Quantitative CT Texture Analysis of COVID-19 Hospitalized Patients during 3-24-Month Follow-Up and Correlation with Functional Parameters.

BACKGROUND: To quantitatively evaluate CT lung abnormalities in COVID-19 survivors from the acute phase to 24-month follow-up. Quantitative CT features as predictors of abnormalities' persistence were investigated. METHODS: Patients who survived COVID-19 were retrospectively enrolled and underwent a chest CT at baseline (T0) and 3 months (T3) after discharge, with pulmonary function tests (PFTs). Patients with residual CT abnormalities repeated the CT at 12 (T12) and 24 (T24) months after discharge. A machine-learning-based software, CALIPER, calculated the CT percentage of the whole lung of normal parenchyma, ground glass (GG), reticulation (Ret), and vascular-related structures (VRSs). Differences (Δ) were calculated between time points. Receiver operating characteristic (ROC) curve analyses were performed to test the baseline parameters as predictors of functional impairment at T3 and of the persistence of CT abnormalities at T12. RESULTS: The cohort included 128 patients at T0, 133 at T3, 61 at T12, and 34 at T24. The GG medians were 8.44%, 0.14%, 0.13% and 0.12% at T0, T3, T12 and T24. The Ret medians were 2.79% at T0 and 0.14% at the following time points. All Δ significantly differed from 0, except between T12 and T24. The GG and VRSs at T0 achieved AUCs of 0.73 as predictors of functional impairment, and area under the curves (AUCs) of 0.71 and 0.72 for the persistence of CT abnormalities at T12. CONCLUSIONS: CALIPER accurately quantified the CT changes up to the 24-month follow-up. Resolution mostly occurred at T3, and Ret persisting at T12 was almost unchanged at T24. The baseline parameters were good predictors of functional impairment at T3 and of abnormalities' persistence at T12.

Real life data on nintedanib safety: idiopathic pulmonary fibrosis versus systemic sclerosis-interstitial lung disease and strategies adopted to manage adverse effects.

OBJECTIVE: Nintedanib (NIN) is an antifibrotic drug approved to slow the progression of idiopathic pulmonary fibrosis (IPF) and systemic sclerosis-related interstitial lung disease (SSc-ILD). NIN can frequently cause gastrointestinal adverse effects. We aimed to investigate the NIN safety profile in a real life setting, comparing IPF and SSc-ILD patients and evaluating the strategies adopted to manage NIN adverse effects. METHODS: Patients taking NIN for IPF or SSc-ILD were enrolled. Alongside epidemiological and disease-specific data, the period of NIN use and the need for dosage reduction and/or interruption were investigated. Particular attention was paid to possible adverse effects and strategies adopted to manage them. RESULTS: Twenty-seven SSc-ILD and 82 IPF patients were enrolled. No significant differences emerged between the two cohorts regarding the frequency of any possible adverse effect. Although the rates of NIN dosage reduction or interruption were similar between the two subgroups, SSc-ILD presented a mean period before NIN dosage reduction and NIN interruption significantly shorter than IPF (3 ± 2.6 vs 10.5 ± 8.9 months-p < 0.001 and 2.3 ± 0.5 vs 10.3 ± 9.9 months-p = 0.008, respectively). Several different strategies were tried to manage NIN adverse effects: especially in SSc-ILD, the variable combination of diet adjustment set by a nutritionist, probiotics and diosmectite was ultimately successful in maintaining patients on an adequate dose of NIN. CONCLUSION: We presented data on the NIN safety profile in a real life setting, which was similar between SSc-ILD and IPF. A combination of multiple managing strategies and dose adjustment appears essential to cope optimally with NIN adverse effects.

Spontaneous Pneumothorax Secondary to Bullous Lung Emphysema Positive for Cannabinoids upon Toxicological Examination.

Cannabis can be related to respiratory diseases, but the relationship between smoking marijuana and the development of a pneumothorax has scarcely been investigated. We aimed to analyze, in patients with a history of cannabis smoking abuse submitted to lung apicectomy for a primary spontaneous pneumothorax (PSP), the correlation between the presence of cannabinoids in the resected lung and the detection of bullous emphysema within the same tissue. Patients undergoing lung apicectomy for a PSP were prospectively enrolled, and the correlation between the presence of cannabinoids in the resected lung tissue and histological finding of bullous emphysema was investigated with Fisher's exact test. There were 21 male patients, with a median age of 27 years. The cannabinoids found by the toxicological examination in surgical specimens were mainly delta-9-tetrahydrocannabinol (THC), cannabinol (CBN), and cannabidiol (CBD). In 14/21 patients, cannabinoids were detected in the resected lung tissue, and bullous emphysema was present in 13/14 of these (93%), while bullous emphysema was found in only 1/7 (14%) of the remaining patients who were negative for cannabinoids in the lung tissue, and the difference was found to be statistically significant (p < 0.0009). Our study demonstrated the presence of bullous emphysema in most cannabinoid-positive patients and its absence in most of those who were cannabinoid-negative, supporting the correlation between cannabinoids in the lung tissue and bullous emphysema with the development of a "secondary" spontaneous pneumothorax.

Lung Cancer Screening with Low-Dose CT: What We Have Learned in Two Decades of ITALUNG and What Is Yet to Be Addressed.

The ITALUNG trial started in 2004 and compared lung cancer (LC) and other-causes mortality in 55-69 years-aged smokers and ex-smokers who were randomized to four annual chest low-dose CT (LDCT) or usual care. ITALUNG showed a lower LC and cardiovascular mortality in the screened subjects after 13 years of follow-up, especially in women, and produced many ancillary studies. They included recruitment results of a population-based mimicking approach, development of software for computer-aided diagnosis (CAD) and lung nodules volumetry, LDCT assessment of pulmonary emphysema and coronary artery calcifications (CAC) and their relevance to long-term mortality, results of a smoking-cessation intervention, assessment of the radiations dose associated with screening LDCT, and the results of biomarkers assays. Moreover, ITALUNG data indicated that screen-detected LCs are mostly already present at baseline LDCT, can present as lung cancer associated with cystic airspaces, and can be multiple. However, several issues of LC screening are still unaddressed. They include the annual vs. biennial pace of LDCT, choice between opportunistic or population-based recruitment. and between uni or multi-centre screening, implementation of CAD-assisted reading, containment of false positive and negative LDCT results, incorporation of emphysema. and CAC quantification in models of personalized LC and mortality risk, validation of ultra-LDCT acquisitions, optimization of the smoking-cessation intervention. and prospective validation of the biomarkers.

Motivation, acceptability and attitudes toward lung cancer screening among persons who attend a tobacco cessation program: A multicenter survey in Italy.

This study aimed to evaluate smoking cessation (SC) motivation and the acceptability of a lung cancer screening (LCS) program with low-dose computed tomography (LDCT) among people who attend SC programs. A multicenter survey was conducted in the period January-December 2021 involving 197 people who attended group or individual SC courses in Reggio Emilia and Tuscany. Questionnaires, information sheets, and decision aids about the potential benefits and harms of LCS with LDCT were distributed at different time points during the course. The wish to protect own health (66%) was the most frequent reason given for quitting smoking, followed by cigarette dependence (40.6%) and current health problems (30.5%). Half of the participants (56%) considered periodic health checks including LDCT, as an advantageous activity. The great majority of participants were in favor of LCS (92%), with only 8% being indifferent, and no one was against these programs. Interestingly, those with sufficiently high smoking-related LC risk to be eligible for LCS and those attending the individual course were less in favor of LCS but also less concerned about the possible harms associated with LCS. The type of counseling was a significant predictor for both LCS acceptability and perceived harm of LCS. The favorable perception of LCS in people attending SC courses, despite the considerable preoccupation with potential harms, is an important finding of this study. Introducing a discussion on the benefits and harms of LCS in SC programs may prepare persons who smoke to make informed decisions on utilizing LCS.

Pulmonary emphysema and coronary artery calcifications at baseline LDCT and long-term mortality in smokers and former smokers of the ITALUNG screening trial.

OBJECTIVES: Cardiovascular disease (CVD), lung cancer (LC), and respiratory diseases are main causes of death in smokers and former smokers undergoing low-dose computed tomography (LDCT) for LC screening. We assessed whether quantification of pulmonary emphysematous changes at baseline LDCT has a predictive value concerning long-term mortality. METHODS: In this longitudinal study, we assessed pulmonary emphysematous changes with densitometry (volume corrected relative area below - 950 Hounsfield units) and coronary artery calcifications (CAC) with a 0-3 visual scale in baseline LDCT of 524 participants in the ITALUNG trial and analyzed their association with mortality after 13.6 years of follow-up using conventional statistics and a machine learning approach. RESULTS: Pulmonary emphysematous changes were present in 32.3% of subjects and were mild (6% ≤ RA950 ≤ 9%) in 14.9% and moderate-severe (RA950 > 9%) in 17.4%. CAC were present in 67% of subjects (mild in 34.7%, moderate-severe in 32.2%). In the follow-up, 81 (15.4%) subjects died (20 of LC, 28 of other cancers, 15 of CVD, 4 of respiratory disease, and 14 of other conditions). After adjusting for age, sex, smoking history, and CAC, moderate-severe emphysema was significantly associated with overall (OR 2.22; 95CI 1.34-3.70) and CVD (OR 3.66; 95CI 1.21-11.04) mortality. Machine learning showed that RA950 was the best single feature predictive of overall and CVD mortality. CONCLUSIONS: Moderate-severe pulmonary emphysematous changes are an independent predictor of long-term overall and CVD mortality in subjects participating in LC screening and should be incorporated in the post-test calculation of the individual mortality risk profile. KEY POINTS: • Densitometry allows quantification of pulmonary emphysematous changes in low-dose CT examinations for lung cancer screening. • Emphysematous lung density changes are an independent predictor of long-term overall and cardio-vascular disease mortality in smokers and former smokers undergoing screening. • Emphysematous changes quantification should be included in the post-test calculation of the individual mortality risk profile.

Long-term lung ultrasound follow-up in patients after COVID-19 pneumonia hospitalization: A prospective comparative study with chest computed tomography.

During COVID-19 pandemic, lung ultrasound (LUS) proved to be of great value in the diagnosis and monitoring of patients with pneumonia. However, limited data exist regarding its use to assess aeration changes during follow-up (FU). Our study aims to prospectively evaluate 232 subjects who underwent a 3-month-FU program after hospitalization for COVID-19 at the University Hospital of Pisa. The goals were to assess the usefulness of standardized LUS compared with the gold standard chest computed tomography (CT) to evaluate aeration changes and to verify LUS and CT agreement at FU. Patients underwent in the same day a standardized 16-areas LUS and high-resolution chest CT reported by expert radiologists, assigning interpretative codes. Based on observations distribution, LUS score cut-offs of 3 and 7 were selected, corresponding to the 50th and 75th percentile, respectively. Patients with LUS scores above both these thresholds were older and with longer hospital stay. Patients with a LUS score ≥3 had more comorbidities. LUS and chest CT showed a high agreement in identifying residual pathological findings, using both cut-off scores of 3 (OR 14,7; CL 3,6-64,5, Sensitivity 91%, Specificity 49%) and 7 (OR 5,8; CL 2,3-14,3, Sensitivity 65%, Specificity 79%). Our data suggest that LUS is very sensitive in identifying pathological findings at FU after a hospitalization for COVID-19 pneumonia, compared to CT. Given its low cost and safety, LUS could replace CT in selected cases, such as in contexts with limited resources or it could be used as a gate-keeper examination before more advanced techniques.

The Italian severe/uncontrolled asthma registry (RItA): A 12-month clinical follow-up.

BACKGROUND: follow-up studies on registries of severe/uncontrolled asthma (SUA) patients are scanty. OBJECTIVE: to analyze baseline and follow-up characteristics of SUA patients and their longitudinal patterns. METHODS: 180 adult patients (age ≥15 yrs) were investigated at baseline and 12-month follow-up through the Italian SUA registry (RItA). Latent transition analysis (LTA) was performed to detect cross-sectional SUA phenotypes and longitudinal patterns. Risk factors for longitudinal patterns were assessed through logistic regression. RESULTS: a significant/borderline improvement of asthma control outcomes in the last 2-4 weeks emerged at follow-up with respect to baseline for: daily activities limitations (Δ -16%), frequent diurnal symptoms (Δ -25%), uncontrolled asthma symptoms according to ACT (Δ -26%). Last 12-month use of oral corticosteroids was less frequent at follow-up than at baseline (Δ -25%). Health status improvement was confirmed by lung function test results. Through LTA, two longitudinal patterns were detected considering last 12-month control outcomes: "persistence/worsening" (53.9%), "under control/improvement" (46.1%). A lower likelihood of having "persistence/worsening" SUA was exhibited by patients under anti-IgE (OR 0.38, 95% CI 0.17-0.84) and inhaled corticosteroids-bronchodilator association treatment (OR 0.13, 95% CI 0.01-1.26, borderline value), while a higher likelihood was shown by older age at first asthma diagnosis (OR 1.04, 95% CI 1.01-1.07). CONCLUSION: the implementation of a SUA registry, the availability of patient-level data and the application of an innovative longitudinal analysis allowed to observe a general improvement in asthma control, one year after baseline, and a lower risk of SUA "persistence/worsening" in patients under anti-IgE and regular ICS-bronchodilator association use.

Characteristics of long-COVID among older adults: a cross-sectional study.

OBJECTIVES: To describe long-COVID symptoms among older adults and to assess the risk factors for two common long-COVID symptoms: fatigue and dyspnea. METHODS: This is a multicenter, prospective cohort study conducted in Israel, Switzerland, Spain, and Italy. Individuals were included at least 30 days after their COVID-19 diagnosis. We compared long-COVID symptoms between elderly (aged >65 years) and younger individuals (aged 18-65 years) and conducted univariate and multivariable analyses for the predictors of long-COVID fatigue and dyspnea. RESULTS: A total of 2333 individuals were evaluated at an average of 5 months (146 days [95% confidence interval 142-150]) after COVID-19 onset. The mean age was 51 years, and 20.5% were aged >65 years. Older adults were more likely to be symptomatic, with the most common symptoms being fatigue (38%) and dyspnea (30%); they were more likely to complain of cough and arthralgia and have abnormal chest imaging and pulmonary function tests. Independent risk factors for long-COVID fatigue and dyspnea included female gender, obesity, and closer proximity to COVID-19 diagnosis; older age was not an independent predictor. CONCLUSION: Older individuals with long-COVID have different persisting symptoms, with more pronounced pulmonary impairment. Women and individuals with obesity are at risk. Further research is warranted to investigate the natural history of long-COVID among the elderly population and to assess possible interventions aimed at promoting rehabilitation and well-being.

Quantitative texture-based analysis of pulmonary parenchymal features on chest CT: comparison with densitometric indices and short-term effect of changes in smoking habit.

PURPOSE: To investigate the correlations between densitometric and Computer Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER)-derived indices of pulmonary emphysema and their change in the short-term period for groups of patients with different smoking habits. METHOD: This retrospective study included 284 subjects from the ITALUNG trial (198 men and 86 women; mean±sd age 60±4 years) who underwent low-dose chest computed tomography at baseline and 2-year follow-up. Subjects were divided into four groups (persistent smokers, restarters, quitters and former smokers) according to their smoking habit at baseline and follow-up. Densitometric and texture analyses were performed, using CALIPER software. A correlation analysis was conducted between CALIPER-derived low-attenuation areas (LAAs) and densitometric indices, including the 15th percentile of the whole-lung attenuation histogram (Perc15) and the relative areas with density ≤-950 HU (RA950). Densitometric indices and LAAs were evaluated at baseline and variation assessed longitudinally with comparisons between groups with different smoking habit. Further analysis of parenchymal changes per pulmonary zone was performed. RESULTS: LAAs were strongly correlated with Perc15 (rs=0.81; p<0.001) and RA950 (rs=0.905; p<0.001). At baseline, the group of smokers showed higher Perc15, lower RA950, lower LAAs (particularly mild sub-class of LAAs) than the group of ex-smokers (p<0.001). At 2-year follow-up, densitometric indices and LAAs increased in persistent smokers, former smokers and quitters (p<0.05). The progression was larger and statistically more significant in quitters (p<0.001). CONCLUSION: CALIPER texture analysis provides an objective measure comparable to traditional density/histogram features to assess the lung parenchymal changes in relation to different smoking habits.

Pirfenidone for Idiopathic Pulmonary Fibrosis and Beyond.

Pirfenidone (PFD) slows the progression of idiopathic pulmonary fibrosis (IPF) by inhibiting the exaggerated fibrotic response and possibly through additional mechanisms, such as anti-inflammatory effects. PFD has also been evaluated in other fibrosing lung diseases. Myocardial fibrosis is a common feature of several heart diseases and the progressive deposition of extracellular matrix due to a persistent injury to cardiomyocytes may trigger a vicious cycle that leads to persistent structural and functional alterations of the myocardium. No primarily antifibrotic medications are used to treat patients with heart failure. There is some evidence that PFD has antifibrotic actions in various animal models of cardiac disease and a phase II trial on patients with heart failure and preserved ejection fraction has yielded positive results. This review summarises the evidence about the possible mechanisms of IPF and modulation by PFD, the main results about IPF or non-IPF interstitial pneumonias and also data about PFD as a potential protective cardiac drug.

Patterns of Long COVID Symptoms: A Multi-Center Cross Sectional Study.

BACKGROUND: Long COVID has become a burden on healthcare systems worldwide. Research into the etiology and risk factors has been impeded by observing all diverse manifestations as part of a single entity. We aimed to determine patterns of symptoms in convalescing COVID-19 patients. METHODS: Symptomatic patients were recruited from four countries. Data were collected regarding demographics, comorbidities, acute disease and persistent symptoms. Factor analysis was performed to elucidate symptom patterns. Associations of the patterns with patients' characteristics, features of acute disease and effect on daily life were sought. RESULTS: We included 1027 symptomatic post-COVID individuals in the analysis. The majority of participants were graded as having a non-severe acute COVID-19 (N = 763, 74.3%). We identified six patterns of symptoms: cognitive, pain-syndrome, pulmonary, cardiac, anosmia-dysgeusia and headache. The cognitive pattern was the major symptoms pattern, explaining 26.2% of the variance; the other patterns each explained 6.5-9.5% of the variance. The cognitive pattern was higher in patients who were outpatients during the acute disease. The pain-syndrome pattern was associated with acute disease severity, higher in women and increased with age. The pulmonary pattern was associated with prior lung disease and severe acute disease. Only two of the patterns (cognitive and cardiac) were associated with failure to return to pre-COVID occupational and physical activity status. CONCLUSION: Long COVID diverse symptoms can be grouped into six unique patterns. Using these patterns in future research may improve our understanding of pathophysiology and risk factors of persistent COVID, provide homogenous terminology for clinical research, and direct therapeutic interventions.

Moderate-severe coronary calcification predicts long-term cardiovascular death in CT lung cancer screening: The ITALUNG trial.

PURPOSE: Coronary artery calcifications (CAC) are very strong indicators for increased cardio-vascular (CV) risk and can be evaluated also in low-dose computed tomography (LDCT) for lung cancer screening. We assessed whether a simple and fast CAC visual score is associated with CV mortality. METHODS: CAC were retrospectively assessed by two observers using a 4-score (absent, mild, moderate and severe) scale in baseline LDCT obtained in 1364 participants to the ITALUNG trial who had 55-69 years of age and a smoking history ≥20 pack-years. Correlations with CV risk factors at baseline and with CV mortality after 11 years of follow-up were investigated. RESULTS: CAC were absent in 470 (34.5%), mild in 433 (31.7%), moderate in 357 (26.2%) and severe in 104 (7.6%) subjects. CAC severity correlated (≤0.001) with age, male sex, pack-years, history of arterial hypertension or diabetes, obesity and treated hypercholesterolemia. Twenty-one CV deaths occurred. Moderate or severe CAC were significantly associated with higher CV mortality after adjustment for all other known risk factors (ARR = 2.72; 95 %CI:1.04-7.11). Notably, also in subjects with none or one only additional CV risk factor, the presence of moderate-severe CAC allowed to identify a subgroup of subjects with higher CV death risk (RR = 3.66; CI95%:1.06-12.6). CONCLUSIONS: Moderate or severe CAC visually assessed in LDCT examinations for lung cancer screening are independently associated with CV mortality.

C-C motive chemokine ligand 2 and thromboinflammation in COVID-19-associated pneumonia: A retrospective study.

PURPOSE: A derangement of the coagulation process and thromboinflammatory events has emerged as pathologic characteristics of severe COVID-19, characterized by severe respiratory failure. CC motive chemokine ligand 2 (CCL2), a chemokine originally described as a chemotactic agent for monocytes, is involved in inflammation, coagulation activation and neoangiogenesis. We investigated the association of CCL2 levels with coagulation derangement and respiratory impairment in patients with COVID-19. METHODS: We retrospectively evaluated 281 patients admitted to two hospitals in Italy with COVID-19. Among them, CCL2 values were compared in different groups (identified according to D-dimer levels and the lowest PaO2/FiO2 recorded during hospital stay, P/Fnadir) by Jonckheere-Terpstra tests; linear regression analysis was used to analyse the relationship between CCL2 and P/Fnadir. We performed Mann-Whitney test and Kaplan-Meier curves to investigate the role of CCL2 according to different clinical outcomes (survival and endotracheal intubation [ETI]). RESULTS: CCL2 levels were progressively higher in patients with increasing D-dimer levels and with worse gas exchange impairment; there was a statistically significant linear correlation between log CCL2 and log P/Fnadir. CCL2 levels were significantly higher in patients with unfavourable clinical outcomes; Kaplan-Meier curves for the composite outcome death and/or need for ETI showed a significantly worse prognosis for patients with higher (> median) CCL2 levels. CONCLUSIONS: CCL2 correlates with both indices of activation of the coagulation cascade and respiratory impairment severity, which are likely closely related in COVID-19 pathology, thus suggesting that CCL2 could be involved in the thromboinflammatory events characterizing this disease.

Prognostic selection and long-term survival analysis to assess overdiagnosis risk in lung cancer screening randomized trials.

OBJECTIVES: Overdiagnosis in low-dose computed tomography randomized screening trials varies from 0 to 67%. The National Lung Screening Trial (extended follow-up) and ITALUNG (Italian Lung Cancer Screening Trial) have reported cumulative incidence estimates at long-term follow-up showing low or no overdiagnosis. The Danish Lung Cancer Screening Trial attributed the high overdiagnosis estimate to a likely selection for risk of the active arm. Here, we applied a method already used in benefit and overdiagnosis assessments to compute the long-term survival rates in the ITALUNG arms in order to confirm incidence-excess method assessment. METHODS: Subjects in the active arm were invited for four screening rounds, while controls were in usual care. Follow-up was extended to 11.3 years. Kaplan-Meyer 5- and 10-year survivals of "resected and early" (stage I or II and resected) and "unresected or late" (stage III or IV or not resected or unclassified) lung cancer cases were compared between arms. RESULTS: The updated ITALUNG control arm cumulative incidence rate was lower than in the active arm, but this was not statistically significant (RR: 0.89; 95% CI: 0.67-1.18). A compensatory drop of late cases was observed after baseline screening. The proportion of "resected and early" cases was 38% and 19%, in the active and control arms, respectively. The 10-year survival rates were 64% and 60% in the active and control arms, respectively (p = 0.689). The five-year survival rates for "unresected or late" cases were 10% and 7% in the active and control arms, respectively (p = 0.679). CONCLUSIONS: This long-term survival analysis, by prognostic categories, concluded against the long-term risk of overdiagnosis and contributed to revealing how screening works.

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.

Health effects of air pollution: a Southern European perspective.

OBJECTIVE: To summarize the main updated evidence about the health effects of air pollution, with a special focus on Southern Europe. DATA SOURCES: Literature was obtained through PubMed Central and the official websites of European Agencies and Scientific Societies. STUDY SELECTION: Recent shreds of evidence about the health effects of air pollution coming from international reports and original research were collected and described in this review. RESULTS: Air pollution is an avoidable risk factor that causes a huge burden for society, in terms of death, health disorders, and huge socio-economic costs. The southern European countries face a more threatening problem because they experience the effects of both anthropogenic pollutants and natural dusts (particulate matter [PM]). The European Environment Agency reported the number of premature deaths in the 28 countries of the European Union attributable to air pollutant exposure in the year 2016: 374,000 for PM2.5, 68,000 for nitrogen dioxide, and 14,000 for ozone. In Italy, time series and analytical epidemiological studies showed increased cardio-respiratory hospital admissions and mortality, as well as increased risk of respiratory diseases in people living in urban areas. CONCLUSIONS: Based on abundant evidence, the World Health Organization, which hosts the Global Alliance against Chronic Respiratory Diseases (GARD), the scientific respiratory societies, and the patients' associations, as well as others in the health sector, must increase their engagement in advocacy for clean air policies.

Electronic cigarette use among Italian smokers: patterns, settings, and adverse events.

OBJECTIVE: Information is scanty on the patterns and settings of electronic cigarette use and on its possible adverse events. To fill the knowledge gap on these issues, we conducted a survey among ever-smokers attending smoking cessation services (SCS) in Italy. METHODS: In 2016-2018, we enrolled 395 ever-smokers aged ⩾18 years who were current or former electronic cigarette users in 12 SCS from northern, central, and southern Italy. RESULTS: In all, 12.4% of ever smokers were regular, 9.4% occasional, and 78.2% past users of electronic cigarettes. Of all users, 93.8% consumed electronic cigarettes with nicotine, 95.9% used refillable devices, and 76.6% purchased electronic cigarette devices or liquids in vape shops. The mean duration of use was 3.7 months and the mean number of puffs per day was 86. Among users, 71.5% used electronic cigarettes in at least 1 smoke-free indoor environment, 53.7% in workplaces, 49.5% in restaurants and bars, 33.5% in train/metro stations or airports, and 18.4% in public transports. The use of electronic cigarettes in smoke-free environments significantly decreased with age and increased with duration of use and nicotine dependence. In our sample, 47.1% reported at least 1 adverse event attributable to electronic cigarette use: 19.5% dry cough, 12.0% dry mouth, 7.6% throat or mouth irritation, and 6.8% sore throat. CONCLUSION: In Italy, most conventional cigarette smokers use electronic cigarettes where smoking conventional cigarettes is prohibited. About half of users reported 1 or more symptoms attributable to electronic cigarettes, despite the relatively short duration of use.

Smoking Cessation in the ITALUNG Lung Cancer Screening: What Does "Teachable Moment" Mean?

BACKGROUND: Changes in smoking habits and predictors of smoking cessation were examined in the randomized ITALUNG lung cancer screening trial. METHODS: In three centers, eligible smokers or ex-smokers (55-69 years, ≥20 pack-years in the last 10 years) were randomized to receive annual invitation for low-dose computed tomography for 4 years or usual care. At invitation, subjects received written information for a free smoking cessation program. Quitting outcome was assessed at year 4. RESULTS: Among participants who completed baseline assessments and year 4 screening, higher quitting (20.8% vs. 16.7%, p = .029) and lower relapse (6.41% vs. 7.56%, p = .50) rates were observed in the active screening group as compared to the usual-care control group. Corresponding figures in the intention-to-treat analysis were as follows: 16.04% versus 14.64% (p = .059) and 4.88% versus 6.43% (p = .26). Quitting smoking was significantly associated to male gender, lower pack-years, and having pulmonary nodules at baseline. Center-specific analyses showed a threefold statistically significant higher probability to quit associated with participating in the smoking cessation program. A subsample of smokers of the scan group from one center showed higher quitting rates over 12-month follow-up as compared to matched controls from the general population who underwent the same smoking cessation program. CONCLUSIONS: Consistently with previous reports, in the ITALUNG trial, screened subjects showed significantly higher quit rates than controls, and higher quit rates were associated with both the presence of pulmonary nodules and participating in a smoking cessation program. Maximal effect on quitting outcome was observed with the participation in the smoking cessation program. IMPLICATIONS: Participating in lung cancer screening promotes smoking cessation. An effective "teachable moment" may be achieved when the smoking cessation intervention is structured as integral part of the screening clinical visits and conducted by a dedicated team of health care professionals. Standardized guidelines for smoking cessation interventions in lung cancer screening are needed.