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.

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.

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.

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.

Cannabinoids Identification in Lung Tissues of Young Cannabis Smokers Operated for Primary Spontaneous Pneumothorax and Correlation with Pathologic Findings.

BACKGROUND: Several studies suggested the association between tobacco and cannabis smoking and the risk of primary spontaneous pneumothorax (PSP), but none demonstrated cannabinoids in human lung tissues. OBJECTIVES: The aim of this study was to identify cannabinoids in lung specimens of young cannabis smokers, operated for PSP, and investigate on their pathologic findings, to determine the role of cannabis in PSP pathogenesis. METHOD: A prospective, multicenter study was conducted, enrolling patients admitted for PSP. Inclusion criteria were PSP requiring surgical treatment and history of cannabis smoking, associated or not to tobacco. Control cases were nonsmokers, and tobacco only smokers operated for PSP. Lung apex wedge resection by video-assisted thoracic surgery was performed. Two lung specimens, for pathological and toxicological examination, were taken from each patient. RESULTS: Twenty-nine male patients were enrolled: 21 (72.4%) tobacco and cannabis smokers, 2 (7%) cannabis only smokers, 3 (10.3%) tobacco only smokers, 3 (10.3%) nonsmokers; all underwent lung apicectomy, 4 bilateral surgery, for a total of 33 procedures. Typical PSP pathologic findings were mainly detected in control cases, other alterations in cannabis users. Lung specimens resulted positive for cannabinoids on 22/33 cases (19/22 reported being, 3/22 not being cannabis smokers), negative on 11/33 (3/11 reported not being, 7/11 having been cannabis smokers, 1/11 cannabis smoker). CONCLUSIONS: Our study demonstrated the presence of cannabinoids and particular pathologic alterations in lung tissues of young cannabis smokers with PSP, supporting the correlation between this disease and marijuana abuse and suggesting spontaneous pneumothorax "secondary to marijuana" as a new nosological entity.

Mortality, survival and incidence rates in the ITALUNG randomised lung cancer screening trial.

BACKGROUND: ITALUNG is contributing to the European evaluation of low-dose CT (LDCT) screening for lung cancer (LC). METHODS: Eligible subjects aged 55-69 years, smokers or ex-smokers (at least 20 pack-years in the last 10 years), were randomised to receive an annual invitation for LDCT screening for 4 years (active group) or to usual care (control group). All participants were followed up for vital status and cause of death (at the end of 2014) and LC incidence (at the end of 2013). Pathological and clinical information was collected from the Tuscan Cancer Registry data. RESULTS: 1613 subjects were randomly assigned to the active group and 1593 to the control group. At the end of the follow-up period 67 LC cases were diagnosed in the active group and 71 in the control group (rate ratio (RR)=0.93; 95% CI 0.67 to 1.30). A greater proportion of stage I LC was observed in the active group (36% vs 11%, p<0.001). Non-significant reductions of 17% (RR=0.83; 95% CI 0.67 to 1.03) for overall mortality and 30% (RR=0.70; 95% CI 0.47 to 1.03) for LC-specific mortality were estimated. CONCLUSIONS: Despite the lack of statistical significance, the ITALUNG trial outcomes suggest that LDCT screening could reduce LC and overall mortality. Moreover, the comparison of the number of LC cases diagnosed in the two groups does not show overdiagnosis after an adequate follow-up period. A pooled analysis of all European screening trials is advocated to assess the benefit-to-harm ratio of LDCT screening and its implementation in public health settings. TRIAL REGISTRATION NUMBER: Results, NCT02777996.

Integrating the care of the complex COPD patient.

Proceedings of the European Seminars in Respiratory Medicine course, Long-Term Integrated Care of COPD Patients held in Stresa, Italy, on 16-17 June, 2016.

Baseline Cell-Free DNA Can Predict Malignancy of Nodules Observed in the ITALUNG Screening Trial.

The role of total plasma cell-free DNA (cfDNA) in lung cancer (LC) screening with low-dose computed tomography (LDCT) is uncertain. We hypothesized that cfDNA could support differentiation between malignant and benign nodules observed in LDCT. The baseline cfDNA was measured in 137 subjects of the ITALUNG trial, including 29 subjects with screen-detected LC (17 prevalent and 12 incident) and 108 subjects with benign nodules. The predictive capability of baseline cfDNA to differentiate malignant and benign nodules was compared to that of Lung-RADS classification and Brock score at initial LDCT (iLDCT). Subjects with prevalent LC showed both well-discriminating radiological characteristics of the malignant nodule (16 of 17 were classified as Lung-RADS 4) and markedly increased cfDNA (mean 18.8 ng/mL). The mean diameters and Brock scores of malignant nodules at iLDCT in subjects who were diagnosed with incident LC were not different from those of benign nodules. However, 75% (9/12) of subjects with incident LC showed a baseline cfDNA ≥ 3.15 ng/mL, compared to 34% (37/108) of subjects with benign nodules (p = 0.006). Moreover, baseline cfDNA was correlated (p = 0.001) with tumor growth, measured with volume doubling time. In conclusion, increased baseline cfDNA may help to differentiate subjects with malignant and benign nodules at LDCT.

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.

[Cigarette smoking in pregnancy: observational prospective study in three towns of Tuscany Region (Central Italy)]. / Fumo di sigaretta in gravidanza: studio osservazionale prospettico in tre città della Toscana.

OBJECTIVE: to assess the prevalence of smoking in pregnancy and its changes after childbirth, and the characteristics associated with a greater likelihood of smoking during pregnancy in a sample of women attending three university hospitals in Tuscany (Central Italy). DESIGN: observational prospective multicentric study. SETTING AND PARTICIPANTS: 1,036 women in ninth month of pregnancy were enrolled at the teaching hospitals of Careggi (Firenze), Pisa and Siena. Women filled a standardized, self-administered questionnaire at enrolment. A second questionnaire was administered by phone to the smoking, ex-smoking and abstinent-during-pregnancy women one year after the delivery. RESULTS: 60.5% of women was never smoker, 17.4% was ex-smoker, 14% of women stopped smoking during pregnancy, and 8.4% were current smokers. Smoking in pregnancy was significantly associated with being younger than 31 years old (OR 1.75; 95%CI 1.01-1.84) and unmarried (OR 1.75; 95%CI 1.10- 2.78), having a low school degree (OR 2.31; 95%CI 1.58-3.36) and a smoking partner (OR 3.03; 95%CI 2.32-3.96). The absolute risk of smoking during pregnancy was 42%. One year after delivery, 44%of women who stopped smoking in pregnancy relapsed. CONCLUSIONS: a not negligible percentage of women residents in Tuscany Region smokes during pregnancy. Relapses after delivery are high. Even if recently in Italy a smoke free legislation was implemented, the study shows a low attention toward passive smoking during pregnancy. Smoking cessation interventions specifically tailored for pregnant women and relapses prevention need to be implemented in Tuscany by all health care professionals who care for women during pregnancy and after delivery.

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.

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.

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.

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.

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.

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.

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.

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.

Geographical information system and environmental epidemiology: a cross-sectional spatial analysis of the effects of traffic-related air pollution on population respiratory health.

BACKGROUND: Traffic-related air pollution is a potential risk factor for human respiratory health. A Geographical Information System (GIS) approach was used to examine whether distance from a main road (the Tosco-Romagnola road) affected respiratory health status. METHODS: We used data collected during an epidemiological survey performed in the Pisa-Cascina area (central Italy) in the period 1991-93. A total of 2841 subjects participated in the survey and filled out a standardized questionnaire on health status, socio-demographic information, and personal habits. A variable proportion of subjects performed lung function and allergy tests. Highly exposed subjects were defined as those living within 100 m of the main road, moderately exposed as those living between 100 and 250 m from the road, and unexposed as those living between 250 and 800 m from the road. Statistical analyses were conducted to compare the risks for respiratory symptoms and diseases between exposed and unexposed. All analyses were stratified by gender. RESULTS: The study comprised 2062 subjects: mean age was 45.9 years for men and 48.9 years for women. Compared to subjects living between 250 m and 800 m from the main road, subjects living within 100 m of the main road had increased adjusted risks for persistent wheeze (OR = 1.76, 95% CI = 1.08-2.87), COPD diagnosis (OR = 1.80, 95% CI = 1.03-3.08), and reduced FEV1/FVC ratio (OR = 2.07, 95% CI = 1.11-3.87) among males, and for dyspnea (OR = 1.61, 95% CI = 1.13-2.27), positivity to skin prick test (OR = 1.83, 95% CI = 1.11-3.00), asthma diagnosis (OR = 1.68, 95% CI = 0.97-2.88) and attacks of shortness of breath with wheeze (OR = 1.67, 95% CI = 0.98-2.84) among females. CONCLUSION: This study points out the potential effects of traffic-related air pollution on respiratory health status, including lung function impairment. It also highlights the added value of GIS in environmental health research.

Percentiles of inspiratory capacity in healthy nonsmokers: a pilot study.

BACKGROUND: Over the past decade inspiratory capacity (IC) has received increasing attention, especially in studies on chronic obstructive pulmonary disease. Though a few recent studies provide reference values for IC, still little is known on the distribution of its values in healthy subjects. OBJECTIVE: To estimate percentiles of IC in a sample of healthy nonsmokers by applying quantile regression. METHODS: We applied quantile regression to estimate seven percentiles of IC from 5 to 95% for a given age, height and body mass index, separately in males and females, in a sample of 411 healthy nonsmokers, aged 8-73 years, drawn from the general population in Northern Italy. RESULTS: The magnitude and statistical significance of the effect of age, height and body mass on IC varied across percentiles and between genders. When the 50th percentile of IC was compared with the predicted values of several studies, including those published by the European Community for Coal and Steel, the differences were as large as 0.86 liters in males and 0.90 liters in females. The possible advantage of the 5th percentile predicted from quantile regression over the 'traditional 5th percentile' as lower limit of normal was also illustrated. CONCLUSIONS: Inference on percentiles, rather than just the mean, of IC and other lung function measures may help in the future to better understand the effect of various risk factors, model growth curves and derive more accurate reference values.