Determinants of lung function decline in adult asthma. Results from the European Community Respiratory Health Survey

Introduzione Il volume espiratorio forzato in 1 secondo (FEV1) \ue8 un predittore della mortalit\ue0 sia nella popolazione generale che in quella asmatica. I soggetti asmatici hanno un declino del FEV1 nel tempo pi\uf9 accentuato rispetto ai soggetti non asmatici; inoltre alcuni pazienti con asma grave sviluppano un'ostruzione progressiva delle vie aeree che non risulta completamente reversibile con la terapia attualmente disponibile. Inoltre, un FEV1 pi\uf9 basso del predetto \ue8 un indicatore di scarso controllo della malattia. Obiettivi Questa tesi ha l'obiettivo di incrementare le conoscenze sui fattori associati al declino del FEV1 negli asmatici, con particolare attenzione nel valutare il potenziale effetto protettivo dell\u2019uso di corticosteroidi inalati (ICS) e l\u2019associazione del declino del FEV1 con l'indice di massa corporea (BMI) e con la variazione del peso corporeo nel tempo. Metodi Sono stati analizzati i dati di una coorte internazionale di soggetti asmatici della popolazione generale, identificati nell\u2019indagine European Community Respiratory Health Survey (ECRHS, 1991-1993) e rivalutati nel 1999-2002. La spirometria \ue8 stata effettuata in entrambe le occasioni, e il declino del FEV1 \ue8 stato messo in relazione con alcuni possibili determinanti misurati all'inizio dello studio e durante il follow-up, utilizzando modelli di regressione lineare ad intercetta casuale. Risultati Negli asmatici con immunoglobuline E (IgE) elevate (>100 kU/L), l'utilizzo di ICS per almeno 4 anni durante il follow-up era associato con un minore declino del FEV1 (23 mL/anno; IC 95%: 8-38 rispetto ai non utilizzatori). Questa associazione non \ue8 stata riscontrata negli asmatici con IgE pi\uf9 basse. Negli asmatici che non avevano ostruzione delle vie aeree (FEV1/FVC<0.70) basale, gli obesi avevano il livello iniziale di FEV1 pi\uf9 basso; si \ue8 osservato un declino del FEV1 pi\uf9 rapido per i soggetti con BMI intermedio rispetto ai soggetti magri oppure obesi; il declino del FEV1 era associato con l'aumento di peso indipendentemente dal BMI iniziale, e questa associazione \ue8 risultata pi\uf9 forte negli uomini (20, IC 95%: 10; 30, mL/anno per kg di aumento di peso) che nelle donne (7, IC 95%: 2; 11, mL/anno); i valori di declino trovati negli asmatici sono circa il 60% superiori a quelli riscontrati negli uomini e nelle donne della popolazione generale che hanno preso parte a ECRHS. Negli asmatici con ostruzione iniziale delle vie aeree, l\u2019assenza di sensibilizzazione agli allergeni e un basso BMI iniziale erano associati con un pi\uf9 rapido declino del FEV1, mentre l\u2019aumento di peso non \ue8 risultato associato con il declino. Conclusioni e implicazioni cliniche I nostri risultati confermano l'associazione favorevole tra utilizzo prolungato di ICS e il declino della funzionalit\ue0 respiratoria negli asmatici. Tuttavia, suggeriscono che gli asmatici con alti livelli di IgE potrebbero beneficiare massimamente del trattamento prolungato con gli ICS. Di conseguenza, potrebbe essere opportuno calibrare la dose di corticosteroidi in relazione al livello di IgE totali del paziente, sebbene siano necessari altri studi per chiarire questo aspetto. L'effetto dannoso dell\u2019aumento di peso sul declino del FEV1 \ue8 particolarmente importante negli asmatici che non hanno ancora un'ostruzione stabile delle vie aeree. Questo effetto potrebbe essere maggiore negli asmatici che nei soggetti della popolazione generale. Di conseguenza, si raccomandano fortemente il controllo del peso negli asmatici e la perdita di peso negli asmatici obesi o sovrappeso. Tra gli asmatici che avevano ostruzione delle vie aeree iniziale, i soggetti magri non sensibilizzati agli allergeni meritano particolare attenzione, perch\ue9 sono quelli che hanno dimostrato il maggiore declino del FEV1. L'aumento di peso non \ue8 risultato associato al declino, e ci\uf2 suggerisce che i meccanismi tipici dell\u2019asma lieve potrebbero essere meno importanti nell'asma grave, mentre un\u2019infiammazione seria e di lungo termine potrebbe svolgere un ruolo cruciale.Introduction Forced expiratory volume in 1 second (FEV1) is a predictor of mortality in the general, as well as in the asthmatic population. Subjects with asthma have a steeper decline in FEV1 over time than subjects without, and some patients with severe asthma develop progressive airflow obstruction that is not fully reversible with currently available therapy. Moreover, a FEV1 lower than predicted is a marker of poor asthma control. Aims This thesis was aimed at shedding some light on the factors associated with the decline in FEV1 in subjects with asthma, with particular attention paid to investigating the potential preventative effect of the use of inhaled corticosteroids (ICSs), as well as to the association of FEV1 decline with body mass index (BMI) and change in body weight over time. Methods We analysed data from an international, population-based cohort of subjects with asthma, identified in the European Community Respiratory Health Survey (ECRHS, 1991-1993) and followed up from 1999 to 2002. Spirometry was performed on both occasions, and FEV1 decline was related to potential determinants evaluated at baseline and during the follow-up by random intercept linear regression models. Results In asthmatic subjects with high (>100 kU/L) immunoglobulin E (IgE), the use of ICSs for 4 years or more during the follow-up was associated with a lower FEV1 decline (23 mL/y; 95% CI: 8-38 compared with non-users). This association was not seen in asthmatic subjects with lower IgE. In asthmatic subjects who did not have airflow obstruction (FEV1/FVC<0.70) at baseline, obese subjects had the lowest level of FEV1 at baseline; a faster FEV1 decline was observed for subjects with intermediate 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/year per kg gained) than in women (7, 95% CI: 2; 11, mL/year); these figures were about 60% greater than the decline found in men and women from the general population who took part in the ECRHS. In asthmatic subjects with airflow obstruction at baseline, the absence of allergen sensitization and a low BMI at baseline were associated with a faster FEV1 decline, while weight gain was not associated with decline. Conclusions and clinical implications Our findings confirm the beneficial association between long-term treatment with ICSs and lung function decline in asthma. However, they suggest that asthmatic subjects with high IgE could maximally benefit from prolonged treatment with ICSs. As a consequence, it could be worth calibrating the corticosteroid dose according to a patient\u2019s level of total IgE, although further studies are needed to clarify this. The detrimental effect of weight gain on FEV1 decline is particularly important in asthmatic subjects who still do not have an established airflow obstruction. This effect could be greater in subjects with asthma than in people from the general population. Accordingly, weight management in asthma and weight loss in overweight or obese asthmatic individuals are strongly recommended. Among asthmatic subjects with airflow obstruction at baseline, lean subjects without sensitization to allergens deserve particular attention, because they had the greatest decline in FEV1. Weight gain was not associated with decline, suggesting that mechanisms that are typical of milder asthma could be less important in severe asthma, while a serious long-lasting inflammation may have a crucial role

Febrile and gynaecological infections in pregnancy increase the risk of childhood respiratory disorders in the offspring

Emerging evidence suggests that foetal and early life environmental factors are critical for determining the susceptibility to allergic and respiratory diseases. In the present study, we investigated whether maternal febrile infections (FI) or gynaecological infections (GI) during pregnancy are associated with allergic respiratory diseases in the offspring, and whether specific pregnancy trimesters are involved.We enrolled 4,577 children, aged 3-14yr. Their parents filled in a standardized questionnaire about children’s respiratory health and the events occurred during pregnancy and at birth. We evaluated the incidence of wheezing, asthma and rhinitis, and the occurrence of five respiratory symptoms in the last 12 months.Children born to mothers who reported FI and GI had more respiratory symptoms in the last 12 months (IRR:1.40, 95%CI:1.12-1.74 and IRR:1.60, 95%CI:1.24-2.06, respectively). This association was stronger when FI occurred in the 1st trimester of pregnancy (IRR:2.12, 95%CI:1.37-3.28).The incidence of asthma was significantly higher in the children whose mothers reported FI or GI in the 1st trimester of pregnancy (HR:2.61, 95%CI:1.01-6.76 and HR:3.50, 95%CI:1.24-9.91, respectively). GI in the 3rd trimester were associated with higher risk of wheezing (HR:1.55, 95%CI:1.11-2.17) and rhinitis (HR:1.82; 95%CI:1.02-3.26).FI and GI might increase the risk of developing respiratory symptoms and diseases, especially when occurring in specific trimesters of pregnancy. These findings suggest that FI and GI might interfere with foetal programming of respiratory and immune system through different mechanisms

Febrile and gynecological infections during pregnancy are associated with a greater risk of childhood eczema

Background:Mounting evidence suggests that fetal exposures may exert long-termeffects on the function of the skin and of the immune system. This study aimed atassessing whether maternal complications during pregnancy are associated with anincreased risk of eczema during childhood.Methods:The associations between hypertension/preeclampsia, febrile infections, orgynecological infections during pregnancy and the occurrence of childhood eczema werestudied in a population (n=3907) of children, aged 3–14 yrs, living in Italy. Theirparents filled in a standardized questionnaire about the presence of children’s eczemaand the events that occurred during pregnancy, birth, and the first year of the child’s life.Results:7.7%, 3.8%, and 6.1% of the pregnancies were complicated by hypertension/preeclampsia, febrile infections, and gynecological infections, respectively. The preva-lence of eczema was significantly higher in children born to mothers who had experiencedfebrile (35.5% vs. 22.0%; p&lt;0.001) or gynecological infections (35.3% vs. 21.6%;p&lt;0.001) compared with those born to mothers who had not suffered from that specificpregnancy complication, while hypertension/preeclampsia was not significantly associ-ated with childhood eczema. After adjusting for potential confounders, the risk ofeczema was significantly higher in children born to mothers who reported febrileinfections during the 1st trimester (OR: 2.32; 95%CI: 1.11–4.82) and gynecologicalinfections during the 3rd trimester of pregnancy (OR: 2.73; 95%CI:1.73–4.31).Conclusions:Fetal exposure to febrile and gynecological infections might enhance therisk of eczema in the offspring, especially when occurring in specific trimesters ofpregnancy. These findings suggest that febrile and gynecological infections mightinterfere with fetal and perinatal programming of the immune function and skinthrough different mechanisms

Weekend mortality in an Italian hospital: immediate versus delayed bedside critical care treatment

Background: a number of studies highlighted increased mortality associated with hospital admissions during weekends and holidays, the so-call "weekend effect". In this retrospective study of mortality in an acute care public hospital in Italy between 2009 and 2015, we compared inpatient mortality before and after a major organizational change in 2012. The new model (Model 2) implied that the intensivist was available on call from outside the hospital during nighttime, weekends, and holidays. The previous model (Model 1) ensured the presence of the intensivist coordinating a Medical Emergency Team (MET) inside the hospital 24 h a day, 7 days a week. Methods: life status at discharge after 9298 and 8223 hospital admissions that occurred during two consecutive periods of 1185 days each (organizational Model 1 and 2), respectively, were classified into "discharged alive", "deceased during nighttime-weekends-holidays" and "deceased during daytime-weekdays". We estimated Relative Risk Ratios (RRR) for the associations between the organizational model and life status at discharge using multinomial logistic regression models adjusted for demographic and case-mix indicators, and timing of admission (nighttime-weekends-holidays vs. daytime-weekdays). Results: there were 802 and 840 deaths under Models 1 and 2, respectively. Total mortality was higher for hospital admissions under Model 2 compared to Model 1. Model 2 was associated with a significantly higher risk of death during nighttime-weekends-holidays (IRR: 1.38, 95% CI 1.20-1.59) compared to daytime-weekdays (RRR: 1.12, 95% CI 0.97-1.31) (p = 0.04). Respiratory diagnoses, in particular, acute and chronic respiratory failure (ICD 9 codes 510-519) were the leading causes of the mortality excess under Model 2. Conclusions: our data suggest that the immediate availability of an intensivist coordinating a MET 24 h, 7 days a week can result in a better prognosis of in-hospital emergencies compared to delayed consultation

Foetal exposure to maternal stressful events increases the risk of having asthma and atopic diseases in childhood

Background:The natural history of asthma and atopic diseases beginsin utero.Studies investigating the influence of foetal exposure to maternal stressful life eventsduring pregnancy (SLEP) on asthma and atopic diseases are lacking.Aim:To test whether the children of mothers who had experienced SLEP are at anincreased risk for asthma, atopic eczema and allergic rhinitis.Methods:The association between maternal SLEP (at least one among: divorce,mourning or loss of the job) and the occurrence of asthma and atopic diseases inchildhood was studied in a population (n = 3854) of children, aged 3–14 yrs, livingin Northern Italy. The parents filled in a standardized questionnaire about the chil-dren’s health and the events occurred to their mothers during pregnancy.Results:Three hundred and thirty-three (9%) of the mothers experienced SLEP.Their children had a statistically significantly higher lifetime prevalence of wheezing(31.6% vs. 23.1%), asthma (8.9% vs. 5.6%), allergic rhinitis (10.9% vs. 7.3%) andatopic eczema (29.7% vs. 21.1%) than those of mothers without SLEP. Afteradjusting for potential confounders, the foetal exposure to SLEP was positivelyassociated with wheezing (OR: 1.41, 95% CI: 1.03–1.94), asthma (OR: 1.71, 95%CI: 1.02–2.89), allergic rhinitis (OR: 1.75, 95% CI: 1.08–2.84) and atopic eczema(OR: 1.53, 95% CI: 1.11–2.10).Conclusion:The children of mothers who had experienced SLEP were at a moder-ately increased risk of having wheezing, asthma, eczema and allergic rhinitis duringtheir childhood. Maternal stress during pregnancy might enhance the expression ofasthma and atopic phenotypes in children.Pediatric Allergy and Immunology724Pediatric Allergy and Immunology23(2012) 724–729ª2012 John Wiley &amp; Sons A/S. Published by Blackwell Publishing Lt

The Coexistence of asthma and Chronic Ostructive Pulmonary Disease (COPD): prevalence and risk factors in young, middle-aged and elderly people from the general population

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 &lt;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&lt;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.</br

Mortality Related to Chronic Obstructive Pulmonary Disease during the COVID-19 Pandemic: An Analysis of Multiple Causes of Death through Different Epidemic Waves in Veneto, Italy

Mortality related to chronic obstructive pulmonary disease (COPD) during the COVID-19 pandemic is possibly underestimated by sparse available data. The study aimed to assess the impact of the pandemic on COPD-related mortality by means of time series analyses of causes of death data. We analyzed the death certificates of residents in Veneto (Italy) aged ≥40 years from 2008 to 2020. The age-standardized rates were computed for COPD as the underlying cause of death (UCOD) and as any mention in death certificates (multiple cause of death-MCOD). The annual percent change (APC) in the rates was estimated for the pre-pandemic period. Excess COPD-related mortality in 2020 was estimated by means of Seasonal Autoregressive Integrated Moving Average models. Overall, COPD was mentioned in 7.2% (43,780) of all deaths. From 2008 to 2019, the APC for COPD-related mortality was -4.9% (95% CI -5.5%, -4.2%) in men and -3.1% in women (95% CI -3.8%, -2.5%). In 2020 compared to the 2018-2019 average, the number of deaths from COPD (UCOD) declined by 8%, while COPD-related deaths (MCOD) increased by 14% (95% CI 10-18%), with peaks corresponding to the COVID-19 epidemic waves. Time series analyses confirmed that in 2020, COPD-related mortality increased by 16%. Patients with COPD experienced significant excess mortality during the first year of the pandemic. The decline in COPD mortality as the UCOD is explained by COVID-19 acting as a competing cause, highlighting how an MCOD approach is needed

Association between daily levels of air pollution and school absences in the proximity of a cement plant in Italy

Background: Emission of dust represents the main hazard associated with cement production and may cause adverse respiratory health effects to the population living nearby. Aim: To evaluate the association between daily levels of PM10 and a morbidity indicator (school absenteeism) in children aged 7-14 years attending a school within 2km from a cement plant in Fumane (Northern Italy). Methods: Data on absences of students (average: 461 students/year) and daily concentrations of PM10 from a fixed monitoring station placed in the schoolyard were collected for 3 school years (541 school days from November 2007 to June 2010). The association between pollution in the same day (Lag 0) and in the previous 4 days (Lag 1 to 4) and school absenteeism was studied using generalized additive Poisson regression models, adjusting for short-term trend, day of the week, flu epidemics and daily temperature. Results: During the considered period, the daily average concentration of PM10 was 34.8 µg/m³. An increase of 10 µg/m³ of PM10 was associated with a significant increase of 2.2% in school absences (RR:1.022; 95%CI: 1.007-1.037) two days after (lag2). The association between average level of pollutants from Lag 0 to Lag 4 and school absences confirmed the presence of a statically significant association with PM10 levels (RR:1.016; 95%CI:1.003-1.029 for each + µg/m³ of PM10). Conclusions: Daily PM10 levels are associated with school absences, a proxy indicator of short-term morbidity, in children who attend schools in proximity to a cement plant. Primary prevention interventions aimed at reducing air pollution in the area are recommended

COVID-19 MORTALITY IN LOMBARDY: THE VULNERABILITY OF THE OLDEST OLD AND THE RESILIENCE OF MALE CENTENARIANS

Italy was the first European nation to be affected by COVID-19. The biggest cluster of cases occurred in Lombardy, the most populous Italian region, and elderly men were the population hit in the hardest way. Besides its high infectivity, COVID-19 causes a severe cytokine storm and old people, especially those with comorbidities, appear to be the most vulnerable, presumably in connection to inflammaging. In centenarians inflammaging is much lower than predicted by their chronological age and females, presenting survival advantage in almost all centenarian populations, outnumber males, a phenomenon particularly evident in Northern Italy. Within this scenario, we wondered if: a) the COVID-19 mortality in centenarians was lower than that in people aged between 50 and 80 and b) the mortality from COVID-19 in nonagenarians and centenarians highlighted gender differences. We checked COVID-19-related vulnerability/mortality at the peak of infection (March 2020), using data on total deaths (i.e. not only confirmed COVID-19 cases). Our conclusion is that excess mortality increases steadily up to very old ages and at the same time men older than 90 years become relatively more resilient than age-matched females