Pietro Pirina

The Coexistence of Asthma and Chronic Obstructive 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 <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.

Allergic rhinitis and asthma comorbidity in a survey of young adults in Italy

Background:  Several studies have provided evidence of a strong association between asthma and allergic or nonallergic rhinitis, leading to the hypothesis that allergic rhinitis (AR) and asthma represent a continuum of the same disease.

IRAK-M Is Involved in the Pathogenesis of Early-Onset Persistent Asthma

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.

Trends in the prevalence of asthma and allergic rhinitis in Italy between 1991 and 2010

The prevalence of asthma increased worldwide until the 1990s, but since then there has been no clear temporal pattern. The present study aimed to assess time trends in the prevalence of current asthma, asthma-like symptoms and allergic rhinitis in Italian adults from 1990 to 2010. The same screening questionnaire was administered by mail or phone to random samples of the general population (age 20–44 yrs) in Italy, in the frame of three multicentre studies: the European Community Respiratory Health Survey (ECRHS) (1991–1993; n=6,031); the Italian Study on Asthma in Young Adults (ISAYA) (1998–2000; n=18,873); and the Gene Environment Interactions in Respiratory Diseases (GEIRD) study (2007–2010; n=10,494). Time trends in prevalence were estimated using Poisson regression models in the centres that repeated the survey at different points in time. From 1991 to 2010, the median prevalence of current asthma, wheezing and allergic rhinitis increased from 4.1% to 6.6%, from 10.1% to 13.9% and from 16.8% to 25.8%, respectively. The prevalence of current asthma was stable during the 1990s and increased (relative risk 1.38, 95% CI 1.19–1.59) from 1998–2000 to 2007–2010, mainly in subjects who did not report allergic rhinitis. The prevalence of allergic rhinitis has increased continuously since 1991. The asthma epidemic is not over in Italy. During the past 20 yrs, asthma prevalence has increased by 38%, in parallel with a similar increase in asthma-like symptoms and allergic rhinitis.

Poor control increases the economic cost of asthma. A multicentre population-based study.

Background/Aims: Up to now, few cost-of-illness (COI) studies have estimated the cost of adult asthma at an individual level on general population samples. We sought to evaluate the cost of current asthma from the societal perspective in young Italian adults and the determinants of cost variation. Methods: In 2000, a COI study was carried out in the frame of the Italian Study on Asthma in Young Adults on 527 current asthmatics (20–44 years) screened out of 15,591 subjects from the general population in seven centres. Detailed information about direct medical expenditures (DMEs) and indirect costs due to asthma was collected at an individual level over the past 12 months. Results: The mean annual cost per patient was EUR 741 (95% CI: 599–884). DMEs represented 42.8% of the total cost, whereas the remaining 57.2% was indirect costs. The largest component of DMEs was medication costs (47.3%; 23.0% was due to hospitalization). The mean annual cost per patient ranged from EUR 379 (95% CI: 216–541)for well-controlled asthmatics to EUR 1,341 (95% CI: 978–1,706) for poorly controlled cases that accounted for 46.2% of the total cost. Poor control, coexisting chronic cough and phlegm, and low socio-economic status were significantly associated with high DMEs and indirect costs. Conclusions: In Italy, asthma-related costs were substantial even in unselected patients and were largely driven by indirect costs. Since about half of the total cost was due to a limited proportion of poorly controlled asthmatics, interventions aimed at these high-cost patients could reduce the economic burden of the disease.

The impact of climate and traffic-related NO2 on the prevalence of asthma and allergic rhinitis in Italy

Background Environmental factors are likely to be involved in explaining the wide geographical variation in asthma and atopic diseases that has been documented in many recent epidemiological studies.

The role of climate on the geographic variability of asthma, allergic rhinitis and respiratory symptoms: results from the Italian study of asthma in young adults

Background:  Variations in the prevalence of respiratory symptoms according to geo‐climatic factors could provide important clues to the knowledge of the aetiology of asthma.

Are the asthma guideline goals achieved in daily practice? A population-based study on treatment adequacy and the control of asthma.

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.

Bacterial Community Acquired Pneumonia in HIV-Infected Inpatients in the Highly Active Antiretroviral Therapy Era

Introduction:Highly active antiretroviral therapy (HAART) has deeply modified HIV/AIDS related morbidity and mortality. However, bacterial community acquired pneumonia (BCAP) still represents one of the most frequent causes of morbidity in HIV-infected patients with an inpatient 10% mortality rate.Objectives:We retrospectively studied the characteristics of BCAP in consecutive HIV-infected inpatients hospitalized from 1999 to 2004 and evaluated the presence of risk factors and the influence of combination antiretroviral therapy receipt on BCAP outcomes.Results:We studied 84 BCAP episodes in 76 HIV-infected inpatients (63 males and 13 females) aged 27–80 years. Thirty-two (42.1%) patients were receiving combination antiretroviral treatment (CART) while 44 (57.9%) were not treated (NART). BCAP incidence progressively increased from 1999 to 2004. The overall percentage of injection drug users was > 84%, of smokers > 88% and alcohol abusers > 32% with no statistical difference between CART and NART. Streptococcus pneumoniae was the most frequently identified pathogen (60%). Time to clinical stability was significantly longer in NART in respect of CART (p = 0.011). In multivariate analysis, CDC stage C, CD4 cell count < 100 × 106 cells/l, and S. pneumoniae etiology were predictors for time to clinical stability > 7 days, while receipt of antiretroviral therapy was protective. The percentage of deaths did not differ between CART and NART; most patients had a CD4 count < 200 × 106 cells/l or severe concomitant diseases.Conclusions:The incidence of BCAP was high in HIV-infected inpatients observed in the present study mainly due to HIV infection itself, IVDU, alcohol abuse and smoking habit. A longer time to clinical stability was associated with advanced HIV infection and with S. pneumoniae etiology, while receipt of antiretroviral therapy was protective. Injection drug abuse treatment, alcohol abuse and smoking cessation programs, antiretroviral treatment adherence support and pneumococcal vaccination should be implemented to reduce the incidence and to improve the outcomes of BCAP in HIV-infected patients.

Clinical phenotypes of Italian and Spanish patients with α1-antitrypsin deficiency

With the aim of providing better clinical characterisation of patients with &agr;1-antitrypsin deficiency (AATD), we analysed the data of adult patients with severe AATD enrolled in the Spanish and Italian national registries. We assessed 745 subjects, 416 of whom were enrolled in the Spanish registry and 329 in the Italian registry. 57.2% were male and 64.9% were smokers or former smokers with a mean±sd age of 49.9±13.8 years. Most (81.2%) were index cases, mainly having the PI*ZZ genotype (73.4%), and the mean±sd diagnostic delay was 9.0±12.1 years. Patients with chronic bronchitis were younger, had better preserved lung function and lower tobacco consumption. Overlap patients (chronic obstructive pulmonary disease with asthma) were mainly females, more frequently never-smokers and received respiratory medications more often. 48% of emphysema, 27.5% of chronic bronchitis and 44.8% of overlap subjects were receiving augmentation therapy. Compared with PI*ZZ patients (n=547), the PI*SZ (n=124) subjects were older at diagnosis and had more preserved lung function, despite a higher mean smoking consumption. Early diagnosis of AATD is still an unmet need. Augmentation therapy is administered to similar proportions of patients with different clinical phenotypes. PI*ZZ patients in both registries had more severe respiratory disease than those with PI*SZ, despite lower smoking levels.