ASTHMA, COPD and the Evidence

ASTHMA
Prevalence of dysfunctional breathing in patients treated for asthma in primary care: cross sectional survey
	BMJ 322: 1098-100 (5th May 2001)

•	Abnormal breathing patterns have been shown to cause breathlessness, chest tightness, chest pain, light-headedness, paraesthesiae, and anxiety
•	Referred to as the hyperventilation syndrome, behavioural breathlessness, and dysfunctional breathing
•	Characteristic symptoms are common to other diseases and there is no standard diagnostic test, therefore symptoms may be wrongly attributed to other causes
•	Asthma has been linked with systematic hyperventilation in several studies

•	This study estimated prevalence of dysfunctional breathing in adults with asthma treated in the community

•	Design
o	Postal questionnaire survey
o	1 general practice with 7033 patients
o	All adult patients aged 17-65 with diagnosed asthma

•	Outcome
o	Score  23 on Nijmegen questionnaire (assesses 16 symptoms associated with abnormal breathing on a five point scale)

•	Results
o	219 questionnaires suitable for analysis
o	63 participants scored  23
o	More likely to be female, younger
o	Patients at different treatment steps of BTS asthma guidelines were affected equally

•	Conclusion
o	About 1/3 women and 1/5 men had scores suggestive of dysfunctional breathing
o	Suggests scope for therapeutic intervention

Cross-sectional observations on the natural history of asthma
	BJGP May 2001, p361-5

•	Uncertain whether asthma is a single clinical entity or a grouping of separate clinical syndromes that share a common set of treatment guidelines

•	Aim
o	To observe symptoms, treatment step, and health service utilisation of a population of patients in UK listed on an asthma register

•	Setting
o	12 203 patients from 393 practices throughout UK

•	Method
o	Database used to observe symptoms, treatment step and health service utilisation of the asthma patients

•	Results
o	Children aged up to 4 years had a distinctive profile of symptoms, including night time cough; they also experienced increased health service utilisation including a high hospital admission rate
o	Symptoms in adults became more common with increasing age 
o	The pattern of symptoms in patients aged 45 years and over suggest many patients on asthma register may have COPD
o	Patients aged 16-30 showed a different pattern of health service usage to those aged 5-15 and 31-45, relying more on unscheduled use of health services
o	Patients aged 16-30 used less asthma medication than those aged 5-15 and 31-45

•	Conclusions
o	Databases useful but problems with bias
o	Several clinical subgroups exist within the broad diagnosis label of asthma

Dose-response relation of inhaled fluticasone propionate in adolescents and adults with asthma: meta-analysis
	BMJ 323: 253-6 (4th August 2001)

•	Design
o	Meta-analysis of placebo controlled, randomised clinical trials that presented data on at least one outcome measure of asthma and that used at least two different doses of fluticasone

•	Setting
o	Medline, Embase and GlaxoWellcome’s internal clinical study registers

•	Outcome
o	FEV1, morning and evening PEFR, night awakenings,  agonist use, and major exacerbations

•	Results
o	8 studies, with 2324 adolescents and adults
o	Data on doses of >500g/day limited
o	Dose-response curve for the raw data began to reach a plateau at around 100-200g/day and peaked by 500g/day
o	Model indicated that 80% of the benefit at 1000g/day was achieved at doses of 70-170g/day and 90% by 100-250g/day
o	Maximum achievable efficacy was obtained by doses of around 500g/day

•	Conclusions
o	Most of the therapeutic benefit of inhaled fluticasone is achieved with a total daily dose of 100-250g/day, and the maximum effect is achieved with a dose of around 500g/day
o	Lack of data on doses >500g/day

Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering corticosteroids in asthma
	BMJ 323: 1-7 (20th October 2001)

•	Design
o	Systematic review of randomised controlled trials

•	Data sources
o	Cochrane Airways Group trials database, pharmaceutical companies and bibliographies of included trials

•	Trials
o	All trials in children or adults with stable asthma that compared a pressurised MDI with any other hand held inhaler device delivering the same inhaled corticosteroid

•	Results
o	24 trials included
o	Significant differences in FEV1, morning PEFR, and use of drugs for additional relief with dry powder inhalers
o	However, these were either within clinically equivalent limits or the differences were not apparent once baseline characteristics had been taken into account
o	No significant difference for: lung function, symptoms, bronchial hyper-reactivity, systemic bioavailability, and use of additional relief bronchodilators

•	Conclusions
o	No evidence that alternative inhaler devices are more effective than pressurised MDIs for delivery of inhaled corticosteroids
o	MDIs remain the most cost effective first line delivery devices

Systematic review of clinical effectiveness of pressurised metered dose inhalers versus other hand held inhaler devices for delivering 2 agonists in asthma
	BMJ 323: 1-7 (20th October 2001)

•	Design and data sources as above

•	Trials
o	All trials in children or adults with stable asthma that compared the pressurised MDI ( spacer) against any other hand held inhaler device containing the same 2 agonist

•	Results
o	84 trials
o	No differences for: lung function, BP, symptoms, bronchial hyper-reactivity, systemic bioavailability, inhaled steroid requirement, serum potassium, and use of additional relief bronchodilators
o	In adults, pulse was lower in those using pressurised MDIs compared with Turbohaler
o	Patients preferred MDI to Rotahaler
o	Hydrofluoroalkane pressurised MDIs reduced the requirement for rescue short course oral steroids

•	Conclusions
o	As above

Burden of corticosteroids in children with asthma in primary care: retrospective observational study
	BMJ 324: 1374 (8th June 2002)

•	In primary care, asthma and rhinitis are common paediatric comorbidities for which long term inhaled or nasal corticosteroid may be prescribed
•	Atopic children may receive both, resulting in high cumulative doses of topical corticosteroids and increasing risk of adverse effects

•	Method and results
o	Children who were chronically prescribed both inhaled and nasal corticosteroid
o	185 general practices, giving 177 752 children
o	Total daily steroid burden calculated
o	Three age bands – 0-4, 5-11, 12-16
o	8913 children chronically prescribed an inhaled corticosteroid
o	560 of these also had repeat prescription for nasal corticosteroid (17, 240 and 303 in each group respectively) equating to prevalence rates per 1000 children of 0.36, 3.2 and 5.5
o	Daily dose ranges equivalent to beclomethasone were 350-2400g, 265-3400g and 300-4800g
o	Nasal corticosteroid accounted for at least a third of total daily intake in each group
•	Comment
o	Definitions of low or high corticosteroid use: 336g/day = low, 378-672g/day = moderate, >672g/day = high
o	Thus between 341 (61%) and 462 (83%) of the 560 children prescribed chronic inhaled and nasal corticosteroids may be subject to high dose steroid use

Sensitisation to airborne moulds and severity of asthma: cross sectional study from European Community respiratory health survey
	BMJ 325: 411-4 (24th August 2002)

•	Design
o	Multicentre epidemiological survey in 30 centres using EC respiratory health survey

•	Outcome
o	Severity of asthma according to score based on FEV1, number of asthma attacks, hospital admissions for breathing problems, and use of corticosteroids in past 12 months

•	Results
o	Frequency of sensitisation to moulds increased significantly with increasing asthma severity
o	Association existed in all areas of the study, although there were differences in the frequency of sensitisation 
o	No association between asthma severity and sensitisation to pollens or cats
o	Sensitisation to D. pteronyssinus was also positively associated with severity

•	Conclusion
o	Sensitisation to moulds is a powerful risk factor for severe asthma in adults

Anti-leukotrienes as add-on therapy to inhaled glucocorticoids in patients with asthma: systematic review of current evidence
	BMJ 324: 1545-8 (29th June 2002)

•	Design
o	Systematic review of RCTs of children and adults with asthma comparing the addition of anti-leukotrienes or placebo to inhaled glucocorticoids

•	Outcome
o	Rate of exacerbations of asthma requiring rescue systemic glucocorticoids when the intervention was compared to same or double dose of inhaled glucocorticoids, and the glucocorticoid sparing effect when the intervention was aimed at tapering the glucocorticoid
•	Results
o	Of 376 citations, 13 were included (12 in adults, 1 in children)
o	Addition of anti-LTs resulted in a non-significant reduction in the risk of exacerbations requiring systemic steroids
o	Use of anti-LTs resulted in no overall group difference in the lowest achievable dose of inhaled glucocorticoids, but was associated with a reduction in withdrawals owing to poor asthma control

•	Conclusions
o	The addition of anti-LTs to inhaled glucocorticoids may modestly improve asthma control compared with inhaled glucocorticoids alone, but cannot be recommended as a substitute for increasing the dose of inhaled glucocorticoids
o	?? Associated with superior asthma control after tapering of glucocorticoids

COPD
Detecting patients at a high risk of developing chronic obstructive pulmonary disease in general practice: cross sectional case finding study
	BMJ 324: 1370-3 (8th June 2002)

•	Design
o	2 semi rural practices in the Netherlands
o	651 smokers aged 35-70 years

•	Outcome
o	Short standardised questionnaire on bronchial symptoms for current smokers, lung function with a spriometer, and the quality of the spirometric curve

•	Results
o	Of 201 smokers not taking drugs for a pulmonary condition, 169 produced an acceptable curve
o	Of these, 30 had an FEV1  <80% of predicted
o	When smokers were preselected on the basis of chronic cough, the proportion with an FEV1  <80% of predicted increased to 27%
o	Chronic cough was a better predictor of airflow obstruction than other symptoms, such as wheeze and dyspnoea
o	There presence of 2 symptoms was a slightly better predictor than cough only
o	Age was a good predictor of obstruction; smokers over 60 with a cough had a 48% chance of obstruction
o	Detecting one smoker with an FEV1  <80% of predicted cost 5 to 10

•	Conclusions
o	Trained practice assistants could check all patients who smoke for COPD at little cost to the practice
o	Cough and age are the most important predictors of age
o	By testing one smoker a day, an average practice could identify one patient at risk a week

Chronic obstructive pulmonary disease and primary care
	BJGP July 2002, p.532-3

•	Accounted for 26 000 deaths in England and Wales in 1999
o	5.6% if all male and 3.9% of all female deaths
o	19 times the number of asthma deaths in same year
o	29 000 deaths from lung ca

•	Annual consultation rates in GP per 10 000 population 
o	417 at age 45-64
o	1032 at age 75-84

•	Prevalence
o	9.9% among 60-75 year olds in semi-rural practice
o	26.4% among urban population of people over 45
o	May be underdiagnosed by as much as a half

•	Severe COPD (FEV1  <40% of predicted) may have mortality as high as 50% at two years
•	None of the current medications for COPD have been shown to modify the decline in lung function, although long-term oxygen improves survival in advanced disease
•	Management focuses on symptom control, reduction and treatment of exacerbations, and optimising quality of life
•	Clear evidence that pulmonary rehabilitation improves exercise capacity, functional ability, and quality of life, even though lung function does not change
o	Widely endorsed for moderate and severe COPD, but its benefits have been recognised at all stages of the disease
•	One study revealed 82% housebound and 36% largely chair bound
o	Also 90% had clinically significant anxiety and treatment, of whom only 4% received further assessment and treatment
o	78% of patients said they did not receive enough information regarding prognosis or management
•	Average GP has only 3 or 4 patients with advanced COPD
•	There is a need to define the size of the problem, to explore models of care – respiratory care, palliative care, and GP, and to identify the manpower and infrastructure support required

Feasibility and effectiveness of a pulmonary rehabilitation programme in a community hospital setting
	BJGP July 2002, p539-42

•	Aim
o	To assess whether a pulmonary rehab programme, similar to that in secondary care, could be established in primary care, and whether they could achieve similar benefits in patients with severe COPD

•	Design
o	Uncontrolled prospective intervention study, set in a primary care-run community hospital

•	Method
o	34 patients with COPD age 53-80 with an FEV1  of 30-50% predicted
o	Assessed at start, on completion of programme and six months after completion using spirometry, shuttle-walking distance, and two questionnaires

•	Results
o	All but 1 patient completed the programme
o	Significant improvements in walking distance and in both questionnaires
o	No significant change in FEV1 or FVC

•	Conclusion
o	Pulmonary rehab programmes can be run in community hospitals
o	Appear to be as effective as those run in secondary care
o	Patients may find them easier to access

A pilot study of pulmonary rehabilitation in primary care
	BJGP July 2002, p.567-8

•	14 patients recruited; 13 completed the programme and one year follow-up
•	Well received by patients and staff
•	Not enough suitable patients among a practice list of 10 500 to justify the running of this programme for a single practice; one primary care group would suffice

Effects of physical activity in mild to moderate COPD: a systematic review
	BJGP July 2002, p.574-8

•	Pulmonary rehab has become an evidence-based treatment for patients with severe COPD (see above)
•	Large numbers of patients with mild to moderate COPD receive treatment form their GP
o	Advice given should be clear, practical and acceptable, esp. with regard to advice about improving physical condition by walking, cycling or swimming
•	Literature search on effects of physical activity in patients with mild/moderate COPD on exercise tolerance, dyspnoea and quality of life (QOL)
o	4968 articles producing 35 original studies and 27 review articles
•	of these 5 original studies and no review articles selected
o	A positive influence of physical activity on exercise tolerance was found in four out of five studies. No clear effect on dyspnoea or QOL (? Due to low numbers of subjects)