Function In Cigarette Smokers Research Articles

Is Adherence to the Healthy Eating Index – 2015 Associated with Rate of Decline in Lung Function

ObjectivesWe investigated the hypothesis that a healthier dietary pattern score is associated with higher lung function with stronger associations in smokers.MethodsWe studied participants in the Health, Aging, and Body Composition study (n = 2,549) and the Respiratory Ancillary Study (n = 2,866). Three dietary pattern scores, based on Healthy Eating Index 2015 (HEI-2015), Alternate Mediterranean Diet (AMED), and Dietary Approaches to Stop Hypertension (DASH), were calculated from FFQs. Associations between the 3 diet pattern scores and lung function [forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), and FEV1/FVC] were estimated using linear mixed effects regression models. Stratified analyses were explored in never vs. ever smokers. Models were run within cohort and meta-analyzed results are presented.ResultsThe cross-sectional association of dietary pattern and lung function was estimated and a 1-point higher HEI-2015, AMED, and DASH score was associated with a 2 mL, 6 mL, and 6 mL, respectively, higher FEV1 (P < 0.05) at any point in the follow-up. Among ever smokers, the associations were stronger with effect sizes of 6 mL (P = 0.002), 25 mL (P < 0.001), and 7 mL (P < 0.001), respectively. There was little to no association of dietary pattern score and the longitudinal rate of decline in lung function. The findings for FVC were similar, with evidence of cross-sectional but not longitudinal associations. There was little to no association of dietary pattern with FEV1/FVC.ConclusionsWe found a positive cross-sectional association of dietary pattern score with lung function, but little to no association of dietary pattern with longitudinal decline in lung function. The cross-sectional associations were modified by smoking status such that a healthier dietary pattern had a stronger positive association with lung function in cigarette smokers.Funding SourcesThis research was supported by R01 HL149352 (PIs: PAC and DBH).

Assessment of industry data on pulmonary and immunosuppressive effects of IQOS

IntroductionHeated tobacco products are being touted as novel reduced-harm tobacco products by tobacco companies. In the USA, Philip Morris International submitted a modified risk tobacco product (MRTP) application to the...

Statins in the treatment of asthma

Current evidence on statin agents as potential alternatives or adjuncts to corticosteroid therapy for asthma is reviewed. Research showing antiinflammatory and antioxidant effects of statins in animal models suggested that the cholesterol-lowering drugs might be useful in mitigating the adverse effects of long-term corticosteroid therapy in patients with asthma, but studies in humans have yielded mixed results. Two small placebo-controlled clinical trials indicated that statins were not effective in combating asthmatic inflammatory processes, and trials of statins as adjunctive therapy have indicated minimal steroid-sparing benefits. In two studies involving a total of more than 1000 current and former smokers with asthma, statin use correlated with reduced acute asthma exacerbations and a slower decline of lung function in some patients. A large population-based study (n = 3965) found that statin therapy was associated with a significantly reduced risk of hospitalization for asthma after an average follow-up period of about 4.5 years; a smaller U.S. retrospective cohort study indicated a significantly lower 1-year rate of asthma-related emergency room visits among patients receiving statins relative to those not using statins (9.08% versus 4.18%). Much of the research on statins and asthma has not controlled for confounding influences such as patient comorbidities and concomitant medication use. Clinical trials have shown that statin therapy is not superior to and does not enhance the beneficial effects of inhaled corticosteroids for the treatment of asthma. Some evidence suggests that statins may help preserve lung function in cigarette smokers with obstructive pulmonary disease and reduce hospitalizations in asthmatic smokers and nonsmokers.

Effect of ω-3 fatty acid supplementation on endothelial function, endogenous fibrinolysis and platelet activation in male cigarette smokers

ObjectiveThe effects of ω-3 fatty acids on endothelial function, fibrinolysis and platelet function are uncertain. We investigated the effects of ω-3 fatty acid supplementation on endothelial vasomotor function, endogenous fibrinolysis,...

Wood Smoke Exposure and Gene Promoter Methylation Are Associated with Increased Risk for COPD in Smokers

Wood smoke-associated chronic obstructive pulmonary disease (COPD) is common in women in developing countries but has not been adequately described in developed countries. Our objective was to determine whether wood smoke exposure was a risk factor for COPD in a population of smokers in the United States and whether aberrant gene promoter methylation in sputum may modify this association. For this cross-sectional study, 1,827 subjects were drawn from the Lovelace Smokers' Cohort, a predominantly female cohort of smokers. Wood smoke exposure was self-reported. Postbronchodilator spirometry was obtained, and COPD outcomes studied included percent predicted FEV₁, airflow obstruction, and chronic bronchitis. Effect modification of wood smoke exposure with current cigarette smoke, ethnicity, sex, and promoter methylation of lung cancer-related genes in sputum on COPD outcomes were separately explored. Multivariable logistic and poisson regression models were used for binary and rate-based outcomes, respectively. Self-reported wood smoke exposure was independently associated with a lower percent predicted FEV₁ (point estimate [± SE] -0.03 ± 0.01) and a higher prevalence of airflow obstruction and chronic bronchitis (odds ratio, 1.96; 95% confidence interval, 1.52-2.52 and 1.64 (95% confidence interval, 1.31-2.06, respectively). These associations were stronger among current cigarette smokers, non-Hispanic whites, and men. Wood smoke exposure interacted in a multiplicative manner with aberrant promoter methylation of the p16 or GATA4 genes on lower percent predicted FEV₁. These studies identify a novel link between wood smoke exposure and gene promoter methylation that synergistically increases the risk for reduced lung function in cigarette smokers.

Accelerated decline in lung function in cigarette smokers is associated with TP53/MDM2 polymorphisms

In vitro studies have shown that p53 mediates a protective response against DNA damage by causing either cell-cycle arrest and DNA repair, or apoptosis. These responses have not yet been demonstrated in humans. A common source of DNA damage in humans is cigarette smoke, which should activate p53 repair mechanisms. As the level of p53 is regulated by MDM2, which targets p53 for degradation, the G-allele of a polymorphism in intron 1 of MDM2 (rs2279744:G/T), that results in higher MDM2 levels, should be associated with a reduced p53 response and hence more DNA damage and corresponding tissue destruction. Similarly, the alleles of rs1042522 in TP53 that encode arginine (G-allele) or proline (C-allele) at codon 72, which cause increased pro-apoptotic (G-allele) or cell-cycle arrest activities (C-allele), respectively, may moderate p53's ability to prevent DNA damage. To test these hypotheses, we examined lung function in relation to cumulative history of smoking in a population-based cohort. The G-alleles in MDM2 and TP53 were found to be associated with accelerated smoking-related decline in lung function. These data support the hypothesis that p53 protects from DNA damage in humans and provides a potential explanation for the variation in lung function impairment amongst smokers.

Lisinopril improves endothelial function in chronic cigarette smokers

Cigarette smoking is a pernicious risk factor for the pathogenesis of coronary artery disease, and endothelial dysfunction is an important antecedent event in this process. This is important, as cigarette smoke is directly toxic to endothelial cells. Inhibitors of angiotensin-converting enzyme (ACE) have been shown to improve endothelial function in diabetes and hypercholesterolaemia, and are a promising option in smokers. We treated 23 subjects (age 38+/-12 years; mean+/-S.D.) for 8 weeks with 20 mg of lisinopril in a randomized controlled trial. Endothelial function was assessed by measurement of forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasodilators and an endothelial-dependent vasoconstrictor [acetylcholine, sodium nitroprusside and monomethyl-L-arginine (L-NMMA) respectively] using venous occlusion plethysmography. Lisinopril significantly increased the forearm blood flow response to acetylcholine by 20% [lisinopril, 3.12+/-0.37 (mean+/-S.E.M.); placebo, 2.58+/-0.25; P=0.02, 95% confidence intervals (CI) 0.09, 1.06] (values given are ratios of flow in the infused arm to that in the control arm); there was no effect on the response to sodium nitroprusside (lisinopril, 3.97+/-0.40; placebo, 3.92+/-0.39; P=0.84; 95% CI -0.50, 0.61). The vasoconstrictor response to L-NMMA demonstrated a significant improvement (lisinopril, 0.77+/-0.06; placebo, 0.95+/-0.05; P<0.001; 95% CI -0.09, -0.27). In conclusion, these results indicate that ACE inhibition can improve endothelial function in cigarette smokers. We show that lisinopril improves both receptor-mediated and tonic NO release. The mechanism could be either that lisinopril limits the angiotensin II-induced production of superoxide radicals which would normally inactivate NO, or that lisinopril may increase bradykinin-mediated NO release.

Lisinopril improves endothelial function in chronic cigarette smokers

Cigarette smoking is a pernicious risk factor for the pathogenesis of coronary artery disease, and endothelial dysfunction is an important antecedent event in this process. This is important, as cigarette smoke is directly toxic to endothelial cells. Inhibitors of angiotensin-converting enzyme (ACE) have been shown to improve endothelial function in diabetes and hypercholesterolaemia, and are a promising option in smokers. We treated 23 subjects (age 38±12 years; mean±S.D.) for 8 weeks with 20 mg of lisinopril in a randomized controlled trial. Endothelial function was assessed by measurement of forearm blood flow responses to intra-arterial infusions of endothelial-dependent and -independent vasodilators and an endothelial-dependent vasoconstrictor [acetylcholine, sodium nitroprusside and monomethyl-l-arginine (l-NMMA) respectively] using venous occlusion plethysmography. Lisinopril significantly increased the forearm blood flow response to acetylcholine by 20% [lisinopril, 3.12±0.37 (mean±S.E.M.); placebo, 2.58±0.25;P = 0.02, 95% confidence intervals (CI) 0.09, 1.06] (values given are ratios of flow in the infused arm to that in the control arm); there was no effect on the response to sodium nitroprusside (lisinopril, 3.97±0.40; placebo, 3.92±0.39; P = 0.84; 95% CI -0.50, 0.61). The vasoconstrictor response to l-NMMA demonstrated a significant improvement (lisinopril, 0.77±0.06; placebo, 0.95±0.05; P &lt; 0.001; 95% CI -0.09, -0.27). In conclusion, these results indicate that ACE inhibition can improve endothelial function in cigarette smokers. We show that lisinopril improves both receptor-mediated and tonic NO release. The mechanism could be either that lisinopril limits the angiotensin II-induced production of superoxide radicals which would normally inactivate NO, or that lisinopril may increase bradykinin-mediated NO release.

The importance of ultramicroscopic emphysema in cigarette smoke-induced lung disease.

To determine the role of the alveolar pores in cigarette smoke-induced lung disease, we examined the alveolar pores of guinea pigs exposed to cigarette smoke for 12 months, and compared these data to those obtained from sham-smoked animals, correlating the data with airspace size and lung function. We found that the smoke-exposed animals had a larger mean number of pores per alveolus (p < 0.001), and the distributions of pore size and shape were significantly shifted to indicate a larger and more irregular pore configuration (p < 0.001, 01 respectively). In the smoke exposed group, there was a significant correlation of pore number with total lung capacity (TLC) (0.68 p < 0.05), RV (0.70, p < 0.05), and FEV(0.1)/FVC(-0.77, p < 0.02). No correlations were identified between pore size or shape and the lung function tests. We conclude that cigarette smoke exposure produces an increase in the number of alveolar pores, a process which we believe represents ultramicroscopic emphysema. These alterations appear to precede any increase in airspace size, and may help to explain abnormal lung function in cigarette smokers without macroscopic emphysema or small airway disease. This is the first study to clearly document an increased number of alveolar pores, with a significant number of either/or large and irregular pores, after chronic smoke exposure, but in the absence of gross emphysema.

Immune function in cigarette smokers who quit smoking for 31 days

A group of 28 healthy, white, male, light-to-moderate smokers, 21 to 35 years of age, were offered a financial inducement to abstain from smoking for 31 days. A matched control group of 11 smokers were paid to continue smoking during the same period. Nonspecific parameters of immune system function were monitored before and at various times after smoking abstinence. Abstinence increased natural killer cell cytotoxic activity but did not alter mitogen-induced T-lymphocyte proliferation as measured by responses to concanavalin A or phytohemagglutinin. Serum cortisol concentrations also decreased after smoking cessation; however, changes in immune function were not correlated with serum cortisol change, nor with indices of smoking such as plasma nicotine and cotinine levels. Responses to concanavalin A and phytohemagglutinin were positively correlated with change in self-reported alcohol ingestion during smoking abstinence. Results indicate that elevation in natural kill cell cytotoxic activity is detectable within 1 month of smoking cessation, even in light-to-moderate smokers. However, elevation in natural killer cell cytotoxic activity appears not to be directly related to cessation-induced reductions in plasma nicotine, cotinine, or circulating cortisol levels. (J A LLERGY C LIN I MMUNOL 1995;95:901–10.)

Lung structure and function in cigarette smokers.

Lung structure and function in cigarette smokers.

Lung structure and function in cigarette smokers.

Cigarette smoking produces an inflammatory response in the airways of everyone but only 15-20% of smokers develop airways obstruction. The present study concerns the relative importance of peripheral airways inflammation and the emphysematous destruction of the parenchymal support of the airways in the pathogenesis of this obstruction. A total of 407 patients with a diagnosis of lung tumour performed pulmonary function tests a day or two before a lung or lobar resection. The specimens were fixed in inflation and analysed at the gross and microscopic level to determine the extent and severity of the emphysematous process, the number of alveoli supporting the outer walls of the airways, and the average distance between alveolar walls. The severity of the inflammatory process in the respiratory and nonrespiratory bronchioles was also assessed using a previously established grading system. The lung function test showed that a decline in FEV1 was associated with an increase in residual volume and a decrease in the diffusing capacity for carbon monoxide and a reduction in the lung maximum elastic recoil pressure. The prevalence of grossly visible emphysema increased as FEV1 declined, but the extent and severity of these lesions and the number of alveoli supporting the outer walls of the peripheral airways was similar at all levels of FEV1. The system used to grade inflammatory response in the peripheral airways failed to identify a specific defect responsible for the physiological abnormalities. The reduction in FEV1 associated with chronic cigarette smoking can be partially explained by loss of lung elastic recoil pressure which reduces the force driving air out of the lung. This loss of elastic recoil pressure is attributed to microscopic enlargement of the air spaces rather than to grossly visible emphysema. The exact nature of the lesions responsible for the peripheral airways obstruction remains to be identified.

The Flow-Ratio Index: An Approach for Measuring the Influence of Age and Cigarette Smoking on Maximum Expiratory Flow-Volume Curve Configuration

A forced expiratory flow ratio, derived from the average slope of the maximum expiratory flow-volume (MEFV) curve over a specified volume interval, was examined in healthy asymptomatic cigarette smokers and nonsmokers. This index was developed to have the properties that it would be (1) simple to calculate, (2) less effort dependent than indices that incorporate peak flow, and (3) free of influence from the configurational detail and noise frequently occurring at higher lung volumes on MEFV curves. Forced expired vital capacity maneuvers were performed by participants in a worksite health promotion program. Data from asymptomatic individuals with normal pulmonary function were analyzed for 49 cigarette smokers and 52 nonsmokers; 25 individuals had MEFV curves collected twice over a one-year interval. The ratio of flow derived from an average MEFV slope to instantaneous flow was calculated over the lower half of the vital capacity. Flow ratios were expressed as a percentage of the instantaneous flow at 75 percent of the expired vital capacity (FR75). This ratio was reproducible from year 1 to year 2 (r = 0.86, p<0.0001). Furthermore, the FR75 was well correlated with age among cigarette smokers and nonsmokers (r = 0.68 and 0.63 respectively). The slope of the least squares regression equation relating FR75 to age was significantly greater among smokers than nonsmokers (2.90 percent per year vs 1.73 percent per year, p<0.025). While there was a significant interactive influence of age and total pack-years on the FR75 (F = 2.91, p=0.02), this index did not differ systematically by gender. We conclude that the FR25 is a more sensitive index of altered lung function in cigarette smokers than are results of conventional pulmonary function.

Immune and inflammatory function in cigarette smokers.

Immune and inflammatory function in cigarette smokers.

Chronic airflow obstruction: Evolution of disordered function in cigarette smokers

Measurements of the mechanical behaviour of the lung, which reflect lung structure, have been used to elucidate the evolution of chronic airflow obstruction in male cigarette smokers and subjects with pulmonary emphysema. The exponent K, from a single exponential function fitted to static pressure-volume data, is an index of lung distensibility directly related to the size of peripheral airspaces. Elastic recoil pressure is inversely related to K. Conductance measured during forced and interrupted deflations of the lungs reflects the dimensions of airways. K increased abnormally with age in smokers suggesting an increase in the airspace size caused by the effects of cigarette smoke which probably acts by intensifying elastase activity in lung tissue. Decreased conductance implying narrowing of airways is found in young smokers, but conductance rises and airways become more distensible in older smokers. A progressive increase in K (with decrease in recoil pressure) and a decrease in conductance are responsible for the advancement of severe airflow obstruction in cigarette smokers.

The Effects of Cigarette Smoking on the Human Placenta

A histological and electronoptical study of placentae from women who smoke cigarettes during pregnancy shows a tendency towards a paucity of vasculosyncytial membranes, villous cytotrophoblastic cell proliferation, focal syncytial necrosis, decreased syncytial pinocytotic and secretory activity, dilatation of syncytial rough endoplasmic reticulum, abnormalities of syncytial microvilli, focal infolding of the free plasma membrane of the syncytiotrophoblast, degeneration of isolated cytotrophoblastic cells, irregular thickening of the trophoblastic basement membrane and degeneration of villous capillary endothelial cells. It is thought that many of these changes are due to placental ischaemia consequent upon nicotine-induced constriction of the uterine vessels; some of the changes cannot be explained on this basis and it is suggested that these may possibly be due either to cadmium toxicity or to accumulation of polycyclic aromatic hydrocarbons. There is apparently some impairment of placental function in cigarette smokers but this is probably offset by the ability of the placenta to repair ischaemic damage and to undergo a compensatory hyperplasia.

The relationship of tar content to decline in pulmonary function in cigarette smokers.

The impact of the tar content of cigarettes on pulmonary function was examined in 1,355 men. These men represented 383 current cigarette smokers, 555 former cigarette smokers, and 417 never smokers enrolled in longitudinal study of aging. Current smokers' cigarette exposure was estimated by the number of cigarettes smoked per day and tar content per cigarette. spirometry was performed twice on all subjects at a 5-yr interval. A multiple regression analysis indicated that tar content did not significantly influence baseline levels of forced vital capacity (FVC) or forced expiratory volume in one second (FEV1), after controlling for age, height, and number of cigarettes smoked. Similarly, tar content did not significantly influence follow-up levels of FVC or FEV1, after controlling for age, height, number of cigarettes, and baseline pulmonary function. These data suggest that low tar cigarettes may not protect smokers from an increased rate of decline in pulmonary function.

The effects of cigarette smoking on the human placenta: a light and electron microscopic study

A histological and electronoptical study of placentae from women who smoke cigarettes during pregnancy shows a tendency towards a paucity of vasculosyncytial membranes, villous cytotrophoblastic cell proliferation, focal syncytial necrosis, decreased syncytial pinocytotic and secretory activity, dilatation of syncytial rough endoplasmic reticulum, abnormalities of syncytial microvilli, focal infolding of the free plasma membrane of the syncytiotrophoblast, degeneration of isolated cytotrophoblastic cells, irregular thickening of the trophoblastic basement membrane and degeneration of villous capillary endothelial cells. It is thought that many of these changes are due to placental ischaemia consequent upon nicotine-induced constriction of the uterine vessels; some of the changes cannot be explained on this basis and it is suggested that these may possibly be due either to cadmium toxicity or to accumulation of polycyclic aromatic hydrocarbons. There is apparently some impairment of placental function in cigarette smokers but this is probably offset by the ability of the placenta to repair ischaemic damage and to undergo a compensatory hyperplasia.