate matter (PM) is generally associated with elevated risk of cardiovascular morbidity and mortality. Elderly and obese subjects may be particularly susceptible, although short-term effects are poorly described. Methods Sixty healthy subjects (25 males, 35 females, age 55 to 83 years, body mass index > 25 kg/m 2 ) were included in a cross-over study with 5 hours of exposure to particle- or sham-filtered air from a busy street using an exposure-chamber. The sham- versus particle-filtered air had average particle number concentrations of ~23.000 versus ~1800/cm 3 and PM 2.5 levels of 24 versus 3 μ g/m 3 , respectively. The PM contained similar fractions of elemental and black carbon (~20-25%) in both exposure scenarios. Reactive hyperemia and nitroglycerin-induced vasodilation in finger arteries and heart rate variability (HRV) measured within 1 h after exposure were primary outcomes. Potential explanatory mechanistic variables included markers of oxidative stress (ascorbate/dehydroascorbate, nitric oxide-production cofactor tetrahydrobiopterin and its oxidation product dihydrobiopterin) and inflammation markers (C-reactive protein and leukocyte differential counts). Results Nitroglycerin-induced vasodilation was reduced by 12% [95% confidence interval: −22%; −1.0%] following PM exposure, whereas hyperemia-induced vasodilation was reduced by 5% [95% confidence interval: −11.6%; 1.6%]. Moreover, HRV measurements showed that the high and low frequency domains were significantly decreased and increased, respectively. Redox and inflammatory status did not change significantly based on the above measures. Conclusions This study indicates that exposure to real-life levels of PM from urban street air impairs the vasomotor function and HRV in overweight middle-aged and elderly adults, although this could not be explained by changes in inflammation, oxidative stress or nitric oxide-cofactors.

Abstract Introduction Relative to non-waterpipe (WP) smokers, WP smokers are more than twice as likely to use alcohol and frequently consume alcohol before or during smoking sessions. Co-use of alcohol and WP may result in greater toxicant exposure compared to WP smoking alone. To date, no study systematically has investigated the impact of acute alcohol intoxication on WP smoking topography, exposure to tobacco-related toxicants, or abuse liability. Methods Dyads of current WP smokers and drinkers (N = 42; age = 21–32 years) completed two in-laboratory ad libitum smoking sessions (≤2 hours) following 12-hour nicotine abstinence in a double-blind, randomized crossover design in which they consumed a placebo versus active drink (sustained breath alcohol concentration = .08). Exhaled carbon monoxide (eCO) and plasma nicotine concentration were assessed. Questionnaires assessed smoking experience and smoking urge. Smoking topography was measured continuously throughout each smoking session. Results The alcohol session was associated with increased inhaled volume, flow rate, and WP session duration compared to placebo. Compared to placebo, participants reported a more positive overall smoking experience following the alcohol session and greater smoking urges pre- and post-smoking session. Although both sessions resulted in significant increases in eCO and plasma nicotine, no significant differences emerged in eCO or nicotine exposure between the active and placebo sessions. Conclusions Co-use of alcohol and WP may contribute to the maintenance of WP smoking through enhanced smoking experiences, increased urge to smoke, and significant exposure to addictive nicotine. Regulations may be necessary to limit the sale of alcohol in WP smoking lounges and reduce exposure to secondhand smoke. Implications The findings suggest co-use of alcohol and WP tobacco likely maintain WP use and dependence by enhancing the smoking experience and increasing urges to smoke. These findings have implications for regulations aimed at limiting co-use of alcohol and WP tobacco in WP lounges and limiting exposure to secondhand smoke. Clinical trials registration NCT03096860

During the first randomized intervention trial (RESPIRE: Randomized Exposure Study of Pollution Indoors and Respiratory Effects) in air pollution epidemiology, we pioneered application of passive carbon monoxide (CO) diffusion tubes to measure long-term personal exposures to woodsmoke. Here we report on the protocols and validations of the method, trends in personal exposure for mothers and their young children, and the efficacy of the introduced improved chimney stove in reducing personal exposures and kitchen concentrations. Passive diffusion tubes originally developed for industrial hygiene applications were deployed on a quarterly basis to measure 48-hour integrated personal carbon monoxide exposures among 515 children 0-18 months of age and 532 mothers aged 15-55 years and area samples in a subsample of 77 kitchens, in households randomized into control and intervention groups. Instrument comparisons among types of passive diffusion tubes and against a continuous electrochemical CO monitor indicated that tubes responded nonlinearly to CO, and regression calibration was used to reduce this bias. Before stove introduction, the baseline arithmetic (geometric) mean 48-h child ( n =270), mother ( n =529) and kitchen ( n =65) levels were, respectively, 3.4 (2.8), 3.4 (2.8) and 10.2 (8.4) p.p.m. The between-group analysis of the 3355 post-baseline measurements found CO levels to be significantly lower among the intervention group during the trial period: kitchen levels: −90%; mothers: −61%; and children: −52% in geometric means. No significant deterioration in stove effect was observed over the 18 months of surveillance. The reliability of these findings is strengthened by the large sample size made feasible by these unobtrusive and inexpensive tubes, measurement error reduction through instrument calibration, and a randomized, longitudinal study design. These results from the first randomized trial of improved household energy technology in a developing country and demonstrate that a simple chimney stove can substantially reduce chronic exposures to harmful indoor air pollutants among women and infants.

Objectives. We examined the impact of Rule 4901, aimed at reducing residential wood burning, on particulate matter levels and hospitalizations in the San Joaquin Valley Air Basin (SJVAB). Methods. Using general linear mixed models and generalized estimating equation models, we compared levels of particulate matter and of hospital admissions (age groups = 45–64 and ≥ 65 years) in the SJVAB for cardiovascular disease (CVD), ischemic heart disease (IHD), and chronic obstructive pulmonary disease during the burn seasons before (2000–2003) and after (2003–2006) implementation. Results. After implementation, we observed reductions of 12%, 11%, and 15% in particulate matter  2.5 micrometers in diameter or smaller (PM2.5), and 8%, 7%, and 11% in coarse particles, in the entire SJVAB and in rural and urban regions of the air basin, respectively. Among those aged 65 years and older, Rule 4901 was estimated to prevent 7%, 8%, and 5% of CVD cases, and 16%, 17%, and 13% of IHD cases, in the entire SJVAB and in rural and urban regions, respectively. Conclusions. The study suggests that Rule 4901 is effective at reducing wintertime ambient PM2.5 levels and decreasing hospital admissions for heart disease among people aged 65 years and older.