Find information on thousands of medical conditions and prescription drugs.

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is an umbrella term for a group of respiratory tract diseases that are characterised by airflow obstruction or limitation. It is usually caused by tobacco smoking. more...

C syndrome
Café au lait spot
Calcinosis cutis
Canavan leukodystrophy
Canga's bead symptom
Canine distemper
Carcinoid syndrome
Carcinoma, squamous cell
Cardiac arrest
Carnitine transporter...
Caroli disease
Carpal tunnel syndrome
Carpenter syndrome
Cartilage-hair hypoplasia
Castleman's disease
Cat-scratch disease
CATCH 22 syndrome
Cayler syndrome
CDG syndrome
CDG syndrome type 1A
Celiac sprue
Cenani Lenz syndactylism
Ceramidase deficiency
Cerebellar ataxia
Cerebellar hypoplasia
Cerebral amyloid angiopathy
Cerebral aneurysm
Cerebral cavernous...
Cerebral gigantism
Cerebral palsy
Cerebral thrombosis
Ceroid lipofuscinois,...
Cervical cancer
Chagas disease
Charcot disease
Charcot-Marie-Tooth disease
CHARGE Association
Chediak-Higashi syndrome
Childhood disintegrative...
Chlamydia trachomatis
Cholesterol pneumonia
Chorea (disease)
Chorea acanthocytosis
Choroid plexus cyst
Christmas disease
Chromosome 15q, partial...
Chromosome 15q, trisomy
Chromosome 22,...
Chronic fatigue immune...
Chronic fatigue syndrome
Chronic granulomatous...
Chronic lymphocytic leukemia
Chronic myelogenous leukemia
Chronic obstructive...
Chronic renal failure
Churg-Strauss syndrome
Ciguatera fish poisoning
Cleft lip
Cleft palate
Cloacal exstrophy
Cluster headache
Cockayne's syndrome
Coffin-Lowry syndrome
Color blindness
Colorado tick fever
Combined hyperlipidemia,...
Common cold
Common variable...
Compartment syndrome
Conductive hearing loss
Condyloma acuminatum
Cone dystrophy
Congenital adrenal...
Congenital afibrinogenemia
Congenital diaphragmatic...
Congenital erythropoietic...
Congenital facial diplegia
Congenital hypothyroidism
Congenital ichthyosis
Congenital syphilis
Congenital toxoplasmosis
Congestive heart disease
Conn's syndrome
Constitutional growth delay
Conversion disorder
Cor pulmonale
Cor triatriatum
Cornelia de Lange syndrome
Coronary heart disease
Cortical dysplasia
Corticobasal degeneration
Costello syndrome
Craniodiaphyseal dysplasia
Craniofacial dysostosis
CREST syndrome
Creutzfeldt-Jakob disease
Cri du chat
Cri du chat
Crohn's disease
Crouzon syndrome
Crow-Fukase syndrome
Cushing's syndrome
Cutaneous larva migrans
Cutis verticis gyrata
Cyclic neutropenia
Cyclic vomiting syndrome
Cystic fibrosis
Dilated cardiomyopathy
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy

Conditions included in this umbrella term are:

  • chronic bronchitis
  • emphysema

Other names

COPD is also known as CORD, COAD, COLD which respectively stand for chronic obstructive respiratory, airways, or lung disease. COPD has been referred to as CAL which stands for chronic airway limitation.

Working definition

COPD is a chronic, progressive disorder related to tobacco abuse and characterized by airways obstruction (FEV1 <80% predicted and FEV1 / VC ratio <70%).

The Global Initiative for Chronic Obstructive Lung Disease (GOLD) defines COPD as "a disease state characterized by airflow limitation that is not fully reversible. The airflow limitation is usually progressive and associated with abnormal inflammatory response of the lungs to noxious particles or gases."


The main risk factor in the development of COPD is smoking. Approximately 15% of all chronic smokers will develop the disease. In susceptible people, this causes chronic inflammation of the bronchi and eventual airway obstruction. Other etiologies include alpha 1-antitrypsin deficiency (augmented by smoking), byssinosis, and idiopathic disease.

Among people over 70 who have never smoked, women make up 85 percent of those with COPD. This appears to be tied to decreases in estrogen as women age. Female mice that had their ovaries removed to deprive them of estrogen lost 45 percent of their working alveoli from their lungs. Upon receiving estrogen, the mice recovered full lung function. Two proteins that are activated by estrogen play distinct roles in breathing. One protein builds new alveoli, the other stimulates the alveoli to expel carbon dioxide. Loss of estrogen hampered both functions in the test mice. (Massaro & Massaro, 2004).


COPD is a progressive disease. Obstructive changes in spirometry and decreases in diffusion capacity are typically seen before symptoms occur. Early signs and symptoms are shortness of breath on exertion, recurrent respiratory infections or a morning cough. As the disease continues, the symptoms are seen with increased frequency and severity. In the late stages, the patient often experiences severe cough, constant wheezing, and shortness of breath with minimal exertion or rest. At this late stage, progression to respiratory failure and death is common. Progression is typically caused by the patient's continued exposure to tobacco smoke. Although medications often decrease symptoms, it is not believed that they prevent the progression if the patient continues to smoke.


[List your site here Free!]

Randomised, double blind, placebo controlled study of fluticasone propionate in patients with moderate to severe chronic obstructive pulmonary disease:
From British Medical Journal, 5/13/00 by P S Burge


Objectives To determine the effect of long term inhaled corticosteroids on lung function, exacerbations, and health status in patients with moderate to severe chronic obstructive pulmonary disease.

Design Double blind, placebo controlled study.

Setting Eighteen UK hospitals.

Participants 751 men and women aged between 40 and 75 years with mean forced expiratory volume in one second ([FEV.sub.1]) 50% of predicted normal.

Interventions Inhaled fluticasone propionate 500 [micro]g twice daily from a metered dose inhaler or identical placebo.

Main outcome measures Efficacy measures: rate of decline in [FEV.sub.1] after the bronchodilator and in health status, frequency of exacerbations, respiratory withdrawals. Safety measures: morning serum cortisol concentration, incidence of adverse events.

Results There was no significant difference in the annual rate of decline in [FEV.sub.1] (P = 0.16). Mean [FEV.sub.1] after bronchodilator remained significantly higher throughout the study with fluticasone propionate compared with placebo (P [is less than] 0.001). Median exacerbation rate was reduced by 25% from 1.32 a year on placebo to 0.99 a year on with fluticasone propionate (P = 0.026). Health status deteriorated by 3.2 units a year on placebo and 2.0 units a year on fluticasone propionate (P = 0.0043). Withdrawals because of respiratory disease not related to malignancy were higher in the placebo group (25% v 19%, P = 0.034).

Conclusions Fluticasone propionate 500 [micro]g twice daily did not affect the rate of decline in [FEV.sub.1] but did produce a small increase in [FEV.sub.1]. Patients on fluticasone propionate had fewer exacerbations and a slower decline in health status. These improvements in clinical outcomes support the use of this treatment in patients with moderate to severe chronic obstructive pulmonary disease.


Chronic obstructive pulmonary disease is a leading cause of morbidity and mortality worldwide,[1 2] and its prevalence is rising.[3] It occurs predominantly in tobacco smokers and is characterised by an increase in the annual rate of decline of forced expiratory volume in one second ([FEV.sub.1]).[4] As lung function deteriorates, substantial changes in general health occur.[5] Smoking cessation reduces the rate of decline in [FEV.sub.1] in people with this disease,[6] but no pharmacological intervention has been shown to modify the progression of disease or the associated decline in health status.

In at least 10% of patients with stable chronic obstructive pulmonary disease [FEV.sub.1] will increase significantly after oral prednisolone.[7] A large, retrospective, open study reported a reduction in the rate of decline of [FEV.sub.1] in those taking oral corticosteroids.[8] Recently, two studies over three years of inhaled budesonide 800 [micro]g in mild to moderate chronic obstructive pulmonary disease found no effect of treatment on the rate of decline in [FEV.sub.1].[9 10] Clinical outcomes such as exacerbations, however, were infrequent and health status either showed no benefit of budesonide[9] or was not assessed.[10]

The inhaled steroids in obstructive lung disease in Europe (ISOLDE) study was designed to test the effect of inhaled fluticasone propionate 500 [micro]g twice daily on the rate of decline of [FEV.sub.1] and other relevant clinical outcomes.

Participants and methods


Eighteen UK hospitals participated. Patients were current or former smokers aged 40-75 years with non-asthmatic chronic obstructive pulmonary disease. Baseline [FEV.sub.1] after bronchodilator was at least 0.8 litres but less than 85% of predicted normal, and the ratio of [FEV.sub.1] to forced vital capacity was less than 70%. Previous use of inhaled and oral corticosteroids was permitted. Patients were excluded if their [FEV.sub.1] response to 400 [micro]g salbutamol exceeded 10% of predicted normal, they had a life expectancy of less than five years from concurrent diseases, or they used [Beta] blockers. Nasal and ophthalmic corticosteroids, theophyllines, and all other bronchodilators were allowed during the study.

The protocol was approved by each centre's local ethical committee and patients provided written informed consent.

Trial design

Patients were recruited between 1 October 1992 and 31 March 1995. Eligible patients entered an eight week run-in period after withdrawal from any oral or inhaled corticosteroids. After clinic visits at 0, 4, and 8 weeks (visits 0, 1, and 2, respectively) patients were randomised to receive either fluticasone propionate 500 [micro]g or an identical placebo twice daily administered from a metered dose inhaler and with a spacer device by using 10 tidal breaths after each of two actuations. We used a computer generated allocation schedule stratified by centre (block size of six). Patients were randomised sequentially from a list comprising treatment numbers only. Throughout the trial patients used salbutamol (100 [micro]g/puff) or ipratropium bromide (40 [micro]g/puff), or both, for symptomatic relief.

Before the double blind phase, and if not contraindicated, patients received oral prednisolone 0.6 mg/kg/day for 14 days, after which spirometry was performed. These data were used to test whether the acute corticosteroid response could predict those patients who would benefit from long term inhaled corticosteroids. During the three year double blind phase, participants visited a clinic every three months for spirometry, recording of exacerbations, and safety assessments.

The primary end point was the decline (ml/year) in [FEV.sub.1] after bronchodilator. About 450 patients with two or more measurements of [FEV.sub.1] during treatment were required to detect a treatment difference of 20 ml/year, assuming a linear decline and a SD of 75 ml/year, with 80% power. Other key end points were frequency of exacerbation, changes in health status, withdrawals because of respiratory disease, morning serum cortisol concentrations, and adverse events.


Spirometry measurements were recorded by well trained staff using a standardised procedure on new Sensormedics 2130D spirometers. Quality control included a computer generated check against the ATS criteria[11] and a central manual check for acceptability and reproducibility for all measurements, resulting in standards comparable with the lung health study.[12] Visits were rescheduled to four weeks after any respiratory infections or exacerbations of the disease.

An exacerbation was defined as worsening of respiratory symptoms that required treatment with oral corticosteroids or antibiotics, or both, as judged by the general practitioner; specific symptom criteria were not used. Patients were withdrawn from the study if the number of exacerbations that required corticosteroids exceeded two in any three month period.

Health status was assessed at baseline and six monthly thereafter by using the disease specific St George's respiratory questionnaire (SGRQ).[13] This questionnaire is sensitive to changes in treatment.[14] A change in total score of four or more units represents a clinically important change in the patient's condition.[5] Serum cortisol concentrations were measured before randomisation (baseline) and every six months during treatment. Samples were taken between 8 am and 10 am and were analysed with the ELISA-Boehringer Mannheim ES700 method.

At each visit patients were questioned about smoking status. Non-smoking was checked with exhaled carbon monoxide and urinary cotinine measurements. Self declared non-smokers were classified as smokers if cotinine was [is greater than] 40 ng/ml or carbon monoxide was [is greater than] 10 ppm at two visits. For analysis patients were categorised as continuous smokers, continuous former smokers, or intermittent smokers during the study.

Statistical analysis

Analyses for each parameter included all randomised patients with at least one valid measurement. To use all patient data we adopted the mixed models approach[15] for the primary analysis of [FEV.sub.1] and total score. This is the most suitable technique for estimating rates of change, with allowance for the correlation structure of repeated measures data. Regression estimates were adjusted for patient differences in the number of observations contributing to the model and for variances within patients.[16] Fixed effects were time and five covariates: baseline value centre, age, sex, and smoking status. Baseline [FEV.sub.1] was the mean at four and eight weeks of the run-in period--that is, at least four weeks after withdrawal of corticosteroids. Subject effects were assumed to be random. The treatment by time interaction tested for a differential treatment effect on the rate of change in [FEV.sub.1] or respiratory questionnaire score. The model for [FEV.sub.1] also included a treatment main effect to help to account for the early non-linear treatment changes. Measurements at the end of the prednisolone trial were excluded from the model of decline in [FEV.sub.1]. [FEV.sub.1] was also compared by using analysis of covariance after 3, 6, 12, 24, and 36 months to investigate treatment differences over time.

Patient exacerbation rates were calculated as the exacerbation number per treatment days and extrapolated-interpolated to a number per treatment year. The Wilcoxon rank sum test,[17] stratified by centre, tested for treatment differences.

Fisher's exact test compared treatment withdrawals due to respiratory causes. These included any non-malignant lower respiratory diseases. Analysis of covariance compared data on log transformed serum cortisol concentration during treatment, adjusted for baseline. Tests were two sided, with a 5% significance level.


Patient demographics

Of the 751 patients randomised, 376 received fluticasone propionate and 375 placebo (figure 1). During the double blind phase, 160 patients (43%) withdrew from the fluticasone propionate group and 195 patients (53%) from the placebo group, the commonest reason being frequent exacerbations of chronic obstructive pulmonary disease. Mean [FEV.sub.1] at visit two was 160 ml lower in patients who withdrew from placebo compared with those who did not withdraw (1.30 litre v 1.46 litre); patients who withdrew from fluticasone propionate had a 40 ml higher [FEV.sub.1] compared with those who did not withdraw (1.44 litre v 1.40 litre). Treatment groups were well matched at baseline (table 1).


Table 1 Baseline characteristics of randomised population. Figures are means (SD) unless stated otherwise

[FEV.sub.1]=forced expiratory volume in one second in litres; FVC=forced vital capacity.

(*) Atopy was defined as being positive response to skin prick testing with common inhalant allergens.

Missing data--placebo: 14; fluticasone propionate: 20.

([dagger]) Missing data--placebo: 37; fluticasone propionate: 16.

([double dagger]) Missing data--placebo: 4; fluticasone propionate: 3.

([sections]) Missing data--placebo: 1; fluticasone propionate: 0.

([paragraph) Score of zero indicates no health impairment and 100 represents worst possible score. Missing data--placebo: 8; fluticasone propionate: 7.

Changes in [FEV.sub.1]

There was a fall in mean [FEV.sub.1] after bronchodilator during the the run-in (placebo 75 ml, fluticasone propionate 65 ml) (fig 2). The effect was greater in patients who withdrew from inhaled corticosteroids at run-in (89 ml compared with 47 ml in the steroid naive group). After oral prednisolone there was a 60 ml (SD 170 ml) improvement in mean [FEV.sub.1] after bronchodilator in both treatment groups. Subsequently mean [FEV.sub.1] declined gradually in the fluticasone propionate group whereas in the placebo group it fell within three months to values before prednisolone treatment.


The annual rate of decline in [FEV.sub.1] was 59 ml/year in the placebo group and 50 ml/year in the fluticasone propionate group (P = 0.16) (table 2). This small difference in slopes was uninfluenced by smoking status, age, sex, or [FEV.sub.1] response to the oral corticosteroid trial. The predicted mean [FEV.sub.1] at three and 36 months in the fluticasone propionate group was 76 ml and 100 ml higher, respectively, than in the placebo group (mixed effects model P [is less than] 0.001). The analysis of covariance showed that [FEV.sub.1] in the fluticasone propionate group was higher than in the placebo group by at least 70 ml at each time point (P [is less than or equal to] 0.001). There was no significant relation between [FEV.sub.1] response to oral corticosteroid or fluticasone propionate (P = 0.056).

Table 2 Results from efficacy analyses. Mixed effects model analyses adjusted for covariates and Wilcoxon Mann-Whitney test adjusted for centre

[FEV.sub.1]=forced expiratory volume in one second in litres.

(*) Numbers are smaller than randomised population for [FEV.sub.1] and health status because of patient withdrawals, missing assessments, or respiratory infections or exacerbations (affects [FEV.sub.1] only).

([dagger]) Zero values are possible in 95% confidence intervals with non-parametric analyses that show P values [is less than or equal to] 0.05 because method of calculation of confidence intervals differs from non-parametric test.


The median yearly exacerbation rate was lower in the fluticasone propionate group (0.99 per year) compared with the placebo group (1.32 per year), a reduction of 25% in those receiving fluticasone propionate (P = 0.026).

Health status

At baseline the total respiratory questionnaire score was not significantly different between treatment groups (table 1), and it did not change significantly over the first six months of treatment (placebo: up 1.2 (SD 11.9); fluticasone propionate: down 0.5 (SD11.8); P = 0.09). Thereafter it increased (that is, health status declined) over time (figs 3 and 4). This increase was linear (P [is less than] 0.0001). The respiratory questionnaire score worsened at a faster rate (P = 0.004) with placebo (3.2 units/year) than with fluticasone propionate (2.0 units/year).



More patients in the placebo group than in the fluticasone propionate group withdrew because of respiratory disease that was not associated with malignancy (25% v 19%, respectively; P = 0.034).


Reported events were similar between treatments (table 3), except for a slightly higher incidence of events related to inhaled glucocorticoid in the fluticasone propionate group.

Table 3 Number of patients with each category of adverse events during double blind period

(*) Includes ecchymotic rash (1 placebo patient, 8 fluticasone propionate patients).

There was a significant (P [is less than or equal to] 0.032) yet small decrease in mean cortisol concentrations with fluticasone propionate compared with placebo (table 4). No more than 5% of patients on fluticasone propionate had values below the normal range during the study at any time. No decreases were associated with any signs or symptoms of hypoadrenalism or other clinical effects.

Table 4 Morning serum cortisol concentration (nmol/l) for patients who provided valid data (8 am to 10 am samples only) during double blind period

(*) Least squares means from analysis of covariance of log transformed serum cortisol concentrations were back transformed to give geometric means.

([dagger]) CV=coefficient of variation (%).


Inhaled corticosteroids have been used widely in the United Kingdom for the empirical treatment of symptomatic chronic obstructive pulmonary disease, but evidence to support this practice is limited. Unlike early reports,[18 19] our study in moderate to severe chronic obstructive pulmonary disease found no effect of corticosteroids on the rate of decline in [FEV.sub.1]--a finding consistent with two recent budesonide studies in mild disease.[9 10] Like Euroscop, a study in continued smokers,[10] we found a small improvement in [FEV.sub.1] after bronchodilator at three months, which was maintained throughout the study. The clinical significance of this change in airway function is unclear. Our study also showed no significant relation between corticosteroid trial response and response to long term inhaled corticosteroid.

The exacerbation rate for placebo was similar to that seen in previous reports,[20] but for fluticasone propionate it was 25% lower. Precise definition of an exacerbation is difficult in ambulant patients with chronic obstructive pulmonary disease, but, by using the operational approach adopted in ISOLDE, reductions in exacerbation severity were seen in another study of patients with moderately severe disease treated for six months with fluticasone propionate.[21] During the ISOLDE run-in we also observed that withdrawal of inhaled corticosteroids was associated with an increased likelihood of an exacerbation.[22] These observations suggest that inhaled corticosteroids do modify the risk of symptomatic deterioration in chronic obstructive pulmonary disease.

Assessment of of health status is recognised as an important additional measurement in patients with chronic respiratory disease and is a better predictor of admission to hospital and death within 12 months than [FEV.sub.1].[23] The baseline respiratory questionnaire score showed significant impairment, in keeping with other populations with similar reductions in [FEV.sub.1].[13 14] This study shows for the first time that, like [FEV.sub.1], health status declines at a measurable rate in patients with moderate to severe chronic obstructive pulmonary disease. Fluticasone propionate significantly reduced this rate of decline, delaying the average time for a clinically important reduction in health status from 15 to 24 months. As the respiratory questionnaire has only a weak correlation with [FEV.sub.1],[5] it must be reflecting other disease components other than airflow limitation.


Several factors, including disease severity, comorbidity, and study duration, contributed to the high withdrawal rate. Patients were also actively withdrawn from the study and not subsequently followed up if they experienced frequent exacerbations; this is an acknowledged limitation of the study. The effect of the differential rate of withdrawal from treatment is difficult to quantify, nevertheless it is likely to have led to a conservative estimate of benefit with fluticasone propionate.

Reports of adverse events for each treatment were generally similar, although the incidence of events related to glucocorticoids was slightly higher in the fluticasone propionate group. The incidence of fractures was low (2%) and similar to that reported in Euroscop.[10] No more than 5% of patients on fluticasone propionate had cortisol concentrations below the normal range at any time during treatment. Similar reassuring data have been reported from a two year placebo controlled study of fluticasone propionate 500 [micro]g twice daily in adults with mild asthma.[24]


We found no benefit of fluticasone propionate on the rate of decline in [FEV.sub.1], although small improvements in [FEV.sub.1] were seen. Unlike the two studies in patients with milder disease, where other clinical outcomes were less measurable,[9 10] we found that fluticasone propionate 500 [micro]g twice daily significantly reduced exacerbations and the rate of decline in health status. These data provide a rationale for the current practice of using use of inhaled corticosteroids at this dose in patients with moderate to severe chronic obstructive pulmonary disease.

Dr G F A Benfield, Dr M D L Morgan, Dr J C Pounsford, Dr R M Rudd, and Professor S G Spiro provided input into the design of the study. The scientific committee members comprised: Dr G F A Benfield, Professor P M A Calverley, Dr J Daniels, Dr A Greening, Professor G J Gibson, Professor P W Jones, Dr M D L Morgan, Dr R Prescott, Dr J C Pounsford, Dr R M Rudd, Professor D Shale, Professor S G Spiro, Mrs J Waterhouse, Dr J A Wedzicha, and Dr D Weir. The steering committee members were Mrs G Bale, Dr P S Burge, Professor P W Jones, and Dr G F A Benfield. Quality control of spirometry data was supervised by Jonathon Daniels and Geraldine Bale, who also acted as study nurse coordinator. Contributions in recruiting patients and with data collection were provided by Professor J G Ayres, Mrs G Bale, Dr N Barnes, Mrs C Baveystock, Dr G F A Benfield, Ms K Bentley, Dr Birenacki, Ms G Boar, Dr P Bright, Ms M Campbell, Ms P Carpenter, Ms S Cattell, Dr I I Coutts, Dr L Davies, Ms C Dawe, Ms J Dowselt, Ms K Dwyer, Mrs C Evans, Ms N Fasey, Dr A G Fennerty, Dr D Fishwick, Ms H Francis, Dr T Frank, Mrs D Frost, Professor G J Gibson, Dr J Hadcroft, Dr M G Halpin, Mrs O Harvey, Dr P Howard, Dr N A Jarad, Ms J Jones, Dr K Lewis, Mrs F Marsh, Mrs N Martin, Dr M D L Morgan, Ms L Morgan, Mrs W McDonald, Ms T Melody, Dr R D H Monie, Dr M F Muers, Dr R Niven, Dr C O'Brien, Ms V O'Dwyer, Ms S Parker, Dr M Peake, Dr W H Perks, Professor C A C Pickering, Dr J C Pounsford, Mrs K Pye, Mr G Rees, Ms A Reid, Ms K Roberts, Mrs C Robertson, Dr R M Rudd, Ms S Rudkin, Mr S Scholey, Dr P Scott, Dr T Seemungal, Ms S Shaldon, Dr C D Sheldon, Ms T Small, Professor S G Spiro, Dr J R Stradling, Ms H Talbot, Mrs J Waterhouse, Mrs L Webber, Dr J A Wedzicha, and Ms M J Wild.

Contributors: PSB and PMAC had the original idea for the present study, helped with the study design, recruited large numbers of patients, advised on data analysis, and helped with the writing of the paper. PSB chaired the scientific committee responsible for coordinating analyses, publications, and substudies. He is also the guarantor of the paper. PMAC chaired the steering committee that facilitated and monitored study progress. PWJ advised on collection and analyses of health status questionnaire data, recruited patients into the study, and helped with the writing of the paper. SS advised on data collection and carried out the health status analyses. JAA analysed the clinical efficacy data. TKM managed data collection and helped with data interpretation and the writing of the paper.

Funding: GlaxoWellcome Research and Development.

Competing interests: PSB has received financial support for research and attending meetings and has received fees for speaking and consulting. He also has shares in GlaxoWellcome. PMAC has received grant support and has spoken at several meetings financially supported by GlaxoWellcome. PWJ has received funds for research and members of staff from GlaxoWellcome. SS has received funds for research and members of staff from GlaxoWellcome. JAA and TKM are both employed by GlaxoWellcome. Fluticasone propionate is manufactured by Allen and Hanburys, which is owned by GlaxoWellcome.

What is already known on this topic

Inhaled corticosteroids are widely prescribed for patients with chronic obstructive pulmonary disease, although there are few studies to support this

A meta-analysis of three small studies showed improvements in [FEV.sub.1] with high dose beclomethasone dipropionate or budesonide but no benefit from medium dose treatment

In two recent large studies, budesonide in medium dose produced either no benefit or a small initial improvement in [FEV.sub.1]

What this study adds

This study measured progressive decline in health status of patients with chronic obstructive pulmonary disease rather than just the [FEV.sub.1]

In patients with moderate to severe disease, fluticasone propionate 1 mg daily resulted in fewer exacerbations, a reduced rate of decline in health status, and higher [FEV.sub.1] values than placebo treatment

Serious side effects were similar to placebo, topical side effects were increased

These data provide a rationale for the use of high dose inhaled corticosteroids in patients with moderate to severe chronic obstructive pulmonary disease

[1] Thom TJ. International comparisons in COPD mortality. Am Rev Respir Dis 1989;140:27-34.

[2] Murray CJ, Lopez AD. Mortality by cause for eight regions of the world: global burden of disease study. Lancet 1997;349:1269-76.

[3] Murray CJL, Lopez AD. Alternative projections of mortality and disability by cause 1990-2020: global burden of disease study. Lancet 1997;349:1498-504.

[4] Fletcher CM, Peto R. The natural history of chronic airflow obstruction. BMJ 1978;1:1645-8.

[5] Jones PW, Quirk FH, Baveystock CM. The St George's respiratory questionnaire. Respir Med 1991;85(suppl B):25-31.

[6] Anthonisen NR, Connett JE, Kiley JP, Altose MD, Bailey WC, Buist AS, et al for the Lung Health Study Research Group. Effects of smoking intervention and the use of an anticholinergic bronchodilator on the rate of decline in [FEV.sub.1].JAMA 1994;272:1497-505.

[7] Callahan CM, Dittus RS, Katz BP. Oral corticosteroid therapy for patients with stable chronic obstructive pulmonary disease. A meta-analysis. Ann Intern Med 1991;114:216-23.

[8] Postma DS, Peters I, Steenhuis EJ, Sluiter HJ. Moderately severe chronic airflow obstruction. Can corticosteroids slow down obstruction? Eur Respir J 1998;1:22-6.

[9] Vestbo J, Sorensen T, Lange P, Brix A, Torre P, Viskum K. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial. Lancet 1999;353:1819-23

[10] Pauwels RA, Lofdahl CG, Laitinen LA, Schouten JP, Postma DS, Pride NB, et al. Long-term treatment with inhaled budesonide in persons with mild chronic obstructive pulmonary disease who continue smoking. N Engl J Med 1999;340:1948-53.

[11] American Thoracic Society. Statement: standardization of spirometry, 1987 update. Am Rev Respir Dis 1987;136:1285-98.

[12] Enright PL, Johnson LR, Connett JE, Voelker H, Buist AS. Spirometry in the lung health study. 1. Methods and quality control. Am Rev Respir Dis 1991;143:1215-23.

[13] Jones PW, Quirk FH, Baveystock CM, Littlejohns P. A self-complete measure of health status for chronic airflow limitation. The St George's respiratory questionnaire. Am Rev Respir Dis 1992; 145:1321-7.

[14] Meecham Jones DJ, Paul EA, Jones PW, Wedzicha JA. Nasal pressure support ventilation plus oxygen compared with oxygen therapy alone in hypercapnic COPD. Am J Respir Crit Care Med 1995;152:538-44.

[15] Goldstein H. Multilevel statistical models. 2nd ed. London: Edward Arnold, 1995.

[16] Bryk AS, Raudenbush SW. Hierarchical linear models. London: Sage Publications, 1992.

[17] Van Elteren PH. On the combination of independent two-sample tests of Wilcoxon. Bull Int Stat Inst 1960;37:351-61.

[18] Dompeling E, van Schayck CP, van Grunsven PM, van Herwaarden CL, Akkermans R, Molema J, et al. Slowing the deterioration of asthma and chronic obstructive pulmonary disease observed during bronchodilator therapy by adding inhaled corticosteroids. A 4-year prospective study. Ann Intern Med 1993;118:770-8.

[19] Ian Grunsven PM, van Schayck CP, Derenne JP, Kerstjens HA, Renkema TE, Postma DS, et al. Long term effects of inhaled corticosteroids in chronic obstructive pulmonary disease: a meta-analysis. Thorax 1999;54:7-14.

[20] Seemungal TA, Donaldson GC, Paul EA, Bestall JC, Jeffries DJ, Wedzicha JA. Effect of exacerbation on quality of life in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1998;157:1418-22.

[21] Paggiaro PL, Dahle R, Bakran I, Frith L, Hollingworth K, Efthimiou J. Multicentre randomised placebo-controlled trial of inhaled fluticasone propionate in patients with chronic obstructive pulmonary disease. Lancet 1998;351:773-80.

[22] Jarad NA, Wedzicha JA, Burge PS, Calverley PMA for the ISOLDE study group. An observational study of inhaled corticosteroid withdrawal in stable chronic obstructive pulmonary disease. Respir Med 1999;93:161-6.

[23] Osman LM, Godden DJ, Friend JAR, Legge JS, Douglas JG. Quality of life and hospital re-admission in patients with chronic obstructive pulmonary disease. Thorax 1997;52:67-71.

[24] Li JTC, Ford LB, Chevinsky P, Weisberg SC, Kellerman DJ, Faulkner KG, et al. Fluticasone propionate powder and lack of clinically significant effects on hypothalamic-pituitary-adrenal axis and bone mineral density over 2 years in adults with mild asthma. J Allergy Clin Immunol 1999;103:1062-8.

(Accepted 7 February 2000)

Department of Respiratory Medicine, Birmingham Heartlands Hospital, Birmingham B9 5SS

P S Burge consultant chest physician

Department of Medicine, University Hospital Aintree, Liverpool L9 7AL

P M A Calverley professor of respiratory medicine

Department of Physiological Medicine, St George's Hospital Medical School, London SW17 ORE

P W Jones professor of respiratory medicine

S Spencer research fellow

GlaxoWellcome Research and Development, Stockley Park West, Uxbridge, Middlesex UB11 1BT

J A Anderson senior statistician

T K Maslen clinical project manager

Correspondence to: P S Burge

BMJ 2000;320:1297-303

COPYRIGHT 2000 British Medical Association
COPYRIGHT 2000 Gale Group

Return to Chronic obstructive pulmonary disease
Home Contact Resources Exchange Links ebay