Effect of Cigarette Smoking on Clinical and Molecular Endpoints in COPD Patients.

Cigarette smoking is a primary contributor to mortality risks and is associated with various diseases. Among these, COPD represents a significant contributor to global mortality and disability. The objective of this study is to investigate the effect of smoking on a selected battery of variables, with an emphasis on DNA damage. A total of 87 elderly patients diagnosed with COPD, divided into three groups based on their smoking history (current, former, never-smokers), were evaluated using a cross-sectional approach. Clinical features including mortality and inflammatory/oxidative parameters (Lymphocytes/Monocytes, Neutrophils/Lymphocytes, Platelets/Lymphocytes ratio), SII, MDA, 8-Oxo-dG, and IL6 (ELISA assay), as well as DNA damage (comet assay), were investigated. Virus infection, i.e., influenza A virus subtype H1N1, JC polyomavirus (JCPyV), BK polyomavirus (BKPyV), and Torquetenovirus (TTV), was also tested. Current smokers exhibit higher levels of comorbidity (CIRS; p < 0.001), Platelets/Lymphocytes ratio (p < 0.001), systemic immune inflammation (p < 0.05), and DNA damage (p < 0.001). Former smokers also showed higher values for parameters associated with oxidative damage and showed a much lower probability of surviving over 5 years compared to never- and current smokers (p < 0.0017). This study showed a clear interaction between events which are relevant to the oxidative pathway and cigarette smoking. A category of particular interest is represented by former smokers, especially for lower survival, possibly due to the presence of more health problems. Our findings raise also the attention to other parameters which are significantly affected by smoking and are useful to monitor COPD patients starting a program of pulmonary rehabilitation (DNA damage, inflammation parameters, and selected viral infections).

The Association of Tobacco Smoking, Second-hand Smoke, and Novel Tobacco Products With COVID-19 Severity and Mortality in Italy: Results From the COSMO-IT Study.

BACKGROUND: Despite the robust evidence of an excess risk of coronavirus disease 2019 (COVID-19) severity and mortality in ever smokers, the debate on the role of current and ex-smokers on COVID-19 progression remains open. Limited or no data are available on the link between electronic cigarette (e-cigarette), heated tobacco product (HTP) and second-hand smoke (SHS) exposure and COVID-19 progression. To fill this knowledge gap, we undertook the COvid19 and SMOking in ITaly (COSMO-IT) study. METHODS: A multi-centre longitudinal study was conducted in 2020-2021 in 24 Italian hospitals on a total of 1,820 laboratory-confirmed COVID-19 patients. We estimated multivariable odds ratios (OR) and 95% confidence intervals (CI) to quantify the association between smoking-related behaviours (ie, smoking status, e-cigarette and HTP use, and SHS exposure) and COVID-19 severity (composite outcome: intubation, intensive care unit admission and death) and mortality. RESULTS: Compared to never smokers, current smokers had an increased risk of COVID-19 mortality (OR 2.17; 95% CI, 1.06-4.41). E-cigarette use was non-significantly associated to an increased risk of COVID-19 severity (OR 1.60; 95% CI, 0.96-2.67). An increased risk of mortality was observed for exposure to SHS among non-smokers (OR 1.67; 95% CI, 1.04-2.68), the risk being particularly evident for exposures of ≥6 hours/day (OR 1.99; 95% CI, 1.15-3.44). CONCLUSION: This multicentric study from Italy shows a dismal COVID-19 progression in current smokers and, for the first time, in SHS exposed non-smokers. These data represent an additional reason to strengthen and enforce effective tobacco control measures and to support smokers in quitting.

Nicotine: From Discovery to Biological Effects.

Nicotine, the primary psychoactive agent in tobacco leaves, has led to the widespread use of tobacco, with over one billion smokers globally. This article provides a historical overview of tobacco and discusses tobacco dependence, as well as the biological effects induced by nicotine on mammalian cells. Nicotine induces various biological effects, such as neoangiogenesis, cell division, and proliferation, and it affects neural and non-neural cells through specific pathways downstream of nicotinic receptors (nAChRs). Specific effects mediated by α7 nAChRs are highlighted. Nicotine is highly addictive and hazardous. Public health initiatives should prioritize combating smoking and its associated risks. Understanding nicotine's complex biological effects is essential for comprehensive research and informed health policies. While potential links between nicotine and COVID-19 severity warrant further investigation, smoking remains a significant cause of morbidity and mortality globally. Effective public health strategies are vital to promote healthier lifestyles.

Tobacco Worker's Lung: A Neglected Subtype of Hypersensitivity Pneumonitis.

Tobacco worker's lung (TWL) is a type of hypersensitivity pneumonitis (HP) affecting workers exposed to tobacco leaves and molds in the humidified environment of the tobacco production industry. Limited epidemiological data point to a prevalence of TWL that is not negligible and probably underestimated. As in other types of HP, an acute vs. chronic presentation depends on the pattern of the exposure. Therefore, the clinical presentation can vary from an acute influenza-like syndrome, mostly self-limiting with the removal of the exposure, to an insidious onset of cough, exertional dyspnea, fatigue and weight loss in chronic presentations, where fibrotic changes may be observed. The main treatment strategy is the removal of the exposure to tobacco dust and molds, while the main aim of corticosteroid therapy is to reduce morbidity and prevent complications, namely the development of pulmonary fibrosis and permanent lung dysfunction. Despite the fact that TWL is quite well described, preventive measures are not usually adopted in the tobacco production industry. We present here a state of the art review of this neglected, preventable, but still prevalent and occupational-related subtype of HP.

[Formaldehyde in electronic cigarettes and in heat-not-burn products: let's make the point]. / La formaldeide nelle sigarette elettroniche e nei riscaldatori di tabacco (HnB): facciamo il punto.

The spread of electronic cigarettes (e-cigs) and of the so-called heat-not-burn (HnB), also known as heated tobacco products, presented as a less harmful alternative to traditional cigarettes, required further in-depth studies to demonstrate the real benefits or possible risks linked to this type of habit among smokers and possible new smokers. There are numerous harmful substances produced by these devices, such as metals, organic compounds, and aldehydes. The presence of formaldehyde is particularly worrying: its indoor concentration is 2.7, 1.2, and 40 µg/m3 for HnB, e-cigs, and traditional cigarettes, respectively. The evidence of this substance, which numerous epidemiological studies have already shown to be harmful to health (in particular, the International Agency for Research on Cancer classified it as a group 1 carcinogen), would lead to the need to modify the legislation with more restrictive rules on the use of these devices in public environment and in particular in the presence of more susceptible subjects, such as minors and pregnant women.

Effects of cannabis smoking on the respiratory system: A state-of-the-art review.

The diminished perception of the health risks associated with the consumption of cannabis (marijuana) lead to a progressive increase in its inhalational use in many countries. Cannabis can be smoked through the use of joints, spliffs and blunts, and it can be vaporised with the use of hookah or e-cigarettes. Delta-9 tetrahydrocannabinol (THC) is the main psychoactive component of cannabis smoke but contains numerous other substances. While the recreational use of cannabis smoking has been legalised in several countries, its health consequences have been underestimated and undervalued. The purpose of this review is to critically review the impact of cannabis smoke on the respiratory system. Cannabis smoke irritates the bronchial tree and is strongly associated with symptoms of chronic bronchitis, with histological signs of airway inflammation and remodelling. Altered fungicidal and antibacterial activity of alveolar macrophages, with greater susceptibility to respiratory infections, is also reported. The association with invasive pulmonary aspergillosis in immunocompromised subjects is particularly concerning. Although cannabis has been shown to produce a rapid bronchodilator effect, its chronic use is associated with poor control of asthma by numerous studies. Cannabis smoking also represents a risk factor for the development of bullous lung disease, spontaneous pneumothorax and hypersensitivity pneumonitis. On the other hand, no association with the development of chronic obstructive pulmonary disease was found. Finally, a growing number of studies report an independent association of cannabis smoking with the development of lung cancer. In conclusion, unequivocal evidence established that cannabis smoking is harmful to the respiratory system. Cannabis smoking has a wide range of negative effects on respiratory symptoms in both healthy subjects and patients with chronic lung disease. Given that the most common and cheapest way of assumption of cannabis is by smoking, healthcare providers should be prepared to provide counselling on cannabis smoking cessation and inform the public and decision-makers.

Cytisine for smoking cessation: A 40-day treatment with an induction period.

INTRODUCTION: Cytisine is a smoking cessation drug now used worldwide. Most of the data available in the literature predict a 25-day treatment, accepted on the basis of previous clinical experience in Eastern Europe. There are few studies on dosing, and only recently some researchers have tried a longer treatment period. METHODS: This real-world retrospective cross-sectional study analyzed data collected consecutively from 2015 to 2021, in seven smoking cessation centers in north-central Italy. The aim of this study is to evaluate the effectiveness and tolerability of a 40-day cytisine treatment with an induction phase and a slower reduction schedule. Data were collected from a group of 871 patients treated with cysteine, varenicline, and nicotine replacement therapy (NRT). The sample was not randomized. Behavioral support (4-6 sessions, each lasting 20-30 min, plus the evaluation session) was delivered to all patients. RESULTS: Subgroups taking cytisine (n=543 for 40 days), varenicline (n=281 for 12 weeks), and NRT (n=47 for eight weeks) showed biochemically confirmed smoking abstinence at 6 months of 50.5%, 55.9%, and 51.0%, respectively, with a statistically significant difference between cytisine versus varenicline (p<0.01) but not between cytisine versus NRT (p=0.5597). Adverse events were 4.4% with cytisine and 33.3% with varenicline. Behavioral support was an important factor in effectiveness. CONCLUSIONS: This study produced preliminary evidence that the 40-day regimen of cytisine, appears to have less effectiveness in comparison to varenicline but the magnitude of the effect is comparable. The results and tolerability seem to be better than in most other studies.

Smoking cessation in the management of Chronic Obstructive Pulmonary Disease (COPD): narrative review and recommendations.

BACKGROUND: The percentage of smokers who develop COPD (Chronic Obstructive Pulmonary Disease) peaks at 40-50% in most recent publications. SUMMARY: Tobacco smoke remains the main cause of COPD, though smoking-related limitation of the flow is rather subjective. For patients who keep on smoking, general practitioners (GPs) and pulmonologists should be able to offer smoking cessation programs as an important part of COPD treatment. This narrative article aims to provide the scientific basis to help healthcare professionals develop this therapy; with this aim in mind, the authors have analyzed the most recent literature. KEY MESSAGES: Only 3% of smokers who try to quit without availing themselves of any support succeed. Effective smoking cessation methods are counselling and pharmacotherapy, which, combined together, are credited with a 24% success rate. Although there are no therapeutic novelties with strong scientific evidence for smoking cessation, it is however advisable to keep the literature updated to new devices and new digital therapies.

Analysis of the direct economic impact of smoking-related hospitalizations in Italy.

INTRODUCTION: Tobacco-related diseases have a substantial economic impact in terms of medical expenses, loss of productivity, and premature death. Tobacco use is estimated to be responsible for more than 90000 deaths each year in Italy. We aimed to evaluate the annual direct economic impact on the National Health System of hospitalizations attributable to tobacco smoking in Italy. METHODS: We analyzed data from all the hospitalizations of patients aged ≥30 years that occurred in Italy for 12 selected tobacco-related diseases, during 2018. These diseases included oropharyngeal cancer, esophageal cancer, gastric cancer, lung cancer, pancreatic cancer, bladder cancer, laryngeal cancer, ischemic heart disease, stroke, diseases of arteries, arterioles, and capillaries, pneumonia and influenza, and chronic obstructive pulmonary disease. We obtained information on 984322 hospital discharge records, including each hospitalization's direct costs. Using relative risk estimates from the scientific literature, we computed the population attributable fraction for various tobacco-related diseases to estimate the economic impact attributable to tobacco smoking. RESULTS: One-third of all hospitalizations occurred in 2018 in Italy among people aged ≥30 years for 12 tobacco-related diseases were found to be attributable to smoking, accounting for a total cost of €1.64 billion. Among the diseases considered, those with the highest expenditures attributable to tobacco smoking were ischemic heart disease, cerebrovascular disease, and lung cancer, accounting for €556 million, €290 million, and €229 million, respectively. CONCLUSIONS: Tobacco has a substantial economic impact in Italy, accounting for around 6% of the total cost of hospitalizations in 2018. This figure is expected to be largely underestimated due to several conservative assumptions adopted in the statistical analyses. It is imperative to prioritize comprehensive tobacco control measures to counteract the huge healthcare costs due to tobacco smoking.

SARS-CoV-2 Infection in San Patrignano, the Largest European Drug Rehabilitation Community.

BACKGROUND: Studies on SARS-CoV-2 conducted in confined settings for prolonged times allow researchers to assess how the coronavirus spreads. San Patrignano (SP), Italy, is the largest European drug rehabilitation facility. METHODS: Between 15 October and 31 December 2020, all SP residents were tested for SARS-CoV-2. We analyzed the relationships between individual characteristics and being SARS-CoV-2-positive. Three selected predictive models were used to calculate the number of expected hospitalizations. For each model, we summed the estimated individual risks to obtain the expected number of hospitalizations in our sample, and we tested whether the observed and expected numbers differed. RESULTS: Of 807 residents, 529 (65.6%) were SARS-CoV-2-positive. Of these 323 (61.1%) were symptomatic. A strong relationship was found between being positive and living connections (p-value < 0.001). No statistically significant relationship was found with age, sex, smoking history, or comorbidities. Although 9 to 17 hospitalizations were expected, no hospitalizations were observed (p-value < 0.001). No one died of COVID-19. CONCLUSIONS: The peculiar characteristics of SP residents or the SP environment might at least partially explain the null hospitalization rates. Despite the extreme uniqueness of our population and despite the protected environment and all precautions that were taken, the fact that the virus was able to circulate and infect a large portion of the population highlights the fundamental role of social interactions in the spread of the disease.

Tobacco smoking and COVID-19 pandemic: old and new issues. A summary of the evidence from the scientific literature.

INTRODUCTION: COVID-19 pandemic burst onto the international scene as a new disease not affecting patients uniformly; hence it has risen many questions yet to be clarified. The aim of this study was to outline the main issues that led tobacco smoking being discussed as a potential risk factor associated with COVID-19. METHODS: articles from MEDLINE and pre-prints published from January to April 2020 were identified. RESULTS: data from China showed that men had more severe outcomes of COVID-19 than women. Since smoking prevalence is very high among Chinese men in comparison to women, it was hypothesized that smoking could be a risk factor for poor prognosis. This was also supported by the higher prevalence of comorbidities, many of which are tobacco-related diseases, in patients with severe COVID-19, who were also more likely to have a smoking history. A meta-analysis confirmed these results reporting an OR=2.25 (95% CI: 1.49-3.39) for developing severe Covid-19 among patients with a smoking history. Some authors, noticing that reported smoking prevalence among hospitalized patients was substantially below smoking prevalence in the corresponding populations, speculated a protective role of nicotine. However, it is likely that low prevalence among hospitalized patients are partially due to many smokers misclassified as nonsmokers. Tobacco smoking seems to cause a dose-dependent upregulation of the angiotensin-converting- enzyme-2 (ACE2), the virus cellular entry receptor, which could explain the higher risk of severe COVID-19 in smokers. CONCLUSIONS: There is need for further independent studies to clarify the role of smoking on COVID-19 incidence, progression and mortality.

The "Polonium In Vivo" Study: Polonium-210 in Bronchial Lavages of Patients with Suspected Lung Cancer.

Few studies have reported on polonium-210, a decay breakdown product of radon-222 and lead-210, in human lungs and there has been no study in patients with suspected lung cancer. The main aim of this "Polonium in vivo" study was to evaluate polonium-210 radioactivity in bronchopulmonary systems of smoker, ex-smoker and never smoker patients with suspected lung cancer. Alpha-spectrometric analyses were performed on bronchial lavage (BL) fluids from two Italian hospitals in 2013-2016. Socio-demographic, smoking, occupational and spirometric characteristics, lung cancer confirmation and histologic type and radon-222 concentration in patients' homes were collected. Seventy BL samples from never (n = 13), former (n = 35) and current smokers (n = 22) were analyzed; polonium-210 was detected in all samples from current and former smokers and in 54% of samples from never smokers (p < 0.001; median values: 1.20, 1.43 and 0.40 mBq, respectively). Polonium-210 levels were significantly higher in COPD versus no COPD patients (median value: 3.60 vs. 0.97 mBq; p = 0.007); former and current smokers, without and with COPD, had significantly increased polonium-210 levels (p = 0.012); 96% of confirmed versus 69% of non-confirmed lung cancer patients recorded detectable polonium-210 levels (p = 0.018). A polonium-210 detectable activity was measured in BL samples from all current and former smokers. Polonium-210 in the lungs could be the result of lead-210 entrapment, which, with its half-life of 22 years, could provide a continuous emission of alpha radioactivity, even many years after quitting, thus proposing a possible explanation for the onset of lung cancer, particularly in former smokers.

Covid-19 and the role of smoking: the protocol of the multicentric prospective study COSMO-IT (COvid19 and SMOking in ITaly).

The emergency caused by Covid-19 pandemic raised interest in studying lifestyles and comorbidities as important determinants of poor Covid-19 prognosis. Data on tobacco smoking, alcohol consumption and obesity are still limited, while no data are available on the role of e-cigarettes and heated tobacco products (HTP). To clarify the role of tobacco smoking and other lifestyle habits on COVID-19 severity and progression, we designed a longitudinal observational study titled COvid19 and SMOking in ITaly (COSMO-IT). About 30 Italian hospitals in North, Centre and South of Italy joined the study. Its main aims are: 1) to quantify the role of tobacco smoking and smoking cessation on the severity and progression of COVID-19 in hospitalized patients; 2) to compare smoking prevalence and severity of the disease in relation to smoking in hospitalized COVID-19 patients versus patients treated at home; 3) to quantify the association between other lifestyle factors, such as e-cigarette and HTP use, alcohol and obesity and the risk of unfavourable COVID-19 outcomes. Socio-demographic, lifestyle and medical history information will be gathered for around 3000 hospitalized and 700-1000 home-isolated, laboratory-confirmed, COVID-19 patients. Given the current absence of a vaccine against SARS-COV-2 and the lack of a specific treatment for -COVID-19, prevention strategies are of extreme importance. This project, designed to highly contribute to the international scientific debate on the role of avoidable lifestyle habits on COVID-19 severity, will provide valuable epidemiological data in order to support important recommendations to prevent COVID-19 incidence, progression and mortality.

210Pb and 210Po concentrations in Italian cigarettes and effective dose evaluation.

It has been known for a long time that cigarette tobacco contains naturally occurring radioactive nuclides such as 210Pb and 210Po. In this study, the concentrations of 210Pb and 210Po in the 10 most widely sold cigarette brands in Italy during the year 2010 were measured, and the effective dose to smokers has been calculated. The results of this study show that 210Pb concentration ranged from 11.6 to 20.0 mBq cig-1 with an arithmetic mean of 14.6 mBq cig-1, while the activity concentration of 210Po ranged from 13.1 to 19.0 mBq cig-1 with an arithmetic mean of 15.7 mBq cig-1, thus confirming previous results and showing that the radioactivity concentration was not reduced in the last few years. The annual effective dose for a typical smoker consuming 20 cigarettes per day ranged from an average of 55 µSv y-1 to about 81 µSv y-1. It is finally put in evidence the need to improve the knowledge about crucial data needed for accurate dose assessment deriving from the inhalation of both radioisotopes contained in the cigarettes, namely the dose conversion coefficients, which strongly depend on several parameters such as the inhalation speed through the mouth, the real fraction of radionuclide transferred from cigarette to mainstream smoke, the lung absorption behavior of the radioisotopes inhaled with mainstream smoke, and the AMAD of particles inhaled by smokers.

Significant others, knowledge, and belief on smoking as factors associated with tobacco use in italian adolescents.

Tobacco use is dramatically increasing among youth. Growing attention has been addressed towards possible predictors of smoking in such a population. We evaluated a sample of Italian adolescents to verify whether adults and peers might influence their smoking status. Cross-sectional study was conducted in 16 schools of North Italy. Data were collected from 2001 to 2010 by means of a self-administered questionnaire on sociodemographic data and individual/social possible predictors of smoking. 2,444 students (56.7% boys; 43.3% girls; mean = 14.32 ± 1.384 years) were analysed. 607 (24.8%) were current smokers; 1,837 (75.2%) were nonsmokers. The presence of smokers in the family, seeing teachers who smoke, the influence of friends, and the feeling of inferiority were predictors of youth smoking as well as unawareness of nicotine dangerous action to health. Running the logistic multivariate analysis with all the variables listed above in the same model, the strongest predictors of smoking were as follows: being unaware that pipe/cigar is harmful to health as cigarettes; not knowing that passive smoking is harmful to the growth of children; having seen teachers smoking. The present findings help to identify the variables that might favour smoking in youth. Such variables should become the target of prevention programs.

Polonium and lung cancer.

The alpha-radioactive polonium 210 (Po-210) is one of the most powerful carcinogenic agents of tobacco smoke and is responsible for the histotype shift of lung cancer from squamous cell type to adenocarcinoma. According to several studies, the principal source of Po-210 is the fertilizers used in tobacco plants, which are rich in polyphosphates containing radio (Ra-226) and its decay products, lead 210 (Pb-210) and Po-210. Tobacco leaves accumulate Pb-210 and Po-210 through their trichomes, and Pb-210 decays into Po-210 over time. With the combustion of the cigarette smoke becomes radioactive and Pb-210 and Po-210 reach the bronchopulmonary apparatus, especially in bifurcations of segmental bronchi. In this place, combined with other agents, it will manifest its carcinogenic activity, especially in patients with compromised mucous-ciliary clearance. Various studies have confirmed that the radiological risk from Po-210 in a smoker of 20 cigarettes per day for a year is equivalent to the one deriving from 300 chest X-rays, with an autonomous oncogenic capability of 4 lung cancers per 10000 smokers. Po-210 can also be found in passive smoke, since part of Po-210 spreads in the surrounding environment during tobacco combustion. Tobacco manufacturers have been aware of the alpha-radioactivity presence in tobacco smoke since the sixties.

[Polonium: the radioactive killer from tobacco smoke]. / Poloniul: ucigasul radioactiv din fumul de tutun.

Among all carcinogenic substances contained in tobacco smoke, Polonium 210 (Po-210), with a half-life of 138 days, is one of the most dangerous, by exerting a devastating, chronic, slow and progressive carcinogenesis activity. The main source of Po-210 in tobacco is represented by fertilizers (polyphosphates) containing radium-226 (Ra-222) which decades to plumb 210 (Pb-210). Through the thricomes Pb-210 is concentrated in the tobacco leaves, where it turns to Po-210, which at the cigarette combustion temperature (800-900 degrees C) reaches the gaseous state and it is absorbed by the micro particles released into tobacco smoke. Thus, smoke becomes radioactive in both its gaseous and corpuscular components and reaches the airways, where, particularly at the branches level and together with other substances, it exerts its carcinogenic activity, especially in those subjects with impaired respiratory mucosal clearance. The carcinogenic risk/one year lifetime of a smoker of 20 cigarettes per day is equivalent to that of undertaking 300 chest x-rays. It is calculated that Po-210 may be independently responsible of 4 lung cancers every 10,000 smokers. During cigarette's combustion, tobacco smoke is also released in the air, contributing to serious health risks for those exposed to passive smoke.