Weeks Of Smoking Cessation Research Articles

Fourteen days of smoking cessation improves muscle fatigue resistance and reverses markers of systemic inflammation

Cigarette smoking has a negative effect on respiratory and skeletal muscle function and is a risk factor for various chronic diseases. To assess the effects of 14 days of smoking cessation on respiratory and skeletal muscle function, markers of inflammation and oxidative stress in humans. Spirometry, skeletal muscle function, circulating carboxyhaemoglobin levels, advanced glycation end products (AGEs), markers of oxidative stress and serum cytokines were measured in 38 non-smokers, and in 48 cigarette smokers at baseline and after 14 days of smoking cessation. Peak expiratory flow (p = 0.004) and forced expiratory volume in 1 s/forced vital capacity (p = 0.037) were lower in smokers compared to non-smokers but did not change significantly after smoking cessation. Smoking cessation increased skeletal muscle fatigue resistance (p < 0.001). Haemoglobin content, haematocrit, carboxyhaemoglobin, total AGEs, malondialdehyde, TNF-α, IL-2, IL-4, IL-6 and IL-10 (p < 0.05) levels were higher, and total antioxidant status (TAS), IL-12p70 and eosinophil numbers were lower (p < 0.05) in smokers. IL-4, IL-6, IL-10 and IL-12p70 had returned towards levels seen in non-smokers after 14 days smoking cessation (p < 0.05), and IL-2 and TNF-α showed a similar pattern but had not yet fully returned to levels seen in non-smokers. Haemoglobin, haematocrit, eosinophil count, AGEs, MDA and TAS did not significantly change with smoking cessation. Two weeks of smoking cessation was accompanied with an improved muscle fatigue resistance and a reduction in low-grade systemic inflammation in smokers.

A Review of the Impact of Smoking on Inhaled Insulin: Would You Stop Smoking if Insulin Can Be Inhaled?

High prevalence of diabetes and the need for tight glycemic control have been well established. With the invention of inhaled insulin, an alternate route has been explored and shows great promise. Inhaled insulin shows a similar physiologic response to subcutaneous insulin, with a faster onset of action, making it suitable for post-prandial hyperglycemia. This comes as a great relief, especially to those who are hesitant to use multiple injections in a day. Many factors affect insulin absorption, including device, particle size, airway patency. Another essential factor is smoking, which is prevalent among people with diabetes, as is in the non-diabetic population. Smoking increases the absorption of inhaled insulin, but it is not a straight fact, since acute smoking, passive smoking, chronic smoking - all have different effects on inhaled insulin. Furthermore, inhaled insulin is also affected by lung diseases. Most studies that have been conducted have included limited populations, thus questioning their generalisability. The studies from inception till 2020 have shown increased permeability of epithelial with acute smoking, change of epithelial layer back to normal after few weeks of smoking cessation, and reverting to chronic smoker levels with just one to two days of start in smoking. Data also suggests that smoking causes a reduction in insulin sensitivity, which could compensate for its increased absorption. Nicotine causes a decrease in the absorption of subcutaneous insulin, but its effect has not been seen on inhaled insulin. More studies, including diabetic smoker patients, need to be performed to give a specific set of variables. This would also add another reason to encourage smokers to quit smoking.

Going Once, Going Twice: Using Willingness-to-Accept Auctions to Promote Smoking Cessation.

Incentive-based smoking cessation interventions increase quit rates. The optimal incentive, however, is unknown. We used a willingness-to-accept (WTA) auction where smokers submitted bids indicating the incentive they would need to receive for 1 week of smoking cessation. Smokers ready to quit (n = 35) participated in a WTA auction, naming the amount they needed to be paid to quit for 1 week. Auction winners received an incentive if they successfully quit. All smokers received nicotine replacement therapy and self-help cessation materials. Carbon monoxide concentrations were monitored remotely three times during the week and in person at the final session. Participants who smoked their first cigarette within 5 min of waking demanded a significantly larger incentive in exchange for quitting than those who waited (p < .05). About 45% of auction winners quit smoking compared to 20% of nonwinners (p < .05). The cost per quit was $466 among auction winners compared to $894 among nonwinners. WTA auctions may be an effective way to determine the amount smokers need to be paid to quit, which would allow researchers to estimate the most cost-effective payment to offer as part of incentive-based smoking cessation programs. Replication evaluating longer-term cessation outcomes with larger samples is warranted. Incentive-based smoking cessation interventions increase quit rates. However, the optimal incentive is unknown. We found that a WTA auction is a feasible technique for estimating the amount smokers need to be paid to quit. Incentives are a surprisingly cost-effective way to facilitate smoking cessation because they are only paid to those who successfully quit. WTA auctions are a promising tool for determining the incentive that strikes the optimal balance between being large enough to motivate cessation, but small enough that it can be offered to the largest possible population of smokers for a given program budget.

Cigarette smoke exposure impairs β-cell function through activation of oxidative stress and ceramide accumulation

ObjectivesEpidemiological studies indicate that first- and second-hand cigarette smoke (CS) exposure are important risk factors for the development of type 2 diabetes (T2D). Additionally, elevated diabetes risk has been reported to occur within a short period of time after smoking cessation, and health risks associated with smoking are increased when combined with obesity. At present, the mechanisms underlying these associations remain incompletely understood. The objective of this study was to test the impact of CS exposure on pancreatic β-cell function using rodent and in vitro models. MethodsBeginning at 8 weeks of age, C57BL/6 J mice were concurrently fed a high-fat diet (HFD) and exposed to CS for 11 weeks, followed by an additional 11 weeks of smoking cessation with continued HFD. Glucose tolerance testing was performed during CS exposure and during the cessation period. Cultured INS-1 β-cells and primary islets were exposed ex vivo to CS extract (CSE), and β-cell function and viability were tested. Since CS increases ceramide accumulation in the lung and these bioactive sphingolipids have been implicated in pancreatic β-cell dysfunction in diabetes, islet and β-cell sphingolipid levels were measured in islets from CS-exposed mice and in CSE-treated islets and INS-1 cells using liquid chromatography-tandem mass spectrometry. ResultsCompared to HFD-fed, ambient air-exposed mice, HFD-fed and CS-exposed mice had reduced weight gain and better glucose tolerance during the active smoking period. Following smoking cessation, CS-mice exhibited rapid weight gain and had accelerated worsening of their glucose tolerance. CS-exposed mice had higher serum proinsulin/insulin ratios, indicative of β-cell dysfunction, significantly lower β-cell mass (p = 0.017), reduced β-cell proliferation (p = 0.006), and increased islet ceramide content compared to non-smoking control mice. Ex vivo exposure of isolated islets to CSE was sufficient to increase islet ceramide levels, which was correlated with reduced insulin gene expression and glucose-stimulated insulin secretion, and increased β-cell oxidative and endoplasmic reticulum (ER) stress. Treatment with the antioxidant N-acetylcysteine markedly attenuated the effects of CSE on ceramide levels, restored β-cell function and survival, and increased cyclin D2 expression, while also reducing activation of β-cell ER and oxidative stress. ConclusionsOur results indicate that CS exposure leads to impaired insulin production, processing, secretion and reduced β-cell viability and proliferation. These effects were linked to increased β-cell oxidative and ER stress and ceramide accumulation. Mice fed HFD continued to experience detrimental effects of CS exposure even during smoking cessation. Elucidation of the mechanisms by which CS exposure impairs β-cell function in synergy with obesity will help design therapeutic and preventive interventions for both active and former smokers.

Two Weeks of Smoking Cessation Reverse Cigarette Smoke-Induced Skeletal Muscle Atrophy and Mitochondrial Dysfunction in Mice.

Apart from its adverse effects on the respiratory system, cigarette smoking also induces skeletal muscle atrophy and dysfunction. Whether short-term smoking cessation can restore muscle mass and function is unknown. We, therefore, studied the impact of 1- and 2-week smoking cessation on skeletal muscles in a mouse model. Male mice were divided into four groups: Air-exposed (14 weeks); cigarette smoke (CS)-exposed (14 weeks); CS-exposed (13 weeks) followed by 1-week cessation; CS-exposed (12 weeks) followed by 2 weeks cessation to examine exercise capacity, physical activity levels, body composition, muscle function, capillarization, mitochondrial function and protein expression in the soleus, plantaris, and diaphragm muscles. CS-induced loss of body and muscle mass was significantly improved within 1 week of cessation due to increased lean and fat mass. Mitochondrial respiration and protein levels of the respiratory complexes in the soleus were lower in CS-exposed mice, but similar to control values after 2 weeks of cessation. Exposing isolated soleus muscles to CS extracts reduced mitochondrial respiration that was reversed after removing the extract. While physical activity was reduced in all groups, exercise capacity, limb muscle force, fatigue resistance, fiber size and capillarization, and diaphragm cytoplasmic HIF-1α were unaltered by CS-exposure. However, CS-induced diaphragm atrophy and increased capillary density were not seen after 2 weeks of smoking cessation. In male mice, 2 weeks of smoking cessation reversed smoking-induced mitochondrial dysfunction, limb muscle mass loss, and diaphragm muscle atrophy, highlighting immediate benefits of cessation on skeletal muscles. Our study demonstrates that CS-induced skeletal muscle mitochondrial dysfunction and atrophy are significantly improved by 2 weeks of cessation in male mice. We show for the first time that smoking cessation as short as 1 to 2 weeks is associated with immediate beneficial effects on skeletal muscle structure and function with the diaphragm being particularly sensitive to CS-exposure and cessation. This could help motivate smokers to quit smoking as early as possible. The knowledge that smoking cessation has potential positive extrapulmonary effects is particularly relevant for patients referred to rehabilitation programs and those admitted to hospitals suffering from acute or chronic muscle deterioration yet struggling with smoking cessation.

Interleukin-1 plays a central role in behaviour abnormalities in mucopolysaccharidosis type III (MPS III)

Nicotine, an important component of cigarette smoke, is a neurotransmitter that contributes to stress, depression and anxiety in smokers. In rodents, it increases anxiety and reduces exploratory behaviours. However, so far, the measurements of exploratory behaviour in rodents have only been semi-quantitative and lacking in sufficient detail to characterise the temporal effect of smoking cessation. As rodents, such as mice and rats, primarily use whiskers to explore their environment, we studied the effect of 3 months smoking with 1 and 2 weeks smoking cessation on whisker movements in mice, using high-speed video camera footage and image analysis. Both protraction and retraction whisker velocities were increased in smoking mice (p < 0.001) and returned to normal following just one week of smoking cessation. In addition, locomotion speeds were decreased in smoking mice, and returned to normal following smoking cessation. Lung function was also impacted by smoking and remained impaired even following smoking cessation. We suggest that the increased whisker velocities in the smoking mice reflect reduced exploration and impeded tactile performance. The increase in whisker velocity with smoking, and its reduction following smoking cessation, also lends support to acetylcholine being involved in awareness, attention and alertness pathways. It also shows that smoking-induced behavioural changes can be reversed with smoking cessation, which may have implications for human smokers.

The effects of smoking on whisker movements: A quantitative measure of exploratory behaviour in rodents

Nicotine, an important component of cigarette smoke, is a neurotransmitter that contributes to stress, depression and anxiety in smokers. In rodents, it increases anxiety and reduces exploratory behaviours. However, so far, the measurements of exploratory behaviour in rodents have only been semi-quantitative and lacking in sufficient detail to characterise the temporal effect of smoking cessation. As rodents, such as mice and rats, primarily use whiskers to explore their environment, we studied the effect of 3 months smoking with 1 and 2 weeks smoking cessation on whisker movements in mice, using high-speed video camera footage and image analysis. Both protraction and retraction whisker velocities were increased in smoking mice (p<0.001) and returned to normal following just one week of smoking cessation. In addition, locomotion speeds were decreased in smoking mice, and returned to normal following smoking cessation. Lung function was also impacted by smoking and remained impaired even following smoking cessation. We suggest that the increased whisker velocities in the smoking mice reflect reduced exploration and impeded tactile performance. The increase in whisker velocity with smoking, and its reduction following smoking cessation, also lends support to acetylcholine being involved in awareness, attention and alertness pathways. It also shows that smoking-induced behavioural changes can be reversed with smoking cessation, which may have implications for human smokers.

Impact of a smoking cessation lifestyle intervention on vascular mechanics in young women.

We tested the hypotheses that smoking-induced changes in vascular mechanics would be detected earlier in the lumped properties of peripheral vascular beds, which include the properties of microvasculature, than in the local properties of central conduits, and that such changes are reversible with lifestyle changes that include smoking cessation and exercise. Vascular measures were made in 53 young (18-40 years) female smokers and 25 age-matched non-smokers. Twenty-two of the smokers were tested before and after a 14-week smoking cessation program and, of these, 13 were tested again after 52 weeks of smoking cessation. Compared with non-smokers, lumped forearm vascular bed compliance (C: mL/mm Hg) was lower, while lumped viscoelasticity (K: mm Hg/(mL·min)) and resistance (R: mm Hg/(mL·min)) were higher in the smoker group. Neither the carotid-to-toe pulse wave velocity nor local carotid artery elasticity indices were different between groups. Compared with non-smokers, brachial artery distensibility was less, and other markers of stiffness higher, in the smoker group. At 14 and 52 weeks of smoking cessation, forearm vascular R was reduced and C was increased while K was unchanged. The changes in C and R occurred while maintaining a constant R×C value, which represents a dynamic time constant. Thus, early changes in K were observed in the forearm vascular bed of smokers, which were not reflected in the local properties of central conduit vessels. Forearm C, but not K, was reversed following smoking cessation, a finding that may represent a persistent effect of smoking on the intercellular matrix of the vessel wall.

Examining the effects of initial smoking abstinence on response to smoking-related stimuli and response inhibition in a human laboratory model.

Research is needed on initial smoking abstinence and relapse risk. This study aims to investigate the effects of different durations of initial abstinence on sensitivity to smoking-related stimuli and response inhibition in the context of a larger battery of outcome measures. Smokers were randomly assigned to receive payment contingent on smoking abstinence across all 15 study days (15C) or just the final 2days (2C). Smoking status and subject ratings were assessed daily. Participants completed fMRI sessions at baseline and day 14 during which they completed craving ratings after exposure to smoking-related and neutral stimuli and performed a response inhibition task. On day 15, participants completed a smoking preference session involving 20 exclusive choices between smoking and money. The payment contingencies were effective in producing greater smoking abstinence in the 15C vs. 2C conditions. Ratings of withdrawal decreased, while ratings of ease and confidence in abstaining increased in the 15C vs. 2C conditions across the 15-day study. 15C participants were less likely to choose the smoking option in the preference session. 15C participants reported greater reductions in craving compared to the 2C participants in the presence of smoking-related and neutral stimuli (i.e., decreases in generalized craving), but no differences were noted in cue reactivity per se or in response inhibition. Results systematically replicate prior observations that a period 2weeks of initial abstinence decreases the relative reinforcing effects of smoking and improves other outcomes associated with relapse risk compared to the initial day or two of a cessation effort, and extends them by underscoring the importance of generalized rather than cue-induced craving in relation to relapse risk during the initial weeks of smoking cessation.

Cigarette smoking induces vascular damage of both conduit arteries and small vessels and persistent elevation of plasma serotonin unresponsive to 8 weeks of smoking cessation

Purpose: Cigarette smoking is one of the major risk factors of cardiovascular diseases and induces deleterious vascular damages. Whereas serotonin released to plasma upon platelet activation modulates vascular tonus and thrombus formation. The purpose of this study was to examine the plasma levels of serotonin in habitual cigarette smokers and the kinetics of plasma serotonin after smoking cessation, and their association with endothelial function. Methods: In study 1, clinical profiles including endothelial function were compared between apparently healthy male smokers (n=27, 40±8 years) and age-adjusted non-smokers (n=21, 40±7 years). In study 2, smokers were instructed to stop smoking and clinical profiles and laboratory findings including serum level of cotinine, principal metabolite of nicotine, were investigated before and after 8 weeks of smoking cessation. Strict precautions were taken to obtain platelet poor plasma (PPP). Serotonin levels in PPP were measured by HPLC. Endothelial function was assessed by 2 distinct techniques, namely flow-mediated dilation (FMD) using ultrasound system for conduit arteries and peripheral arterial tonometry (PAT) using End-PAT 2000 for peripheral small vessels. Results: In Study 1, levels of PPP serotonin and serotonin corrected by platelets number (serotonin/plt) in smokers were higher than those in non-smokers (6.90±2.91 vs 4.60±2.32 nmol/L, P<0.01; and 31.3±16.6 vs 20.6±11.9 x10-9 pmol/plt, P<0.05; respectively), and FMD in smokers was lower than that in non-smokers (3.12±1.15 vs 4.11±1.93%, P<0.05). In study 2, serotonin/plt in PPP (33.5±19.4 x10-9 pmol/plt) correlated positively with serum level of cotinine (152±140 ng/ml, r=0.45, P<0.05) and inversely with HDL cholesterol (61±16 mg/dl, r=-0.46, P<0.05) and PAT ratio (0.25±0.10, r=-0.45, P<0.05). Smokers who completely attained smoking cessation indicated significantly increased PAT ratio (P<0.05) although serotonin and serotonin/plt in PPP were not significantly changed. Conclusions: Cigarette smoking is associated with increase of plasma serotonin and impaired endothelial function in middle-aged healthy subjects. Moreover, the change was unresponsive to 8 weeks of smoking cessation, suggesting that caution should be taken during plasma serotonin levels are not decreased even after improvement of endothelial function.

Novel and Reversible Mechanisms of Smoking-Induced Insulin Resistance in Humans

Smoking is the most common cause of preventable morbidity and mortality in the United States, in part because it is an independent risk factor for the development of insulin resistance and type 2 diabetes. However, mechanisms responsible for smoking-induced insulin resistance are unclear. In this study, we found smokers were less insulin sensitive compared with controls, which increased after either 1 or 2 weeks of smoking cessation. Improvements in insulin sensitivity after smoking cessation occurred with normalization of IRS-1ser636 phosphorylation. In muscle cell culture, nicotine exposure significantly increased IRS-1ser636 phosphorylation and decreased insulin sensitivity, recapitulating the phenotype of smoking-induced insulin resistance in humans. The two pathways known to stimulate IRS-1ser636 phosphorylation (p44/42 mitogen-activated protein kinase [MAPK] and mammalian target of rapamycin [mTOR]) were both stimulated by nicotine in culture. Inhibition of mTOR, but not p44/42 MAPK, during nicotine exposure prevented IRS-1ser636 phosphorylation and normalized insulin sensitivity. These data indicate nicotine induces insulin resistance in skeletal muscle by activating mTOR. Therapeutic agents designed to oppose skeletal muscle mTOR activation may prevent insulin resistance in humans who are unable to stop smoking or are chronically exposed to secondhand smoke.

Cigarette smoking induces vascular damage and persistent elevation of plasma serotonin unresponsive to 8 weeks of smoking cessation

Cigarette smoking induces vascular damage and persistent elevation of plasma serotonin unresponsive to 8 weeks of smoking cessation

Sex‐specific differences in GABAA‐benzodiazepine receptor availability: relationship with sensitivity to pain and tobacco smoking craving

Sex differences exist in tobacco smoking behaviors. Nicotine, the primary addictive ingredient in tobacco smoke, indirectly affects γ-amino butyric acid (GABA) function. Previous studies reported sex-by-smoking interactions in brain GABA levels. The goal of the present study was to evaluate if there is a sex-by-smoking interaction at the GABA(A)-benzodiazepine receptors (GABA(A)-BZRs), as well as relationships between GABA(A)-BZR availability and behavioral variables before and after 1 week of smoking cessation. Twenty-six women (8 non-smokers, age 36.0 ± 13.4 years; 19 smokers, age 34.6 ± 8.9 years) and 25 men (8 non-smokers, age 37.9 ± 13.8 years; 17 smokers, 34.1 ± 12.4 years) were imaged using [123I]iomazenil and single-photon emission computed tomography. Smokers were imaged at baseline 7 hours after the last cigarette. A significantly great number of men were able to abstain from smoking for 1 week (P = 0.003). There were no significant differences in nicotine dependence and cigarette craving, mood or pain sensitivity between male and female smokers. There was a significant effect of gender across all brain regions (frontal, parietal, anterior cingulate, temporal and occipital cortices, and cerebellum; P < 0.05), with all women (smokers and non-smokers combined) having a higher GABA(A)-BZR availability than all men. There was a negative correlation between GABA(A)-BZR availability and craving (P ≤ 0.02) and pain sensitivity (P = 0.04) in female smokers but not male smokers. This study provides further evidence of a sex-specific regulation of GABA(A)-BZR availability in humans and demonstrates the potential for GABA(A)-BZRs to mediate tobacco smoking craving and pain symptoms differentially in female and male smokers.

The Role of Intrusive Thoughts during the First Weeks of Smoking Cessation

Intrusive thoughts could impair smoking cessation or cause relapse to the extent that the thoughts are stimuli for smoking. This is a secondary analysis of data provided by 61 participants attempting to quit smoking. Participants used a hand-held computer to capture, in real time, the experience of quitting smoking. Intrusive thoughts related to smoking were assessed and participants completed assessments when they had an urge to smoke or after they slipped. The outcomes included were proximal measures of smoking cessation: number of slips, number of resisted temptations to smoke, and urge levels of during cessation. Independent variables were smoking stimuli, intrusive thoughts and depressive symptoms. Data were analyzed using multilevel modeling. Intrusive thoughts were significantly and positively related to each cessation outcome (slips, resists, urge levels). Smoking stimuli were differentially related to outcomes; cigarette availability was related to slips; being in usual smoking situations was ass...

Changes in plasma brain-derived neurotrophic factor levels in smokers after smoking cessation

Several studies have reported that brain-derived neurotrophic factor (BDNF) might be associated with nicotine dependence. However, there are few studies on BDNF levels in humans with nicotine dependence. In the present study, we compared the differences in plasma BDNF levels in patients with nicotine dependence and in healthy nonsmokers, and we investigated serial changes in plasma BDNF levels in patients with nicotine dependence following smoking cessation. Forty-five voluntary smokers and 66 nonsmokers were recruited in this study. Of the 45 smokers, 12 were taking varenicline, 21 were using a nicotine patch, and 12 were unaided in their cessation effort by their own choice. Plasma BDNF levels were measured at baseline using an enzyme-linked immunosorbent assay (both smokers and nonsmokers) and at weeks 4 and 12 after smoking cessation (abstinent smokers only). A total of 19 smokers were able to remain abstinent during the entire study period. Baseline plasma BDNF levels were significantly lower in smokers compared to nonsmokers ( F = 4.410, p = 0.002). The plasma BDNF levels in the abstinent smokers significantly increased from baseline after 4 weeks of smoking cessation ( z = −2.86, p = 0.004) but had a tendency of decrease in the period between weeks 4 and 12. We could not find differences in the plasma BDNF levels among the three smoker subgroups at week 12 following cessation. Changes in plasma BDNF levels might be related to the process of abstinence and the pathophysiology of nicotine dependence.

Use of nicotine substitute prescribed at hourly plus ad libitum intake or ad libitum for heavy smokers willing to quit: a randomized controlled trial

ObjectiveTo assess the impact of instructional guidance in the regular use of use nicotine nasal spray (NNS) on the true use of NNS during the first three weeks of smoking cessation for heavy smokers who are willing to quit.MethodsThis randomized, open, controlled trial included 50 patients who were heavy smokers, were willing to quit, and attending an academic outpatient clinic in Western Switzerland. Patients were randomised to instruction on NNS use as "ad libitum" (administration whenever cravings appear; control group) or to use NNS when craving appears and at least every hour when awake (intervention group). Intakes were monitored using an electronic device fixed in the spray unit (MDILog™) during the first three weeks of use. Self reported abstinence from smoking at six months was confirmed by expired-air carbon monoxide. Using intention-to-treat analysis, random-effect GLS regression was used to calculate the mean difference of daily doses between groups controlling for lack of independence between measures from the same individual.ResultsOne patient was lost to follow-up. At baseline randomization, the group receiving instruction to use NNS hourly included more women, patients with previous desires to quit, and patients with more psychiatric comorbidities and less somatic complaints compared to the group instructed to use NNS with cravings (group imbalance). Both groups self-administered more than the daily recommended dosage of 8 uses. Mean daily usage was 13.6 dose/day and 11.1 dose/day for the group instructed to use NNS hourly and with cravings, respectively. Adjusting for baseline imbalance, the increased daily doses in the intervention group (hourly use) remained nonsignificant compared to ad libitum use (-0.5 dose/day; CI 95% -6.2; 5.3, from day 1 to day 7; and 2.3 dose/day; CI 95% -5.4; 10.0, from day 8 to day 21). Instructing patients to use the NNS daily had no effect on smoking cessation at six months (RR = 0.69; CI 95% 0.34; 1.39).ConclusionHeavy smokers willing to quit use NNS frequently, regardless of the instructions given. Recommending the use of NNS only when craving appears for heavy smokers willing to quit seems acceptable compared to prescribing hourly administration.Trial registration-ClinicalTrials.gov: NCT00861276

Effect of smoking cessation on airway inflammation of rats with chronic bronchitis

Smoking is the major cause of airway inflammation in chronic obstructive pulmonary disease (COPD), and smoking cessation is regarded as one of the important strategies for prevention and treatment of the inflammation. The inflammation of the chronic airway may be present and deteriorated even if the COPD patients stop smoking. Whether and how early smoking cessation affects the progress of inflammation is still obscure. This study was conducted to find the appropriate time for smoking cessation to terminate the airway inflammation in rats with smoke-induced chronic bronchitis. A rat model of COPD was established by passively inhaling smoke mixture. Fifty-four young male Sprague-Dawley rats were randomly divided into 9 groups with different periods of smoke exposure and different time points of cessation. The inflammation markers to be detected included inflammatory cells in the bronchoalveolar lavage fluid (BALF), the myeloperoxidose (MPO) activity, the morphologic changes and the expression of ICAM-1 on the airway epithelium. When smoking was terminated at early stage, the inflammatory markers and related indexes were different from those of the typical chronic bronchitis group (group M7) (P < 0.01). The pathologic score of group SC7 (2 weeks of smoking cessation after occurrence of typical chronic bronchitis) was not different from that of group M7, and the level of ICAM-1 was still up-regulated (compared to group M7, P > 0.05). Meanwhile, most of inflammatory cells in BALF were neutrophils compared to other groups (P < 0.01). When smoking was terminated, the MPO activity was significantly lower than that of group M7 (P < 0.01). Smoking cessation at early stage can effectively inhibit the inflammatory reaction of COPD. Once chronic bronchitis occurs, little could be improved by smoking cessation.

Effect of smoking cessation on cough reflex sensitivity

Recent studies have shown that cigarette smokers have diminished cough reflex sensitivity compared with nonsmokers. The current authors proposed a mechanism of chronic cigarette smoke-induced desensitisation of airway cough receptors. To investigate this hypothesis, cough sensitivity to inhaled capsaicin (C5) in chronic smokers was measured both while they were actively smoking and 2, 6, 12 and 24 weeks after smoking cessation. In total, 29 subjects underwent baseline capsaicin challenge while smoking and 2 weeks after smoking cessation. Mean+/-sem log C5 fell from 1.86+/-0.12 to 1.60+/-0.12, demonstrating significant enhancement of cough reflex sensitivity. Of the total, 20, 18 and 14 subjects successfully abstained from smoking for 6, 12 and 24 weeks, respectively. Mean log C5 values after 12 and 24 weeks of smoking cessation were significantly diminished from baseline. In a control group of smokers, mean log C5 did not decrease from baseline after 6, 12 and 24 weeks. Overall, the log C5 profile of the smoking cessation group showed a clear, linearly decreasing trend over time compared with the control group. Even after many years of smoking, cough sensitivity is enhanced as early as 2 weeks after smoking cessation. Given the importance of an intact cough reflex, these changes may provide clinical benefit.

The effect of chronic tobacco smoking on arterial stiffness.

Cardiovascular disease caused by smoking is related to the pathophysiological burden placed on the vascular endothelium. We studied the effect of chronic cigarette smoking on arterial wave reflection (study 1) and smoking cessation on pulse wave analysis (study 2). Fifty smokers and 50 age- and sex-matched nonsmokers participated in study 1. Study 2 recruited 20 volunteers from the stop smoking clinic at the Royal Hallamshire Hospital, Sheffield, UK. Systemic augmentation index (AIx) and carotid-femoral pulse wave velocity (PWV) were measured using the SphygmoCor system. Brachial blood pressure (BP) (Omron 705-CP-E), AIx and PWV were recorded at a single visit in study 1. Study 2 measured these variables on 'quit day' and 4 weeks later. In study 1, AIx was significantly higher in smokers than in nonsmokers (median 17.25 vs. 11.75%, P = 0.004). Multiple regression analysis showed a significant correlation between AIx and age, diastolic BP, smoking status (P < 0.001), blood glucose (P = 0.045) and weight (P = 0.049). In study 2, AIx significantly reduced after 4 weeks of abstinence in successful quitters (n = 10) compared with relapsed smokers (n = 4) (median 5.0 vs.- 9.5; P = 0.013). PWV did not reach significance in either study. Chronic tobacco smoking is associated with endothelial dysfunction and increased AIx in subjects of a wide age range free from additional cardiovascular risk factors, which is partially reversible after 4 weeks of smoking cessation.

Only two-week smoking cessation improves platelet aggregability and intraplatelet redox imbalance of long-term smokers

We investigated whether and how soon smoking cessation ameliorates the smoking-induced intracellular oxidative stress and platelet aggregability in long-term smokers. Smoking is a major risk factor of atherothrombosis. Smoking cessation reduces cardiac events. However, the underlying mechanisms of the beneficial effects remain to be elucidated. Twenty-seven male long-term smokers were divided into two groups. Group A (n = 14) quit smoking for four weeks whereas group B (n = 13) resumed smoking two weeks after quitting. Smoking status was monitored by measurement of urinary cotinine. Using gel-filtered platelets, agonist (adenosine diphosphate and collagen)-induced platelet aggregation, platelet-derived nitric oxide (PDNO), intraplatelet nitrotyrosine production, intraplatelet levels of the reduced form of glutathione (GSH) and its oxidized form (GSSG), and urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG) and urinary 8-iso-prostaglandin F(2alpha) (8-iso-PGF(2alpha)), as markers of systemic oxidative stress, were measured. The baseline measurements were similar between the two groups. Smoking cessation quickly reduced agonist-induced platelet aggregations, intraplatelet nitrotyrosine level, and urinary productions of 8-OHdG and 8-iso-PGF(2alpha) by two weeks in both groups. In group A, they were maintained at the low levels until four weeks, whereas they were reversed by resmoking in group B; PDNO release and intraplatelet GSH/GSSG ratio were time-dependently increased by smoking cessation but reversed by resmoking. The present findings are the first demonstration that only two weeks of smoking cessation can ameliorate the enhanced platelet aggregability and intraplatelet redox imbalance in long-term smokers, possibly by decreasing oxidative stress. Our findings may strengthen the motivation for smokers to quit smoking.