Relationship of long-term air pollution exposure with asthma and rhinitis in Italy: an innovative multipollutant approach.

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 PM10, PM2.5, NO2 and mean summer concentrations of O3 (µg/m3) 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/m3 for PM2.5, 29.2 ± 7.0 µg/m3 for PM10, 28.0 ± 11.2 µg/m3 for NO2, and 70.9 ± 4.3 µg/m3 for summer O3. Through the multipollutant models the following associations emerged: PM10 and PM2.5 were related to 14-25% increased odds of rhinitis, 23-34% of asthma and 30-33% of night awakening; NO2 was related to 6-9% increased odds of rhinitis, 7-8% of asthma and 12% of night awakening; O3 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.

Symptom control and health-related quality of life in allergic rhinitis with and without comorbid asthma: A multicentre European study.

BACKGROUND: Allergic rhinitis (AR) is a major non-communicable disease that affects the health-related quality of life (HRQoL) of patients. However, data on HRQoL and symptom control in AR patients with comorbid asthma (AR + asthma) are lacking. METHODS: In this multicentre, cross-sectional study, patients with AR were screened and administered questionnaires of demographic characteristics and health conditions (symptoms/diagnosis of AR and asthma, disease severity level, and allergic conditions). HRQoL was assessed using a modified version of the RHINASTHMA questionnaire (30, 'not at all bothered' - 150 'very much bothered') and symptom control was evaluated by a modified version of the Control of Allergic Rhinitis/Asthma Test (CARAT) (0, 'no control' - 30, 'very high control'). RESULTS: Out of 643 patients with AR, 500 (78%) had asthma as a comorbidity, and 54% had moderate-severe intermittent AR, followed by moderate-severe persistent AR (34%). Compared to the patients with AR alone, patients with AR + asthma had significantly higher RHINASTHMA (e.g., median RHINASTHMA-total score 48.5 vs. 84, respectively) and a significantly lower CARAT score (median CARAT-total score 23 vs. 16.5, respectively). Upon stratifying asthma based on severity, AR patients with severe persistent asthma had worse HRQoL and control than those with mild persistent asthma. The association was significantly higher among non-obese participants compared to obese ones, with RHINASTHMA-upper symptoms score but not with CARAT. CONCLUSIONS: Our observation of poorer HRQoL and symptoms control in AR patients with comorbid asthma supports the importance of a comprehensive approach for the management of AR in case of a comorbid allergic condition.

Impact of asthma and comorbid allergic rhinitis on quality of life and control in patients of Italian general practitioners.

OBJECTIVE: Asthma is a disease with elevated prevalence within the general population. Although general practitioners (GPs) are among the first health-care professionals to whom patients refer for their symptoms, there are few evaluations of this disease based on data provided by the GPs. The aim of this observational study is to assess the impact of asthma and comorbid allergic rhinitis on individual/social burden, quality of life, and disease control in asthmatic patients of Italian GPs. METHODS: Throughout Italy, 107 GPs enrolled 995 patients diagnosed with asthma and using anti-asthmatic drug prescriptions, or with asthma-like symptoms during the previous 12 months. Data were collected through questionnaires filled out by GPs and patients. RESULTS: Of the 995 asthmatic patients, 60.6% had concomitant allergic rhinitis (R+A), 39.4% had asthma alone. The latter, compared to those with R+A, showed significantly lower prevalence of intermittent asthma (37.5% vs. 55.6%) and higher prevalence of mild, moderate, and severe persistent asthma (28.4% vs. 23.2%, 28.7% vs. 18.8%, and 5.4% vs 2.4%, respectively). Individual/social burden due to asthma was frequent and increased with disease severity: 87.5% of severe persistent asthma patients reported at least one medical consultation in the last 12 months, 37.5% emergency department visits, 26.7% hospitalization, and 62.5% limitations in daily activities. Control and quality of life were inversely associated with disease severity and were worse in patients with R+A than in those with asthma alone. CONCLUSIONS: This study showed the negative impact of high severity levels and comorbid allergic rhinitis on quality of life of asthmatic patients and on individual/social burden due to asthma in an Italian GPs setting.

The Italian severe/uncontrolled asthma registry (RItA): A 12-month clinical follow-up.

BACKGROUND: follow-up studies on registries of severe/uncontrolled asthma (SUA) patients are scanty. OBJECTIVE: to analyze baseline and follow-up characteristics of SUA patients and their longitudinal patterns. METHODS: 180 adult patients (age ≥15 yrs) were investigated at baseline and 12-month follow-up through the Italian SUA registry (RItA). Latent transition analysis (LTA) was performed to detect cross-sectional SUA phenotypes and longitudinal patterns. Risk factors for longitudinal patterns were assessed through logistic regression. RESULTS: a significant/borderline improvement of asthma control outcomes in the last 2-4 weeks emerged at follow-up with respect to baseline for: daily activities limitations (Δ -16%), frequent diurnal symptoms (Δ -25%), uncontrolled asthma symptoms according to ACT (Δ -26%). Last 12-month use of oral corticosteroids was less frequent at follow-up than at baseline (Δ -25%). Health status improvement was confirmed by lung function test results. Through LTA, two longitudinal patterns were detected considering last 12-month control outcomes: "persistence/worsening" (53.9%), "under control/improvement" (46.1%). A lower likelihood of having "persistence/worsening" SUA was exhibited by patients under anti-IgE (OR 0.38, 95% CI 0.17-0.84) and inhaled corticosteroids-bronchodilator association treatment (OR 0.13, 95% CI 0.01-1.26, borderline value), while a higher likelihood was shown by older age at first asthma diagnosis (OR 1.04, 95% CI 1.01-1.07). CONCLUSION: the implementation of a SUA registry, the availability of patient-level data and the application of an innovative longitudinal analysis allowed to observe a general improvement in asthma control, one year after baseline, and a lower risk of SUA "persistence/worsening" in patients under anti-IgE and regular ICS-bronchodilator association use.

Longitudinal Asthma Patterns in Italian Adult General Population Samples: Host and Environmental Risk Factors.

BACKGROUND: Asthma patterns are not well established in epidemiological studies. AIM: To assess asthma patterns and risk factors in an adult general population sample. METHODS: In total, 452 individuals reporting asthma symptoms/diagnosis in previous surveys participated in the AGAVE survey (2011-2014). Latent transition analysis (LTA) was performed to detect baseline and 12-month follow-up asthma phenotypes and longitudinal patterns. Risk factors associated with longitudinal patterns were assessed through multinomial logistic regression. RESULTS: LTA detected four longitudinal patterns: persistent asthma diagnosis with symptoms, 27.2%; persistent asthma diagnosis without symptoms, 4.6%; persistent asthma symptoms without diagnosis, 44.0%; and ex -asthma, 24.1%. The longitudinal patterns were differently associated with asthma comorbidities. Persistent asthma diagnosis with symptoms showed associations with passive smoke (OR 2.64, 95% CI 1.10-6.33) and traffic exposure (OR 1.86, 95% CI 1.02-3.38), while persistent asthma symptoms (without diagnosis) with passive smoke (OR 3.28, 95% CI 1.41-7.66) and active smoke (OR 6.24, 95% CI 2.68-14.51). CONCLUSIONS: LTA identified three cross-sectional phenotypes and their four longitudinal patterns in a real-life setting. The results highlight the necessity of a careful monitoring of exposure to active/passive smoke and vehicular traffic, possible determinants of occurrence of asthma symptoms (with or without diagnosis). Such information could help affected patients and physicians in prevention and management strategies.

18-yr cumulative incidence of respiratory/allergic symptoms/diseases and risk factors in the Pisa epidemiological study.

BACKGROUND: Few population-based studies on the effects of environmental exposure variation exist. AIM: Assessing respiratory symptom/disease incidence related to risk factor exposure changes. METHODS: A longitudinal general population sample from two surveys (PISA2:1991-1993; PISA3:2009-2011; no. = 970), aged ≥20 years at baseline, completed a questionnaire on respiratory symptoms/diseases, risk factor exposure and performed spirometry. 18-year follow-up cumulative incidence of respiratory symptoms/diseases and longitudinal changes (persistence, incidence, remittance) in risk factor exposure were computed. RESULTS: Cumulative incidence values were: 3.2% (corresponding to a 1.8‰/year incidence rate), asthma; 6.6% (3.8‰/year), asthma attacks; 4.5% (2.6‰/year), wheeze; 31.7% (21.0‰/year), allergic rhinitis-AR; 7.6% (4.4‰/year), chronic obstructive pulmonary disease-COPD; 16.1% (9.7‰/year), usual cough; 18.5% (11.3‰/year), usual phlegm; 30.7% (20.1‰/year), dyspnoea 1+; 13.9% (8.3‰/year), airway obstruction. The following associations emerged among respiratory symptom/disease cumulative incidence and risk factor exposure changes: a two-to-five fold higher risk for COPD, phlegm, cough, dyspnoea, asthma attacks, airway obstruction in persistent smokers; a two-to-three fold higher risk for COPD in remittent smokers; a two-fold higher risk for AR, phlegm and a four-fold higher risk for asthma in subjects with persistent occupational exposure; a two-fold higher risk for cough, phlegm, dyspnoea, AR in subjects with incident occupational exposure; a two-fold higher risk for AR, asthma attacks, COPD in subjects with incident traffic exposure. CONCLUSIONS: Our study showed noteworthy respiratory symptom/disease incidence values and indicated that life-style and environmental exposure changes can differently influence onset. This information could be useful for primary prevention strategies in order to reduce the chronic disease burden in the general population.

Prescriptive adherence to GINA guidelines and asthma control: An Italian cross sectional study in general practice.

BACKGROUND: Although general practitioners (GPs) are frequently the first healthcare professionals whom asthma patients refer to for their symptoms, few studies have explored the extent of adherence to guidelines for asthma management based on data provided directly by GPs. Aims of the present study were to assess drug prescriptions for asthma by GPs and to evaluate prescriptive adherence to GINA guidelines (GL) and its relationship with disease control in real life. METHODS: 995 asthmatic patients (45% males, mean age 43.3 ±â€¯17.7 yrs) were enrolled by 107 Italian GPs distributed throughout the country. Data on diagnosis, disease severity, prescribed anti-asthmatic drugs and control were collected through questionnaires filled out by GPs taking into consideration the 2009 GINA Guidelines. Data on drug use and chronic sinusitis, nasal polyposis, chronic bronchitis, emphysema were reported by patients through a self-administered questionnaire. RESULTS: The large majority of patients were classified by GPs as having intermittent (48.4%) or mild persistent asthma (25.3%); 61% had co-morbid allergic rhinitis (AR). The prevalent therapeutic regimen used by patients was a combination of inhaled corticosteroids (ICS) plus long-acting ß2-agonists (LABA) (54.1%), even in the intermittent/mild persistent group. ICS as mono-therapy or in combination with other drugs but LABA, was the second most frequently adopted treatment (14.4%). In general, the GPs adherence to GL treatment indications was 28.8%, with a significant association with a good asthma control (OR 1.85, 95% CI 1.18-2.92). On the other hand, comorbidity (OR 0.52, 95% CI 0.32-0.84), moderate (0.44, 0.28-0.69) and severe (0.06, 0.02-0.20) persistent asthma showed significant negative effects on asthma control. CONCLUSIONS: Our results show that over-treatment of intermittent/mild persistent asthma is frequent in the GPs setting while therapeutic regimens are more appropriately applied for moderate/severe asthma. In general, we found low adherence to GINA GL treatment recommendations even if its relevance in asthma control was confirmed.

Respiratory symptoms/diseases, impaired lung function, and drug use in two Italian general population samples.

BACKGROUND: Research and practice indicate that a sizeable amount of prescribed drugs is never used. AIM: To assess the habitual up-take of medicines in subjects with respiratory symptoms/diseases or impaired lung function in general population samples. METHODS: Data regard 4010 subjects (8-88 years) from the rural area of Po River Delta (North Italy) and the urban area of Pisa (North-Central Italy). Analyses concern the habitual use of any or specific medicines (broncho-pulmonary, anti-allergic, cardio-vascular, diuretic) in subjects with asthma, chronic bronchitis/emphysema (COPD), COPD or chronic cough/phlegm (COPDsx), and airways obstruction (AO, FEV(1)/FVC<70%). RESULTS: Asthma, COPD, COPDsx, and AO were present in 6%, 5%, 21%, and 13% of cases, respectively. Only 37% and 21% of subjects with respiratory symptoms/diseases used any or specific medicines, respectively. The subjects with COPD exhibited the highest prevalence of assumption (59% for any drug, 38% for specific medicines), followed by asthmatics (42% and 30%), and subjects with AO (40% and 25%). After accounting for sex, age, residence area, smoking habit, education, and presence of comorbidity, the conditions significantly related to any medicine up-take were COPD (OR 1.65, 95% CI 1.08-2.53) and asthma (OR 1.47, 95% CI 1.01-2.12). Only asthma resulted significantly associated with the use of specific drugs (OR 3.11, 95% CI 1.94-4.97). Drug use was higher in the urban than in the rural area. CONCLUSION: The results indicate that most people in the general population do not use drugs, in spite of reported respiratory disorders. The underuse of medicines seems lower in the urban area.

Respiratory symptoms/diseases prevalence is still increasing: a 25-yr population study.

BACKGROUND: Few epidemiological surveys on general population samples estimated changes in prevalence of respiratory symptoms/diseases over a long time interval; our study aims to quantify the temporal changes in the prevalence rates of asthma, allergic rhinitis and Chronic Obstructive Pulmonary Disease (COPD) after 25 years from baseline. METHODS: A general population sample participated in 3 cross-sectional surveys carried out in Central Italy (Pisa) in 1985-88 (n = 3865), 1991-93 (n = 2841), 2009-11 (n = 1620). 2276 (47%) subjects participated in at least 1 survey, 1723 (35.5%) in at least 2 surveys and 849 (17.5%) in all the 3 surveys. All subjects filled in a standardized questionnaire about health status and risk factors; a sub-sample performed spirometry. Chi-square test was used to compare adjusted prevalence rates of respiratory symptoms/diseases and descriptive characteristics among the surveys. Generalised estimating equations (GEE) were used to analyze the association between respiratory symptoms/diseases and risk factors. RESULTS: There was an increasing trend in prevalence rates of all respiratory symptoms/diseases throughout the surveys: current asthma attacks (1st-3rd survey prevalence: 3.4-7.2%), allergic rhinitis (16.2-37.4%), usual phlegm (8.7-19.5%) and COPD (2.1-6.8%) more than doubled. The GEE model confirmed these increasing trends, indicating higher risk of having respiratory symptoms/diseases in the second and third surveys. CONCLUSIONS: While asthma and allergic rhinitis increasing trends were confirmed, with respect to other international studies, also a COPD increasing prevalence rates was shown.

The proportional Venn diagram of obstructive lung disease in the Italian general population.

STUDY OBJECTIVES: The Venn diagram of obstructive lung disease (OLD) has been recently quantified. We aimed to quantify the proportion of the general population with OLD, and the intersections of physician-diagnosed asthma, chronic bronchitis (CB), and emphysema in two Italian general population samples, in relationship to airflow obstruction (AO) determined through spirometry. DESIGN AND PARTICIPANTS: We analyzed data from two prospective studies (4,353 patients) carried out in the rural area of Po River delta from 1988 to 1991 and in the urban area of Pisa from 1991 to 1993. RESULTS: Prevalence rates of asthma, CB, and emphysema were 5.3%, 1.5%, and 1.2% in the Po delta, and 6.5%, 2.5%, and 3.6% in Pisa. A double Venn diagram, which was used to quantify the distribution of CB, emphysema, and asthma in relation to the presence/absence of AO, identified 15 categories. Isolated AO was the most frequent category (Po delta, 11.0%; Pisa, 6.7%), followed by asthma only without AO (Po delta, 3.3%; Pisa, 4.3%). The combination of the three OLD conditions was the only category that always showed higher prevalence rates for those with AO (Po delta, 0.20%; Pisa, 0.16%) than for those without AO (Po delta, 0.04%; Pisa, 0.05%). Of those with either OLD or AO, there were 61.4% in Po delta and 38.2% in Pisa with isolated AO, 24.8% and 41.9%, respectively, with an OLD without AO, and 13.8% and 19.9%, respectively, with simultaneous OLD and AO. For both genders, the frequency of isolated asthma decreased with age, while that of isolated AO, CB-emphysema, and the combination of asthma and CB-emphysema increased. CONCLUSION: About 18% of the Italian general population samples either reported the presence of OLD or showed spirometric signs of AO. We confirmed that the Venn diagram of OLD can be quantified in the general population by extending the mutually exclusive disease categories (including a concomitant diagnosis of asthma, CB, or emphysema) to 15.

Indoor exposures and acute respiratory effects in two general population samples from a rural and an urban area in Italy.

A study of indoor air exposures and acute respiratory effects in adults was conducted in the Po Delta (rural) and Pisa (urban) areas of Italy. Indoor exposures were monitored for nitrogen dioxide (NO(2)) and particulate matter <2.5 microm (PM(2.5)) for 1 week during the winter or summer in a total of 421 houses (2/3 in Pisa). Information on house characteristics, subjects' daily activity pattern and presence of acute respiratory symptoms was collected by a standardized questionnaire. Peak expiratory flow (PEF) maneuvers were performed by adult subjects four times daily; maximum amplitude and diurnal variation were taken into account. Indices of NO(2) and PM(2.5) exposures were computed as the product of weekly mean pollutant concentration by the time of daily exposure. Mean levels of pollutants were significantly higher in winter than in summer, regardless of the area. The relationship between exposure indices and acute respiratory symptoms was investigated only in winter. In spite of a slightly lower indoor level in the urban than in the rural area in winter (NO(2): 15 vs. 22 ppb; PM(2.5): 67 vs. 76 microg/m(3)), prevalence rates of acute respiratory symptoms were significantly higher in the urban than in the rural area. Acute respiratory illnesses with fever were significantly associated with indices of NO(2) (odds ratio (OR)=1.66; 95% CI=1.08-2.57) and PM(2.5) exposures (OR=1.62; 95% CI=1.04-2.51), while bronchitic/asthmatic symptoms were associated only with PM(2.5) (OR=1.39; 95% CI=1.17-1.66). PEF variability was positively related only to PM(2.5) exposure index (OR=1.38; 95% CI=1.24-1.54, for maximum amplitude; OR=1.37; 95% CI=1.23-1.53, for diurnal variation). In conclusion, indoor pollution exposures were associated with the presence of acute respiratory symptoms and mild lung function impairment in a rural and an urban area of Northern-Central Italy.

The complex link between severity of asthma and rhinitis in mite allergic patients.

AIM: The aim of the study was to evaluate the link between the severity of upper and lower airways diseases in mite allergic patients with respiratory allergy. PATIENTS AND METHOD: A multicentre, observational, cross-sectional study was carried out in 556 consecutively enrolled mite allergic patients with rhinitis and asthma comorbidity attending a specialist unit. Severity assessment of rhinitis and asthma was evaluated in accordance with ARIA and GINA guidelines. RESULTS: Reliable data were available for 518 patients. The distribution of rhinitis severity was: 15.6% mild intermittent rhinitis, 4.4% moderate-severe intermittent rhinitis, 30.3% mild persistent rhinitis and 49.6% moderate persistent rhinitis. The distribution of asthma severity was: 41.3% mild intermittent asthma, 14.3% mild persistent asthma, 19.1% moderate persistent asthma and 25.3% severe persistent asthma. In patients with moderate-severe persistent rhinitis (49.5%) a significant trend (p = 0.005) was found pointing to an increased link with asthma severity. CONCLUSION: A link between respective severities of rhinitis and asthma was found in only half of mite allergic patients with rhinitis and asthma.

Urban residence is associated with bronchial hyperresponsiveness in Italian general population samples.

BACKGROUND: The role of different risk factors for bronchial hyperresponsiveness (BHR), such as gender, atopy, IgE, and environmental factors (smoking, occupational exposure, infections), has been described. Indoor and outdoor pollution play an important role too, but few studies have analyzed the association with BHR. The aim of this study was to assess the effect of urban residence on BHR. METHODS: We studied two general population samples enrolled in two cross-sectional epidemiological studies performed in Northern Italy (Po Delta, rural area) and Central Italy (Pisa, urban area). We analyzed 2,760 subjects (age range, 8 to 74 years). We performed analysis of variance and logistic regression analysis using ln slope of the dose-response curve of the methacholine challenge test as dependent variable, and sex, age, smoking habits, respiratory symptoms, skin-prick test results, IgE value, residence, and airway caliber as independent variables. RESULTS: The mean value of ln slope of the dose-response curve adjusted for initial airways caliber (by baseline FEV(1) percentage of predicted value) was significantly higher in female subjects, in smokers, in subjects with respiratory symptoms, in younger and older ages, in subjects with high values of IgE, and in subjects with positive skin-prick test results. After controlling for the independent effects of all these variables, living in urban area was an independent risk factor for having BHR (odds ratio, 1.41; 95% confidence interval, 1.13 to 1.76). CONCLUSION: Living in urban area is a risk factor for increased bronchial responsiveness.