Laura Carrozzi

Definition, epidemiology and natural history of COPD

Chronic obstructive pulmonary disease (COPD) is the fifth cause of morbidity and mortality in the developed world and represents a substantial economic and social burden. Patients experience a progressive deterioration up to end-stage COPD, characterised by very severe airflow limitation, severely limited and declining performance status with chronic respiratory failure, advanced age, multiple comorbidities and severe systemic manifestations/complications. COPD is frequently underdiagnosed and under-treated. Today, COPD develops earlier in life and is less gender specific. Tobacco smoking is the major risk factor for COPD, followed by occupation and air pollution. Severe deficiency for α1-antitrypsin is rare; several phenotypes are being associated with elevated risk for COPD in the presence of risk factor exposure. Any patient presenting with cough, sputum production or dyspnoea should be assessed by standardised spirometry. Continued exposure to noxious agents promotes a more rapid decline in lung function and increases the risk for repeated exacerbations, eventually leading to end-stage disease. Without major efforts in prevention, there will be an increasing proportion of end-stage patients who can live longer through long-term oxygen therapy and assisted ventilation, but with elevated suffering and huge costs. Smoking prevention and smoking cessation are the most important epidemiological measurements to counteract chronic obstructive pulmonary disease epidemics.

Epidemiology of Chronic Obstructive Pulmonary Disease (COPD)

Chronic Obstructive Pulmonary Disease (COPD) is one of the leading causes of morbidity and mortality in the industrialized and the developing countries. During 1997, COPD has been estimated to be the number four cause of death after cardiovascular diseases, tumors and cerebrovascular diseases in the United States. In 2020 COPD will probably become the third leading cause of death all over the world, following the trend of increasing prevalence of lung cancer. The impact of this respiratory disease worldwide is expected to increase with a heavy economic burden on individuals and society. In the United States direct and indirect costs of COPD were estimated at about USD24 billion in 1993. Unfortunately, there are few data on health-care utilization despite the great interest in COPD among researchers. As all chronic diseases, the prevalence of COPD is strongly associated with age. Data collected in a general population sample (living in Italy) showed a progressive increase of the prevalence of chronic bronchitis and emphysema with age, both in males and in females. COPD is determined by the action of a number of various risk factors either singly or interacting among themselves in a synergistic way. Among these, the most important is cigarette smoking, ranking at the first level for developing chronic bronchitis and emphysema. Also air pollution and some occupational exposures represent risks for developing COPD. Many epidemiological studies have indicated an association between the prevalence of chronic bronchitis and a low socioeconomic status. Furthermore, in the etiology of COPD we must consider endogenous risk factors such as gender, genetic features, presence of respiratory troubles in childhood, and family history. To date, epidemiologic studies have been of great importance for the characterization of the disease at a population level, indicating possible causes and assessing its impact on the individual and on society as a whole. Unfortunately, international standards for the diagnosis of COPD are lacking, which complicates the organization of appropriate epidemiological surveys.

Design, recruitment and baseline results of the ITALUNG trial for lung cancer screening with low-dose CT

BACKGROUND Results of randomized clinical trials (RCTs) are needed to assess the efficacy of lung cancer screening with low-dose chest computed tomography (CT) in reducing lung cancer mortality. We report design and results of enrolment and baseline screening test in the ITALUNG trial, a RCT. METHODS Invitation letters were sent to subjects of 55-69 years of age clients of 269 general practitioners. Smokers or former smokers of at least 20 pack/years were eligible and after written consent were randomized in an active arm undergoing a low-dose CT annually for 4 years and in a control arm receiving no screening. Management of positive screening test was carried out using follow-up low-dose CT, fluorodeoxyglucose positron emission tomography, fine needle aspiration cytology and fiber optic bronchoscopy. RESULTS A sample of 3206 eligible subjects was achieved by sending 71,232 letters (enrolment efficacy = 4.5%). Subjects in control (n = 1593) and active (n = 1613) arm were balanced for age, gender and smoking history. Two-hundred and seven (12.8%) subjects did not undergo CT after randomization. The baseline screening test was positive in 426 (30.3%) of 1406 subjects. Twenty-one lung cancers (prevalence = 1.5%) were found in 20 subjects: 18 non-small cell lung cancer (NSCLC), 2 small cell lung cancer (SCLC) and a case of typical carcinoid. Ten NSCLC (47.6%) were in Stage I. Sixteen fine needle aspirations were performed in 15 lung cancers, with a positive result in 12 (75%) cases. One biopsy only (6.3%) was performed on a benign lesion. Seventeen lung cancers (81%) were treated with surgical resection in 16 subjects. One subject underwent surgery for a benign lesion (5.5% of all surgical resections). CONCLUSIONS Recruitment by mail of high risk subjects for a lung cancer screening RCT is feasible but not efficient. Results of the baseline screening test in the active arm of the ITALUNG trial are substantially in line with those of RCT and observational studies.

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.

Importance of baseline cotinine plasma values in smoking cessation: results from a double-blind study with nicotine patch

Nicotine replacement by transdermal patches is more effective than placebo in smoking cessation, but has a low success rate after one year (9-18%). We tested whether this was attributed to insufficient nicotine replacement. We conducted a randomized trial to investigate the effect on outcome of different doses of transdermal nicotine replacement after stratification according to baseline plasma cotinine values. Two hundred and ninety seven adult smokers were enrolled. Those with baseline cotinine < or = 250 ng.ml-1 (low cotinine) were randomly assigned to placebo (LC-P) or to 15 mg 16 h nicotine patches (LC-15), and those with baseline cotinine > 250 ng.mL-1 (high cotinine) were randomly assigned to 15 mg (HC-15) or 25 mg (HC-25) 16 h nicotine patches. Plasma nicotine and cotinine values, expired carbon monoxide and withdrawal symptoms were measured at scheduled intervals during treatment. Smokers in the LC-15 group had a significantly higher success rate than placebo (28 vs 9%). Smokers with high baseline cotinine had lower success rates, and a high dose of nicotine did not increase success rate (HC-25 9% vs HC-15 11%). Subjects in the HC-15 group had the lowest percentage of nicotine replacement and a higher prevalence of withdrawal symptoms than the HC-25 group. Replacement was similar in groups LC-15 and HC-25, but the success rate was significantly lower in HC-25 group, despite similar levels of withdrawal symptoms. We conclude that a higher success rate was obtained after one year in smokers with low baseline plasma cotinine values. Determination of plasma cotinine values may be, thus, helpful in identifying smokers who could benefit from transdermal nicotine replacement.

Epidemiology of chronic obstructive pulmonary disease: Health effects of air pollution

Abstract:  COPD is one of the leading causes of morbidity and mortality in the industrialized and the developing countries. According to the prediction of the World Health Organization, COPD will become the third leading cause of mortality and the fifth cause of disability in 2020 worldwide. In epidemiology, distinct phenotypic entities converge on the term COPD, so that prevalence and mortality data may be inclusive of chronic bronchitis, emphysema and asthma; moreover, the assessment of prevalence rates may change considerably according to the diagnostic tools used. Thus, a considerable problem is to estimate the real prevalence of COPD in the general population. COPD is determined by the action of a number of various risk factors, among which, the most important is cigarette smoking. However, during the last few decades, evidence from epidemiological studies finding consistent associations between air pollution and various outcomes (respiratory symptoms, reduced lung function, chronic bronchitis and mortality), has suggested that outdoor air pollution is a contributing cause of morbidity and mortality. In conclusion, epidemiological studies suggest that air pollution plays a remarkable role in the exacerbation and in the pathogenesis of chronic respiratory diseases. Thus, respiratory physicians, as well as public health professionals, should advocate for a cleaner environment.

Longitudinal changes of body mass index, spirometry and diffusion in a general population

The aim of this study was to evaluate the effects of body mass index (BMI) changes over an 8-yr follow-up, on longitudinal changes of vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), and carbon monoxide diffusing capacity of the lung (DL,CO) indices in a general population sample of North Italy. To avoid including weight changes possibly related to physical growth, only the 1,426 adults (>24 yrs, 46% males) with complete follow-up were selected. Median linear regression models were applied to estimate the medians of change (computed as follow-up minus baseline values) of VC, FVC, FEV1 and DL,CO indices, as functions of changes of BMI over the follow-up period, separately by sex, after considering several potential confounders and effect modifiers. The extent of lung function loss tended to be higher among those who, at baseline, reported greater BMI values. Males experienced larger losses than females (20 and 16 mL FEV1 median reduction for a BMI unit increase in males and females, respectively). Conversely, longitudinal changes of BMI caused a slight and nonsignificant increase in DL,CO values in both sexes. Over an 8-yr follow-up, the detrimental effect of gaining weight might be reversible for many adults as most of those who reduced their body mass index values also increased their lung function. Overweight patients with ventilatory impairment should be routinely encouraged to lose weight for improving their lung function.

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.

PREVALENCE RATES OF RESPIRATORY SYMPTOMS IN ITALIAN GENERAL POPULATION SAMPLES EXPOSED TO DIFFERENT LEVELS OF AIR POLLUTION

We surveyed two general population samples aged 8 to 64 living in the unpolluted, rural area of the Po Delta (northern Italy) (n = 3289) and in the urban area of Pisa (central Italy) (n = 2917). Each subject filled out a standardized interviewer-administered questionnaire. The Pisa sample was divided into three groups according to their residence in the urban-suburban areas and to outdoor air pollution exposure (automobile exhaust only or industrial fumes as well). Significantly higher prevalence rates of all the respiratory symptoms and diseases were found in Pisa compared with the Po Delta. In particular, rhinitis and wheezing symptoms were higher in all the three urban zones; chronic cough and phlegm were higher in the zone with the automobile exhaust and the additional industrial exposure. Current smoking was more frequent in the rural area, but the urban smokers had a higher lifetime cigarette consumption. Childhood respiratory trouble and recurrent respiratory illnesses were evenly distributed. Exposure to parental smoking in childhood and lower educational level were more frequent in Po Delta, whereas familial history of respiratory/allergic disorders and work and indoor exposures were more often reported in the city. Multiple logistic regression models estimating independently the role of the various risk factors showed significant odds ratios associated with residence in Pisa for all the symptoms but chronic phlegm. For example, those living in the urban-industrial zone had an odds ratio of 4.0 (4.3-3.7) for rhinitis and 2.8 (3.0-2.6) for wheeze with respect to those living in the Po Delta.(ABSTRACT TRUNCATED AT 250 WORDS)

Skin prick test reactivity to common aeroallergens in relation to total IgE, respiratory symptoms, and smoking in a general population sample of northern Italy.

Skin prick test (SPT) reactivity to common airborne allergens and its relationships to sex, age, smoking habits, and respiratory symptoms/ diseases were evaluated in a general population sample (n= 2841, 8–75 years of age) living in the Po delta area (northern Italy). Subjects completed a standardized questionnaire and underwent prick tests (12 local allergens, a negative and a positive control) and determination of total serum IgE. Atopy was evaluated by measuring the maximal diameter for each allergen, after subtracting that of the negative control. Thirty‐one percent of subjects showed a positive skin response at a 3‐mm threshold. Pollens, Dermatophagoides pteronyssinus, and D. farinae caused the highest frequencies of reactions. Young people and those who had never smoked had higher prevalence rates of SPT reactivity. Asthma, asthma symptoms, and rhinitis were significantly associated with SPT reactivity in both sexes (cough only in females) and with the number of positive reactions. IgE values were also significantly associated with SPT reactivity. In conclusion, our findings indicate that almost one‐third of the general population of an Italian rural area is skin test positive, emphasizing the importance of assessing atopy in respiratory epidemiologic surveys.