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To verify whether the new hemodynamic definition of pulmonary hypertension (PH) has any implication in treatment of Chronic Thrombo-Embolic Pulmonary Disease (CTEPD) patients without PH, we retrospectively analysed the clinical and functional changes determined by pulmonary endarterectomy (PEA) in 63 CTEPD patients without PH who underwent surgery at our center, comparing those in whom the hemodynamic diagnosis of PH met recent guideline recommendations versus those in whom the diagnosis only met previous hemodynamic thresholds. The results show that the vast majority of CTEPD patients without PH operated at our center would now be defined as chronic thromboembolic pulmonary hypertension (CTEPH) patients. PEA did not result in any improvement in exercise capacity nor in right ventricular function or lung function test in patients with mean pulmonary artery pressure (mPAP) ≤ 20 mm Hg and pulmonary vascular resistance (PVR) ≤ 2 WU; on the contrary, hemodynamic parameters, exercise capacity, right ventricular function and lung function significantly improved in patients with mPAP between 21 and 24 mm Hg. [ABSTRACT FROM AUTHOR]

Homozygous ZZ alpha-1 antitrypsin (AAT) deficiency produces mutant AAT (Z-AAT) proteins in hepatocytes, leading to progressive liver fibrosis. We evaluated the safety and efficacy of an investigational RNA interference therapeutic, fazirsiran, that degrades Z-AAT messenger RNA, reducing deleterious protein synthesis. This ongoing, phase 2 study randomized 40 patients to subcutaneous placebo or fazirsiran 25, 100, or 200 mg. The primary endpoint was percent change in serum Z-AAT concentration from baseline to week 16. Patients with fibrosis on baseline liver biopsy received treatment on day 1, at week 4, and then every 12 weeks and had a second liver biopsy at or after weeks 48, 72, or 96. Patients without fibrosis received 2 doses on day 1 and at week 4. At week 16, least-squares mean percent declines in serum Z-AAT concentration were −61%, −83%, and −94% with fazirsiran 25, 100, and 200 mg, respectively, vs placebo (all P <.0001). Efficacy was sustained through week 52. At postdose liver biopsy, fazirsiran reduced median liver Z-AAT concentration by 93% compared with an increase of 26% with placebo. All fazirsiran-treated patients had histologic reduction from baseline in hepatic globule burden. Portal inflammation improved in 5 of 12 and 0 of 8 patients with a baseline score of >0 in the fazirsiran and placebo groups, respectively. Histologic meta-analysis of histologic data in viral hepatitis score improved by >1 point in 7 of 14 and 3 of 8 patients with fibrosis of >F0 at baseline in the fazirsiran and placebo groups, respectively. No adverse events led to discontinuation, and pulmonary function tests remained stable. Fazirsiran reduced serum and liver concentrations of Z-AAT in a dose-dependent manner and reduced hepatic globule burden. (ClinicalTrials.gov , Number NCT03945292) [Display omitted] This study showed the potential benefit of treatment with fazirsiran in patients with alpha-1 antitrypsin deficiency–associated liver disease, which will be confirmed in a larger ongoing study. [ABSTRACT FROM AUTHOR]

Great interest has been raised by the possible protective role of vitamin D in coronavirus disease 2019 (COVID-19), but objective data on 25(OH)vitamin D deficiency in hospitalized COVID-19 patients are not conclusive. The aim of this study was to determine the prevalence of 25(OH)vitamin D deficiency in COVID-19 patients admitted to an Italian referral hospital and explore its association with clinical outcomes and the markers of disease severity. In this single-center cohort study, 129 consecutive adult COVID-19 patients hospitalized in an Italian referral center were enrolled from March to April 2020. 25(OH)Vitamin D serum levels were assessed 48 h since hospital admission and categorized into: normal (≥30 ng/mL), insufficient (<30 - ≥20 ng/mL), moderately deficient (<20 - ≥10 ng/mL), severely deficient (<10 ng/mL). The prevalence of 25(OH)vitamin D insufficiency, moderate deficiency and severe deficiency was 13.2%, 22.5% and 54.3%, respectively. 25(OH)Vitamin D deficiency (<20 ng/mL) was not associated with COVID-19 clinical features and outcomes. Unexpectedly, after adjusting for major confounders, a significant positive association between increasing 25(OH)vitamin D levels and in-hospital mortality (on a continuous logarithmic scale, odds ratio = 1.73 [95% CI, 1.11 to 2.69]; P =.016) was observed. Very low 25(OH)vitamin D levels were highly prevalent and suggestive of deficiency among our hospitalized severe COVID-19 patients, but low 25(OH)vitamin D levels were not associated with outcome variables. Whether 25(OH)vitamin D adequacy may influence clinical outcomes in COVID-19 and the unexpected correlation between higher 25(OH)vitamin D levels and mortality require further investigations by large intervention trials. [ABSTRACT FROM AUTHOR]

Abstract: Background: The association between smoking habits and asthma is complex because subjects with asthma could avoid smoking, whereas smoking could increase asthma severity or incidence. Purpose: The relation between asthma in childhood (0–10 years) and smoking initiation in the second decade (11–20 years) was investigated using the database of the Italian Study on Asthma in Young Adults, performed in 1998–2000 on people aged 20–45 years. Methods: The cumulative incidence of smoking initiation was compared among (1) subjects not reporting asthma attacks in the first 20 years of life (n = 17,384), (2) subjects reporting asthma onset in the first decade and no disease remission by the age of 20 years (n = 305), (3) subjects reporting asthma onset in the first decade and remission in the first and second decades (n = 573). Results: Among men, the cumulative incidence of smoking onset was higher among nonasthmatics (49%) than among asthmatics (35.6%), and intermediate among asthmatics with disease remission (44.2%) (p = .001). These differences were larger in males born between 1953 and 1965, and tended to decrease in males born between 1966 and 1979: cumulative incidence of smoking onset decreased from 54.3% to 43.8% in nonasthmatics, whereas it remained stable in asthmatics (from 36.8% to 35%). Women, instead, had similar cumulative incidence of smoking initiation, irrespective of asthma onset or remission (p = .849). Conclusion: Asthma in childhood reduces smoking initiation during the subsequent teenage in men, but not in women. This protective effect tends to fade when asthma remission occurs. In the last decades, smoking initiation has decreased among nonasthmatic males, but not among asthmatic males. [Copyright &y& Elsevier]

Summary: Rationale and objectives: Response to mailed epidemiological surveys has decreased in recent decades. Since subjects with respiratory symptoms are usually early responders to surveys performed in Southern Europe, this trend could bias prevalence estimates. The present study aimed at evaluating the impact of non-response bias on prevalence estimates of respiratory symptoms and smoking habits. Methods: In 9 centres, participating in the Italian Study on Asthma in Young Adults (ISAYA), random samples of people aged 20–45 years were administered a mailed questionnaire between 1998 and 2000. Non-responders were contacted again first by mail and then by phone. Cumulative response percentage was 30.5%, 52.4% and 72.7% (18,873/25,969), respectively, after the 1st, 2nd and 3rd contact. Results: The prevalence of self-reported current asthma, asthma-like symptoms, and chronic cough/phlegm was more than halved from the first contact (5.6%, 17.8%, 14.6% respectively) to the third contact (2.7%, 6.4%, 6.9%). This pattern was less pronounced when considering allergic rhinitis and past asthma, whose prevalence decreased, respectively, from 21.5% to 15.6% and from 3.5% to 2.6%. At the same time the proportion of current smokers increased from 29.2% to 38%, while the proportion of ex-smokers decreased from 16.5% to 10.1%. In a multinomial logistic model current asthma, asthma-like symptoms, chronic cough/phlegm and smoking habits, and to a lower extent past asthma and allergic rhinitis, were significant predictors of late response. Conclusions: In Italy when response percentage is low, the prevalence of current asthma, chronic cough/phlegm and ex-smokers is overestimated, while the proportion of current smokers is underestimated. [Copyright &y& Elsevier]

Background: Epidemiologic evidence related to asthma control in patients from the general population is scanty. Objectives: We sought to assess asthma control in several European centers according to the Global Initiative for Asthma (GINA) guidelines and to investigate its determinants. Methods: In the European Community Respiratory Health Survey II (1999-2002), 1241 adults with asthma were identified and classified into inhaled corticosteroid (ICS) users and non-ICS users in the last year. Control was assessed in both groups by using the GINA proposal (controlled, partly controlled, and uncontrolled asthma), and it was related to potential determinants. Results: Only 15% (95% CI, 12% to 19%) of subjects who had used ICSs in the last year and 45% (95% CI, 41% to 50%) of non-ICS users had their asthma under control; individuals with uncontrolled asthma accounted for 49% (95% CI, 44% to 53%) and 18% (95% CI, 15% to 21%), respectively. Among ICS users, the prevalence of uncontrolled asthma showed great variability across Europe, ranging from 20% (95% CI, 7% to 41%; Iceland) to 67% (95% CI, 35% to 90%; Italy). Overweight status, chronic cough and phlegm, and sensitization to Cladosporium species were associated with poor control in ICS users. About 65% and 87% of ICS users with uncontrolled and partly controlled asthma, respectively, were on a medication regimen that was less than recommended by the GINA guidelines. Conclusion: Six of 7 European asthmatic adults using ICSs in the last year did not achieve good disease control. The large majority of subjects with poorly controlled asthma were using antiasthma drugs in a suboptimal way. A wide variability in asthma control emerged across Europe. Clinical implications: Greater attention should be paid to asthma management and to the implementation of the GINA guidelines. [Copyright &y& Elsevier]

Summary: Background: A major reason of the poor control of asthma is that patients fail to adhere to their treatment. The aim of the study was to identify factors affecting changes in asthma treatment adherence in an international cohort. Methods: A follow-up study was carried out by means of a structured clinical interview in 971 subjects with asthma from 12 countries who participated in both the European Community Respiratory Health Survey: ECRHS-I (1990–94) and ECRHS-II (1998–2002). Subjects were considered adherent if they reported they normally took all the prescribed drugs. A logistic model was used to study the adjusted effect of the determinants. Results: The net change in adherence to anti-asthmatic treatment per 10 years of follow-up was −2% (95% CI: −9.5, 5.5), 7.5% (−2.6, 17.6), 15.0% (6.6, 23.5) and 19.8% (4.1, 35.5), respectively, in Nordic, Mediterranean, Continental and extra-European areas. Among the 428 non-adherent subjects in ECRHS-I, having regular consultations with health care professionals was the strongest predictor of increased adherence (OR 3.32; 95% CI: 1.08–10.17). Among the 543 adherent subjects in ECRHS-I, using inhaled corticosteroids significantly predicted a persistence of adherence (OR 2.04; 95% CI: 1.11–3.75). No effect of gender, age, duration of the disease, smoking habit and educational level was observed. Conclusions: Our findings highlight the key role of doctors and nurses in educating and regularly reviewing the patients and support the efforts for an improvement of clinical communication. [Copyright &y& Elsevier]

Background: Few studies have investigated the long-term association between inhaled corticosteroids (ICSs) and lung function decline in asthma. Objective: To evaluate whether prolonged treatment with ICSs is associated with FEV1 decline in adults with asthma. Methods: An international cohort of 667 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions. FEV1 decline was analyzed according to age, sex, height, body mass index, total IgE, time of ICS use, and smoking, while adjusting for potential confounders. Results: As ICS use increased, the decline in FEV1 was lower (P trend = .025): on average, decline passed from 34 mL/y in nonusers (half of the sample) to 20 mL/y in subjects treated for 48 months or more (18%). When adjusting for all covariates, there was an interaction (P = .02) between ICS use and total IgE: in subjects with high (>100 kU/L) IgE, ICS use for 4 years or more was associated with a lower FEV1 decline (23 mL/y; 95% CI, 8-38 compared with nonusers). This association was not seen in those with lower IgE. Conclusion: Although confirming a beneficial long-term association between ICSs and lung function in asthma, our study suggests that subjects with high IgE could maximally benefit from a prolonged ICS treatment. Clinical implications: This study adds further evidence to the beneficial effect of inhaled steroids on lung function in asthma; future studies will clarify whether calibrating the corticosteroid dose according to the level of total IgE is a feasible approach in asthma management. [Copyright &y& Elsevier]

Summary: Background: In most developed countries the prevalence of smoking habits is decreasing in men, while in women the prevalence seems to decline in Northern Europe but to increase in the Mediterranean area. The present research aims at assessing time trends in smoking habits in Italy. Methods: In the frame of the Italian Study on Asthma in Young Adults (ISAYA) a random sample of the Italian population aged 20–45 years was administered a mailed questionnaire in 9 Italian centers between 1998 and 2000. Cumulative response was 72.7% (18873/25969). Kaplan–Meier survival curves and log-rank test were used to compare probability of remaining a life-time non-smoker across birth cohorts (1953–58, 1959–63, 1964–68, 1969–73, 1974–78). Probability to quit smoking was also evaluated among ever-smokers. Results: Probability to persist as a non-smoker significantly increased across subsequent generations in both sexes. At the age of 20 years this probability amounted to 41.7% (95% CI 39.4–44.0%) in men and 52.7% (50.4–54.9%) in women born between 1953 and 1958, and it increased to 57% (54.8–59.1%) in men and 68.7% (66.6–70.7%) in women born in 1969-73, but no further decline in smoking habits was observed in the next birth cohort (1974–78). Also the probability to quit smoking significantly increased from the 1953–58 birth cohort to the 1969–73 one. Conclusions: Smoking has declined among Italian young adults of both genders. Further efforts are necessary to promote active anti-smoking campaign, especially among adolescents, which are at higher risk of starting to smoke. [Copyright &y& Elsevier]

Background: The natural history of asthma severity is poorly known. Objective: To investigate prognostic factors of asthma severity. Methods: All current patients with asthma identified in 1991 to 1993 in the European Community Respiratory Health Survey were followed up, and their severity was assessed in 2002 by using the Global Initiative for Asthma categorization (n = 856). Asthma severity (remittent, intermittent, mild, moderate, severe) was related to potential determinants evaluated at baseline and during the follow-up by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios (RRRs). Results: Asthma severity measured at baseline was a determinant of a patient''s severity at the end of the follow-up. At baseline, severe persistent had a poorer FEV1% predicted, a poorer symptom control, higher IgE levels (RRR, 2.06; 95% CI, 1.38-3.06), and a higher prevalence of chronic cough/mucus hypersecretion (RRR, 4.90; 95% CI, 2.18-11.02) than patients with intermittent asthma. Moderate persistent showed the same prognostic factors as severe persistent, even if the associations were weaker. Mild persistent had a distribution of prognostic factors that was similar to patients with intermittent asthma, although the former showed a poorer symptom control than the latter. Remission mainly occurred in patients with less severe asthma and was negatively associated with a change in body mass index (RRR, 0.86; 95% CI, 0.75-0.97). Allergic rhinitis, smoking, and respiratory infections in childhood were not associated with asthma severity. Conclusion: Patients with moderate and severe persistent asthma are characterized by early deterioration of lung function. High IgE levels and persistent cough/mucus hypersecretion are strong markers of moderate/severe asthma, which seems to be a different phenotype from mild persistent or intermittent asthma. Clinical implications: Our results suggest that the evolution of asthma severity is to a large extent predictable. [Copyright &y& Elsevier]

Summary: Chronic obstructive pulmonary disease (COPD) exacerbations could represent an opportunity for pro-active COPD management rather than mere treatment if previously unknown disease is discovered; the extent of underdiagnosis and undertreatment of COPD in patients attending an emergency department (ED) with an exacerbation is not known. During 2002, we recalled 131 COPD patients in stable conditions, 4–8 weeks after they had attended the ED or been discharged from our University Hospital (North-West of Italy). Information on diagnosis and management prior to the ED attendance were collected; spirometry and arterial blood gas analyses were performed. One-third of patients had never been diagnosed and treated even though 83% of them had moderate-to-very-severe COPD and about 30% already had respiratory failure. Only 20% had received information on the nature of the disease and none had received a written action plan. Only 60% were receiving long-acting bronchodilators and 41% of patients with respiratory failure were receiving long-term oxygen. A substantial number of undiagnosed and untreated patients with moderate-to-very-severe COPD came to our attention through an exacerbation. This enforces the importance of exacerbations as the starting point of pro-active COPD management and of the ED as a valuable sentinel to identify this subset of patients. [Copyright &y& Elsevier]

Summary: An unusual case of smoking-related centrilobular emphysema with normal spirometry. A 64-year-old man presented with severe dyspnoea and respiratory failure. Pulmonary function and mechanics were normal except for a marked reduction in diffusing capacity of the lung. High-resolution CT scan showed diffuse centrilobular emphysema also involving lower lobes. Pulmonary embolism, cardiac or pulmonary shunt and immunopathologically based vasculitis were excluded. Pulmonary pressure was at the upper limit of normality but within few months he developed a severe pulmonary hypertension. Although spirometry is the only physiologic measure recommended by the updated Global Initiative for Chronic Obstructive Lung Disease guidelines for confirming the diagnosis it should be recognized that diffuse emphysema may occur with only abnormalities in gas exchange without airflow obstruction. The identification of different phenotypes within COPD is important for understanding disease heterogeneity and progression. [Copyright &y& Elsevier]

Few studies addressed the issue of risk stratification in patients with residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). This study tested the potential added value of parameters that have not been included in existing risk models. We evaluated 546 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent PEA and were followed-up for a median period of 58 months. Among the 242 with residual PH, 27 died and had 127 a clinical worsening event. At univariable analysis, the parameters associated with poor survival were pulmonary vascular resistance (PVR) ≥425 dyn·s·cm−5 (p ≤ 0.001), mean pulmonary artery pressure (mPAP) ≥38 mmHg (p = 0.003) and pulmonary artery compliance (CPA) ≤1.8 ml/mmHg (p = 0.014). In the bivariable models including either PVR or mPAP as first parameter, the addition of CPA was not statistically significant. The parameters associated with poor clinical worsening were CPA ≤1.8 ml/mmHg (p < 0.001), PVR ≥425 dyn·s·cm−5 (p = 0.002), arterial oxygen tension (PaO2) ≤ 75 mmHg (p = 0.003), mPAP ≥38 mmHg (p = 0.008). In a multivariable analysis which included PVR ≥425 as the first parameter, the addition of both CPA ≤1.8 ml/mmHg and of PaO2 ≤ 75 mmHg significantly improved prognostic stratification (Harrel's C of the model = 0.64, p < 0.001). Noticeably, the lower tertile of the model's predictor index identified a subgroup of 91 patients who had an event rate numerically similar to that of patients without residual PH. Risk stratification in residual PH can be refined if CPA and PaO2 are considered in association with standard hemodynamic parameters. • Few studies address the issue of risk stratification in patients with residual pulmonary hypertension after pulmonary endarterectomy • Risk stratification can be refined if pulmonary arterial compliance and arterial oxygen tension are considered with hemodynamic parameters. • It is thus possible to identify a subgroup of patients who have an event rate similar to that of patients without residual pulmonary hypertension. • Risk stratification can be used to guide therapy in such patients. [ABSTRACT FROM AUTHOR]

Background Cross-sectional studies have reported a lower prevalence of sensitization in older adults, but few longitudinal studies have examined whether this is an aging or a year-of-birth cohort effect. Objective We sought to assess changes in sensitization and total IgE levels in a cohort of European adults as they aged over a 20-year period. Methods Levels of serum specific IgE to common aeroallergens (house dust mite, cat, and grass) and total IgE levels were measured in 3206 adults from 25 centers in the European Community Respiratory Health Survey on 3 occasions over 20 years. Changes in sensitization and total IgE levels were analyzed by using regression analysis corrected for potential differences in laboratory equipment and by using inverse sampling probability weights to account for nonresponse. Results Over the 20-year follow-up, the prevalence of sensitization to at least 1 of the 3 allergens decreased from 29.4% to 24.8% (−4.6%; 95% CI, −7.0% to −2.1%). The prevalence of sensitization to house dust mite (−4.3%; 95% CI, −6.0% to −2.6%) and cat (−2.1%; 95% CI, −3.6% to −0.7%) decreased more than sensitization to grass (−0.6%; 95% CI, −2.5% to 1.3%). Age-specific prevalence of sensitization to house dust mite and cat did not differ between year-of-birth cohorts, but sensitization to grass was most prevalent in the most recent ones. Overall, total IgE levels decreased significantly (geometric mean ratio, 0.63; 95% CI, 0.58-0.68) at all ages in all year-of-birth cohorts. Conclusion Aging was associated with lower levels of sensitization, especially to house dust mite and cat, after the age of 20 years. [ABSTRACT FROM AUTHOR]

Background: Little is known about factors associated with lung function decline in asthma. Objective: To identify the determinants of FEV1 decline in adults with asthma with and without airflow obstruction at baseline. Methods: An international cohort of 638 subjects with asthma (20-44 years old) was identified in the European Community Respiratory Health Survey (1991-1993) and followed up from 1998 to 2002. Spirometry was performed on both occasions. FEV1 decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. The analyses were stratified by the presence of airflow obstruction (FEV1/forced vital capacity < 0.70) at baseline. Results: In the group of individuals without airflow obstruction (n = 544), a faster FEV1 decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV1 decline was associated with weight gain independently of baseline BMI, and this association was stronger in men (20; 95% CI, 10-30, mL/y/kg gained) than in women (6; 95% CI, 1-11, mL/y). In the group of individuals with airflow obstruction (n = 94), the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV1 decline, whereas weight gain was not associated with decline. Conclusions: The detrimental effect of weight gain on FEV1 decline is particularly relevant in subjects with asthma who still do not have an established airflow obstruction. Our findings support the importance of weight management in asthma and recommend weight loss in overweight or obese individuals with asthma. [Copyright &y& Elsevier]

• Worldwide, the prevalence of asthma is high among teenagers and school children. • Monitoring adverse events following coronavirus disease 2019 (COVID-19) vaccination is important for practitioners. • There are plans for mass COVID-19 vaccination of teenagers and school children. • The effect of COVID-19 vaccination on asthmatic individuals is unknown and unreported. • This article reports the first case of asthma exacerbation following COVID-19 vaccination. There is ongoing debate regarding the role of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in asthma exacerbation, and its long-term impact on the lung function of individuals with asthma. In contrast, the potential impact of coronavirus disease 2019 (COVID-19) vaccination on asthma is entirely unexplored. This study examined a challenging case of severe asthma exacerbation in a 28-year-old female following two doses of the mRNA-based vaccine BNT162b2 (Pfizer-BioNTech) at IRCCS Policlinico San Matteo in Pavia, Italy. The patient, a fourth-year resident at the hospital, was vaccinated in early 2021. She was an occasional smoker with a 10-year history of asthma and seasonal allergic rhinitis. She tested negative for SARS-CoV-2 on several molecular swabs and serology tests. After receiving the second dose of vaccine, the patient started to experience worsening of respiratory symptoms. Following several episodes and a severe asthma attack, the patient required treatment with mepolizumab, a biologic drug (interleukin-5) antagonist monoclonal antibody. This single case study is insufficient to draw conclusions about the association between asthma exacerbation and the COVID-19 vaccine. While the cause–effect link between vaccination against SARS-CoV-2 and worsening of asthmatic disease might only be suggested at present, this case is a valuable prompt for further investigation. This is particularly true from the perspective of mass vaccination of adolescents and children currently underway across the globe. [ABSTRACT FROM AUTHOR]

Abstract Background Very few studies have examined whether a long-term beneficial effect of physical activity on lung function can be influenced by living in polluted urban areas. Objective We assessed whether annual average residential concentrations of nitrogen dioxide (NO 2) and particulate matter with aerodynamic diameters < 2.5 μm (PM 2.5) and <10 μm (PM 10) modify the effect of physical activity on lung function among never- (N = 2801) and current (N = 1719) smokers in the multi-center European Community Respiratory Health Survey. Methods Associations between repeated assessments (at 27–57 and 39–67 years) of being physically active (physical activity: ≥2 times and ≥1 h per week) and forced expiratory volume in 1 s (FEV 1) and forced vital capacity (FVC) were evaluated using adjusted mixed linear regression models. Models were conducted separately for never- and current smokers and stratified by residential long-term NO 2 , PM 2.5 mass and PM 10 mass concentrations (≤75th percentile (low/medium) versus >75th percentile (high)). Results Among current smokers, physical activity and lung function were positively associated regardless of air pollution levels. Among never-smokers, physical activity was associated with lung function in areas with low/medium NO 2 , PM 2.5 mass and PM 10 mass concentrations (e.g. mean difference in FVC between active and non-active subjects was 43.0 mL (13.6, 72.5), 49.5 mL (20.1, 78.8) and 49.7 mL (18.6, 80.7), respectively), but these associations were attenuated in high air pollution areas. Only the interaction term of physical activity and PM 10 mass for FEV 1 among never-smokers was significant (p-value = 0.03). Conclusions Physical activity has beneficial effects on adult lung function in current smokers, irrespective of residential air pollution levels in Western Europe. Trends among never-smokers living in high air pollution areas are less clear. Highlights • Air pollution may modify associations between physical activity and lung function. • Physical activity was positively associated with lung function in current smokers regardless of air pollution levels. • Results in never smokers were less clear. • Air pollution control policies would ensure maximal benefit of physical activity promotion policies. [ABSTRACT FROM AUTHOR]

Congenital alpha-1 antitrypsin deficiency (AATD) is a rare inherited disorder caused by the mutation of the SERPINA1 gene on chromosome 14. At pulmonary level, AAT deficiency leads to an increased risk of chronic obstructive pulmonary disease (COPD) and emphysema, starting from the third-fourth decade of life. At hepatic level, some variants of the allelic, in particular PI*Z, cause a conformational change of the AAT molecule, which polymerizes within the hepatocytes. Excessive hepatic accumulation of these abnormal molecules can lead to liver disease in both adults and children, with clinical presentation ranging from cholestatic jaundice in the newborn to abnormal blood indices of liver function in children and adults, up to fatty liver, cirrhosis and hepatocarcinoma. Nutritional interventions in AATD aim to provide the necessary calories, stop protein catabolism, prevent and treat malnutrition as in the case of common COPD, and even take into account any liver disease that is a distinctive trait, compared to common COPD. Actually, there is a lack of formal research regarding the effects of specific nutritional recommendations in patients with AATD, proper eating habits may help to preserve lung and liver function. For practical dietary advice in patients with AATD and COPD, recently a food pyramid proposal has been published. It has been observed that there is a marked overlap between AATD liver disease and obesity-related liver disease, suggesting shared molecular basis and, therefore, similar nutritional strategies. In this narrative review dietary advice for all possible stages of liver disease have been reported. • DAAT is a rare inherited disorder caused by the mutation of the SERPINA1 gene. • There is an overlap between DAAT liver disease and obesity-related liver disease. • Dietary advice for patients with DAAT have been reported. • Dietary advice for NAFLD, NASH and cirrhosis have been reported. • Patients with DAAT should be screened for malnutrition every 6–12 months. [ABSTRACT FROM AUTHOR]