Health-related quality of life varies in different respiratory disorders: a multi-case control population based study.

BACKGROUND AND OBJECTIVE: Health-related quality of life (HRQL) in respiratory diseases has been generally investigated in clinical settings, focusing on a single disorder. In this study on a general population sample, we assessed the relationship between HRQL and several respiratory diseases studied simultaneously (COPD, current (CA) and past (PA) asthma, allergic (AR) and non-allergic (NAR) rhinitis and chronic bronchitis (CB). METHODS: Controls (n = 328) and cases of NAR (n = 95), AR (n = 163), CB (n = 48), CA (n = 224), PA (n = 126) and COPD (n = 28) were recruited in the centre of Verona in the frame of the Italian multi-case control GEIRD (Gene Environment Interactions in Respiratory Diseases) study; HRQL was measured through the SF-36 questionnaire. The relationships between HRQL (in terms of Physical (PCS) and Mental Component Scores (MCS)), respiratory diseases, and covariates were evaluated. RESULTS: With respect to controls, the adjusted PCS median score was worse in subjects suffering from current asthma (- 1.7; 95%CI:-2.8;-0.6), CB (- 3.8; 95%CI:-5.7;-1.9), and COPD (- 5.6; 95%CI:-8.1;-3.1). MCS was worse in current asthmatics (- 2.2; 95%CI:-4.1;-0.3), CB (- 5.5; 95%CI:-8.7;-2.2), and COPD cases (- 4.6; 95%CI:-8.8;-0.5) as well. CONCLUSIONS: To our knowledge, this is the first study in the general population that analyzed HRQL performing a simultaneous comparison of HRLQ in several respiratory disorders. We found that subjects suffering from COPD, CA, and CB had the poorest HRQL. Clinicians should carefully consider the possible impact of respiratory disorders as CB and not only that of CA and COPD.

Correction: Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on Incidence and Remission of Self-Reported Asthma from 1940 to 2010.

[This corrects the article DOI: 10.1371/journal.pone.0138570.].

Biomarkers related to respiratory symptoms and lung function in adults with asthma.

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 FEV1% predicted and FEV1/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 FEV1/FVC. Finally, neutrophils were negatively associated with FEV1% 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.

Prevalence of asthma-like symptoms with ageing.

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.

Smoking and New-Onset Asthma in a Prospective Study on Italian Adults.

BACKGROUND: The existence of a cause-effect relation between active smoking and new-onset asthma in adults, although supported by several studies, has not been proven yet. AIMS: We aimed to prospectively study asthma incidence as a function of smoking habits in the Italian adult population. METHODS: A population-based cohort of 5,241 non-asthmatics was enrolled in Verona and Sassari in 1998-2000. The cohort was contacted again in 2007-2009 within the Gene-Environment Interactions in Respiratory Diseases study, and 3,187 subjects (60.8%) answered a screening questionnaire on smoking habits and respiratory disorders. The relation between smoking habits and self-reported new-onset asthma, defined as asthma attacks/use of medicines for asthma, was investigated by a multivariable logistic model. RESULTS: During follow-up, 145 new cases of asthma were observed, yielding a cumulative incidence of 4.6% (95% CI 3.9-5.4); cumulative incidence of asthma did not significantly differ among never-smokers (76/1,666 = 4.6%), ex-smokers (30/554 = 5.4%) and current smokers (39/883 = 4.4%) (p = 0.641). In a multivariable analysis, the most important risk factor for asthma onset was allergic rhinitis (OR = 4.00, 95% CI 3.68-4.35). Compared to never-smokers, the risk of asthma onset was slightly increased in ex-smokers (OR = 1.28, 1.09-1.49) but not in current smokers (OR 1.01, 0.66-1.53). Current smoking became a significant predictor only when both new-onset wheezing and new-onset asthma were considered as the outcome (OR = 2.03, 1.35-3.05). CONCLUSIONS: In this prospective study, current smoking was not a risk factor for new-onset asthma, unless new-onset wheezing was also considered. The increase in asthma incidence among ex-smokers was likely due to reverse causation.

Persistence with inhaled corticosteroids reduces the risk of exacerbation among adults with asthma: A real-world investigation.

BACKGROUND AND OBJECTIVE: Real-world evidence suggests that persistence with inhaled corticosteroids (ICS), the mainstay of asthma drug therapy, is generally poor. The effect of persistence with ICS on the risk of asthma exacerbation was addressed in a population-based study. METHODS: The cohort of 2335 beneficiaries of the National Health Service provided by the Italian Region of Lombardy, aged 18-40 years and newly treated with ICS during 2005-2008, was followed from their first ICS dispensation until 2010. Discontinuation of treatment with ICS and starting oral corticosteroid therapy during follow-up were respectively regarded as proxies of poor persistence with asthma medication and asthma exacerbation (outcomes). A proportional hazards model was fitted to identify predictors of ICS discontinuation. Case-crossover and case-case-time-control designs and conditional logistic regressions were used to estimate the association between persistence with ICS and asthma exacerbation. RESULTS: Cumulative incidences of discontinuation were 36%, 57% and 78% at 6 months, 1 year and 5 years, respectively. Predictors of poor persistence were female gender, use of antibiotics during follow-up, absence of use of short-acting beta-agonists prior to and after starting treatment with ICS and starting and maintaining ICS monotherapy during follow-up. The odds ratios of asthma exacerbation (and 95% confidence intervals) associated with ICS exposure during the current period, contrasted with exposure during the reference period, were 0.4 (0.2, 0.9) and 0.3 (0.1, 1.0) from case-crossover and case-case-time-control estimates, respectively. CONCLUSION: Persistence with ICS treatment in adults with asthma reduces the risk of exacerbation in the real-life setting.

An Interleukin 13 Polymorphism Is Associated with Symptom Severity in Adult Subjects with Ever Asthma.

Different genes are associated with categorical classifications of asthma severity. However, continuous outcomes should be used to catch the heterogeneity of asthma phenotypes and to increase the power in association studies. Accordingly, the aim of this study was to evaluate the association between single nucleotide polymorphisms (SNPs) in candidate gene regions and continuous measures of asthma severity, in adult patients from the general population. In the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (www.geird.org), 326 subjects (aged 20-64) with ever asthma were identified from the general population in Verona (Italy) between 2007 and 2010. A panel of 236 SNPs tagging 51 candidate gene regions (including one or more genes) was analysed. A symptom and treatment score (STS) and pre-bronchodilator FEV1% predicted were used as continuous measures of asthma severity. The association of each SNP with STS and FEV1% predicted was tested by fitting quasi-gamma and linear regression models, respectively, with gender, body mass index and smoking habits as potential confounders. The Simes multiple-test procedure was used for controlling the false discovery rate (FDR). SNP rs848 in the IL13 gene region (IL5/RAD50/IL13/IL4) was associated with STS (TG/GG vs TT genotype: uncorrected p-value = 0.00006, FDR-corrected p-value = 0.04), whereas rs20541 in the same gene region, in linkage disequilibrium with rs848 (r(2) = 0.94) in our sample, did not reach the statistical significance after adjusting for multiple testing (TC/CC vs TT: uncorrected p-value = 0.0003, FDR-corrected p-value = 0.09). Polymorphisms in other gene regions showed a non-significant moderate association with STS (IL12B, TNS1) or lung function (SERPINE2, GATA3, IL5, NPNT, FAM13A) only. After adjusting for multiple testing and potential confounders, SNP rs848 in the IL13 gene region is significantly associated with a continuous measure of symptom severity in adult subjects with ever asthma.

Incidence, Predictors, and Clinical Implications of Discontinuing Therapy with Inhaled Long-Acting Bronchodilators among Patients with Chronic Obstructive Pulmonary Disease.

Incidence, predictors and effect of discontinuation of long-acting bronchodilators on the risk of death or hospital admission among adults with Chronic Obstructive Pulmonary Disease (COPD) were assessed in a large population-based prospective study carried out by linking Italian healthcare utilization databases. Specifically, the cohort of 17,490 beneficiaries of the National Health Service in the Italian Region of Lombardy, aged 40 years or older, who started long-acting bronchodilators therapy during 2005-2008 was followed from first dispensation until 2012. During this period, patients who experienced discontinuation of long-acting bronchodilators were identified. Hospitalizations for COPD and deaths for any cause (composite clinical outcome) were also identified during follow-up. A Cox proportional hazards model was fitted to identify predictors of discontinuation. The case-crossover design was used to assess the implications of treatment discontinuation on the clinical outcome risk. Cumulative incidences of discontinuation were, respectively, 67%, 80%, and 92% at 6 months, 1 year, and 5 years since initial treatment. Significant predictors of discontinuation were female gender, younger age, starting treatment with fixed-dose combination of inhaled bronchodilators and corticosteroids, using antibiotics, inhaled long-acting bronchodilators and corticosteroids and not using short-acting bronchodilators, other respiratory drugs and systemic corticosteroids during follow-up. Odds ratios (95% confidence intervals) for the clinical outcome associated with not discontinuing long-acting bronchodilators was 0.64 (0.50 to 0.82). In conclusion, in the real-life setting, discontinuation of inhaled long-acting bronchodilators in adults with COPD is high even after just 6 months, even though persistence to these drugs reduces the risk of severe outcomes.

Early Life Origins of Lung Ageing: Early Life Exposures and Lung Function Decline in Adulthood in Two European Cohorts Aged 28-73 Years.

OBJECTIVES: Early life environment is essential for lung growth and maximally attained lung function. Whether early life exposures impact on lung function decline in adulthood, an indicator of lung ageing, has scarcely been studied. METHODS: Spirometry data from two time points (follow-up time 9-11 years) and information on early life exposures, health and life-style were available from 12862 persons aged 28-73 years participating in the European population-based cohorts SAPALDIA (n = 5705) and ECRHS (n = 7157). The associations of early life exposures with lung function (FEV1) decline were analysed using mixed-effects linear regression. RESULTS: Early life exposures were significantly associated with FEV1 decline, with estimates almost as large as personal smoking. FEV1 declined more rapidly among subjects born during the winter season (adjusted difference in FEV1/year of follow-up [95%CI] -2.04ml [-3.29;-0.80]), of older mothers, (-1.82 ml [-3.14;-0.49]) of smoking mothers (-1.82ml [-3.30;-0.34] or with younger siblings (-2.61ml [-3.85;-1.38]). Less rapid FEV1-decline was found in subjects who had attended daycare (3.98ml [2.78;5.18]), and indicated in subjects with pets in childhood (0.97ml [-0.16;2.09]). High maternal age and maternal smoking appeared to potentiate effects of personal smoking. The effects were independent of asthma at any age. CONCLUSION: Early life factors predicted lung function decline decades later, suggesting that some mechanisms related lung ageing may be established early in life. Early life programming of susceptibility to adult insults could be a possible pathway that should be explored further.

Changes in IgE sensitization and total IgE levels over 20 years of follow-up.

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

The gender, age and risk factor distribution differs in self-reported allergic and non-allergic rhinitis: a cross-sectional population-based study.

BACKGROUND: Few population-based studies have assessed the prevalence and the risk factors of non-allergic rhinitis (NAR) in comparison to allergic rhinitis (AR). Moreover, epidemiologic data on rhinitis in the elderly subjects and in southern Europe are scarce. OBJECTIVE: This study aimed at estimating the prevalence and at comparing the risk factor distribution of AR and NAR in a general population sample aged 20-84 years in Italy. METHODS: A questionnaire on respiratory symptoms and risk factors was administered to random samples of the Italian population aged 20-44 (n = 10,494) 45-64 (n = 2167) and 65-84 (n = 1030) in the frame of the Gene Environment Interactions in Respiratory Diseases (GEIRD) study. Current AR and NAR were defined according to the self-reported presence of nasal allergies or of nasal symptoms without a cold or the flu. RESULTS: NAR showed a significant descending pattern in females from 12.0 % (95 % CI 11.1, 13.1) in the 20-44 year age class, to 7.5 % (5.4, 10.3) in the 65-84 year age class (p = 0.0009), and a roughly stable pattern in males, from 10.2 % (9.3, 11.2) to 11.1 % (8.4, 13.9) (p = 0.5261). AR decreased from 26.6 % (25.7, 27.6) in 20-44 years age class to 15.6 % (13.3, 18.0) in the 65-84 years age class (p < 0.0001), without gender difference. Subjects living near industrial plants and ex- and current smokers had a higher risk of NAR. Current smokers had a lower risk and subjects living in a Mediterranean climate a higher risk of AR. CONCLUSION: AR and NAR are fairly distinct conditions, as they have a different age, gender and risk factor distribution.

Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on Incidence and Remission of Self-Reported Asthma from 1940 to 2010.

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.

Asthma, COPD and overlap syndrome: a longitudinal study in young European adults.

We compared risk factors and clinical characteristics, 9-year lung function change and hospitalisation risk across subjects with the asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), asthma or COPD alone, or none of these diseases.Participants in the European Community Respiratory Health Survey in 1991-1993 (aged 20-44 years) and 1999-2001 were included. Chronic airflow obstruction was defined as pre-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity

The impact of asthma, chronic bronchitis and allergic rhinitis on all-cause hospitalizations and limitations in daily activities: a population-based observational study.

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.

Ambient air pollution and adult asthma incidence in six European cohorts (ESCAPE).

BACKGROUND: Short-term exposure to air pollution has adverse effects among patients with asthma, but whether long-term exposure to air pollution is a cause of adult-onset asthma is unclear. OBJECTIVE: We aimed to investigate the association between air pollution and adult onset asthma. METHODS: Asthma incidence was prospectively assessed in six European cohorts. Exposures studied were annual average concentrations at home addresses for nitrogen oxides assessed for 23,704 participants (including 1,257 incident cases) and particulate matter (PM) assessed for 17,909 participants through ESCAPE land-use regression models and traffic exposure indicators. Meta-analyses of cohort-specific logistic regression on asthma incidence were performed. Models were adjusted for age, sex, overweight, education, and smoking and included city/area within each cohort as a random effect. RESULTS: In this longitudinal analysis, asthma incidence was positively, but not significantly, associated with all exposure metrics, except for PMcoarse. Positive associations of borderline significance were observed for nitrogen dioxide [adjusted odds ratio (OR) = 1.10; 95% CI: 0.99, 1.21 per 10 µg/m3; p = 0.10] and nitrogen oxides (adjusted OR = 1.04; 95% CI: 0.99, 1.08 per 20 µg/m3; p = 0.08). Nonsignificant positive associations were estimated for PM10 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 10 µg/m3), PM2.5 (adjusted OR = 1.04; 95% CI: 0.88, 1.23 per 5 µg/m3), PM2.5absorbance (adjusted OR = 1.06; 95% CI: 0.95, 1.19 per 10-5/m), traffic load (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 4 million vehicles × meters/day on major roads in a 100-m buffer), and traffic intensity (adjusted OR = 1.10; 95% CI: 0.93, 1.30 per 5,000 vehicles/day on the nearest road). A nonsignificant negative association was estimated for PMcoarse (adjusted OR = 0.98; 95% CI: 0.87, 1.14 per 5 µg/m3). CONCLUSIONS: Results suggest a deleterious effect of ambient air pollution on asthma incidence in adults. Further research with improved personal-level exposure assessment (vs. residential exposure assessment only) and phenotypic characterization is needed.

Measurement of a urinary marker (8-hydroxydeoxy-guanosine, 8-OHdG) of DNA oxidative stress in epidemiological surveys: a pilot study.

BACKGROUND: 8-Hydroxydeoxyguanosine (8-OHdG) is a commonly used marker of DNA oxidative stress in epidemiological studies. The aim of this study was to establish whether the urinary concentration of 8-OHdG varies during the first part of the day, when clinical tests are usually performed, and whether it can therefore be measured without bias in spot urine samples. MATERIAL AND METHODS: Spot urine samples were collected using a convenience sample. A linear mixed-effects model for repeated measurements was used to analyze 8-OHdG levels. RESULTS: A significant increasing trend in time in the 8-OHdG concentration was found among smokers, but not in the case of nonsmokers. CONCLUSIONS: In epidemiological studies on oxidative stress, all participants should collect their early morning urine specimens - before their first cigarette if they are smokers - to gather information on individual background oxidation levels.

The Heterogeneity Hidden in Allergic Rhinitis and Its Impact on Co-Existing Asthma in Adults: A Population-Based Survey.

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.

Socioeconomic inequalities in smoking habits are still increasing in Italy.

BACKGROUND: Socioeconomic inequalities in smoking habits have stabilized in many Western countries. This study aimed at evaluating whether socioeconomic disparities in smoking habits are still enlarging in Italy and at comparing the impact of education and occupation. METHODS: In the frame of the GEIRD study (Gene Environment Interactions in Respiratory Diseases) 10,494 subjects, randomly selected from the general population aged 20-44 years in seven Italian centres, answered a screening questionnaire between 2007 and 2010 (response percentage = 57.2%). In four centres a repeated cross-sectional survey was performed: smoking prevalence recorded in GEIRD was compared with prevalence recorded between 1998 and 2000 in the Italian Study of Asthma in Young Adults (ISAYA). RESULTS: Current smoking was twice as prevalent in people with a primary/secondary school certificate (40-43%) compared with people with an academic degree (20%), and among unemployed and workmen (39%) compared with managers and clerks (20-22%). In multivariable analysis smoking habits were more affected by education level than by occupation. From the first to the second survey the prevalence of ever smokers markedly decreased among housewives, managers, businessmen and free-lancers, while ever smoking became even more common among unemployed (time-occupation interaction: p = 0.047). At variance, the increasing trend in smoking cessation was not modified by occupation. CONCLUSION: Smoking prevalence has declined in Italy during the last decade among the higher socioeconomic classes, but not among the lower. This enlarging socioeconomic inequality mainly reflects a different trend in smoking initiation.

Longterm follow-up in European respiratory health studies - patterns and implications.

BACKGROUND: Selection bias is a systematic error in epidemiologic studies that may seriously distort true measures of associations between exposure and disease. Observational studies are highly susceptible to selection bias, and researchers should therefore always examine to what extent selection bias may be present in their material and what characterizes the bias in their material. In the present study we examined long-term participation and consequences of loss to follow-up in the studies Respiratory Health in Northern Europe (RHINE), Italian centers of European Community Respiratory Health Survey (I-ECRHS), and the Italian Study on Asthma in Young Adults (ISAYA). METHODS: Logistic regression identified predictors for follow-up participation. Baseline prevalence of 9 respiratory symptoms (asthma attack, asthma medication, combined variable with asthma attack and/or asthma medication, wheeze, rhinitis, wheeze with dyspnea, wheeze without cold, waking with chest tightness, waking with dyspnea) and 9 exposure-outcome associations (predictors sex, age and smoking; outcomes wheeze, asthma and rhinitis) were compared between all baseline participants and long-term participants. Bias was measured as ratios of relative frequencies and ratios of odds ratios (ROR). RESULTS: Follow-up response rates after 10 years were 75% in RHINE, 64% in I-ECRHS and 53% in ISAYA. After 20 years of follow-up, response was 53% in RHINE and 49% in I-ECRHS. Female sex predicted long-term participation (in RHINE OR (95% CI) 1.30(1.22, 1.38); in I-ECRHS 1.29 (1.11, 1.50); and in ISAYA 1.42 (1.25, 1.61)), as did increasing age. Baseline prevalence of respiratory symptoms were lower among long-term participants (relative deviations compared to total baseline population 0-15% (RHINE), 0-48% (I-ECRHS), 3-20% (ISAYA)), except rhinitis which had a slightly higher prevalence. Most exposure-outcome associations did not differ between long-term participants and all baseline participants, except lower OR for rhinitis among ISAYA long-term participating smokers (relative deviation 17% (smokers) and 44% (10-20 pack years)). CONCLUSIONS: We found comparable patterns of long-term participation and loss to follow-up in RHINE, I-ECRHS and ISAYA. Baseline prevalence estimates for long-term participants were slightly lower than for the total baseline population, while exposure-outcome associations were mainly unchanged by loss to follow-up.