Search

Background: Understanding the natural history of abnormal spirometric patterns at different stages of life is critical to identify and optimise preventive strategies. We aimed to describe characteristics and risk factors of restrictive and obstructive spirometric patterns occurring before 40 years (young onset) and between 40 and 61 years (mid-adult onset)., Methods: We used data from the population-based cohort of the European Community Respiratory Health Survey (ECRHS). Prebronchodilator forced expiratory volume in one second (FEV 1 ) and forced vital capacity (FVC) were assessed longitudinally at baseline (ECRHS1, 1993-1994) and again 20 years later (ECRHS3, 2010-2013). Spirometry patterns were defined as: restrictive if FEV 1 /FVC≥LLN and FVC<10th percentile, obstructive if FEV 1 /FVC

Severe asthma affects about 10% of the population with asthma and is characterized by low lung function and a high count of blood leukocytes, mainly eosinophils. Various definitions are used in clinical practice and in the literature to identify asthma remission: clinical remission, inflammatory remission, and complete remission. This work highlights a consensus for asthma remission using a Delphi method. In the context of the Severe Asthma Network Italy, which accounts for 57 severe asthma centers and more than 2,200 patients, a board of six experts drafted a list of candidate statements in a questionnaire, which has been revised to minimize redundancies and ensure clear and consistent wording for the first round (R1) of the analysis. Thirty-two statements were included in the R1 questionnaire and then submitted to a panel of 80 experts, which used a 5-point Likert scale to measure agreement regarding each statement. Then, an interim analysis of R1 data was performed, and items were discussed and considered to produce a consistent questionnaire for round 2 (R2) of the analysis. Then, the board set the R2 questionnaire, which included only important topics. Panelists were asked to vote on the statements in the R2 questionnaire afterward. During R2, the criteria of complete clinical remission (the absence of the need for oral corticosteroids, symptoms, exacerbations or attacks, and pulmonary function stability) and those of partial clinical remission (the absence of the need for oral corticosteroids, and two of three criteria: the absence of symptoms, exacerbations or attacks, and pulmonary stability) were confirmed. This Severe Asthma Network Italy Delphi analysis defined a valuable and independent tool that is easy to use, to test the efficacy of different treatments in patients with severe asthma enrolled into the SANI registry., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: occupational exposure to vapours, gases, dusts and fumes (VGDF) plays an important role in the development and exacerbation of respiratory diseases. The aim of this study is to evaluate the possible association of occupational exposure to airborne pollutants and chronic respiratory diseases., Design: multicase-control study., Setting and Participants: cases of chronic respiratory diseases and controls from the Italian multicentric study Gene Environment Interaction in Respiratory Diseases (GEIRD)., Main Outcome Measures: the occurrence of rhinitis, asthma, chronic bronchitis/chronic obstructive pulmonary disease (COPD), asthma severity, spirometry data, exhaled nitric oxide (FeNO) were examined in relation to chronic and acute occupational exposures to airborne pollutants using multiple regression models., Results: 2,943 subjects were enrolled in the study. Regularm exposure to VGDF was associated with a higher prevalence of chronic bronchitis/COPD (OR 1.40, 95%CI 0.98-1.99), especially in those also having asthma (OR 1.80, 95%CI 1.14-2.85), a lower prevalence of remittent asthma (OR 0.53, 95%CI 0.29-0.96) and, in those with asthma, an increased activity of the disease (severity score) (OR 1.77, 95%CI 1.20-2.60). No associations were observed between occupational exposure and prevalence of rhinitis, spirometry and FeNO data. Finally, an association was found between acute exposure to airborne pollutants (occupational and non-occupational) and the respiratory diseases investigated, in particular active asthma and asthma associated chronic bronchitis/BPCO., Conclusions: these data confirm a significant role of occupational exposure to airborne pollutants on respiratory health, underlying the importance of workplace exposure prevention, in particular for more susceptible subjects, as those with respiratory diseases.

Long-term exposure to air pollution has adverse respiratory health effects. We investigated the cross-sectional relationship between residential exposure to air pollutants and the risk of suffering from chronic respiratory diseases in some Italian cities. In the BIGEPI project, we harmonised questionnaire data from two population-based studies conducted in 2007-2014. By combining self-reported diagnoses, symptoms and medication use, we identified cases of rhinitis (n = 965), asthma (n = 328), chronic bronchitis/chronic obstructive pulmonary disease (CB/COPD, n = 469), and controls (n = 2380) belonging to 13 cohorts from 8 Italian cities (Pavia, Turin, Verona, Terni, Pisa, Ancona, Palermo, Sassari). We derived mean residential concentrations of fine particulate matter (PM 10 , PM 2.5 ), nitrogen dioxide (NO 2 ), and summer ozone (O 3 ) for the period 2013-2015 using spatiotemporal models at a 1 km resolution. We fitted logistic regression models with controls as reference category, a random-intercept for cohort, and adjusting for sex, age, education, BMI, smoking, and climate. Mean ± SD exposures were 28.7 ± 6.0 μg/m 3 (PM 10 ), 20.1 ± 5.6 μg/m 3 (PM 2.5 ), 27.2 ± 9.7 μg/m 3 (NO 2 ), and 70.8 ± 4.2 μg/m 3 (summer O 3 ). The concentrations of PM 10 , PM 2.5 , and NO 2 were higher in Northern Italian cities. We found associations between PM exposure and rhinitis (PM 10 : OR 1.62, 95%CI: 1.19-2.20 and PM 2.5 : OR 1.80, 95%CI: 1.16-2.81, per 10 μg/m 3 ) and between NO 2 exposure and CB/COPD (OR 1.22, 95%CI: 1.07-1.38 per 10 μg/m 3 ), whereas asthma was not related to environmental exposures. Results remained consistent using different adjustment sets, including bi-pollutant models, and after excluding subjects who had changed residential address in the last 5 years. We found novel evidence of association between long-term PM exposure and increased risk of rhinitis, the chronic respiratory disease with the highest prevalence in the general population. Exposure to NO 2 , a pollutant characterised by strong oxidative properties, seems to affect mainly CB/COPD., Competing Interests: Declaration of competing interest Sara Maio reports financial support was provided by National Institute for Insurance against Accidents at Work., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Chronic cough is a common symptom, addressed in the clinical setting by empirical treatment together with some laboratory investigations. The aim of the present study was to investigate the value of testing eosinophilic cationic protein (ECP) serum levels combined with other diagnostic procedures and empirical treatment in the diagnostic workup of chronic cough., Methods: In this study, we evaluated 194 patients with chronic cough. No subject had received any anti-inflammatory treatment before clinical evaluation, and none was an active smoker. ECP was measured with a commercially available fluoroenzyme immunoassay and results were expressed as µg/L., Results: The analysis of variance showed that mean ECP level differs among the various diagnosis categories (P<0.001). Mean ECP level was significantly higher in asthmatic patients, particularly in the active disease., Conclusions: Serum ECP concentration could represent a useful biomarker in the clinical work-up of chronic cough, managing to differentiate asthma from other chronic disorders.

Background: Inhaled corticosteroids have been widely used for the regular treatment of asthma and chronic obstructive pulmonary diseases (COPD) over the past few decades. To date, studies investigating the effects of inhaled corticosteroids (ICS) on bone in populations including asthma and COPD patients, show conflicting results. The skeletal effects of ICS remain poorly understood. We assessed the association between ICS exposure and self-reported osteoporosis diagnosis in a European cohort study., Methods: The analysis was carried out by using clinical and questionnaire data available for subjects participating in the ECRHS III (European Community Respiratory Health Survey) with age >55 years., Results: Among the 3004 enrolled subjects, 245 were ICS users with an exposure ≥12 months. Osteoporosis was reported by 16 subjects in the ICS group (6.5%) and by 167 in the not exposed group (6.1%). The adjusted risk of osteoporosis in ICS users (≥12 months) was not greater in exposed subjects when compared with the unexposed ones (OR=1.02, 95CI%: 0.51, 2.03). The same result was observed even when considering in the analysis a longer exposure to the ICS use (≥36.5 months, the median ICS exposure for all subjects). History of COPD, use of oral corticosteroids, Body Mass Index, smoking and physical activity did not show any evidence of an association with osteoporosis., Conclusions: Our study did not show any significant association between long- term ICS use and self-reported diagnosis of osteoporosis in subjects aged >55 years. To explore the real effect of ICS on bone status, further studies are needed, especially in the long-term ICS exposure.

Objective: The prevalence of asthma in Italy is estimated to be around 4%; it affects approximately 2,000,000 citizens, and up to 80-90% of patients have mild-to-moderate asthma. Despite the clinical relevance of mild-to-moderate asthma, longitudinal observational data are very limited, including data on disease progression (worsening vs. improvement), the response to treatment, and prognosis. Studies are needed to develop long-term, observational, real-life research in large cohorts. The primary outcomes of this study will be based on prospective observation and the epidemiological evolution of mild and moderate asthma. Secondary outcomes will include patient-reported outcomes, treatments over time, disease-related functional and inflammatory patterns, and environmental and life-style influences., Methods: This study, called the Mild/Moderate Asthma Network of Italy (MANI), is a research initiative launched by the Italian Respiratory Society and the Italian Society of Allergology, Asthma and Clinical Immunology. MANI is a cluster-based, real world, cross-sectional, prospective, observational cohort study that includes 20,000 patients with mild-to-moderate asthma. (ClinicalTrials.gov Identifier: NCT04796844)., Results and Conclusion: Despite advances in asthma care, several research gaps remain to be addressed through clinical research. This study will add important new knowledge about long-term disease history, the transferability of clinical research results to daily practice, the efficacy of currently recommended strategies, and their impact on the burden and evolution of the disease., Abbreviations: MANI:Mild/Moderate Asthma Network of ItalySANI:Severe Asthma Network ItalyGINA:Global Initiative for AsthmaSABA:short acting β2-agonistsICS:inhaled corticosteroidsCRF:Case Report Form.

Background: Fractional exhaled nitric oxide (FeNO) is a well-known marker of type-2 inflammation. FeNO is elevated in asthma and allergic rhinitis, with IgE sensitization as a major determinant., Objective: We aimed to see whether there was an independent association between upper airway inflammatory disorders (UAID) and FeNO, after adjustment for asthma and sensitization, in a multi-centre population-based study., Methods: A total of 741 subjects with current asthma and 4155 non-asthmatic subjects participating in the second follow-up of the European Community Respiratory Health Survey (ECRHS III) underwent FeNO measurements. Sensitization status was based on measurement of IgE against airborne allergens; information on asthma, UAID and medication was collected through interview-led questionnaires. Independent associations between UAID and FeNO were assessed in adjusted multivariate regression models and test for interaction with perennial sensitization and asthma on the relation between UAID and FeNO were made., Results: UAID were associated with higher FeNO after adjusting for perennial sensitization, asthma and other confounders: with 4.4 (0.9-7.9) % higher FeNO in relation to current rhinitis and 4.8 (0.7-9.2) % higher FeNO in relation to rhinoconjunctivitis. A significant interaction with perennial sensitization was found in the relationship between current rhinitis and FeNO (p = .03) and between rhinoconjunctivitis and FeNO (p = .03). After stratification by asthma and perennial sensitization, the association between current rhinitis and FeNO remained in non-asthmatic subjects with perennial sensitization, with 12.1 (0.2-25.5) % higher FeNO in subjects with current rhinitis than in those without., Conclusions & Clinical Relevance: Current rhinitis and rhinoconjunctivitis was associated with higher FeNO, with an interaction with perennial sensitization. This further highlights the concept of united airway disease, with correlations between symptoms and inflammation in the upper and lower airways and that sensitization needs to be accounted for in the relation between FeNO and rhinitis., (© 2021 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.)

Patients with concomitant features of asthma and chronic obstructive pulmonary disease (COPD) have a heavy disease burden.Using data collected prospectively in the European Community Respiratory Health Survey, we compared the risk factors, clinical history and lung function trajectories from early adulthood to late sixties of middle-aged subjects with asthma+COPD (n=179), past (n=263) or current (n=808) asthma alone, COPD alone (n=111) or none of these (n=3477).Interview data and pre-bronchodilator forced expiratory volume in 1 s (FEV 1 ) and forced vital capacity (FVC) were obtained during three clinical examinations in 1991-1993, 1999-2002 and 2010-2013. Disease status was classified in 2010-2013, when the subjects were aged 40-68 years, according to the presence of fixed airflow obstruction (post-bronchodilator FEV 1 /FVC below the lower limit of normal), a lifetime history of asthma and cumulative exposure to tobacco or occupational inhalants. Previous lung function trajectories, clinical characteristics and risk factors of these phenotypes were estimated.Subjects with asthma+COPD reported maternal smoking (28.2%) and respiratory infections in childhood (19.1%) more frequently than subjects with COPD alone (20.9% and 14.0%, respectively). Subjects with asthma+COPD had an impairment of lung function at age 20 years that tracked over adulthood, and more than half of them had asthma onset in childhood. Subjects with COPD alone had the highest lifelong exposure to tobacco smoking and occupational inhalants, and they showed accelerated lung function decline during adult life.The coexistence between asthma and COPD seems to have its origins earlier in life compared to COPD alone. These findings suggest that prevention of this severe condition, which is typical at older ages, should start in childhood., Competing Interests: Conflict of interest: A. Marcon has nothing to disclose. Conflict of interest: F. Locatelli has nothing to disclose. Conflict of interest: S.C. Dharmage has nothing to disclose. Conflict of interest: C. Svanes has nothing to disclose. Conflict of interest: J. Heinrich has nothing to disclose. Conflict of interest: B. Leynaert has nothing to disclose. Conflict of interest: P. Burney has nothing to disclose. Conflict of interest: A. Corsico has nothing to disclose. Conflict of interest: G. Caliskan has nothing to disclose. Conflict of interest: L. Calciano has nothing to disclose. Conflict of interest: T. Gislason has nothing to disclose. Conflict of interest: C. Janson has nothing to disclose. Conflict of interest: D. Jarvis has nothing to disclose. Conflict of interest: R. Jõgi received grants from the Estonian Research Council (Personal Research Grant n. 562), and personal fees for consultancy and lecturing from GSK, Boehringer and Novartis, and for travels/accommodation/meetings from GSK and Boehringer. Conflict of interest: T. Lytras has nothing to disclose. Conflict of interest: A. Malinovschi has nothing to disclose. Conflict of interest: N. Probst-Hensch has nothing to disclose. Conflict of interest: K. Toren has nothing to disclose. Conflict of interest: L. Casas has nothing to disclose. Conflict of interest: G. Verlato has nothing to disclose. Conflict of interest: J. Garcia-Aymerich has nothing to disclose. Conflict of interest: S. Accordini has nothing to disclose., (Copyright ©The authors 2021.)

Introduction: The global burden of chronic airway diseases represents an important public health concern. The role of oxidative stress and inflammation in the pathogenesis of these diseases is well known. The aim of this study is to evaluate the behavior of both inflammatory and oxidative stress biomarkers in patients with chronic bronchitis, current asthma and past asthma in the frame of a population-based study., Methods: For this purpose, data collected from the Gene Environment Interactions in Respiratory Diseases (GEIRD) Study, an Italian multicentre, multicase-control study, was evaluated. Cases and controls were identified through a two-stage screening process of individuals aged 20-65 years from the general population. Out of 16,569 subjects selected from the general population in the first stage of the survey, 2259 participated in the clinical evaluation. Oxidative stress biomarkers such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), 8-isoprostane and glutathione and inflammatory biomarkers such as Fractional Exhaled Nitric Oxide (FENO) and white blood cells were evaluated in 1878 subjects., Results: Current asthmatics presented higher levels of FENO (23.05 ppm), leucocytes (6770 n/µL), basophils (30.75 n/µL) and eosinophils (177.80 n/µL), while subjects with chronic bronchitis showed higher levels of GSH (0.29 mg/mL) and lymphocytes (2101.6 n/µL). The multivariable multinomial logistic regression confirmed high levels of leucocytes (RRR = 1.33), basophils (RRR = 1.48), eosinophils (RRR = 2.39), lymphocytes (RRR = 1.26) and FENO (RRR = 1.42) in subjects with current asthma. Subjects with past asthma had a statistically significant higher level of eosinophils (RRR = 1.78) with respect to controls. Subjects with chronic bronchitis were characterized by increased levels of eosinophils (RRR = 2.15), lymphocytes (RRR = 1.58), GSH (RRR = 2.23) and 8-isoprostane (RRR = 1.23)., Conclusion: In our study, current asthmatics show a greater expression of the inflammatory profile compared to subjects who have had asthma in the past and chronic bronchitis. On the other hand, chronic bronchitis subjects showed a higher rate of expression of oxidative stress biomarkers compared to asthmatic subjects. In particular, inflammatory markers such as circulating inflammatory cells and FENO seem to be more specific for current asthma, while oxidative stress biomarkers such as glutathione and 8-isoprostane appear to be more specific and applicable to patients with chronic bronchitis.

Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's medical management.The aim of the current expert consensus report is to provide a "state-of-the-art" review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research.A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors., Competing Interests: Conflict of interest: M. Bonini has nothing to disclose. Conflict of interest: M. Di Paolo has nothing to disclose. Conflict of interest: D. Bagnasco has nothing to disclose. Conflict of interest: I. Baiardini has nothing to disclose. Conflict of interest: F. Braido has nothing to disclose. Conflict of interest: M. Caminati has nothing to disclose. Conflict of interest: E. Carpagnano has nothing to disclose. Conflict of interest: M. Contoli reports grants from Chiesi, personal fees from Chiesi, AstraZeneca, Boehringer Ingelheim, Novartis Menarini, Mundipharma, Almirall and Zambon, and grants from University of Ferrara (Italy), outside the submitted work. Conflict of interest: A. Corsico has nothing to disclose. Conflict of interest: S. Del Giacco has nothing to disclose. Conflict of interest: E. Heffler has nothing to disclose. Conflict of interest: C. Lombardi has nothing to disclose. Conflict of interest: I. Menichini has nothing to disclose. Conflict of interest: M. Milanese has nothing to disclose. Conflict of interest: N. Scichilone has nothing to disclose. Conflict of interest: G. Senna has nothing to disclose. Conflict of interest: G.W. Canonica has nothing to disclose., (Copyright ©ERS 2020.)

Background: Mepolizumab (MEP) has been recently introduced to treat severe eosinophilic asthma. Trials have demonstrated a significant effectiveness in this asthma phenotype. We evaluated MEP efficacy on lung function, symptoms, asthma exacerbations, biologic markers, steroid dependence and controller treatment level in real-life., Methods: We retrospectively analyzed 134 severe asthmatics (61 males; mean age 58.3 ± 11; mean FEV 1 %:72 ± 21), treated with MEP for at least 6 months (mean duration:10.9 ± 3.7 months)., Results: FEV 1 % improved significantly after MEP. Mean FEF 25-75 also increased from 37.4 ± 25.4% to 47.2 ± 27.2% (p < 0.0001). Mean baseline blood eosinophil level was 712 ± 731/μL (8.4 ± 5.2%) decreasing to 151 ± 384/μL (1.6 ± 1.6%) (p < 0.0001), FENO levels decreased likewise. MEP treatment also led to a significant ACT improvement (mean pre:14.2 ± 4.4; mean post:20.5 ± 28) and exacerbations significantly fell from 3.8 ± 1.9 to 0.8 ± 1.1 (p < 0.0001). 74% of patients were steroid-dependent before MEP. 45.4% and 46.4% of them showed a suspension and dose reduction respectively (p < 0.0001). A significant number reduced also ICS doses. Only 67% of subjects used SABA as needed before MEP, falling to 20% after MEP. About 40% of patients highlighted a maintenance therapy step-down. Subjects showing an omalizumab treatment failure before MEP had a similar positive response when compared with omalizumab untreated patients., Conclusion: In real-life, MEP improved significantly all outcomes even small airway obstruction, suggesting its possible role also in distal lung region treatment. Furthermore, it demonstrated its high effectiveness in OC/ICS-sparing, in reducing SABA as needed and in stepping-down maintenance therapy. MEP is a valid alternative for patients with previous omalizumab treatment failure., Competing Interests: Declaration of competing interest On behalf of all authors, the corresponding author states that there is no conflict of interest., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Inhaled corticosteroids (ICSs) are the mainstay of asthma treatment, but response to medication is variable. Patients with allergic inflammation generally show a better short-term response to ICSs; however, studies on predictors of long-term response are few., Objective: To assess whether allergic sensitization can modify the association between ICS use and lung function decline over 20 years in adult asthma., Methods: We used data from the 3 clinical examinations of the European Community Respiratory Health Survey. We measured ICS use (no use, and use for <1.3, 1.3-8, and >8 years) and FEV 1 decline among subjects with asthma over the 2 periods between consecutive examinations. We conducted a cohort study combining data of the 2 periods (906 observations from 745 subjects) to assess whether the association between ICS use and FEV 1 decline was modified by allergic sensitization (IgE > 0.35 kU/L for any of house-dust mite, timothy grass, cat, or Cladosporium)., Results: FEV 1 decline was similar for non-ICS users, as well as ICS users for less than 1.3 years, with and without allergic sensitization. However, among subjects on ICSs for a longer period, sensitization was associated with an attenuated decline (P interaction  = .006): in the group treated for more than 8 years, FEV 1 decline was on average 27 mL/y (95% CI Bonferroni-adjusted , 11-42) lower for subjects with sensitization compared with nonsensitized subjects., Conclusions: Our study suggests that biomarkers of atopy can predict a more favorable long-term response to ICSs. Randomized controlled studies are needed to confirm these findings., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Although many studies have highlighted the link between asthma/rhinitis and depression, it is still unclear which characteristics of these diseases are associated with the risk of depression. We aimed to explore the relationship between depression and asthma or rhinitis in a representative sample of the Italian general population., Methods: The data were collected in GEIRD, an Italian multicenter, population-based, multicase-control study. 2227 participants (age 21-86 years, female 50%) underwent standardized interviews, skin prick and lung function tests, and were divided into cases of current asthma (n = 528), rhinitis without asthma (n = 972), and controls (n = 727). Two specific questions from the Patient Health Questionnaire (PHQ-2) were asked to identify symptoms of depressed mood and anhedonia, which were used as a proxy of major depression disorder., Results: The prevalence of depression was 16.7%, 11.9%, and 5.1% in subjects with asthma, rhinitis and controls, respectively. Both in asthma and rhinitis, subjects with depression had worse respiratory-health related quality of life and more frequent disease-related symptoms than their non-depressed counterparts. In asthma, depression was associated with poorer disease control. In rhinitis, depression was significantly associated with a disease-related limitations in daily activities and greater risk of symptom exacerbations and prescriptions of medicines for breathing. Cases of rhinitis with depression were less likely to be atopic., Conclusions: Our results suggest that rhinitis exacerbations, particularly in non-atopic subjects, and low asthma control are strongly related to the presence of depressed mood in adults from the general population., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Mothers' smoking during pregnancy increases asthma risk in their offspring. There is some evidence that grandmothers' smoking may have a similar effect, and biological plausibility that fathers' smoking during adolescence may influence offspring's health through transmittable epigenetic changes in sperm precursor cells. We evaluated the three-generation associations of tobacco smoking with asthma., Methods: Between 2010 and 2013, at the European Community Respiratory Health Survey III clinical interview, 2233 mothers and 1964 fathers from 26 centres reported whether their offspring (aged ≤51 years) had ever had asthma and whether it had coexisted with nasal allergies or not. Mothers and fathers also provided information on their parents' (grandparents) and their own asthma, education and smoking history. Multilevel mediation models within a multicentre three-generation framework were fitted separately within the maternal (4666 offspring) and paternal (4192 offspring) lines., Results: Fathers' smoking before they were 15 [relative risk ratio (RRR) = 1.43, 95% confidence interval (CI): 1.01-2.01] and mothers' smoking during pregnancy (RRR = 1.27, 95% CI: 1.01-1.59) were associated with asthma without nasal allergies in their offspring. Grandmothers' smoking during pregnancy was associated with asthma in their daughters [odds ratio (OR) = 1.55, 95% CI: 1.17-2.06] and with asthma with nasal allergies in their grandchildren within the maternal line (RRR = 1.25, 95% CI: 1.02-1.55)., Conclusions: Fathers' smoking during early adolescence and grandmothers' and mothers' smoking during pregnancy may independently increase asthma risk in offspring. Thus, risk factors for asthma should be sought in both parents and before conception., Funding: European Union (Horizon 2020, GA-633212).

Background: There is a need for easily measurable biomarkers that are able to identify different levels of asthma severity., Aim: To assess the association between peripheral blood cell counts, fractional nitric oxide in exhaled air (FeNO), urinary biomarkers of oxidative stress (8-hydroxy-2'-deoxyguanosine and 8-isoprostane), and asthma severity in adult patients from the general population., Methods: In the Gene Environment Interactions in Respiratory Diseases study, 287 subjects with asthma (aged 20-64) were identified from the general population in Verona (Italy) (2008-2010). Self-reported asthma attacks, asthma-like symptoms and the use of hospital services in the past year were synthesized in a score of respiratory symptoms (SRS). The association of biomarkers with SRS and lung function measures (pre-bronchodilator FEV 1 % predicted and FEV 1 /FVC) was assessed using quasi-Poisson and Gaussian regression models, respectively., Results: Eosinophils (ratio of expected scores: RES[95%CI] = 1.19[1.09,1.30]), basophils (RES[95%CI] = 1.24[1.10,1.40]), lymphocytes (RES[95%CI] = 1.27[1.12,1.45]) and FeNO (RES[95%CI] = 1.18[1.02,1.37]) were positively associated with SRS. However, only eosinophils (RES[95%CI] = 1.15[1.02,1.30]) and lymphocytes (RES[95%CI] = 1.25[1.06,1.47]) showed an independent association. Furthermore, eosinophils (change in the expected outcome for 1-SD increase: CEO[95%CI] = -1.18[-2.09, -0.27]%), basophils (CEO[95%CI] = -1.24[-2.16, -0.33]%) and lymphocytes (CEO[95%CI] = -1.07[-1.99, -0.14]%) were individually, but not independently, associated with FEV 1 /FVC. Finally, neutrophils were negatively associated with FEV 1 % predicted (CEO[95%CI] = -2.22[-4.00, -0.44]%)., Conclusions: We identified a pattern of association between a set of biomarkers and asthma endotypes in adult patients from the general population, which could improve understanding of the heterogeneity and severity of the disease and could be useful in defining targeted therapeutic approaches.

Background: Change in the prevalence of asthma-like symptoms in populations of ageing adults is likely to be influenced by smoking, asthma treatment and atopy., Methods: The European Community Respiratory Health Survey collected information on prevalent asthma-like symptoms from representative samples of adults aged 20-44 years (29 centres in 13 European countries and Australia) at baseline and 10 and 20 years later (n=7844). Net changes in symptom prevalence were determined using generalised estimating equations (accounting for non-response through inverse probability weighting), followed by meta-analysis of centre level estimates., Findings: Over 20 years the prevalence of 'wheeze' and 'wheeze in the absence of a cold' decreased (-2.4%, 95% CI -3.5 to -1.3%; -1.5%, 95% CI -2.4 to -0.6%, respectively) but the prevalence of asthma attacks, use of asthma medication and hay fever/nasal allergies increased (0.6%, 95% CI 0.1 to 1.11; 3.6%, 95% CI 3.0 to 4.2; 2.7%, 95% CI 1.7 to 3.7). Changes were similar in the first 10 years compared with the second 10 years, except for hay fever/nasal allergies (increase seen in the first 10 years only). Decreases in these wheeze-related symptoms were largely seen in the group who gave up smoking, and were seen in those who reported hay fever/nasal allergies at baseline., Interpretation: European adults born between 1946 and 1970 have, over the last 20 years, experienced less wheeze, although they were more likely to report asthma attacks, use of asthma medication and hay fever. Decrease in wheeze is largely attributable to smoking cessation, rather than improved treatment of asthma. It may also be influenced by reductions in atopy with ageing., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Asthma considerably impairs patients' quality of life and increases healthcare costs. Severity, morbidity, and degree of disease control are the major drivers of its clinical and economic impact. National scientific societies are required to monitor the application of international guidelines and to adopt strategies to improve disease control and better allocate resources., Aim: to provide a detailed picture of the characteristics of asthma patients and modalities of asthma management by specialists in Italy and to develop recommendations for the daily management of asthma in a specialist setting., Method: A quantitative research program was implemented. Data were collected using an ad hoc questionnaire developed by a group of specialists selected by the Italian Pneumology Society/Italian Respiratory Society., Results: The records of 557 patients were analyzed. In the next few years, specialists are expected to focus their activity patients with more severe disease and will be responsible for selection of patients for personalized biological therapy; however, only 20% of patients attending Italian specialist surgery can be considered severe. In 84.4% of cases, the visit was a follow-up visit requested in 82.2% of cases by the specialist him/herself. The Asthma Control Test is used only in 65% of patients. When available, a significant association has been observed between the test score and asthma control as judged by the physician, although concordance was only moderate (κ = 0.68). Asthma was considered uncontrolled by the specialist managing the case in 29.1% of patients; nevertheless, treatment was not stepped up in uncontrolled or partly controlled patients (modified in only 37.2% of patients)., Conclusions: The results of this survey support re-evaluation of asthma management by Italian specialists. More resources should be made available for the initial visit and for more severely ill patients. In addition, more extensive use should be made of validated tools, and available drugs should be used more appropriately., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Background: In epidemiological studies, continuous measures of asthma severity should be used to catch the heterogeneity of phenotypes. This study aimed at developing and validating continuous measures of asthma severity in adult patients with ever asthma from the general population, to be used in epidemiological studies., Methods: Respiratory symptoms, anti-asthmatic treatment and lung function were measured on 520 patients with ever asthma aged 20-64 years from the general Italian population (GEIRD study; 2007/2010). The variables that represent the same dimension of asthma severity were identified through an exploratory factor analysis and were summarized through a multiple factor analysis., Results: Only respiratory symptoms and anti-asthmatic treatment were summarized in a continuous score (STS). STS ranges from 0 (no symptoms/treatment) to 10 (maximum symptom frequency and treatment intensity). STS was positively correlated with the Global Initiative for Asthma classification of asthma severity computed on the 137 cases with a doctor's diagnosis (Spearman's coefficient = 0.61, p-value<0.0001) (concurrent validity). Furthermore, using a cohort of 1,097 European asthmatics (ECRHS II study; 1999/2002), increasing STS levels at baseline (1991/1993) were positively associated with long-term outcomes (hospitalization and lost workdays for breathing problems, asthma attack frequency and use of asthma controllers) (predictive validity). Finally, the STS scores computed from the GEIRD and ECRHS II data were comparable (Lin's coefficient = 0.95, p-value<0.0001) (replication analysis)., Conclusions: STS is a valid and replicable measure of asthma severity in adults, which could be used in association studies.

Asthma is the most commonly occurring respiratory complication during pregnancy, and is associated with a wide range of adverse maternal and perinatal outcomes. However, there is strong evidence that an adequate control of asthma can improve the health of both mothers and their babies. Despite the well-known risks of poorly-controlled asthma during pregnancy, a large proportion of women have sub-optimal asthma control, due to concerns surrounding risks related to pharmacological agents and uncertainties regarding the effectiveness and safety of different management strategies. A recent retrospective study showed that step-up therapy with low-dose inhaled corticosteroids / long-acting β2-agonist inhalers (ICS/LABA) or high-dose ICS presents the same risk profile in terms of major congenital malformations. These results are consistent with asthma management guidelines and provide scientific evidence to help physicians and mothers make evidence-based treatment decisions during pregnancy, particularly when stepping up to higher doses of ICS or addition of a LABA are required. These reassuring results should encourage women to continue their asthma medications when required to control their asthma during pregnancy and increase the likelihood of healthy pregnancies and newborns. This commentary focuses on some critical issues of this recent work and to the need of future study to evaluate the safety during pregnancy of novel molecules recently introduced for asthma treatment.

Allergen-specific immunotherapy (AIT) is considered the only treatment capable of modifying the natural history of allergic respiratory disorders. The possible adverse events related to AIT have, until now, limited its use to mild and controlled asthma. The pre-administration or concomitant treatment of AIT and omalizumab (an anti-IgE humanized antibody), recommended for the treatment of severe allergic asthma, could be useful in reducing the adverse events due to AIT and to allow its use in patients with more severe or uncontrolled asthma. AIT/omalizumab combination has been explored in a few trials on asthma patients and also in other allergic disorders, such as rhinitis, hymenoptera systemic reaction and food allergy with significant results. We are at the beginning a new era where phenotype/endotype-based treatment will be associated with drug mass therapy and/or nonpharmacological phenotype/endotype-driven treatment to optimize disease control and/or to make the use of other treatments safer.

Background: Chronic respiratory diseases are a significant cause of morbidity and mortality worldwide. We sought to evaluate the impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities in adults., Methods: In the Gene Environment Interactions in Respiratory Diseases study (2007/2010), a screening questionnaire was mailed to 9,739 subjects aged 20-44 (response rate: 53.0%) and to 3,480 subjects aged 45-64 (response rate: 62.3%), who were randomly selected from the general population in Italy. The questionnaire was used to: identify the responders who had asthma, chronic bronchitis, allergic rhinitis or asthma-like symptoms/dyspnoea/other nasal problems; evaluate the total burden [use of hospital services (at least one ED visit and/or one hospital admission) and number of days with reduced activities (lost working days and days with limited, not work related activities) due to any health problems (apart from accidents and injuries) in the past three months]; evaluate the contribution of breathing problems to the total burden (hospitalizations and number of days with reduced activities specifically due to breathing problems)., Results: At any age, the all-cause hospitalization risk was about 6% among the subjects without any respiratory conditions, it increased to about 9-12% among the individuals with allergic rhinitis or with asthma-like symptoms/dyspnoea/other nasal problems, and it peaked at about 15-18% among the asthmatics with chronic bronchitis aged 20-44 and 45-64, respectively. The expected number of days with reduced activities due to any health problems increased from 1.5 among the subjects with no respiratory conditions in both the age classes, to 6.3 and 4.6 among the asthmatics with chronic bronchitis aged 20-44 and 45-64, respectively. The contribution of breathing problems to the total burden was the highest among the asthmatics with chronic bronchitis (23-29% of the hospitalization risk and 39-50% of the days with reduced activities, according to age)., Conclusions: The impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities is substantial, and it is markedly different among adults from the general population in Italy. The contribution of breathing problems to the total burden also varies according to the respiratory condition.

Background: It has been suggested that there is some overlap between allergic rhinitis (AR), sinusitis and polyposis, but this has not been fully documented. The present study aimed to evaluate the prevalence of these co-existing diseases and their impact on bronchial asthma in the general population of Italy., Methods: Within the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study, a postal screening questionnaire including questions about self-reported symptoms of asthma, AR, AR with sinusitis without nasal polyps (AR + SsNP) and AR with sinusitis with nasal polyps (AR + SwNP) was administered. Random samples of subjects aged between 20 and 44 years (n = 5,162) answered the postal questionnaire in 4 Italian centres (Pavia, Sassari, Turin, Verona). In AR subjects, the association among AR only, AR + SsNP, AR + SwNP and bronchial asthma was estimated by the relative risk ratio (RRR) using multinomial regression models., Results: The prevalence of AR in the sample was 25.4% (95% CI 24.2-26.6). A self-reported diagnosis of AR + SsNP and AR + SwNP was reported by 5.7% (95% CI 5.0-6.3) and by 1.2% (95% CI 0.9-1.5) of the subjects, respectively. Current asthma was reported by 17.5% of the AR subjects. In the adjusted multivariate analysis, the risk of having current asthma (RRR = 2.31, 95% CI 1.29-4.15), of having at least 1 asthma attack per year (RRR = 2.30, 95% CI 1.19-4.46) and of having had an emergency department admission for respiratory diseases (RRR = 5.61, 95% CI 1.81-23.92) was higher for subjects with AR + SwNP than subjects with AR only., Conclusions: The diagnosis of AR in the epidemiological setting includes heterogeneous upper airway diseases that affect the clinical features of AR and its interactions with asthma., (© 2016 S. Karger AG, Basel.)

Background: Only few longitudinal studies on the course of asthma among adults have been carried out., Objective: The aim of the present prospective study, carried out between 2000 and 2009 in Italy, is to assess asthma remission and control in adults with asthma, as well as their determinants., Methods: All the subjects with current asthma (21-47 years) identified in 2000 in the Italian Study on Asthma in Young Adults in 6 Italian centres were followed up. Asthma remission was assessed at follow-up in 2008-2009 (n = 214), asthma control at baseline and follow-up. Asthma remission and control were related to potential determinants by a binomial logistic and a multinomial logistic model. Separate models for remission were used for men and women., Results: The estimate of the proportion of subjects who were in remission was 29.7% (95%CI: 14.4%;44.9%). Men who were not under control at baseline had a very low probability of being in remission at follow-up (OR = 0.06; 95%CI:0.01;0.33) when compared to women (OR = 0.40; 95%CI:0.17;0.94). The estimates of the proportion of subjects who were under control, partial control or who were not under control in our sample were 26.3% (95%CI: 21.2;31.3%), 51.6% (95%CI: 44.6;58.7%) and 22.1% (95%CI: 16.6;27.6%), respectively. Female gender, increasing age, the presence of chronic cough and phlegm and partial or absent asthma control at baseline increased the risk of uncontrolled asthma at follow-up., Conclusion: Asthma remission was achieved in nearly 1/3 of the subjects with active asthma in the Italian adult population, whereas the proportion of the subjects with controlled asthma among the remaining subjects was still low.

Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]., Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values., Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost., Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe., (Copyright © 2012 S. Karger AG, Basel.)

Background: The prevalence rates of smoking in subjects with asthma have frequently been reported as similar to those in the general population; however, available data are not up-to-date. There is only limited and somewhat conflicting information on the long-term effects of smoking on health outcomes among population-based cohorts of subjects with asthma. We aimed to investigate changes in smoking habits and their effects on forced expiratory volume in 1 s (FEV(1)) in subjects with asthma in comparison with the rest of the population, focusing on the healthy smoker effect., Methods: We studied 9,092 subjects without asthma and 1,045 with asthma at baseline who participated in both the European Community Respiratory Health Survey I (20-44 years old in 1991-1993) and II (1999-2002)., Results: At follow-up, smoking was significantly less frequent among subjects with asthma than in the rest of the population (26 vs. 31%; p < 0.001). Subjects with asthma who were already ex-smokers at the beginning of the follow-up in the 1990 s had the highest mean asthma score (number of reported asthma-like symptoms, range 0-5), probably as a result of the healthy smoker effect (2.80 vs. 2.44 in never smokers, 2.19 in quitters and 2.24 in smokers; p < 0.001). The influence of smoking on FEV(1) decline did not depend on asthma status. Smokers had the highest proportion of subjects with chronic cough/phlegm (p < 0.01)., Conclusion: One out of 4 subjects with asthma continues smoking and reports significantly more chronic cough and phlegm than never smokers and ex-smokers. This stresses the importance of smoking cessation in all patients with asthma, even in those with less severe asthma., (Copyright © 2012 S. Karger AG, Basel.)

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 © 2011 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Restrictive definitions of current asthma are used in epidemiological studies to achieve a highly specific classification of subjects. However, undiagnosed asthmatics should be taken into account to correctly evaluate the impact of the disease in the general population., Methods: In an Italian multi-centre cross-sectional survey carried out in 1998-2000, 18,647 responders (20-44 years old) to a screening questionnaire were classified as having physician-diagnosed current asthma or current respiratory symptoms. Similarities in the risk factor profile and in the socioeconomic burden were considered suggestive of undiagnosed current asthma., Results: In Italy, the prevalence of physician-diagnosed current asthma was 4.9% (95% CI 4.4-5.4), while that of 'asthma attacks and/or use of anti-asthmatic drugs in the past 12 months without a diagnosis of asthma' (ADWD) was 1.5% (95% CI 1.3-1.7). Allergic rhinitis was highly associated with diagnosed current asthma [relative risk ratio (RRR) 12.48; 95% CI 9.12-17.07; reference category: neither asthma during lifetime nor current respiratory symptoms] and with ADWD (RRR 8.42; 95% CI 6.33-11.19). Chronic cough/phlegm was homogeneously associated with all the respiratory conditions, and the strongest relationship was with ADWD (RRR 7.79; 95% CI 4.95-12.25). Subjects with ADWD and diagnosed current asthmatics were characterised by high and homogeneous percentages of individuals who reported productivity losses (19.0 and 15.1%) and hospitalisations (9.2 and 6.2%) because of respiratory problems in the past year., Conclusions: The impact of current asthma seems to be largely underestimated among Italian adults, since the individuals with ADWD may be undiagnosed current asthmatics., (Copyright © 2011 S. Karger AG, Basel.)

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.

Background: The identification of the factors associated with severe asthma may shed some light on its etiology and on the mechanisms of its development. We aimed to describe asthma severity using the Global Initiative for Asthma (GINA) classification and to investigate its determinants in a cross-sectional, population-based sample in Europe., Methods: In the European Community Respiratory Health Survey II (1999-2002), 1,241 adults with asthma were identified. Severity was assessed using the 2002 GINA classification (intermittent, mild persistent, moderate persistent, severe persistent) and it was related to potential determinants by a multinomial logistic model, using the intermittent group as the reference category for relative risk ratios., Results: About 30% of asthmatic subjects were affected by moderate-to-severe asthma. Sensitization to Cladosporium was associated with a more than 5-fold greater risk of having (mild, moderate or severe) persistent asthma than intermittent asthma. Persistent asthma was positively associated with sensitization to house dust mite, nonseasonal asthma, an older age at asthma onset, and chronic cough and phlegm. Sensitization to cat increased the risk of severe asthma only. Smoking was more strongly associated with asthma severity in men, while rhinitis was more strongly associated with asthma severity in women., Conclusions: One third of the asthmatic population have moderate-to-severe asthma. Sensitization to perennial indoor allergens, particularly Cladosporium, is strongly associated with asthma severity. The role of smoking and rhinitis in determining asthma severity may differ between the sexes, and it should be further investigated.

Background: Little is known about factors associated with lung function decline in asthma., Objective: To identify the determinants of FEV(1) 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. FEV(1) 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 (FEV(1)/forced vital capacity < 0.70) at baseline., Results: In the group of individuals without airflow obstruction (n = 544), a faster FEV(1) decline was observed for subjects with intermediate body mass index (BMI) than for lean and obese subjects. FEV(1) 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 FEV(1) decline, whereas weight gain was not associated with decline., Conclusions: The detrimental effect of weight gain on FEV(1) 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.

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.

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.

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 FEV(1) 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. FEV(1) 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 FEV(1) 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 FEV(1) 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.

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.

Background: The guidelines for asthma recommend that the use of anti-inflammatory therapy should be adapted to the severity of the disease. However, few data are available to assess the adequacy of the use of drugs and its influence on the control of asthma in 'real life'., Methods: The adequacy of the current use of anti-asthmatic medication according to the Global Initiative for Asthma (GINA) guidelines was assessed in a random sample of 400 asthmatics identified in the frame of the Italian Study on Asthma in Young Adults. Asthma severity was assessed using the GINA criteria; accordingly, a patient was classified as receiving inadequate treatment if his/her current use of drugs was lower than that suggested by the guidelines for the corresponding severity level. The absence of asthma attacks in the last 3 months was used as an indicator of the disease control., Results: Fifty-five percent of the patients had persistent asthma. Overall, 48% (95% CI 41.2-54.8) of persistent asthmatics were receiving inadequate treatment, and 66% (95% CI 59.5-72.4) had not used their medication daily over the past 3 months. Persistent asthmatics who were inadequately treated had a significantly greater frequency of asthma attacks (geometric mean ratio 3.7; 95% CI 2.1-6.6) than those using an adequate dose of medication. Mild and moderate persistent asthmatics using an adequate medication regimen reported a low number of asthma attacks (median 0). At the multivariate analysis, a good control of the disease was positively associated with an adequate dose of anti-inflammatory medication (OR = 2.2; 95% CI 1.1-4.5) and was negatively associated with a later onset of asthma (OR = 0.96; 95% CI 0.93-0.99) and severe asthma (OR = 0.37; 95% CI 0.17-0.81)., Conclusions: Despite the increase in the use of inhaled corticosteroids, half of the persistent asthmatics from the general population are using a medication regimen below their severity level. When the use of drugs follows the GINA guideline recommendations, a good control of asthma is also achievable in the daily management of the disease, particularly in the case of mild and moderate asthmatics.

Background: The prevalence of asthma and allergic rhinitis has increased worldwide during the 1970s and 1980s., Objective: This study was aimed at evaluating whether the increasing trend in prevalence persisted during the 1990s in the young adult Italian population., Methods: In 1998 to 2000 a screening questionnaire was sent by mail to a general population sample aged 20 to 44 years; nonresponders were contacted again first by mail and then by phone, achieving a final response rate of 78.1% (6876 of 8800). Prevalence estimates, adjusted to correct for nonresponse bias, were compared with those recorded in Italy in 1991 to 1993 during the European Community Respiratory Health Survey, when response rate had been slightly higher (87.6%). Temporal variations in symptom prevalence were analyzed by a logistic regression model, controlling for sex, age, site of residence (urban vs suburban areas), season of response, response rate, and type of contact (mail vs phone)., Results: The prevalence of asthma attacks did not vary significantly from 1991 to 1993 (3.6%) to 1998 to 2000 (3.2%) (P =.188). The prevalence of asthma-like symptoms (wheezing, chest tightness, shortness of breath) tended to decrease in the age classes of 32.5 to 45 years, while increasing in the youngest age class (20 to 26 years). A clear-cut increase from 15.4% to 18.3% was observed for the prevalence of allergic rhinitis (P <.001), whereas the proportion of people under antiasthmatic treatment increased in suburban areas but not in urban areas (interaction time-site of residence, P <.001)., Conclusion: Asthma prevalence has not increased during the last decade in Italy. The persistence of an increasing trend in allergic rhinitis prevalence deserves attention.

Abstract Background No study has been carried out on the time trend in the prevalence of chronic bronchitis (CB) in recent years, despite its clinical and epidemiological relevance. We evaluated the trend in CB prevalence during the past decade among young Italian adults. Methods A screening questionnaire was mailed to general population samples of 20–44 year-old subjects in two cross-sectional surveys: the Italian Study on Asthma in Young Adults (ISAYA) (1998/2000; n = 18,873, 9 centres) and the screening stage of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007/2010; n = 10,494, 7 centres). CB was defined as having cough and phlegm on most days for a minimum of 3 months a year and for at least 2 successive years. The prevalence rates and the risk ratios (RRs) for the association between CB and each potential predictor were adjusted for gender, age, season of response, type of contact, cumulative response rate, and centre. Results CB prevalence was 12.5% (95% CI: 12.1-12.9%) in 1998/2000 and 12.6% (95% CI: 11.7-13.7%) in 2007/2010; it increased among never smokers (from 7.6 to 9.1%, p = 0.003), current light smokers ( Conclusions Despite the significant reduction in current smoking, CB prevalence did not vary among young Italian adults. The temporal pattern of CB prevalence can only be partly explained by the increase of unemployment/premature retirement, asthma and allergic rhinitis, and suggests that other factors could have played a role.

Background: It is not clear whether mepolizumab is differently effective in allergic and nonallergic severe eosinophilic asthmatics (SEA) in real life. Objective: We tested mepolizumab effectiveness in allergic/nonallergic SEA in real life. A strict criterion to identify the 2 phenotypes was used. Method: We retrospectively considered 134 consecutive patients divided into allergic, with a positivity to at least 1 allergen to prick tests and/or IgE values ≥100 UI/mL (severe allergic eosinophilic asthma [SAEA]; n: 97–72.4%), and nonallergic, with no prick test results and normal IgE levels <100 UI/mL (severe nonallergic eosinophilic asthma [SNAEA]; n: 37–27.6%). They had taken mepolizumab for at least 6 months. Results: After 10.9 ± 3.7 months, improvements in FEV1%, FEF25–75%, exacerbation numbers, blood eosinophil (BE) counts, fractional exhaled nitric oxide (FENO) (ppb), percentages of patients that stopped/reduced short-acting β2-agonists (SABAs) or oral corticosteroid (OC), observed after treatment, were similar in both groups. Only Asthma Control Test (ACT) increases were higher in SNAEA (8 [5–9]) than in SAEA (5 [2.5–8.5]; p = 0.016). However, no differences were found after treatment in percentages of subjects with ACT ≥20, as well as with FEV1 >80%, FEF25–75 >65%, exacerbations ≤2, BE <300 cells/µL, and FENO <25 ppb between SAEA and SNAEA. Besides, no significant relationships were found, comparing SNAEA with SAEA, for FEV1% (β = −0.110; p = 0.266), FEF25–75% (β = −0.228; p = 0.06), BE counts (β = −0.012; p = 0.918), FENO (β = 0.234; p = 0.085), ACT (β = 0.046; p = 0.660), and exacerbations (β = −0.070; p = 0.437). No different associations between lung function and SNAEA occurrence when compared to SAEA condition (FEV1 >80%: OR = 1.04 [95% CI: 0.43–2.55], p = 0.923; FEF25–75 >65%: OR = 0.41 [95% CI: 0.08–2.03], p = 0.272) were detected. Neither all other parameters, such as ACT >20 (OR = 0.73 [95% CI: 0.32–1.63], p = 0.440), presence of exacerbations (OR = 1.35 [95% CI: 0.55–3.27], p = 0.512), SABA discontinuation (OR = 1.16 [95% CI: 0.40–3.39], p = 0.790), and OC cessation/reduction (OR = 3.44 [95% CI: 0.40–29.27], p = 0.258), were differently associated with 1 or the other phenotype. Conclusion: Mepolizumab can be considered as a valid therapeutic choice for either allergic or nonallergic SEA in real life. [ABSTRACT FROM AUTHOR]

Background: It has been suggested that there is some overlap between allergic rhinitis (AR), sinusitis and polyposis, but this has not been fully documented. The present study aimed to evaluate the prevalence of these co-existing diseases and their impact on bronchial asthma in the general population of Italy. Methods: Within the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study, a postal screening questionnaire including questions about self-reported symptoms of asthma, AR, AR with sinusitis without nasal polyps (AR + SsNP) and AR with sinusitis with nasal polyps (AR + SwNP) was administered. Random samples of subjects aged between 20 and 44 years (n = 5,162) answered the postal questionnaire in 4 Italian centres (Pavia, Sassari, Turin, Verona). In AR subjects, the association among AR only, AR + SsNP, AR + SwNP and bronchial asthma was estimated by the relative risk ratio (RRR) using multinomial regression models. Results: The prevalence of AR in the sample was 25.4% (95% CI 24.2-26.6). A self-reported diagnosis of AR + SsNP and AR + SwNP was reported by 5.7% (95% CI 5.0-6.3) and by 1.2% (95% CI 0.9-1.5) of the subjects, respectively. Current asthma was reported by 17.5% of the AR subjects. In the adjusted multivariate analysis, the risk of having current asthma (RRR = 2.31, 95% CI 1.29-4.15), of having at least 1 asthma attack per year (RRR = 2.30, 95% CI 1.19-4.46) and of having had an emergency department admission for respiratory diseases (RRR = 5.61, 95% CI 1.81-23.92) was higher for subjects with AR + SwNP than subjects with AR only. Conclusions: The diagnosis of AR in the epidemiological setting includes heterogeneous upper airway diseases that affect the clinical features of AR and its interactions with asthma. © 2016 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30-54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30-54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Severe asthma is an important topic in respiratory diseases, due to its high impact on morbidity and mortality as well as on health-care resources. The many challenges that still exist in the management of the most difficult-to-treat forms of the disease, and the acknowledgement of the existence of unexplored areas in the pathophysiological mechanisms and the therapeutic targets represent an opportunity to gather experts in the field with the immediate goals to summarize current understanding about the natural history of severe asthma and to identify gaps in knowledge and research opportunities, with the aim to contribute to improved medical care and health outcomes. This article is a consensus document from the "International Course on Severe Asthma" that took place in Palermo, Italy, on May 10–11, 2019. Emerging topics in severe asthma were addressed and discussed among experts, with special focus on patient's needs and research opportunities, with the aim to highlight the unanswered questions in the diagnostic process and therapeutic approach. [ABSTRACT FROM AUTHOR]