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    Massimo Caruso

    During the last decade electronic cigarettes (e-cigarettes) have been studied as an alternative devices to the tobacco cigarette, but with better safety for the health of smokers, so as to create a new approach to smoking addiction, such... more
    During the last decade electronic cigarettes (e-cigarettes) have been studied as an alternative devices to the tobacco cigarette, but with better safety for the health of smokers, so as to create a new approach to smoking addiction, such as the “smoking harm reduction”. This new approach, suggested by a part of the scientific world, aroused interest and debates in the regulatory field, involving all the major regulatory bodies and often creating divergences from nation to nation on the rules driving the production, distribution and consumption of these alternative products. Many studies have been conducted both in vitro and in vivo, to clarify the effects of the e-cigarette compared to the classic one. In this context, the Center of Excellence for the Acceleration of HArm Reduction (CoEHAR) was established within the University of Catania (Italy) and the multi-center project, created under its leadership, the REPLICA project, which aims to replicate in vitro studies originally condu...
    The prevalence of vaping, also known as using e-cigarettes, vapes and vape pens, has prompted a demand for reliable, evidence-based research. However, published literature on the topic of vaping often raises concerns, characterized by... more
    The prevalence of vaping, also known as using e-cigarettes, vapes and vape pens, has prompted a demand for reliable, evidence-based research. However, published literature on the topic of vaping often raises concerns, characterized by serious flaws and a failure to adhere to accepted scientific methodologies. In this narrative review, we analyze popular vaping studies published in medical journals that purport to evaluate the association of vaping and smoking cessation, smoking initiation or health outcomes. We analyzed 24 included studies to identify the questions they claimed to address, stated methods, manner of implementation, discussions, and stated conclusions. After critical appraisal, we noted a multiplicity of flaws in these studies, and identified patterns as to the nature of such flaws. Many studies lacked a clear hypothesis statement: to the extent that a hypothesis could be inferred, the methods were not tailored to address the question of interest. Moreover, main outco...
    Background: Tobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former... more
    Background: Tobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers have been shown to exhibit similar STTT as never smokers. The impact on STTT of switching from smoking to combustion-free tobacco products such as e-cigarettes (ECs) and heated tobacco products (HTPs) is not known. Methods: We report STTT of exclusive EC and HTP users. Test results were compared with those obtained in current, former, and never smokers. Results: STTT were obtained from 39 current, 40 former, 40 never smokers, and from 20 EC and 20 HTP users. Comparison of STTT values showed significant difference among the five study groups ( p < 0.00001) with current smokers having a median [interquartile range (IQR)] STTT of 13.15 min, which was significantly longer compared with that of all other study groups. In particular, compared with fo...
    Cigarette smoking is associated with impairment of repair mechanisms necessary for vascular endothelium homeostasis. Reducing the exposure to smoke toxicants may result in the mitigation of the harmful effect on the endothelium and... more
    Cigarette smoking is associated with impairment of repair mechanisms necessary for vascular endothelium homeostasis. Reducing the exposure to smoke toxicants may result in the mitigation of the harmful effect on the endothelium and cardiovascular disease development. Previous investigations performed by the tobacco industries evaluated in vitro the effect of electronic cigarette (e-cig) compared to cigarette smoke demonstrating a significant reduction in endothelial cell migration inhibition following e-cig aerosol exposure. In the present study, we replicated one of these studies, evaluating the effects of cigarette smoke on endothelial cell migration compared to e-cig and heated tobacco products. We used a multi-center approach (ring-study) to verify the robustness and reliability of the results obtained in the replicated study. Consistently with the original study, we observed a substantial reduction of the effects of e-cig and tobacco heated products on endothelial cell migratio...
    Cigarette smoking is the leading cause of preventable deaths worldwide. Electronic Nicotine Delivery Systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of... more
    Cigarette smoking is the leading cause of preventable deaths worldwide. Electronic Nicotine Delivery Systems (ENDS) may reduce health risks associated with chronic exposure to smoke and their potential benefits have been the matter of intense scientific debate. Here we replicated three key published studies from the Tobacco Industry on cytotoxic and inflammatory effects of cigarette smoke and ENDS aerosol in an independent multicentric study. We aimed to establish the reliability of results and the robustness of conclusions by replicating the authors’ experimental protocols and further validating them with different techniques. We exposed human bronchial epithelial cell (NCI-H292) to cigarette smoke and to aerosol from ENDS. All the exposure were conducted at air-liquid interface to assess cytotoxicity effects of smoke and aerosol. Moreover, we aimed to assess different inflammatory mediators release (IL-6, IL-8 and MMP-1) from cells exposed to whole smoke and to smoke without parti...
    Prevalence studies of current smoking among hospitalized COVID-19 patients demonstrated an unexpectedly low prevalence of current smoking among patients with COVID-19. The aim of the present proposal was to evaluate the effect of smoke... more
    Prevalence studies of current smoking among hospitalized COVID-19 patients demonstrated an unexpectedly low prevalence of current smoking among patients with COVID-19. The aim of the present proposal was to evaluate the effect of smoke from cigarettes on ACE-2 in bronchial epithelial cells. Normal bronchial epithelial cells (H292) were exposed to smoke by an air-liquid-interface (ALI) system and ACE-2 membrane protein expression was evaluated after 24 hours from exposure. Our transcriptomics data analysis showed a significant selective reduction of membrane ACE-2 expression (about 25%) following smoking exposure. Interestingly, we observed a positive direct correlation between ACE-2 reduction and nicotine delivery. Furthermore, by stratifying GSE52237 as a function of ACE-2 gene expression levels, we highlighted 1012 genes related to ACE-2 in smokers and 855 in non-smokers. Furthermore, we showed that 161 genes involved in the endocytosis process were highlighted using the online pa...
    ABSTRACTTobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers... more
    ABSTRACTTobacco smoking impairs mucociliary clearance (MCC) efficiency as shown by prolonged saccharin test transit time (STTT). Avoiding exposure to tobacco smoke from combustible cigarettes may restore MCC function and former smokers have been shown to exhibit similar STTT as never smokers. The impact of switching from smoking to combustion-free tobacco products such as e-cigarettes (ECs) and heated tobacco products (HTPs) on STTT is not known. We report STTT of exclusive EC and HTP users. Test results were compared to those obtained in current, former, and never smokers.STTT were obtained from 39 current, 40 former, 40 never smokers and from 20 EC and 20 HTP users. Comparison of STTT values showed significant difference among the five study groups (p< 0.00001) with current smokers having a median (IQR) STTT of 13.15 min, which was significantly longer compared to that of all other study groups. In particular, compared to former (7.26 min) and never smokers (7.24 min), exclusiv...
    Minimization of post-cessation weight gain in quitters is important, but existing approaches (e.g., antismoking medications) shows only limited success. We investigated changes in body weight in smokers who quit or reduced substantially... more
    Minimization of post-cessation weight gain in quitters is important, but existing approaches (e.g., antismoking medications) shows only limited success. We investigated changes in body weight in smokers who quit or reduced substantially their cigarette consumption by switching to electronic cigarettes (ECs) use. Body weight and smoking/vaping history were extracted from medical records of smokers and ex-smokers to match three study groups: (1) regular EC users on at least two consecutive follow-up visits; (2) regular smokers (and not using ECs); (3) subjects who reported sustained smoking abstinence after completing a cessation program. Review of their medical records was conducted at two follow-up visits at 6- (F/U 6m) and 12-months (F/U 12m). A total of 86 EC users, 93 regular smokers, and 44 quitters were studied. In the EC users study group, cigarettes/day use decreased from 21.1 at baseline to 1.8 at F/U 12m ( < 0.0001). Dual usage was reported by approximately 50% of EC use...
    This study evaluated the effect of training pharmacists in the stage-of-change model for smoking cessation and motivational interviewing on smoking cessation outcomes. A training based on the stage-of-change model for smoking cessation... more
    This study evaluated the effect of training pharmacists in the stage-of-change model for smoking cessation and motivational interviewing on smoking cessation outcomes. A training based on the stage-of-change model for smoking cessation and motivational interviewing was introduced to pharmacists. Pharmacists were randomly assigned to the intervention or control group. The control group attended a 3-hour training session, whereas the intervention group also attended a further 6-hour training session. At week 24, 12.2 percent of the smokers quit smoking in the intervention group, whereas 1.6 percent of the smokers quit smoking in the control group. The findings of this study showed that training pharmacists, in the stage-of-change model for smoking cessation and motivational interviewing, improves smoking reduction and cessation rates.
    Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalised management approach can be provided. We stratified patients with... more
    Asthma is a heterogeneous disease in which there is a differential response to asthma treatments. This heterogeneity needs to be evaluated so that a personalised management approach can be provided. We stratified patients with moderate-to-severe asthma based on clinico-physiological parameters and performed an -omics analysis of sputum. Partition-around-medoid clustering was applied to a training set of 266 asthma participants from the European U-BIOPRED adult cohort using 8 pre-specified clinic-physiological variables. This was repeated in a separate validation set of 152 asthmatics. The clusters were compared based on sputum proteomic and transcriptomic data. Four reproducible and stable clusters of asthmatics were identified. The training set cluster T1 consists of well-controlled moderate-to-severe asthmatics, while cluster T2 is a group of late-onset severe asthmatics with history of smoking and chronic airflow obstruction. Cluster T3 is similar to cluster T2 in terms of chroni...
    Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite high intensity treatment. These severe unrelenting symptoms have a huge impact on heathcare resources due to frequent... more
    Patients with severe asthma have a significant unmet need with persistent symptoms and/or frequent exacerbations despite high intensity treatment. These severe unrelenting symptoms have a huge impact on heathcare resources due to frequent hospital admissions and requirement for intensive and expensive medications. There is a compelling need for more effective and safer therapies to help severe asthma sufferers to achieve adequate control of their disease. Expanding knowledge of innate and adaptive immune responses has led to development of new biologic approaches for severe asthma. Here, the authors will review the existing efficacy and safety data from clinical trials of some of the new biologic therapies that are in development for severe asthma. Their specific role in distinctively targeted subpopulations of severe asthmatics will be also discussed. Defining and phenotyping severe asthma patients will become increasingly important as some patients who were previously classified as having severe asthma may become well-controlled with a targeted phenotype-specific treatment. However, pharmacoeconomic concerns should also be taken into account given the elevated acquisition costs of recombinant human monoclonals and of the diagnostic screening procedures for the identification of potential responders.
    Quitting smoking is the most important step smokers can take to improve their health. Nonetheless, there is little information on long-term improvements in lung function and/or respiratory symptoms after smoking cessation. Here we... more
    Quitting smoking is the most important step smokers can take to improve their health. Nonetheless, there is little information on long-term improvements in lung function and/or respiratory symptoms after smoking cessation. Here we illustrate long-term changes in spirometric indices as well as in respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to electronic cigarettes (ECs). Prospective evaluation of cigarette consumption, spirometry and symptoms was performed in a 1-year randomized controlled trial of smokers receiving EC containing 2.4%, 1.8% or 0% nicotine. Spirometric data are presented on the basis of participants’ pooled continuous smoking phenotype classification (Quitters, Reducers, Failures), whereas respiratory symptoms on the basis of their point prevalence-smoking phenotype. Smoking phenotype classification (Quitters, Reducers, Failures) had no significant effect on spirometric indices (FEV1, FVC and FEV1/FVC) with the ex...
    BackgroundElectronic cigarette (EC) use is an emerging behaviour that has been shown to help smokers to reduce cigarette consumption. The aim of this study was to illustrate long‐term changes in exhaled breath measurements and respiratory... more
    BackgroundElectronic cigarette (EC) use is an emerging behaviour that has been shown to help smokers to reduce cigarette consumption. The aim of this study was to illustrate long‐term changes in exhaled breath measurements and respiratory symptoms in smokers invited to quit or reduce their cigarette consumption by switching to ECs.Materials and methodsProspective evaluation of cigarette consumption, fractional nitric oxide concentration in exhaled breath (FeNO), exhaled carbon monoxide (eCO) and symptom scores was performed in a 1‐year randomized, controlled trial of ‘healthy’ smokers receiving 2·4% nicotine, 1·8% nicotine or no nicotine ECs. FeNO and eCO data are presented on the basis of participants’ pooled continuous smoking phenotype classification (failures, reducers and quitters).ResultsA significant effect of quitting classification was found on FeNo and eCO at all time points (P < 0·0001). Among quitters, FeNO (medians and interquartile range) rose from 5·5 (4·5–6·9) ppb...
    There is merit in considering a simple toxicological screening method that evaluates the total cytotoxic potential of e-liquids or electronic cigarettes (ECs) aerosol emissions in one single testing. However, there is growing confusion,... more
    There is merit in considering a simple toxicological screening method that evaluates the total cytotoxic potential of e-liquids or electronic cigarettes (ECs) aerosol emissions in one single testing. However, there is growing confusion, with several researchers endorsing their personal solution to the problem. Here, we discuss as an example the recent paper by Scheffler and colleagues, in which the authors suggest that more relevant and well differentiated cell lines from human airways could be the most suitable candidates for toxicological evaluation of ECs aerosol emissions. We advance recommendations for validated protocols and advocate for an international coordinated effort aimed at establishing consensus on methodology.
    Stop smoking it is often associated to weight gain that is one of the most important causes for relapse. This is the first study to describe long-term changes in body weight in smokers invited to quit or reduce smoking by switching to... more
    Stop smoking it is often associated to weight gain that is one of the most important causes for relapse. This is the first study to describe long-term changes in body weight in smokers invited to quit or reduce smoking by switching to ECs. Conventional cigarettes consumption and body weight were measured prospectively in a randomized controlled trial of smokers invited to switch to ECs. Post cessation weight changes from baseline at week-12, -24 and -52 were compared among 1) high, medium and zero nicotine strength products and 2) pooled continuous smoking failure, smoking reduction and abstinence phenotypes. Saliva cotinine levels and appetite levels were also measured. No significant changes in body weight were observed among high, medium and zero nicotine strength products. Differences among continuous smoking phenotypes were significant only at week-12 (p = 0.010) and week-24 (p = 0.012) with quitters gaining 2.4{plus minus}4.3 Kg and 2.9{plus minus}4.4 Kg respectively. However,...
    We present prospective blood pressure (BP) and hear rate (HR) changes in smokers invited to switch to e-cigarettes in the ECLAT study. BP and HR changes were compared among (1) different study groups (users of high, low, and zero nicotine... more
    We present prospective blood pressure (BP) and hear rate (HR) changes in smokers invited to switch to e-cigarettes in the ECLAT study. BP and HR changes were compared among (1) different study groups (users of high, low, and zero nicotine products) and (2) pooled continuous smoking phenotype classification (same phenotype from week 12 to -52), with participants classified as quitters (completely quit smoking), reducers (≥50 % reduction in smoking consumption) and failures (<50 % or no reduction in smoking consumption). Additionally, the latter comparison was repeated in a subgroup of participants with elevated BP at baseline. No significant changes were observed among study groups for systolic BP, diastolic BP, and HR. In 145 subjects with a continuous smoking phenotype, we observed lower systolic BP at week 52 compared to baseline but no effect of smoking phenotype classification. When the same analysis was repeated in 66 subjects with elevated BP at baseline, a substantial redu...
    The respiratory system is a primary target of the harmful effects of key air pollutants of health concern. Several air pollutants have been implicated including particulate matter (PM), ozone (O3), nitrogen dioxide (NO2) polycyclic... more
    The respiratory system is a primary target of the harmful effects of key air pollutants of health concern. Several air pollutants have been implicated including particulate matter (PM), ozone (O3), nitrogen dioxide (NO2) polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs). It is well known that episodes of exposure to high concentrations of outdoor air pollutants can cause acute respiratory exacerbations. However, there is now increasing evidence suggesting that significant exposure to outdoor air pollutants may be also associated with development of lung cancer and with incident cases of chronic obstructive pulmonary disease (COPD) and respiratory allergies. Here we provide a critical appraisal of the impact of air pollution on respiratory diseases and discuss strategies for preventing excessive exposure to harmful air pollutants. However, the evidence that significant exposure to air pollutants is causing COPD, lung cancer or respiratory allergies is not ...
    Stem cells are capable of self-renewal and differentiation into a wide range of cell types with multiple clinical and therapeutic applications. Stem cells are providing hope for many diseases that currently lack effective therapeutic... more
    Stem cells are capable of self-renewal and differentiation into a wide range of cell types with multiple clinical and therapeutic applications. Stem cells are providing hope for many diseases that currently lack effective therapeutic methods, including strokes, Huntington's disease, Alzheimer's and Parkinson's disease. However, the paucity of suitable cell types for cell replacement therapy in patients suffering from neurological disorders has hampered the development of this promising therapeutic approach. The innovative aspect of this study has been to evaluate the neural differentiation capability of different tissue-derived stem cells coming from different tissue sources such as bone marrow, umbilical cord blood, human endometrium and amniotic fluid, cultured under the same supplemented media neuro-transcription factor conditions, testing the expression of neural markers such as GFAP, Nestin and Neurofilaments using the immunofluorescence staining assay and some typical clusters of differentiation such as CD34, CD90, CD105 and CD133 by using the cytofluorimetric test assay. Amniotic fluid derived stem cells showed a more primitive phenotype compared to the differentiating potential demonstrated by the other stem cell sources, representing a realistic possibility in the field of regenerative cell therapy suitable for neurodegenerative diseases.
    U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology... more
    U-BIOPRED is a European Union consortium of 20 academic institutions, 11 pharmaceutical companies and six patient organisations with the objective of improving the understanding of asthma disease mechanisms using a systems biology approach.This cross-sectional assessment of adults with severe asthma, mild/moderate asthma and healthy controls from 11 European countries consisted of analyses of patient-reported outcomes, lung function, blood and airway inflammatory measurements.Patients with severe asthma (nonsmokers, n=311; smokers/ex-smokers, n=110) had more symptoms and exacerbations compared to patients with mild/moderate disease (n=88) (2.5 exacerbations versus 0.4 in the preceding 12 months; p<0.001), with worse quality of life, and higher levels of anxiety and depression. They also had a higher incidence of nasal polyps and gastro-oesophageal reflux with lower lung function. Sputum eosinophil count was higher in severe asthma compared to mild/moderate asthma (median count 2....

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