P. Vermeire

Optimal assessment and management of chronic obstructive pulmonary disease (COPD). The European Respiratory Society Task Force

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality. In the European Union, COPD and asthma, together with pneumonia, are the third most common cause of death. In North America, COPD is the fourth leading cause of death, and mortality rates and prevalence are increasing. The major characteristic of COPD is the presence of chronic airflow limitation that progresses slowly over a period of years and is, by definition, largely irreversible. Most patients with COPD are, or were, cigarette smokers. Prevention by reducing the prevalence of smoking remains a priority. Although much of the damage is irreversible at the time of clinical presentation, treatments are available to improve the quality of life, the life expectancy, and perhaps the functional ability of patients with COPD. Several national and international consensus statements on optimal assessment and management of asthma have been published in recent years. These consensus statements have led to international standardization of diagnosis and management and to better care. They also form a basis for clinical audits and suggest areas of future research. However, there have been few attempts to develop consensus guidelines on management of COPD [1, 2]. The European Respiratory Society (ERS) has taken the initiative of producing a consensus statement on COPD. A Task Force of scientists and clinicians was invited to provide this European consensus. The guidelines are intended for use by physicians involved in the care of patients with COPD, and their main goals are to inform health professionals and to reverse a widespread nihilistic approach to the management of these patients. This Task Force firmly believes that treatment can significantly improve the quality and length of life of patients suffering from this chronic, progressive condition. Subcommittees of the Task Force focused on the five main sections of this project: Pathology/Pathophysiology, Epidemiology, Assessment, Treatment, and Management. Experts produced papers within each section, and these papers were brought together by the subcommittee heads. At a plenary meeting held in Wiesbaden, Germany on November 11–13, 1993, all contributions were extensively discussed, and additional working group meetings were arranged. Flowcharts for management in common clinical situations were produced. However, at all stages, members of the Task Force found themselves confronted by unresolved questions and regional differences in management across Europe. A practical approach was adopted, combining established scientific evidence and a consensus view when current data were inadequate. This approach identified more clearly those areas where further research is needed. Comments on drafts of the consensus statement were invited from participants of the original meeting, which included colleagues from North America. The edited document was sent to independent experts for external review. All members had an opportunity to comment on the document at the ERS meeting in Nice on October 2, 1994. As chairmen of the Task Force, we hope that the final document will promote better management of COPD in Europe. We would like to thank all who contributed to it. On behalf of the ERS, we also gratefully acknowledge a generous educational grant from Boehringer Ingelheim and the organizational assistance provided by M.T. Lopez-Vidriero.

Epidemiology and costs of chronic obstructive pulmonary disease

SERIES “THE GLOBAL BURDEN OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE” Edited by K.F. Rabe and J.B. Soriano Number 1 in this Series Chronic obstructive pulmonary disease (COPD) is a leading but under-recognised cause of morbidity and mortality worldwide 1. The prevalence of COPD in the general population is estimated to be ∼1% across all ages rising steeply to >10% amongst those aged ≥40 yrs. The prevalence climbs appreciably higher with age. The 30-yr projections for the global increase in COPD from 1990–2020 are startling. COPD is projected to move from the sixth to the third most common cause of death worldwide, whilst rising from fourth to third in terms of morbidity within the same time-frame 2. The cofactors responsible for this remarkable increase are the continued use of tobacco, coupled with the changing demographics of the world, such that many more people, especially those in developing countries, are living into the COPD age range. COPD is under-diagnosed not only in its early stages, but even when lung function is severely impaired. This is perhaps surprising, since simple and inexpensive spirometers that are suitable in clinical practice are now available, and lung function is a powerful predictor of all-cause mortality, regardless of smoking status. No other disease that is responsible for comparable morbidity, mortality and cost is neglected by healthcare providers as much as COPD. It may well be that the true burden of the disease is not fully appreciated, and the message that COPD is both preventable and treatable has yet to be fully understood by most healthcare providers. The hope is that highlighting these facts will help to raise the profile of COPD and begin to change long-held attitudes. Up to 2001, only 32 prevalence surveys of COPD had been reported 3. This is remarkable given the hundreds …

EPIDEMIOLOGY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) is a leading cause of world-wide mortality and disability. On average approximately 5-15% of adults in industrialized countries have COPD defined by spirometry. In 1990, COPD was considered to be at the twelfth position world-wide as a cause of combined mortality and disability but is expected to become the fifth cause by the year 2020. COPD has a chronic long-lasting course characterized by irreversible decline of forced expiratory volume in one second (FEV1), increasing presence of dyspnoea and other respiratory symptoms, and progressive deterioration of health status. After diagnosis the 10-yr survival rate is approximately 50% with more than one-third of patients dying due to respiratory insufficiency. Several environmental exposures such as air pollution increase the risk of death in COPD patients. The aetiology of COPD is overwhelmingly dominated by smoking although many other factors could play a role. Particular genetic variants are likely to increase the susceptibility to environmental factors although little is known about which are the relevant genes. There is clear evidence about the role of the alpha-1-antitrypsin but the fraction of COPD attributable to the relevant variants is only 1%. Phenotypic traits that are considered to play a role in the development of COPD include sex, with females being at a higher risk, bronchial responsiveness and atopy. There is strong causal evidence regarding the relationship between smoking and COPD with decline in FEVI levelling off after smoking cessation. Passive smoking has been found to be associated with a small though statistically significant decline in FEV1. Other risk factors that are likely to be relevant in the development of COPD are occupation, low socioeconomic status, diet and possibly some environmental exposures in early life. Although there is accumulating evidence that oxygen therapy, pharmacological treatment and rehabilitation may improve the course of chronic obstructive pulmonary disease, preventing smoking continues to be the most relevant measure, not only to prevent chronic obstructive pulmonary disease, but also to arrest its development.

Does the use of antibiotics in early childhood increase the risk of asthma and allergic disease

One of the mechanisms evoked to explain the increasing prevalences of asthma and allergy, in particular among children, is the ‘Western lifestyle’ or ‘hygiene’ hypothesis. As early childhood infections are assumed to hold a protective effect on the development of asthma and allergies, the use of antibiotics at that sensitive age may lead to an increased risk of asthma and allergy.

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.

Increased prevalence of sleep disturbances and daytime sleepiness in subjects with bronchial asthma: a population study of young adults in three European Countries.

The aim of this study was to investigate whether asthma is associated with decreased quality of sleep and increased daytime sleepiness. The study involved a random population of 2,202 subjects supplemented by 459 subjects with suspected asthma, aged 20-45 yrs. The subjects were from Reykjavik (Iceland), Uppsala and Göteborg (Sweden) and Antwerp (Belgium), and participated in the European Community Respiratory Health Survey. The investigation included a structured interview, methacholine challenge, skinprick tests and a questionnaire on sleep disturbances. Participants in Iceland and Sweden also estimated their sleep times and made peak expiratory flow (PEF) recordings during a period of 1 week. Asthma was defined as self-reported physician-diagnosed asthma with current asthma-related symptoms (n = 267). Difficulties inducing sleep (DIS) and early morning awakenings (EMA) were about twice as common, and daytime sleepiness 50% more common, in asthmatics compared with subjects without asthma. After adjusting for possible confounders, a positive association was found between asthma and: DIS (odds ratio (OR) = 1.8); EMA (OR = 2.0); daytime sleepiness (OR = 1.6); snoring (OR = 1.7); and self reported apnoeas (OR = 3.7). Allergic rhinitis, which was reported by 71% of subjects with asthma, was independently related to DIS (OR = 2.0) and daytime sleepiness (OR = 1.3). A significant correlation was found between the number of asthma-related symptoms and sleep disturbances (p < 0.001). Asthma is associated with decreased subjective quality of sleep and increased daytime sleepiness. Concurrent allergic rhinitis may be an important underlying cause of sleep impairment in asthmatic 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.

L-Arginine-dependent production of nitrogen oxides by rat pulmonary macrophages

Rat alveolar and pleural macrophages incubated with lipopolysaccharide, opsonized zymosan or recombinant interferon-gamma, but not with recombinant tumor necrosis factor-alpha, produced nitrite dose and time dependently. This production depends on the presence and amount of L-arginine in the culture medium. The precursor of the nitrite was demonstrated as being nitric oxide, by bleaching of ferredoxin at 410 nm when added to the culture medium. Addition of NG-monomethyl-L-arginine, an inhibitor of nitric oxide synthesis, and cycloheximide, a protein synthesis inhibitor, to the medium resulted in a decrease of nitrite production. Glucocorticoids were able to block the induction of nitrite production in alveolar macrophages. These data indicate that pulmonary macrophages are capable of secreting L-arginine-derived nitrogen oxides.

Daytime sleepiness, snoring and gastro‐oesophageal reflux amongst young adults in three European countries

Abstract. Objectives. To study the geographical variation in daytime sleepiness, snoring and disrupted breathing during sleep and to identify and compare risk factors using the same method in four European cities.