Isa Cerveri

Rhinitis and onset of asthma: a longitudinal population-based study

BACKGROUND A close relation between asthma and allergic rhinitis has been reported by several epidemiological and clinical studies. However, the nature of this relation remains unclear. We used the follow-up data from the European Community Respiratory Health Survey to investigate the onset of asthma in patients with allergic and non-allergic rhinitis during an 8.8-year period. METHODS We did a longitudinal population-based study, which included 29 centres (14 countries) mostly in western Europe. Frequency of asthma was studied in 6461 participants, aged 20-44 years, without asthma at baseline. Incident asthma was defined as reporting ever having had asthma confirmed by a physician between the two surveys. Atopy was defined as a positive skin-prick test to mites, cat, Alternaria, Cladosporium, grass, birch, Parietaria, olive, or ragweed. Participants were classified into four groups at baseline: controls (no atopy, no rhinitis; n=3163), atopy only (atopy, no rhinitis; n=704), non-allergic rhinitis (rhinitis, no atopy; n=1377), and allergic rhinitis (atopy+rhinitis; n=1217). Cox proportional hazards models were used to study asthma onset in the four groups. FINDINGS The 8.8-year cumulative incidence of asthma was 2.2% (140 events), and was different in the four groups (1.1% (36), 1.9% (13), 3.1% (42), and 4.0% (49), respectively; p<0.0001). After controlling for country, sex, baseline age, body-mass index, forced expiratory volume in 1 s (FEV(1)), log total IgE, family history of asthma, and smoking, the adjusted relative risk for asthma was 1.63 (95% CI 0.82-3.24) for atopy only, 2.71 (1.64-4.46) for non-allergic rhinitis, and 3.53 (2.11-5.91) for allergic rhinitis. Only allergic rhinitis with sensitisation to mite was associated with increased risk of asthma independently of other allergens (2.79 [1.57-4.96]). INTERPRETATION Rhinitis, even in the absence of atopy, is a powerful predictor of adult-onset asthma.

An international survey of chronic obstructive pulmonary disease in young adults according to GOLD stages

Background: The recently published GOLD guidelines provide a new system for staging chronic obstructive pulmonary disease (COPD) from mild (stage I) to very severe (stage IV) and introduce a stage 0 (chronic cough and phlegm without airflow obstruction) that includes subjects “at risk” of developing the disease. Methods: In order to assess the prevalence of GOLD stages of COPD in high income countries and to evaluate their association with the known risk factors for airflow obstruction, data from the European Community Respiratory Health Survey on more than 18 000 young adults (20–44 years) were analysed. Results: The overall prevalence was 11.8% (95% CI 11.3 to 12.3) for stage 0, 2.5% (95% CI 2.2 to 2.7) for stage I, and 1.1% (95% CI 1.0 to 1.3) for stages II–III. Moderate to heavy smoking (⩾15 pack years) was significantly associated with both stage 0 (relative risk ratio (RRR) = 4.15; 95% CI 3.55 to 4.84) and stages I+ (RRR = 4.09; 95% CI 3.17 to 5.26), while subjects with stages I+ COPD had a higher likelihood of giving up smoking (RRR = 1.39; 95% CI 1.04 to 1.86) than those with GOLD stage 0 (RRR = 1.05; 95% CI 0.86 to 1.27). Environmental tobacco smoke had the same degree of positive association in both groups. Respiratory infections in childhood and low socioeconomic class were significantly and homogeneously associated with both groups, whereas occupational exposure was significantly associated only with stage 0. All the GOLD stages showed a significantly higher percentage of healthcare resource users than healthy subjects (p<0.001), with no difference between stage 0 and COPD. Conclusions: A considerable percentage of young adults already suffered from COPD. GOLD stage 0 was characterised by the presence of the same risk factors as COPD and by the same high demand for medical assistance.

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.

Long-term Outcome after Pulmonary Endarterectomy

RATIONALE There are few follow-up studies on long-term cardiopulmonary function after pulmonary endarterectomy (PEA), the operation of choice for chronic thromboembolic pulmonary hypertension (CTEPH). OBJECTIVES To prospectively evaluate long-term outcome of patients with CTEPH treated with PEA. METHODS Between 1994 and 2006, 157 patients (mean age 55 yr) were treated with PEA at Pavia University Hospital. The patients were evaluated before PEA and at 3 months (n = 132), 1 year (n = 110), 2 years (n = 86), 3 years (n = 69), and 4 years (n = 49) afterward by NYHA class, right heart hemodynamic, spirometry, carbon monoxide transfer factor (Tl(CO)), arterial blood gas, and treadmill incremental exercise test. MEASUREMENTS AND MAIN RESULTS Cumulative survival was 84%. Within 3 months, 18 patients died in-hospital and 2 had lung transplantation; during long-term follow-up, 6 died, 1 had lung transplantation, and 3 had a second PEA (2.5 events per 100 person-years). NYHA class III-IV was the most important predictor of late death, lung transplant, or PEA redo (hazard ratio, 3.94). Extraordinary improvement in NYHA class, hemodynamic, and Pa(O(2)) were achieved in the first 3 months (P < 0.001) and persisted during follow-up; exercise tolerance progressively increased over time (P < 0.001). At 4 years, although 74% of the patients were in NYHA class I and none was in class IV, 24% had pulmonary vascular resistance greater than 500 dyne.s/cm(5) or Pa(O(2)) less than 60 mm Hg; they were significantly older and were more frequently in NYHA class III-IV 3 months after surgery than the others. CONCLUSIONS After PEA, long-term survival and cardiopulmonary function recovery is excellent in most patients.

Smoking cessation, lung function, and weight gain : a follow-up study

BACKGROUND Only one population-based study in one country has reported effects of smoking cessation and weight change on lung function, and none has reported the net effect. We estimated the net benefit of smoking cessation, and the independent effects of smoking and weight change on change in ventilatory lung function in the international European Community Respiratory Health Survey. METHODS 6654 participants in 27 centres had lung function measured in 1991-93, when aged 20-44 years, and in 1998-2002. Smoking information was obtained from detailed questionnaires. Changes in lung function were analysed by change in smoking and weight, adjusted for age and height, in men and women separately and together with interaction terms. FINDINGS Compared with those who had never smoked, decline in FEV1 was lower in male sustained quitters (mean difference 5.4 mL per year, 95% CI 1.7 to 9.1) and those who quit between surveys (2.5 mL, -1.9 to 7.0), and greater in smokers (-4.8 mL, -7.9 to -1.6). In women, estimates were 1.3 mL per year (-1.5 to 4.1), 2.8 mL (-0.8 to 6.3) and -5.1 mL (-7.5 to -2.8), respectively. These sex differences were not significant. FEV1 changed by -11.5 mL (-13.3 to -9.6) per kg weight gained in men, and by -3.7 mL per kg (-5.0 to -2.5) in women, which diminished the benefit of quitting by 38% in men, and by 17% in women. INTERPRETATION Smoking cessation is beneficial for lung function, but maximum benefit needs control of weight gain, especially in men.

Increase in diagnosed asthma but not in symptoms in the European Community Respiratory Health Survey

Background: Information on the epidemiology of asthma in relation to age is limited and hampered by reporting error. To determine the change in the prevalence of asthma with age in young adults we analysed longitudinal data from the European Community Respiratory Health Survey. Methods: A self-administered questionnaire was completed by 11 168 randomly selected subjects in 14 countries in 1991–3 when they were aged 20–44 years and 5–11 years later from 1998 to 2003. Generalised estimating equations were used to estimate net change in wheeze, nocturnal tightness in chest, shortness of breath, coughing, asthma attacks in the last 12 months, current medication, “diagnosed” asthma, and nasal allergies. Results: Expressed as change in status per 10 years of follow up, subjects reporting asthma attacks in the previous 12 months increased by 0.8% of the population (95% CI 0.2 to 1.4) and asthma medication by 2.1% (95% CI 1.6 to 2.6), while no statistically significant net change was found in reported symptoms. Reported nasal allergies increased, especially in the youngest age group. Conclusions: As this cohort of young adults has aged, there has been an increase in the proportion treated for asthma but not in the proportion of those reporting symptoms suggestive of asthma. Either increased use of effective treatments has led to decreased morbidity among asthmatic subjects or those with mild disease have become more likely to label themselves as asthmatic.

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.

Risk factors for chronic obstructive pulmonary disease in a European cohort of young adults.

RATIONALE Few studies have investigated the factors associated with the early inception of chronic obstructive pulmonary disease (COPD). OBJECTIVES We investigated COPD risk factors in an international cohort of young adults using different spirometric definitions of the disease. METHODS We studied 4,636 subjects without asthma who had prebronchodilator FEV(1)/FVC measured in the European Community Respiratory Health Survey both in 1991 to 1993 (when they were 20-44 yr old) and in 1999 to 2002. COPD was defined according to the Global Initiative for Chronic Obstructive Lung Disease fixed cut-off criterion (FEV(1)/FVC < 0.70), and two criteria based on the Quanjer and LuftiBus reference equations (FEV(1)/FVC less than lower limit of normal). COPD determinants were studied using two-level Poisson regression models. MEASUREMENTS AND MAIN RESULTS COPD incidence ranged from 1.85 (lower limit of normal [Quanjer]) to 2.88 (Global Initiative for Chronic Obstructive Lung Disease) cases/1,000/yr. Although about half of the cases had smoked less than 20 pack-years, smoking was the main risk factor for COPD, and it accounted for 29 to 39% of the new cases during the follow-up. Airway hyperresponsiveness was the second strongest risk factor (15-17% of new cases). Other determinants were respiratory infections in childhood and a family history of asthma, whereas the role of sex, age, and of being underweight largely depended on the definition of COPD used. CONCLUSIONS COPD may start early in life. Smoking prevention should be given the highest priority to reduce COPD occurrence. Airway hyperresponsiveness, a family history of asthma, and respiratory infections in childhood are other important determinants of COPD. We suggest the need for a definition of COPD that is not exclusively based on spirometry.

Long-term durable benefit after whole lung lavage in pulmonary alveolar proteinosis

Whole lung lavage (WLL) is still the gold-standard therapy for pulmonary alveolar proteinosis (PAP). The few studies on the duration of the effect of WLL, belonging to a rather remote period, show significant but transient benefits. In 21 patients with idiopathic PAP, the duration of any benefit and, in 16 of them, the time course of lung function improvement (at baseline, 1 week, 6 months, 1 yr and then every 2 yrs after WLL) were evaluated. The present WLL technique takes longer, is invasively monitored and partially modified with respect to past techniques. More than 70% of patients remained free from recurrent PAP at 7 yrs. The bulk of the improvement in spirometric results was almost completely gained in the immediate post‐WLL period due to the efficient clearance of the alveoli. At a median of 5 yrs, recovery of diffusing capacity of the lung for carbon monoxide was incomplete (75±19% of the predicted value) and there were residual gas exchange abnormalities (alveolar to arterial oxygen tension difference 3.6±1.5 kPa (27±11 mmHg)) and exercise limitation, probably explained by engorgement of lymphatic vessels. In conclusion, whole lung lavage for idiopathic pulmonary alveolar proteinosis is currently a safe procedure in an experienced setting, and provides long-lasting benefits in the majority of patients.

The Cost of Persistent Asthma in Europe : An International Population-Based Study in Adults

Background: This study is aimed at providing a real-world evaluation of the economic cost of persistent asthma among European adults according to the degree of disease control [as defined by the 2006 Global Initiative for Asthma (GINA) guidelines]. Methods: A prevalence-based cost-of-illness study was carried out on 462 patients aged 30–54 years with persistent asthma (according to the 2002 GINA definition), who were identified in general population samples from 11 European countries and examined in clinical settings in the European Community Respiratory Health Survey II between 1999 and 2002. The cost estimates were computed from the societal perspective following the bottom-up approach on the basis of rates, wages and prices in 2004 (obtained at the national level from official sources), and were then converted to the 2010 values. Results: The mean total cost per patient was EUR 1,583 and was largely driven by indirect costs (i.e. lost working days and days with limited, not work-related activities 62.5%). The expected total cost in the population aged 30–54 years of the 11 European countries was EUR 4.3 billion (EUR 19.3 billion when extended to the whole European population aged from 15 to 64 years). The mean total cost per patient ranged from EUR 509 (controlled asthma) to EUR 2,281 (uncontrolled disease). Chronic cough or phlegm and having a high BMI significantly increased the individual total cost. Conclusions: Among European adults, the cost of persistent asthma drastically increases as disease control decreases. Therefore, substantial cost savings could be obtained through the proper management of adult patients in Europe.