Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up.

BACKGROUND: The single breath nitrogen (SBN2) test was proposed for early detection of "small airways disease" in the seventies. Few longitudinal studies have subsequently evaluated the relationships between SBN2 test measurements and lung function decline or COPD incidence. AIM: This study evaluates whether SBN2 test abnormalities may be significant predictors of lung function decline and COPD incidence over an 8-year follow-up. STUDY DESIGN AND METHODS: In this longitudinal study, 907 adults (20+ years old; 56% males) from the prospective Po River Delta epidemiological study underwent SBN2 test at baseline and spirometry testing at both baseline and follow-up 8-year apart. Multinomial and multiple regression models were used to assess associations of SBN2 indexes and rates of FEV1 decline or risk of COPD incidence over time, after adjusting for sex, height and baseline age, FEV1 and smoking status. COPD was defined according to either GOLD or ATS-ERS criteria. RESULTS: Among SBN2 indexes, only the slope of alveolar plateau (N2-slope) was significantly associated with rates of FEV1 decline (7.93 mL/year for a one-unit change in N2-slope, p<0.0001), and with an increased risk of developing COPD as defined by GOLD (RR 1.81, 95%CI 1.29-2.52, mild; RR 2.78, 95%CI 1.70-4.53, moderate or severe obstruction) and ATS-ERS criteria (RR 1.62, 95%CI 1.14-2.29, mild; RR 3.40, 95%CI 1.72-6.73, moderate or severe obstruction). CONCLUSION: In this population-based study, N2-slope from SBN2 test is a significant predictor of lung function decline and COPD incidence over an 8-year follow-up, confirming the role of the "small airways disease" in the natural history of COPD.

Venous Thromboembolism in Cancer: Frequently Asked Questions When Guidelines are Inconclusive.

Management of Venous thromboembolism (VTE) in cancer patients is difficult when guidelines are inconclusive. To share a reasonable and homogeneous behavior in such circumstances, four issues, which are felt as problematic by oncologists and surgeons, have been selected; all were uncovered or only partially covered by current guidelines. Results from the literature and author's specific experience in the field were utilized to suggest reasonable solutions to the raised questions. The reported experience is the first to provide real-world management guidance for VTE in cancer patients. The effort of putting together literature review and author's experience brought to the adoption of a common behavior.

Impact of long-term exposure to cigarette smoking on skin microvascular function.

In order to evaluate the impact of cigarettes smoking and smokers' clinical characteristics on skin microvascular function, we measured the skin forearm blood flux, basally and during post-occlusive reactive hyperaemia, in 100 current smokers (mean age 51±11 years; range: 18 to 86 years) and in 66 healthy never-smokers matched for age and sex, by using laser Doppler fluximetry (LDF). Basal and post-ischemic LDF tracings were analyzed in the frequency domain within 0.009-0.02 Hz, 0.021-0.06 Hz and 0.061-0.2 Hz ranges, related to endothelial-dependent, sympathetic-dependent and myogenic-dependent vasomotion, respectively, using an adapted version of the Fourier analysis. The post-ischemic percentage change from baseline of the area under the LDF curve (AUC%) was significantly lower in smokers than in never-smokers [162.5% (139.3-183.0) vs 190.1% (156.3-216.8); p=0.00016]. Compared to controls, smokers also showed a reduced basal power spectral density (PSD) in the myogenic-dependent vasomotion (p=0.0034) and a reduced post-ischemic percentage increase in PSD of the endothelial-dependent vasomotion (p=0.0010) and sympathetic-dependent vasomotion (p=0.0016). An inverse relationship was observed in smokers between AUC% and smoking exposure duration (r=0.23, p=0.018), pack-years (r=0.33, p=0.0007), age (r=0.26, p=0.008) and body mass index (r=0.21, p=0.037). In the multiple linear regression model, pack-years was the only variable independently associated with AUC% (r=0.21, p=0.03). This study confirms that smoking is associated with cutaneous microvascular dysfunction and shows that the severity of this impairment is independently related to the duration and intensity of the exposure to smoking.

Recommendations for epidemiological studies on COPD.

The prevalence of chronic obstructive pulmonary disease (COPD) has been extensively studied, especially in Western Europe and North America. Few of these data are directly comparable because of differences between the surveys regarding composition of study populations, diagnostic criteria of the disease and definitions of the risk factors. Few community studies have examined phenotypes of COPD and included other ways of characterising the disease beyond that of spirometry. The objective of the present Task Force report is to present recommendations for the performance of general population studies in COPD in order to facilitate comparable and valid estimates on COPD prevalence by various risk factors. Diagnostic criteria in epidemiological settings, and standardised methods to examine the disease and its potential risk factors are discussed. The paper also offers practical advice for planning and performing an epidemiological study on COPD. The main message of the paper is that thorough planning is worth half the study. It is crucial to stick to standardised methods and good quality control during sampling. We recommend collecting biological markers, depending on the specific objectives of the study. Finally, studies of COPD in the population at large should assess various phenotypes of the disease.

Weight gain after smoking cessation.

Both overweight or obesity and cigarette smoking are relevant risk factors for public health. Cigarette smoking is associated with lower body weight while smoking cessation is associated with weight gain. Most smokers who quit experience a weight gain, particularly within one year, and it may persist up to 8 years after smoking cessation. However, only a minority of quitters gain excessive weight. Some individual characteristics have been found to be associated with excessive weight gain after smoking cessation while methodological problems may affect estimates of weight gain observed in different studies. Main mechanisms to explain weight gain after smoking cessation include increased energy intake, decreased resting metabolic rate, and decreased physical activity. The health benefits of smoking cessation far exceed any health risks that may result from smoking cessation-induced body weight gain. As weight gain may be a barrier against quitting smoking or a reason to restart smoking, behavioural and pharmacological methods have been evaluated to control weight gain after smoking cessation. Physicians should apply efficient strategies to promote smoking cessation on their weight-concerned smoking patient. This review briefly addresses some issues on the relationship between smoking cessation and weight gain, with regard to the size of the problem, mechanisms, health risks and control strategies.

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 alpha(1)-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 the chronic obstructive pulmonary disease: environmental and occupational risk]. / Epidemiologia della broncopneumopatia cronico-ostruttiva: fattori di rischio ambientali ed occupazionali.

FACTORS. Chronic Obstructive Pulmonary Disease (COPD) is a very important cause of morbidity and mortality in industrialized and developing countries. According to the World Health Organization (WHO), in 2020 COPD will become the third leading cause of death all over the world. To date, several risk factors for developing COPD have been studied. They can act either singly or interacting among themselves in a synergistic way. Smoking habits and aging are the most important factor for development and exacerbation of COPD, but environmental conditions, such as air pollution and work exposure, can be relevant factors. Recommendations for the prevention of COPD, beside the promotion of smoking cessation, may be air pollution abatement and control of professional exposure. In view of historical trend of risk factors exposure, further epidemiological studies are necessary for a better knowledge of COPD natural history.

Rhinitis is an independent risk factor for developing cough apart from colds among adults.

BACKGROUND: In cross-sectional clinical studies, rhinitis has been shown to be strongly associated with co-existing chronic cough. However, to date, this association has been poorly delineated from a prospective and epidemiological standpoint. METHODS: We used data from the 'Pisa Prospective Study', a population-based longitudinal cohort study composed of a baseline and a follow-up survey taken approximately 5 years apart from each other. Information on cough, rhinitis, and other risk factors was collected by standardized questionnaire. Cough apart from colds was defined as either 'chronic' (most days for at least 3 months for at least two consecutive years) or 'occasional' (if the three above temporal conditions were not met). 'Any' cough was defined as the presence of either occasional or chronic cough. RESULTS: Complete information was available for 1670 subjects who were > or =15 years old and had no positive history of cough apart from colds at the baseline survey. Among them, 299 (18%) had rhinitis at baseline. By the follow-up survey, 16% of the subjects with rhinitis had developed any cough apart from colds, as compared with only 10% of the subjects without rhinitis (OR 1.7, 95% CI 1.2-2.5, P < 0.005). After adjustment for age, gender, asthma status, smoking, and occupational exposure, rhinitis remained significantly associated with an increased risk both for any cough (OR 1.8, 95% CI 1.2-2.6) and for occasional and chronic cough separately (OR 2.2, 95% CI 1.1-4.5, and OR 1.7, 95% CI 1.1-2.6, respectively). CONCLUSIONS: Rhinitis is a significant and independent risk factor for developing cough among adults. Further research is needed to assess potential implications in terms of prevention.

Indoor air pollution and airway disease.

Scientific interest in indoor pollution has been increasing since the second half of the 1980s. Growing scientific evidence has shown that because people generally spend the majority of their time indoors, indoor pollution plays a significant role in affecting health and is thus an important health issue. Indoor environments include dwellings, workplaces, schools and day care centres, bars, discotheques and vehicles. Common indoor pollutants are environmental tobacco smoke, particulate matter, nitrogen dioxide, carbon monoxide, volatile organic compounds and biological allergens. In developing countries, relevant sources of indoor pollution include biomass and coal burning for cooking and heating. Concentrations of these pollutants can be many times higher indoors than outdoors. Indoor air pollution may increase the risk of irritation phenomena, allergic sensitisation, acute and chronic respiratory disorders and lung function impairment. Recent conservative estimates have shown that 1.5-2 million deaths per year worldwide could be attributed to indoor air pollution. Approximately 1 million of these deaths occur in children aged under 5 years due to acute respiratory infections, and significant proportions of deaths occur due to chronic obstructive pulmonary disease and lung cancer in women. Today, indoor air pollution ranks tenth among preventable risk factors contributing to the global burden of disease. Further research is necessary to better evaluate the respiratory health effects of indoor pollution and to implement protective programmes for public health.

Questionnaires, spirometry and PEF monitoring in epidemiological studies on elderly respiratory patients.

Questionnaires are the most used subjective instrument of measurement in respiratory epidemiology. The standardisation of the questionnaires aims to limit bias by maximising validity and reliability, and comparability. Within the European Union project BIOMED1, a compendium of respiratory standard questionnaires (CORSQ) was developed for adults covering 18 topics from general information to early life events, through environmental risk factors and respiratory symptoms and diseases. Reliable spirometry data needs a rigorous quality control programme, as in the "Salute Respiratoria nell'Anziano" (Sa.R.A.) project, Italian for "Respiratory Health in the Elderly". Reproducibility rates were 95.8% for forced expiratory volume in one second (FEV1). Male sex and age were independent risk factors for a poorer reproducibility, as well as cognitive and physical impairment (shorter 6-min walking distance) and lower educational level for a poorer acceptability. Reference values for people aged 65-85 yrs have been produced; these results suggest that the effect of aging should be corrected for physical and mental disability. A revision of interpretative strategies included in current guidelines is needed. Peak expiratory flow monitoring has several methodological problems: reliability and sensitivity of the measurement in order to detect changes in airway calibre; compliance with long-term monitoring; choice of the best variability index; difference between asthmatic and nonasthmatic subjects; age-related differences. Despite these methodological problems, peak expiratory flow monitoring has been successfully used in the evaluation of the effects of air pollution in normal and asthmatic subjects, and in the elderly.

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.

An 8-year follow-up of carbon monoxide diffusing capacity in a general population sample of northern italy.

STUDY OBJECTIVE: Diffusing capacity of the lung for carbon monoxide (DLCO) is frequently assessed as part of a thorough pulmonary function assessment in patients with pulmonary or cardiopulmonary diseases. However, little information regarding the longitudinal trends of DLCO is available. In this study, we examined the temporal trends in DLCO to determine the effects of smoking and changes in smoking habits. DESIGN: A longitudinal study was recently conducted in the Po River Delta area of northern Italy, in which DLCO measurements were taken approximately 8 years apart in the same subjects; this offered the unique opportunity to assess the temporal changes in DLCO. The longitudinal DLCO data were analyzed independently in two age groups (20 to 40 years, and > or = 40 years) using a repeated-measures analysis. RESULTS: Included were 928 subjects > 20 years old who had DLCO assessments both at baseline and follow-up. Male subjects had higher mean levels of DLCO than female subjects in the older age group (> or = 40 years). Continuous smokers had significantly lower DLCO levels than "never-smokers," but their changes in DLCO during follow-up were the same. This suggests that the lung damage due to smoking had occurred prior to DLCO testing. We also found that the annual decline in DLCO accelerated with age in adults > or = 40 years old. CONCLUSIONS: We conclude that in adults > or = 40 years of age from the general population, DLCO accelerates downwards regardless of gender, smoking, and initial FEV(1) level.

Smoking reduction in smokers compliant to a smoking cessation trial with nicotine patch.

The aim of this retrospective analysis was to assess the extent of smoking reduction in smokers who were compliant to a smoking cessation trial with nicotine patch, and failed to completely quit smoking. Out of 297 smokers in total, 237 participants received active treatment (60 received placebo). Eighty treated subjects attended all the scheduled visits and were classified as either abstainers (nonsmokers), regular smokers or occasional smokers. Compared to the remaining 157 participants, these 80 subjects had significantly lower mean baseline daily cigarette consumption (24 versus 30; p < 0.001), expired carbon monoxide levels (25 versus 33 ppm; p < 0.001), plasma nicotine and cotinine levels, and Fagerström Tolerance Questionnaire score (5.7 versus 7.0; p < 0.001). All subjects received active treatment for up to 18 weeks (full dose for 12 weeks plus tapering dose for 6 weeks), with follow-up visits scheduled up to 1 yr. A statistically significant reduction in cigarette consumption (versus baseline) was observed among both the occasional (-99%) and regular (-77%) smokers between week 1 and week 52 (p < 0.001). Concomitant smoking and patch use was well tolerated since adverse events were infrequent, mild and transient. Thus, in addition to those subjects who successfully quit smoking, a further group of subjects who attended all the follow-up visits during the smoking cessation trial significantly reduced their mean daily cigarette consumption.

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.

Characteristics of women exposed and unexposed to environmental tobacco smoke (ETS) in a general population sample of North Italy (Po River Delta epidemiological study).

To define qualitative and quantitative categories of exposure to environmental tobacco smoke (ETS) and to assess possible differences for life-style factors between exposed and unexposed women, we studied 867 nonsmoking women (8-73 aged), selected from a general population sample living in the Po Delta area (near Venice, North Italy). Information was collected by a standardized questionnaire. ETS exposure at home, at work or elsewhere was considered. There was a prevalence of ETS exposure of 46% in the whole sample; the rate had a negative association with age. Exposure to ETS occurred more frequently at home, either singly (56%) or in combination with school/work and other places (75%). Exposed women were significantly younger, taller and lighter than those unexposed. Logistic regression on 20+ aged women showed that single-separated-widowed, workers, women living in a rental house, and women with a central forced air heating were significantly more exposed to ETS. Crowding index (n inhabitants/n rooms of the house) was significantly higher in those exposed. These results indicate that ETS exposure is quite frequent in Italian women and that some life-style factors (e.g. marital status or occupational status or some home characteristics), should be considered in the study of relationship between passive smoking and respiratory health.

Prevalence of airways obstruction in a general population: European Respiratory Society vs American Thoracic Society definition.

STUDY OBJECTIVES: To evaluate the distribution of airways obstruction in a general population sample. METHODS: Cross-sectional epidemiologic survey of a general population sample living in Po Delta area (North Italy). Data on respiratory symptoms, diseases, and risk factors were collected through standardized interviewer-administered questionnaires. Lung function tests were performed, with criteria for defining airways obstruction based on the 1995 European Respiratory Society (ERS) statement (FEV(1)/vital capacity ratio < 88% predicted and < 89% predicted in men and women, respectively), "clinical" criteria (FEV(1)/FVC ratio < 70%), and the 1986 American Thoracic Society (ATS) statement (FEV(1)/FVC ratio < 75%). RESULTS: A total of 1,727 subjects aged > 25 years investigated from 1988 to 1991 were included. Prevalence rates of airways obstruction for subjects 25 to 45 years old and subjects >/= 46 years old were as follows: ERS, 10.8% and 12.2%; clinical, 9.9% and 28.8%; and ATS, 27% and 57%, respectively. When considering only moderate/severe obstruction, the rates were as follows: ERS, 0.4% and 3.6%; clinical, 0.3% and 4.4%; and ATS, 0.5% and 5.2%, respectively. The trend was confirmed after stratifying for smoking habit and the presence/absence of respiratory symptoms/diseases. The highest specificity and predictive value for any respiratory symptom/disease was shown by the ERS, and the lowest was shown by the ATS criterion, while the reverse was true for sensitivity; overall accuracy was slightly lower for the ATS criterion. Multiple logistic regression models indicated a higher number of significant associations with known risk factors for airways obstruction according to clinical and ATS criteria than ERS criterion. CONCLUSIONS: The prevalence of COPD in a general population depends very much on the criterion used for definition of airways obstruction. Further research is needed to reach a standardized and epidemiologically consistent criterion for airways obstruction.

Inter-laboratory comparison of flow-volume curve measurements as quality control procedure in the framework of an international epidemiological study (PEACE project).

The aim of this work was to describe the results of a simple quality control procedure for the flow-volume curve adopted in a multicentre epidemiological study (PEACE). In 14 centres, 8-15 individuals (n = 157) performed forced vital capacity (FVC) manoeuvres following a standard protocol with both the local spirometer/pneumotachograph and a portable spirometer (i.e. the 'reference instrument' for this study). Deviances of measurements were assessed by computing the differences (delta) between the former and the latter, the ratios of such differences on portable spirometer values (delta %) and the coefficients of variation (CV). The portable spirometer yielded lower mean AFVC and deltaFEV1 (forced in 1 sec) than local instruments (except for two and four centres, respectively). In most instances, differences were statistically significant. Absolute mean A%FVC ranged from 4.9-18.2%, while delta%FEV1 ranged from 2.3-18.5%. The Bland and Altman analysis showed a good agreement between the portable and local instruments, except for two centres, where a systematic trend towards higher individual absolute deltaFVC and deltaFEV1 was observed. The overall variability, assessed by CV, was within 6.2% and 5.1% for FVC and FEV1, respectively: it was similar to other quality control studies ranging from 2.0-5.5% for FVC and 2.2-5.8% for FEV1. Our results point out the importance of performing interlaboratory comparisons as a quality control procedure in multicentre epidemiological studies on lung function, and of stimulating manufacturers to extend the accuracy and precision of the instruments.

Smooth reference equations for slow vital capacity and flow-volume curve indexes.

We derived reference values for slow vital capacity (VC) and flow-volume curve indexes (FVC, FEV(1), and flows) from the 1,185 tracings provided by 1,039 "normal" subjects who participated in one or both cross-sectional surveys of the Po River Delta study in 1980-1982 and in 1988-1991. Definition of "normal" was based on negative answers to questions on respiratory symptoms/diseases or recent infections, current/past tobacco smoking, and work exposure to noxious agents. Reference equations were derived separately by sex as linear regressions of body mass index (BMI = weight/height(2)), BMI-squared, height, height-squared, and age. Age entered all the models by natural cubic splines using two break points, except for the ratios FEV(1)/VC and FEV(1)/FVC. Random effects models were applied to adjust for the potential intrasubject correlation. BMI, along with height and age, appeared to be an important predictor, which was significantly associated with VC, FEV(1), FVC, FEV(1)/FVC, and PEF in both sexes, and with FEV(1)/VC and FEF(25-75) in females. Natural cubic splines provided smooth reference equation curves (no "jumps" or "angled points") over the entire age span, differently from the conventional reference equations. Thus, we recommend the use of smooth continuous equations for predicting lung function indexes, along with the inclusion of BMI in the equations.