Neil B. Pride

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.

Long-Term Treatment with Inhaled Budesonide in Persons with Mild Chronic Obstructive Pulmonary Disease Who Continue Smoking

Background and Methods Although patients with chronic obstructive pulmonary disease (COPD) should stop smoking, some do not. In a double-blind, placebo-controlled study, we evaluated the effect of the inhaled glucocorticoid budesonide in subjects with mild COPD who continued smoking. After a six-month run-in period, we randomly assigned 1277 subjects (mean age, 52 years; mean forced expiratory volume in one second [FEV1], 77 percent of the predicted value; 73 percent men) to twice-daily treatment with 400 μg of budesonide or placebo, inhaled from a dry-powder inhaler, for three years. Results Of the 1277 subjects, 912 (71 percent) completed the study. Among these subjects, the median decline in the FEV1 after the use of a bronchodilator over the three-year period was 140 ml in the budesonide group and 180 ml in the placebo group (P=0.05), or 4.3 percent and 5.3 percent of the predicted value, respectively. During the first six months of the study, the FEV1 improved at the rate of 17 ml per year in the bud...

Recent trends in physician diagnosed COPD in women and men in the UK

BACKGROUND Recent trends in physician diagnosed chronic obstructive pulmonary disease (COPD) in the UK were estimated, with a particular focus on women. METHODS A retrospective cohort of British patients with COPD was constructed from the General Practice Research Database (GPRD), a large automated database of UK general practice data. Prevalence and all-cause mortality rates by sex, calendar year, and severity of COPD, based on treatment only, were estimated from January 1990 to December 1997. RESULTS A total of 50 714 incident COPD patients were studied, 23 277 (45.9%) of whom were women. From 1990 to 1997 the annual prevalence rates of physician diagnosed COPD in women rose continuously from 0.80% (95% CI 0.75 to 0.83) to 1.36% (95% CI 1.34 to 1.39), (p for trend <0.01), rising to the rate observed in men in 1990. Increases in the prevalence of COPD were observed in women of all ages; in contrast, a plateau was observed in the prevalence of COPD in men from the mid 1990s. All-cause mortality rates were higher in men than in women (106.8 versus 82.2 per 1000 person-years), with a consistently increased relative risk in men of 1.3 even after controlling for the severity of COPD. Significantly increased mortality rates were also observed in adults aged less than 65 years. The mean age at death was 76.5 years; patients with severe COPD died an average of three years before those with mild disease (p<0.01) and four years before the age and sex matched reference population. CONCLUSIONS While prevalence rates of COPD in the UK seem to have peaked in men, they are continuing to rise in women. This trend, together with the ageing of the population and the long term cumulative effect of pack-years of smoking in women, is likely to increase the present burden of COPD in the UK.

Exhaled nitric oxide from lung periphery is increased in COPD

Single constant flow exhaled nitric oxide (eNO) cannot distinguish between the sources of NO. The present study measured eNO at multiple expired flows (MEFeNO) to partition NO into alveolar (Calv,NO) and bronchial (Jaw,NO) fractions to investigate peripheral lung contribution to eNO in chronic obstructive lung disease (COPD). MEFeNO were made in 81 subjects including 18 nonsmokers, 16 smokers and 47 COPD patients of different severity by the classification of the Global Initiative for Chronic Obstructive Lung Disease (GOLD): 0 (n = 14), 1 (n = 7), 2 (n = 11), 3 (n = 8) and 4 (n = 7). COPD severity was correlated with an increased Calv,NO regardless of the patients smoking habit or current treatment. The levels of Calv,NO (in ppb) were 1.4±0.09 in nonsmokers, 2.1±0.1 in smokers categorised as GOLD stage 0 (smokers-GOLD0), 3.3±0.18 in GOLD1–2 and 3.4±0.1 in GOLD3–4. Jaw,NO levels (pL·s−1) were higher in nonsmokers than smokers-GOLD0 (716.2±33.3 versus 464.7±41.8), GOLD3–4 (609.4±71). Diffusion of NO in the airways (Daw,NO pL·ppb−1s−1) was higher (p<0.05) in GOLD3–4 than in nonsmokers (15±1.2 versus 11±0.5) and smokers-GOLD0 (11.6±0.5). MEFeNO measurements were reproducible, free from day-to-day and diurnal variation and were not affected by bronchodilators. In conclusion, chronic obstructive pulmonary disease is associated with elevated alveolar nitric oxide. Measurements of nitric oxide at multiple expired flows may be useful in monitoring inflammation and progression of chronic obstructive pulmonary disease, and the response to anti-inflammatory treatment.

BONE MINERAL DENSITY IN PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY DISEASE TREATED WITH BUDESONIDE TURBUHALER

There is a need for studying the effects of long-term inhaled corticosteroid therapy on bone mineral density (BMD) and vertebral fracture rates in patients with mild chronic obstructive pulmonary disease (COPD). Patients (n=912, mean age 52 yrs) with mild COPD (mean forced expiratory volume in one second (FEV1) 77% of predicted; mean FEV1/slow vital capacity ratio 62%) were randomized to receive budesonide 400 µg, or placebo twice daily via Turbuhaler®. BMD was measured at the L2–L4 vertebrae and the femoral neck, trochanter and Wards triangle by dual-energy X-ray absorptiometry at baseline and after 6, 12, 24 and 36 months (n=161). Radiographs of the thoracic and lumbar spine were obtained at the beginning and end of treatment (n=653). Previous fractures were present at baseline in 43 budesonide-treated patients (13.4%) and 38 placebo-treated patients (11.5%). New fractures occurred in five budesonide-treated patients, compared with three in the placebo group (p=0.50). There were no significant changes in BMD at any site in budesonide-treated patients, compared with the placebo group, during the course of the study. Budesonide treatment was associated with a slight but statistically significant decrease in the area under the concentration-time curve for serum osteocalcin. In the present study, involving a large group of patients with chronic obstructive pulmonary disease, long-term treatment with budesonide 800 µg·day−1 via Turbuhaler® had no clinically significant effects on bone mineral density or fracture rates.

Possible protection by inhaled budesonide against ischaemic cardiac events in mild COPD.

Epidemiological studies have indicated that chronic obstructive pulmonary disease (COPD) may be associated with an increased incidence of ischaemic cardiac events. The current authors performed a post hoc analysis of the European Respiratory Society’s study on Chronic Obstructive Pulmonary Disease (EUROSCOP); a 3-yr, placebo-controlled study of an inhaled corticosteroid budesonide 800 μg·day−1 in smokers (mean age 52 yrs) with mild COPD. The current study evaluates whether long-term budesonide treatment attenuates the incidence of ischaemic cardiac events, including angina pectoris, myocardial infarction, coronary artery disorder and myocardial ischaemia. Among the 1,175 patients evaluated for safety, 49 (4.2%) patients experienced 60 ischaemic cardiac events. Patients treated with budesonide had a significantly lower incidence of ischaemic cardiac events (18 out of 593; 3.0%) than those receiving placebo (31 out of 582; 5.3%). The results of the present study support the hypothesis that treatment with inhaled budesonide reduces ischaemic cardiac events in patients with mild chronic obstructive pulmonary disease.

Size and strength of the respiratory and quadriceps muscles in patients with chronic asthma

There have been few studies of respiratory and limb muscle size and function in middle-aged patients with asthma and persistent airways obstruction. We have compared the forces generated by the respiratory and thigh muscles with their dimensions assessed by ultrasound in nine middle-aged patients with chronic asthma (mean age 56 (SD 8) yrs; functional residual capacity/total lung capacity ratio (FRC/TLC) 60 (10)%), and in nine normal subjects (aged 53 (7) yrs; FRC/TLC 55 (5)%). Diaphragm thickness was measured at the zone of apposition by B-mode ultrasound during relaxation (DiTrelax) and during a maximum-effort inspiratory manoeuvre (DiTpI,max) at FRC. Cross-sectional area of the relaxed rectus femoris muscle (ARF) was determined by ultrasound at mid-thigh level. Isometric strength of the right quadriceps muscle group was measured during maximum voluntary contraction. Asthmatic patients had preserved quadriceps strength and ARF but moderately impaired maximum inspiratory pressure (PI,max) (-52 (18) cmH2O) and thicker DiTrelax (2.2 (0.4) mm), compared to normal subjects (-73 (21) cmH2O and 1.7 (0.3) mm, respectively). Middle-aged patients with chronic asthma and a small increase in functional residual capacity/total lung capacity ratio have preserved limb muscle force and dimensions, modestly impaired inspiratory muscle strength, and slightly increased thickness of the costal diaphragm. Future studies of respiratory muscle function in asthma should be aided by measurement of diaphragm thickness and of limb muscle strength and size. Such studies are required particularly in older patients with severe hyperinflation who are most likely to have impairment of muscle function.

Chronic obstructive pulmonary disease in the United Kingdom: trends in mortality, morbidity, and smoking.

Current trends in chronic obstructive pulmonary disease (COPD) in the UK differ from those in many other countries because, in the past, COPD was much more common than in other countries undergoing a smoking epidemic at the same time, and peak cigarette consumption in men and women occurred more 25 years ago. Male mortality from COPD has been falling for 30 years, while female mortality has risen steadily during the same period. A strong socioeconomic gradient in morbidity and mortality persists. Emergency hospital admissions for exacerbations and home oxygen account for a large proportion of the healthcare costs.

Predictors of COPD symptoms: does the sex of the patient matter?

1. Department of Epidemiology and Bioinformatics, University Medical Centre Groningen, University of Groningen, Netherlands 2. Department of Pulmonology, University Medical Centre Groningen, University of Groningen, Netherlands 3. Department of Respiratory Medicine and Allergology, University Hospital, Lund, Sweden 4. Respiratory Division, Hammersmith Campus, NHLI, Imperial College, London, UK 5. Department of Medicine, University Central Hospital, Helsinki, FinlandAlthough chronic obstructive pulmonary disease (COPD) patients frequently report symptoms, it is not known which factors determine the course of symptoms over time and if these differ according to the sex of the patient. The current study investigated predictors for presence, development and remission of COPD symptoms in 816 males and 312 females completing 3-yr-follow-up in the European Respiratory Society Study on Chronic Obstructive Pulmonary Disease (EUROSCOP). The following were included in generalised estimating equations logistic regression analyses: explanatory variables of treatment; pack-yrs smoking; age, forced expiratory volume in one second % predicted (FEV1 % pred); annual increase in FEV1 and number of cigarettes smoked; body mass index; and phadiatop. Interaction terms of sex multiplied by explanatory variables were tested. Over 3 yrs, similar proportions of males and females reported symptoms. In males only, higher FEV1 % pred was associated with reduction in new symptoms of wheeze and dyspnoea, and symptom prevalence was reduced with annual FEV1 improvement and phlegm prevalence reduced with budesonide treatment (odds ratio 0.66; 95% confidence interval 0.52–0.83). Additionally an increase in the number of cigarettes smoked between visits increased the risk of developing phlegm (1.40 (1.14–1.70)) and wheeze (1.24 (1.03–1.51)) in males but not females. The current study shows longitudinally that symptom reporting is similar by sex. The clinical course of chronic obstructive pulmonary disease can differ by sex, as males show greater response to cigarette exposure and treatment.

Estimation of diaphragm length in patients with severe chronic obstructive pulmonary disease

In patients with advanced chronic obstructive pulmonary disease (COPD) diaphragm function may be compromised because of reduced muscle fibre length. Diaphragm length (L(Di)) can be estimated from measurements of transverse diameter of the rib cage (D(Rc)) and the length of the zone of apposition (L(Zapp)) in healthy subjects, but this method has not been validated in patients with COPD. Postero-anterior chest radiographs were obtained at total lung capacity (TLC), functional residual capacity (FRC) and residual volume (RV) in nine male patients with severe COPD (mean [S.D.]; FEV(1), 23 [6] %pred.; FRC, 199 [15] %pred.). Radiographs taken at TLC were used to identify the lateral costal insertions of the diaphragm (L(Zapp) assumed to approach zero at TLC). L(Di) was measured directly and also estimated from measurements of L(Zapp) and D(Rc) using a prediction equation derived from healthy subjects. The estimation of L(Di) was highly accurate with an intraclass correlation coefficient of 0.93 and 95% CI of approximately +/-8% of the true value. L(Di) decreased from 426 (64) mm at RV to 305 (31) mm at TLC. As there were only small and variable changes in D(Rc) across the lung volume range, most of the L(Di) changes occurred in the zone of apposition. Additional studies showed that measurements of L(Di) from PA and lateral radiographs performed at different lung volumes were tightly correlated. These results suggest that non-invasive measurements of L(Zapp) in the coronal plane (e.g. using ultrasonography) and D(Rc) (e.g. using magnetometers) can be used to provide an accurate estimate of L(Di) in COPD patients.