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Background: air pollution is a complex mixture; novel multipollutant approaches could help understanding the health effects of multiple concomitant exposures to air pollutants., Aim: to assess the relationship of long-term air pollution exposure with the prevalence of respiratory/allergic symptoms and diseases in an Italian multicenter study using single and multipollutant approaches., Methods: 14420 adults living in 6 Italian cities (Ancona, Pavia, Pisa, Sassari, Turin, Verona) were investigated in 2005-2011 within 11 different study cohorts. Questionnaire information about risk factors and health outcomes was collected. Machine learning derived mean annual concentrations of PM 10 , PM 2.5 , NO 2 and mean summer concentrations of O 3 (μg/m 3 ) at residential level (1-km resolution) were used for the period 2013-2015. The associations between the four pollutants and respiratory/allergic symptoms/diseases were assessed using two approaches: a) logistic regression models (single-pollutant models), b) principal component logistic regression models (multipollutant models). All the models were adjusted for age, sex, education level, smoking habits, season of interview, climatic index and included a random intercept for cohorts., Results: the three-year average (± standard deviation) pollutants concentrations at residential level were: 20.3 ± 6.8 μg/m 3 for PM 2.5 , 29.2 ± 7.0 μg/m 3 for PM 10 , 28.0 ± 11.2 μg/m 3 for NO 2 , and 70.9 ± 4.3 μg/m 3 for summer O 3. Through the multipollutant models the following associations emerged: PM 10 and PM 2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO 2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O 3 was associated with 37% increased odds of asthma attacks. Overall, the Odds Ratios estimated through the multipollutant models were attenuated when compared to those of the single-pollutant models., Conclusions: this study enabled to obtain new information about the health effects of air pollution on respiratory/allergic outcomes in adults, applying innovative methods for exposure assessment and multipollutant analyses., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Maria Beatrice Bilò had speaking and lecture fees supported by Astra Zeneca, GSK, Novartis, Sanofi. The other authors have no competing financial interests or personal relationships to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: It is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma., Objective: To evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010., Methods: The subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20-84 and born between 1925-1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models., Results: The average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1-4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease., Conclusions: After 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias.

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: The joint distribution of asthma and chronic obstructive pulmonary disease (COPD) has not been well described. This study aims at determining the prevalence of self-reported physician diagnoses of asthma, COPD and of the asthma-COPD overlap syndrome and to assess whether these conditions share a common set of risk factors., Methods: A screening questionnaire on respiratory symptoms, diagnoses and risk factors was administered by mail or phone to random samples of the general Italian population aged 20-44 (n = 5163) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the multicentre Gene Environment Interactions in Respiratory Diseases (GEIRD) study., Results: A physician diagnosis of asthma or COPD (emphysema/chronic bronchitis/COPD) was reported by 13% and 21% of subjects aged <65 and 65-84 years respectively. Aging was associated with a marked decrease in the prevalence of diagnosed asthma (from 8.2% to 1.6%) and with a marked increase in the prevalence of diagnosed COPD (from 3.3% to 13.3%). The prevalence of the overlap of asthma and COPD was 1.6% (1.3%-2.0%), 2.1% (1.5%-2.8%) and 4.5% (3.2%-5.9%) in the 20-44, 45-64 and 65-84 age groups. Subjects with both asthma and COPD diagnoses were more likely to have respiratory symptoms, physical impairment, and to report hospital admissions compared to asthma or COPD alone (p<0.01). Age, sex, education and smoking showed different and sometimes opposite associations with the three conditions., Conclusion: Asthma and COPD are common in the general population, and they coexist in a substantial proportion of subjects. The asthma-COPD overlap syndrome represents an important clinical phenotype that deserves more medical attention and further research.

Asthma is a multifactorial disease influenced by genetic and environmental factors. In the past decade, several loci and >100 genes have been found to be associated with the disease in at least one population. Among these loci, region 12q13-24 has been implicated in asthma etiology in multiple populations, suggesting that it harbors one or more asthma susceptibility genes. We performed linkage and association analyses by transmission/disequilibrium test and case-control analysis in the candidate region 12q13-24, using the Sardinian founder population, in which limited heterogeneity of pathogenetic alleles for monogenic and complex disorders as well as of environmental conditions should facilitate the study of multifactorial traits. We analyzed our cohort, using a cutoff age of 13 years at asthma onset, and detected significant linkage to a portion of 12q13-24. We identified IRAK-M as the gene contributing to the linkage and showed that it is associated with early-onset persistent asthma. We defined protective and predisposing SNP haplotypes and replicated associations in an outbred Italian population. Sequence analysis in patients found mutations, including inactivating lesions, in the IRAK-M coding region. Immunohistochemistry of lung biopsies showed that IRAK-M is highly expressed in epithelial cells. We report that IRAK-M is involved in the pathogenesis of early-onset persistent asthma. IRAK-M, a negative regulator of the Toll-like receptor/IL-1R pathways, is a master regulator of NF- kappa B and inflammation. Our data suggest a mechanistic link between hyperactivation of the innate immune system and chronic airway inflammation and indicate IRAK-M as a potential target for therapeutic intervention against asthma.