Acute Effects Of Cigarette Smoking Research Articles

The Impact of Heat-Not-Burn, E-Cigarettes, and Cigarettes on Small Airway Function.

E-cigarettes and heated tobacco products (HTPs) are gaining worldwide significance. The tobacco industry is promoting these products as healthier alternatives to conventional cigarettes. In this four-arm crossover study, we examined the acute effects of cigarette smoking, vaping IQOS, or vaping e-cigarettes (with or without nicotine) on hemodynamics, arterial stiffness, and small airways. Twenty subjects (10 male, 10 female), all occasional smokers, completed each study arm. There was at least a 48h washout period before each test day. Arterial stiffness and peripheral and central hemodynamics were assessed using Mobil-O-Graph™ (I.E.M., Germany), whereas tremoFlo® c-100 (Thoracic Medical Systems Inc) was used to evaluate the effects on the small airways and resistance. Cigarettes, IQOS, e-cigarettes containing nicotine, and nicotine-free e-cigarettes had similar effects on peripheral and central hemodynamics as well as on arterial stiffness. We observed a significant increase in all parameters. However, only nicotine-containing products lead to increased bronchial obstruction, higher reactance, and a higher tidal volume. Therefore, we concluded that cigarettes, IQOS, and e-cigarettes have similar effects on hemodynamics. No differences were observed between the nicotine-containing and nicotine-free e-cigarettes. All nicotine-containing products also influence small airways. These findings suggest that e-cigarettes and HTPs are not healthier alternatives than conventional cigarettes.

Abstract 14753: Cigarette Smoking is Acutely Associated With Increased Cardiac Arrhythmias

Background: Chronic cigarette smoking is a known risk factor for the eventual development of atrial fibrillation (AF). However, the acute effects of cigarette smoking on arrhythmias in patients with AF have not been elucidated. Methods/Approaches: We conducted a prospective observational study enrolling consenting adults with a diagnosis of paroxysmal AF and who actively smoked. Participants were equipped with continuously recording ECG devices (iRhythm, San Francisco, CA) for up to 14 days and used a smart lighter (Quitbit, San Francisco, CA or Slighter, Cary, NC) or button presses on the ECG device to time-stamp cigarette smoking events in real-time. Outcomes included any AF, atrial flutter (AFL), supraventricular tachycardia (SVT), ventricular tachycardia (VT), atrial ectopic rhythms (EAR), and ventricular bigeminy and trigeminy. For this case-crossover study, we used a generalized linear mixed model with a Poisson distribution and accounted for the clustering of repeated measures for each participant to estimate the incidence rate ratio (IRR) between arrhythmias and smoking events. Results: We enrolled 29 participants (45% female, mean 55 ± 13 years old, 76% non-Hispanic white), where 22 used a smart lighter, and 7 relied on real-time button presses to document smoking events. Mean study duration was 12 ± 4 days. While wearing the monitor, 24 participants experienced ≥ 1 arrhythmia, including AF (n = 3), SVT (n = 19), VT (n= 5), EAR (n = 23), and ventricular bigeminy/trigeminy (n =12), and 9 participants had ≥ 1 sustained arrhythmia (arrhythmic events >30 secs). Every additional cigarette smoked per day was associated with a 6% increase in arrhythmia events (IRR 1.06, 95% CI 1.05-1.07, P < 0.001; Figure ). No statistically significant relationships were observed between smoking events and sustained arrhythmias per day. Conclusion: The data suggest smoking acutely increases the chance an arrhythmia will occur.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness.

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats ( Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results . Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT ( r 2 = 0.584, β = -0.764, p < 0.001), whereas VCAM-1 expression did not correlate with aortic IMT ( r 2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats (Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results. Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT (r2 = 0.584, β = -0.764, p &lt; 0.001), whereas VCAM-1 expression did not correlate with aortic IMT (r2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Effects of cigarette smoke on in situ mitochondrial substrate oxidation of slow- and fast-twitch skeletal muscles

Epidemiological and clinical evidence suggests that cigarette smoke exposure alters glucose and fatty acid metabolism, leading to greater susceptibility to metabolic disorders. However, the effects of cigarette smoke exposure on mitochondrial substrate oxidation in the skeletal muscle are still poorly understood. Accordingly, this study aimed to examine the acute effects of cigarette smoke on mitochondrial respiratory capacity, sensitivity, and concurrent utilization of palmitoylcarnitine (PC), a long-chain fatty acid, and pyruvate, a product of glycolysis, in permeabilized gastrocnemius and soleus muscle fibers exposed to an acute (1 h) dose (4 %) of cigarette smoke concentrate. Cigarette smoke decreased both mitochondrial respiratory capacity (CONTROL: 50.4 ± 11.8 pmolO2/s/mgwt and SMOKE: 22.3 ± 4.4 pmolO2/s/mgwt, p < 0.01) and sensitivity for pyruvate (CONTROL: 0.10 ± 0.04 mM and SMOKE: 0.11 ± 0.04 mM, p < 0.01) in the gastrocnemius muscle. In the soleus, only the sensitivity for pyruvate-stimulated mitochondrial respiration trended toward a decrease (CONTROL: 0.11 ± 0.04 mM and SMOKE: 0.23 ± 0.15 mM, p = 0.08). In contrast, cigarette smoke did not significantly alter palmitoylcarnitine-stimulated mitochondrial respiration in either muscle. In the control condition, pyruvate-supported respiration was inhibited by the concurrent addition of palmitoylcarnitine in the fast-twitch gastrocnemius muscle (−27.1 ± 19.7 %, p < 0.05), but not in the slow-twitch soleus (−9.2 ± 17.0 %). With cigarette smoke, the addition of palmitoylcarnitine augmented the maximal respiration rate stimulated by the concurrent addition of pyruvate in the gastrocnemius (+18.5 ± 39.3 %, p < 0.05). However, cigarette smoke still significantly impaired mitochondrial respiratory capacity with combined substrates compared to control (p < 0.05). Our findings underscore that cigarette smoke directly impairs mitochondrial respiration of carbohydrate-derived substrates and is a primary mechanism underlying cigarette smoke-induced muscle dysfunction, which leads to a vicious cycle involving excess glucose conversion into fatty acids and lipotoxicity.

Chronic obstructive pulmonary disease and the modulation of CFTR by acute exposure to cigarette smoke.

Chronic obstructive pulmonary disease (COPD) is a leading cause of death and cigarette smoke is the main risk factor. Detecting its earliest stages and preventing a decline in lung function are key goals. The pathogenesis of COPD is complex but has some similarities to cystic fibrosis (CF), a disease caused by mutations in the cftr gene. CF leads to chronic inflammation, abnormal mucus, and cycles of infection. Cigarette smoke exposure also causes CFTR dysfunction, and it is probably not a coincidence that inflammation, mucus obstruction, and infections are also characteristics of COPD, although the exacerbations can be quite different. We review here the acute effects of cigarette smoke on CFTR function and its potential role in COPD. Understanding CFTR regulation by cigarette smoke may identify novel drug targets and facilitate the development of therapeutics that reduce the progression and severity of COPD.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats (Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results. Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT (r2 = 0.584, β = -0.764, p &lt; 0.001), whereas VCAM-1 expression did not correlate with aortic IMT (r2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Acute effects of cigarette smoke on Endothelial Nitric Oxide synthase, vascular cell adhesion molecule 1 and aortic intima media thickness

Background. Cigarette smoking could induce endothelial dysfunction and the increase of circulating markers of inflammation by activation of monocytes. This can lead to increased intima media thickness (IMT) of entire blood vessels and result in acceleration of the atherosclerosis process. However, to our knowledge, little is known about the role of cigarette smoking in this atherosclerotic inflammatory process. The aim of this study is to explore the link between cigarette smoking and its effect on endothelial nitric oxide synthase (e-NOS) and vascular cell adhesion molecule 1 (VCAM-1). Methods. An experimental study with a post-test only controlled group design was used. We used 18 Wistar rats (Rattus norvegicus) randomly subdivided into two groups: group K (-) were not exposed to tobacco smoke, whereas group K (+) were exposed to smoke equivalent of more than 40 cigarettes for 28 days daily. After 28 days, samples were analyzed for e-NOS, VCAM-1 and aortic IMT. Results. Our results indicate that tobacco smoke can enhance the expression of VCAM-1 on rat cardiac vascular endothelial cells, resulting in a decreased expression of e-NOS level and increase of aortic IMT. Linear regression model found that eNOS level negatively correlated wiith aortic IMT (r2 = 0.584, β = -0.764, p &lt; 0.001), whereas VCAM-1 expression did not correlate with aortic IMT (r2 = 0.197, p = 0.065). Conclusion. Low e-NOS level and high VCAM-1 level observed after cigarette smoke exposure which may increase aortic IMT.

Acute cigarette smoke exposure induces oxidative damage and inflammation in Wistar rats: impact on lungs and erythrocytes

Smoking of cigarettes worsens morbidity and mortality rates by prompting cancer, pulmonary, cardiovascular, and oral diseases. Despite having all these severe risks of smoking, the habit is unacceptably widespread, particularly among teenagers in many countries, including Bangladesh. In this investigation, the acute effect of cigarette smoking on oxidative stress and inflammation (Tumor Necrosis Factor- α (TNF-α)) has been analyzed in the cigarette smoke (CS)-exposed rats. Exposure of smoke in vivo significantly increased the levels of Lipid Peroxide (LPO) and TNFα in the experimental rats, when compared to those of the control rats. Furthermore, washed erythrocytes isolated from control rats were exposed directly to CS in vitro. The time-dependent exposure of smoke to erythrocytes increased the oxidative stress in the erythrocytes, as indicated by increased levels of LPO in the erythrocytes. The toxic effect of acute cigarette smoke was also visible in the morphological studies of erythrocytes. Cigarette smoke-exposed erythrocytes revealed numerous leakage, breaks and membrane blobs in the plasma membrane of erythrocytes. Our results thus suggest that cigarette smoke not only affects the lung tissues but may also deteriorate the morphology of erythrocytes by instigating the oxidative stress in the erythrocytes.

Evaluation of the acute effects of cigarette smoking on the eye of non-Smoking healthy young male subjects by optical coherence tomography angiography

Purpose: Investigation of the acute effects of cigarette smoking on the eye using optical coherence tomography angiography (OCTA) on young healthy non-smoking male subjects.Materials and methods: The right eye of 25 healthy non-smoking male subjects were included in this study. Selected parameters of the macular and circumpapillary vasculature were measured, including macular flow indices, foveal avascular zone, vessel densities of macula and optic disc using OCTA. The measurements of the subjects were performed on the first day without smoking at 0 min, 5 min, 30 min and 60 min. Measurements were repeated at the same regime on the second day after smoking. Paired samples t-test and repeated measures one-way analysis of variance test was used for the statistical analysis.Results: The repeated measures analysis of variance test using the Bonferroni adjustment demonstrated a significant change for superficial and deep foveal vessel density, flow area of choriocapillaris, and circumpapillary capillary density following smoking (range of p value was <0.001–0.004). Intraocular pressure, foveal avascular zone area, flow area of outer retina and foveal non-flow area of superficial layer measurements did not have any significant changes following smoking (range of p value was 0.192–0.812).Conclusion: In non-smoking cases, even smoking only one cigarette significantly decreased the vessel density parameters at the acute period. Even though there was an increase in measured parameters shortly after smoking, it had lessened when compared to non-smokers, even one hour following smoking.

Effects of acute smoking on heart rate variability in students

Cigarette smoking is a major cause of preventable morbidity and mortality in the world. There is altered autonomic activity in smokers which also predisposes to cardiovascular morbidity and mortality. To monitor the autonomic activity, heart rate variability has emerged as efficient tool. This study attempted to clarify the acute effects of cigarette smoking on autonomic nervous function among smokers.Twenty one light smokers (smoking less than 10 cigarettes a day) with a mean age of 22.36±0.16 years take part in the study (52% men, 48% women). They were studied in the morning hours in a quiet room at a comfortable temperature. Time domain (SDNN, RMSSD, pNN50), frequency domain (TP, HF, VLF, LF and LF/HF ratio) and nonlinear (SD1, SD2, ApEn, SampEn, D2, DFA1, DFA2) parameters of HRV were obtained from all participants for 10 minutes before and 10 minutes after smoking a cigarette while subjects were resting in a supine position and. Statistical analysis was performed using Mann‐Whitney test.There were no significant differences in heart rate during non‐smoking and smoking period (70.75±2.30 vs 73.37±2.33 beat/min, p=0.217). Time domain parameters were found to be lower during smoking period than that during non‐smoking period (SDNN: 38.07±3.91 vs 50.53±5.64 ms, p=0.001; RMSSD: 39.39±4.87 vs 56.4±7.57 ms, p=0.001 and pNN50: 17.08±3.61 vs 28.63±4.28 %, p=0.002). Frequency domain measures were also significantly lower during smoking period than that during non‐smoking period (TP: 1578.31±387.76 vs 2975.75±788.91 ms2, p=0.001; VLF: 52.52±10.11 vs 108.96±24.56 ms2, p=0.008; LF: 719.5±130.54 vs 1210.54±262.29 ms2, p=0.013 and HF: 804.96±275.86 vs 1650.12±578.23 ms2, p=0.0009). Nonlinear measures were significantly lower during smoking period than that during non‐smoking period (SD1: 27.88±3.45 vs 39.92±5.36 ms, p=0.001; SD2: 45.79±4.45 vs 58.84±6.5 ms, p=0.003; D2: 1.83±0.36 vs 3.09±0.37, p=0.013). The other HRV parameters including LF/HF ratio, pLF, pHF, ApEn, SampEn, DFA1, DFA2 were not significantly different.These results suggest that acute smoking has been associated with increased activity of the sympathetic nervous system and decrease in vagal cardiac control.

Acute effect of cigarette smoking on frontal planar QRS-T angle in apparently healthy subjects with habitual smoking

Aim: It has been well recognized that smoking exerts various detrimental cardiovascular effects. Although the effect of chronic smoking on cardiac electrophysiology is well known, little is known about the effect of acute smoking on surface ECG. Previous reports suggested that frontal planar QRS-T angle (fpQRS-Ta), measured by surface ECG, may be associated with ventricular arrhythmias and cardiac death. Hence, we primarily aimed to assess the effect of acute smoking on fpQRS-Ta. Methods: A total of 92 apparently healthy subjects [44 female, 48 male, mean age 38.7(8.02) years] with smoking habit were enrolled in this prospective cohort study between May-July 2019. Demographic and clinical characteristics were recorded, and fpQRS-Ta together with some ECG parameters were noted before and 10 minutes after smoking for comparison. Spearman’s analysis was implemented to seek the probable correlation of the difference between pre- and post-smoking ECG parameters. Results: Ten minutes after smoking, median heart rate, QRS duration and fpQRS-Ta increased significantly (72.6 beats/min vs 81.5 beats/min, P<0.001; 84 ms vs 86 ms, P=0.012; 14.5° vs 25°, P<0.001; respectively), while PR and QTc duration did not significantly change (150.0 ms vs 150.0 ms, P=0.774; and, 423.5 ms vs 429.5 ms, P=0.372). In Spearman’s correlation analysis, the difference between pre- and post-smoking fpQRS-Ta significantly and negatively correlated with C-reactive protein (CRP) levels (r: -0.272, P=0.027). Conclusion: Acute smoking may widen fpQRS-Ta in healthy habitual smokers, and serum CRP negatively correlates with the degree of fpQRS-Ta widening. Our observation may further enlighten the pathophysiological mechanism of smoking in cardiac arrhythmias and sudden death.

Effect of Cigarette Smoking on Fasting Serum Glucose in Healthy Male Population

Acute effects of cigarette smoking include impaired insulin action that leads to abnormal glucose metabolism. Smoking is an independent risk factor for type 2 diabetes which is one of the global health crises and insulin resistance is one of the main risk factors for cardiovascular disease. This cross-sectional study was done to examine whether fasting serum glucose differs between cigarette smokers compared to non-smokers and to investigate the association of cigarette smoking with the development of impaired fasting glucose and type 2 diabetes. This study was done in the Physiology department of Mymensingh Medical College, an outpatient department of Mymensingh Medical College Hospital, for over a period of one year from July 2014 to June 2015. Fasting serum blood glucose was done by enzymetric colorometric GOD-PAP method in a total of 150 subjects, in which non-smokers were 50 and numbers of smokers were 100 with the duration of smoking 5 - 10 years and &gt;10 years. A questionnaire including data was completed in all cases. The data were checked, coded, and entered into an SPSS 11.5. Statistical significance of difference among the groups was calculated by Students unpaired t' test. P-value &lt;0.05 was considered as a level of significance. Fasting Serum Glucose level was increased gradually with the duration of smoking in smokers than the non-smokers. Results were statistically highly significant. Fasting Serum Glucose gradually increase with the duration of smoking and results were within the physiological limit in two study groups (Group-II A with 5-10 years duration of smoking and Group- II B with more than 10 years duration of smoking) but not statistically significant. This study showed cigarette smoking has deleterious effects on insulin metabolism causing an increase in serum glucose with duration of smoking period.&#x0D; CBMJ 2019 July: Vol. 08 No. 02 P: 36-39

The Acute Effects of Cigarette Smoking on the Functional State of High Density Lipoprotein

BackgroundCigarette smoking disturbs plasma lipid level and lipoprotein metabolism; however, the effects of smoking on the functional state of high density lipoprotein (HDL) are still not clear. This study aimed to determine the antioxidant and antichemotactic properties of HDL and HDL-mediated cholesterol efflux in healthy subjects after cigarette smoking. Materials and MethodsHealthy male subjects, including nonsmokers (n = 16) and chronic smokers (n = 8), were enrolled. After smoking 8 cigarettes within 2 hours, plasma HDL was isolated and tested. Copper-induced low density lipoprotein (LDL) oxidation was used to determine the antioxidant ability of HDL. The concentration of serum amyloid A was measured by Enzyme Linked Immunosorbent Assay. Chemotaxis was detected by transwell assay. HDL-mediated cholesterol efflux was measured using fluorescent cholesterol analog. ResultsLDL baseline oxidation state was higher in chronic smokers than that in nonsmokers. Meanwhile, HDL-induced cholesterol efflux in macrophages in chronic smokers was significantly enhanced compared with that in nonsmokers. After acute smoking, both the antioxidant and antichemotactic ability of HDL declined in nonsmokers. However, in healthy chronic smokers, the effect of HDL on the susceptibility of LDL to oxidation was compensatorily enhanced. Nevertheless, their bodies were still in a higher oxidation state. Also, acute smoking did not affect HDL-mediated cholesterol efflux significantly in both nonsmokers and chronic smokers. ConclusionsOur data suggest that acute smoking attenuates the antioxidant and antichemotactic abilities of HDL in nonsmokers. Chronic smokers are in a higher oxidative state, although the antioxidant function of their HDL is compensatorily enhanced.

Cigarette Smoking-Associated Alterations in Serotonin/Adrenalin Signaling Pathways of Platelets.

BackgroundCigarette smoking plays a major role in cardiovascular diseases. The acute effects of cigarette smoking produce central nervous system–mediated activation of the sympathetic nervous system. The overactive sympathetic nervous system stimulates the secretion of serotonin (5‐HT) and catecholamine into blood at supraphysiological levels. The correlation between these pathological conditions induced by smoking and the increased risk of thrombosis has not been thoroughly investigated. The goal of our study was to explore cigarette smoking–associated changes in platelet biology mediated by elevated 5‐HT and catecholamine levels in blood plasma.Methods and ResultsUsing blood samples collected from healthy nonsmokers and smokers (15 minutes after smoking), we determined that cigarette smoking increased the plasma 5‐HT/catecholamine concentration by several fold and the percent aggregation of platelets 2‐fold. Liquid chromatography–tandem mass spectrometry analysis of proteins eluted from platelet plasma membranes of smokers and nonsmokers demonstrated that GTPase‐activating proteins and proteins participating in the actin cytoskeletal network were differentially and significantly elevated in smokers' platelet membranes compared with those of nonsmokers. Interestingly, Matrix‐assisted laser desorption/ionization–mass spectrometry analyses of the glycans eluted from platelet plasma membranes of the smokers demonstrated that the level and structures of glycans are different from the nonsmokers' platelet surface glycans. Pharmacological blockade of 5‐HT or catecholamine receptors counteracted the 5‐HT/catecholamine‐mediated aggregation and altered the level and composition of glycan on platelet surfaces.ConclusionsBased on our findings, we propose that smoking‐associated 5‐HT/catecholamine signaling accelerates the trafficking dynamics of platelets, and this remodels the surface proteins and glycans and predisposes platelets to hyperactive levels. Smokers' platelets also had correspondingly higher resting concentrations of intracellular calcium and transglutaminase activity. These findings suggest a link among smoking, platelet 5‐HT, catecholamine signaling, and their downstream effectors—including phospholipase C and inositol‐1,4,5‐triphosphate pathways—resulting in an increased tonic level of platelet activation in smokers.

Acute cigarette smoke exposure activates apoptotic and inflammatory programs but a second stimulus is required to induce epithelial to mesenchymal transition in COPD epithelium

BackgroundSmoking and aberrant epithelial responses are risk factors for lung cancer as well as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis. In these conditions, disease progression is associated with epithelial damage and fragility, airway remodelling and sub-epithelial fibrosis. The aim of this study was to assess the acute effects of cigarette smoke on epithelial cell phenotype and pro-fibrotic responses in vitro and in vivo.ResultsApoptosis was significantly greater in unstimulated cells from COPD patients compared to control, but proliferation and CXCL8 release were not different. Cigarette smoke dose-dependently induced apoptosis, proliferation and CXCL8 release with normal epithelial cells being more responsive than COPD patient derived cells. Cigarette smoke did not induce epithelial-mesenchymal transition. In vivo, cigarette smoke exposure promoted epithelial apoptosis and proliferation. Moreover, mimicking a virus-induced exacerbation by exposing to mice to poly I:C, exaggerated the inflammatory responses, whereas expression of remodelling genes was similar in both.ConclusionsCollectively, these data indicate that cigarette smoke promotes epithelial cell activation and hyperplasia, but a secondary stimulus is required for the remodelling phenotype associated with COPD.

The Cystic Fibrosis Transmembrane Conductance Regulator Potentiator Ivacaftor Augments Mucociliary Clearance Abrogating Cystic Fibrosis Transmembrane Conductance Regulator Inhibition by Cigarette Smoke.

Acquired cystic fibrosis transmembrane conductance regulator (CFTR) dysfunction may contribute to chronic obstructive pulmonary disease pathogenesis and is a potential therapeutic target. We sought to determine the acute effects of cigarette smoke on ion transport and the mucociliary transport apparatus, their mechanistic basis, and whether deleterious effects could be reversed with the CFTR potentiator ivacaftor (VX-770). Primary human bronchial epithelial (HBE) cells and human bronchi were exposed to cigarette smoke extract (CSE) and/or ivacaftor. CFTR function and expression were measured in Ussing chambers and by surface biotinylation. CSE-derived acrolein modifications on CFTR were determined by mass spectroscopic analysis of purified protein, and the functional microanatomy of the airway epithelia was measured by 1-μm resolution optical coherence tomography. CSE reduced CFTR-dependent current in HBE cells (P < 0.05) and human bronchi (P < 0.05) within minutes of exposure. The mechanism involved CSE-induced reduction of CFTR gating, decreasing CFTR open-channel probability by approximately 75% immediately after exposure (P < 0.05), whereas surface CFTR expression was partially reduced with chronic exposure, but was stable acutely. CSE treatment of purified CFTR resulted in acrolein modifications on lysine and cysteine residues that likely disrupt CFTR gating. In primary HBE cells, CSE reduced airway surface liquid depth (P < 0.05) and ciliary beat frequency (P < 0.05) within 60 minutes that was restored by coadministration with ivacaftor (P < 0.005). Cigarette smoking transmits acute reductions in CFTR activity, adversely affecting the airway surface. These effects are reversible by a CFTR potentiator in vitro, representing a potential therapeutic strategy in patients with chronic obstructive pulmonary disease with chronic bronchitis.

Metabolomic profiles of current cigarette smokers.

Smoking-related biomarkers for lung cancer and other diseases are needed to enhance early detection strategies and to provide a science base for tobacco product regulation. An untargeted metabolomics approach by ultra-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q-TOF MS) totaling 957 assays was used in a novel experimental design where 105 current smokers smoked two cigarettes 1 h apart. Blood was collected immediately before and after each cigarette allowing for within-subject replication. Dynamic changes of the metabolomic profiles from smokers' four blood samples were observed and biomarkers affected by cigarette smoking were identified. Thirty-one metabolites were definitively shown to be affected by acute effect of cigarette smoking, uniquely including menthol-glucuronide, the reduction of glutamate, oleamide, and 13 glycerophospholipids. This first time identification of a menthol metabolite in smokers' blood serves as proof-of-principle for using metabolomics to identify new tobacco-exposure biomarkers, and also provides new opportunities in studying menthol-containing tobacco products in humans. Gender and race differences also were observed. Network analysis revealed 12 molecules involved in cancer, notably inhibition of cAMP. These novel tobacco-related biomarkers provide new insights to the effects of smoking which may be important in carcinogenesis but not previously linked with tobacco-related diseases. © 2016 Wiley Periodicals, Inc.

PS237 Acute Effects of Cigarette Smoking on the Right and Left Ventricular Functions Among Chronic and Light Smokers

Despite the great number of methods proposed, assessing the causal role of a drug in the occurrence of an adverse medical event remains one of the most controversial issues. Qualifying terms for criteria, such as “compatible”, “suggestive” of “inconclusive”, have never been strictly defined, leading to low reproducibility. Weights of the criteria are usually not adapted to the injured organ, decreasing the specificity of the method. In this paper, a new method for drug causality assessment is described. Contents and limits of the criteria have been defined by experts convened to organ-oriented international consensus meetings. Additional criteria have been introduced and weights attributed. The method was applied to reports of acute liver injuries. The reproducibility was tested by an independent team. The validity of this novel method is studied in the following paper, based on an original approach using reports with positive rechallenge as external standard.

Is the Exhaled Breath Temperature Sensitive to Cigarette Smoking?

The smoking habit is accompanied by an acute inflammatory response which follows tissue injury. It would be desirable to find a non-invasive inflammatory marker that would simplify the task of studying and monitoring smokers more simply and allow us to identify populations at risk of contracting Chronic Obstructive Pulmonary Disease (COPD). Today's expectations regarding research focus on issues ranging from inflammatory markers to those of exhaled breath temperature (EBT) are considerable. That said, although the EBT has been largely studied in asthma and COPD, there have not been any studies thus far that have analysed the effect of cigarette smoking on the EBT. Bearing this in mind, in this longitudinal study we aim to analyse the EBT in current smokers, monitor the effects both of cigarette smoking on EBT and of what happens after smoking cessation. Twenty-five (25) smokers (59.5 ± 3.1 yrs, 12 M) who participated in a multi-disciplinary smoking cessation programme and 25 healthy never-smokers (58.7 ± 2.9, 13 M) underwent EBT measurement. EBT values were higher in smokers before smoking (T0) than in never-smokers [34.6 (34.2–35) vs 33.2 (32.4–33.7)°C, p < 0.001. The smokers repeated measurement 5 minutes after smoking a cigarette (T1) and 2 hours after (T2). They repeated EBC measurement after 1 week (T3) and then after 3 months (T4) from smoking cessation. EBT is higher in smokers compared to controls. EBT increases after cigarette smoking and progressively decreases with the increase of time from when the last cigarette was smoked. Thus, we can conclude that EBT is increased in smokers and also sensitive to the acute effect of cigarette smoke.