The aim of this guideline is to provide recommendations, evidence based when possible, to guide primary healthcare professionals in their management of adults with asthma. The development group assumes that healthcare professionals will use general medical knowledge and clinical judgment in applying the general principles and specific recommendations of this document to the management of individual patients. Decisions to adopt any particular recommendation must be made by the practitioner in the light of available resources.

Guideline development group

The guideline development group was composed of three broad groups: relevant healthcare professionals; a specialist resource and a specialist small group leader; and members of the research team (members are listed in the acknowledgements). It was important that the group contained individuals from appropriate sectors: the sectors approached were general practitioners, practice nurses, and secondary care physicians. These group members were there to ensure adequate relevant discussion of the evidence, of topics for which there was no evidence, and of the subsequent recommendations in the guideline. The specialist resource was a chest physician. He worked closely with the research team, discussing the literature search strategy, reviewing and summarising the literature, and feeding this information back to the group. The small group leader had the role of ensuring that the group worked effectively. Together the research team were responsible for drafting the guideline and resourcing the guideline development group.

Identification, review, and synthesis of evidence

The guideline was based on an original systematic review but also made use of existing systematic reviews when appropriate. When existing systematic reviews were used the authors’ conclusions were reproduced; we did not attempt to replicate their meta-analysis. However, this approach created several problems. We took on trust the quality of the reviews, as all but one were Cochrane reviews. There were occasions when the focus of the review did not exactly match the clinical question or, if appropriately focused, did not fully answer it. When this occurred it is flagged within the guideline.

Search strategy

The aim of the evidence review was to identify and synthesise relevant evidence within the published literature to allow recommendations to be based on evidence whenever possible.⁽¹⁾ The search strategy was carried out with the electronic databases Medline, Embase, and the Cochrane library and covered the period January 1994 to December 1997 (appendix). This built on the search for the previous version of the guideline that was based on January 1984 to September 1994. Our search strategies attempted to locate studies using a combination of MeSH headings and free text searches. The search strategy was also backed up by the expert knowledge and experience of group members. We did not attempt to access the grey literature (unpublished reports and abstracts) nor did we identify letters in response to original articles.

Sifting the literature

The set of references generated by the search was sifted for relevance to the clinical specialty of the guideline. The initial sifting was done by a clinically qualified health services researcher on the basis of the article titles. Articles concerned with non-relevant clinical areas were removed as were editorials and letters. If there was any doubt about an article’s relevance it was retained for the next round of sifting. This was performed by the specialist resource (the chest physician) and was done on the basis of title and abstract (where this was available). This identified references that needed to be collected for more detailed assessment. Table 1 shows the number of references remaining after each stage of this sifting process.
 

Table 1 Number of references remaining at various stages of sifting process

 

Stage of process	Total No of papers remaining
Medline and Embase searches	9240
After duplicate check	7560
After clinical health service researcher (title) sift	420
After consultant (abstract) sift	182
Plus 26 references from other sources (references cited by papers, Cochrane etc)	208
Papers within scope of guideline	170
Papers with acceptable method	79
Plus 58 papers from previous guideline	137

Reviewing the literature

Table 2 shows the numbers of papers rejected at the review of literature and the reason for rejection. The total number of reasons is greater than the number of papers rejected as several papers had more than one design flaw.
 

Table 2 Criteria for rejecting papers

 

Reason for rejecting paper	No rejected
Relevance:
Not relevant (patient group, setting)	36
Superseded by good review	31
Methodological criteria:
Less than 80% follow up	18
Group sizes smaller than 20	13
No control group	2
Not an RCT in clinical area where         RCTs already available	16
Open when could be blinded	24
Other design flaws	10
Duplicate publication (results reported         in more than one journal)	5

Synthesising the literature

The guideline group members considered the relevant clinical areas of the guideline and defined the questions that they wanted the evidence to answer within these areas. This guided the interpretation of the evidence. The retrieved papers were assessed for their quality and their ability to provide valid answers. Assessment of study quality concentrated on questions of internal validity (the extent to which the study measured what it set out to measure), external validity (the extent to which the findings could be generalised to other treatment settings), and construct validity (the extent to which measurement corresponds to theoretical understanding of a disease).⁽²⁾ After individual papers had been checked for methodology and clinical significance, the information was synthesised. Questions were answered by using the best evidence available. When we considered the effect of an intervention, if a question could be answered by category I evidence provided by a meta-analysis or randomised controlled trial then we did not use studies of weaker design. The evidence was synthesised by using qualitative methods. These involved summarising the content of identified papers into brief statements that the group thought accurately reflected relevant evidence. Qualitative (meta-analysis) techniques were not used. Recommendations were derived with informal consensus methods.

Evidence categories were adapted from the Agency for Health Care Policy and Research classification.⁽³⁾ Four categories are available; this categorisation is most appropriate for questions of causal relations. Similar taxonomies for other types of research questions do not yet exist.

Categories of evidence

· Evidence from meta-analysis of randomised controlled trials or from at least one randomised controlled trial (I)

· Evidence from at least one controlled study without randomisation or at least one other type of quasi-experimental study (II)

· Evidence from non-experimental descriptive studies, such as comparative studies, correlation studies, and case-control studies (III)

· Evidence from expert committee reports or opinions and/or clinical experience of respected authorities (IV)

Strength of recommendation

In the meetings summaries of the evidence were presented to the group. These were interpreted in the light of the clinical area and the recommendations in the previous version of the guideline. Recommendations were graded A to D as shown below. The guideline distinguishes between the category of evidence and the strength of the associated recommendation. It is possible to have methodologically sound (category I) evidence about an area of practice that is clinically irrelevant or has such a small effect that it is of little clinical importance and would therefore attract a lower strength of recommendation. More commonly, a statement of evidence would cover only one part of an area in which a recommendation had to be made or would cover it in a way that conflicted with other evidence. Consequently, to produce comprehensive recommendations, the group had to extrapolate from the available evidence. This leads to lower strength recommendations based on evidence category I statements.

· Directly based on category I evidence (A)

· Directly based on category II evidence or extrapolated recommendation from category I evidence (B)

· Directly based on category III evidence or extrapolated recommendation from category I or II evidence (C)

· Directly based on category IV evidence or extrapolated recommendation from category I, II, or III evidence (D)

Areas without evidence

We accepted that there would be several areas without evidence where recommendations had to be made and that consensus would be required to deal with these areas. When such an area was identified we agreed to refer to the British Thoracic Society asthma guidelines,⁽⁴⁾ drawing on the consensus recommendations of this national expert group; if these were thought to have been superseded then the group came to its own decisions. When this process identified important unanswered research questions these were recorded at the end of the relevant section of the guideline.

Involving consumers in guideline development

To incorporate the views of consumers within the guideline we arranged a meeting with 11 patients with asthma (under the auspices of the National Asthma Campaign). Each was given a copy of the guideline, and there was a 90 minute discussion about their experiences of asthma and its management and the content of the guideline. The main issue that emerged was that they required information, in a form that they could understand, about their condition (asthma) and its management. They made no comment on the technical content of the guideline.

Scheduled review of the guideline

We recommend that this guideline is reviewed no later than three years after its completion.

Background

From the most recent national Morbidity Survey in General Practice for England and Wales⁽⁵⁾ and based on a nominal list size of 2000 patients, a general practitioner (GP) will see, on average, 85 patients for asthma each year who make on average three consultations each (figure 1). If we assume that all patients with asthma severe enough to require intervention see their GP at least once a year, this suggests a prevalence of disease of 4.3%. However, some patients may not see their GPs so often if they are receiving repeat prescriptions, making this estimate conservative.

Figure1

 
Prevalence of patients consulting for asthma per general practitioner per year (assuming list size of 2000)

Of adult respondents who had experienced asthma in the past five years, the most common self reported precipitating factors were chest infections, colds, and flu (58%), specific allergens (42%), and cigarette smoke (34%). Of these patients, 33% were prescribed b₂ agonists and 21% corticosteroids; 53% had not taken any medication.

There were 93 870 ordinary admissions for asthma in England in 1994-5, with an average length of stay of 3.5 days, and 838 admissions as day cases.⁽⁷⁾ Asthma as a cause of death is rare (1459 deaths in 1995 in England and Wales, of which 67% occurred in those aged 65 or more).⁽⁸⁾ However, its relation with other more prevalent causes of death, particularly chronic airways obstruction (21 199 deaths in 1995), is unclear.

Cost effectiveness and asthma

An analysis of the cost effectiveness of different strategies for the treatment or care of asthma requires assessment of the relative use of resources (for example, drugs, contacts in primary and secondary health care, time from work) and health consequences (control of asthma, activities of daily living, quality of life). This level of information is generally unavailable to inform decisions about care. There is some uncertainty about the cost effectiveness of education and management strategies, and whether these should be directed at all or a subgroup of patients. The available evidence and its shortcomings are discussed in the guideline.

With regard to the choice of drug, the guideline takes the position that when drug treatment is indicated, the cheapest available forms available should be used in the absence of reliable evidence to differentiate between different delivery, form, or brand of product.

Prescribing patterns and cost

In 1997 the Prescription Pricing Authority reimbursed the pharmaceutical industry £465 million for drugs prescribed in primary care for reversible airways disease. This amounts to about 10% of the cost of all reimbursed drugs and appliances.

Because prescriptions may not adequately describe the volume of use of drugs, we applied World Health Organization defined daily doses⁽⁹⁾ to data on prescribed quantity provided by the Prescription Pricing Authority for each drug by dose and form to provide an estimate of the number of patient years of treatment. Defined daily doses are not necessarily the doses recommended in the British National Formulary (BNF), and tend to be at the top end of the recommended range of use, but provide a consistent point for comparison between drugs (table 3).
 

Table 3 Defined daily doses (DDDs) used to adjust quantity data to person years of treatment

 

BNF section and drug	Inhaled aerosol (mg)	Inhaled powder (mg)	Oral tablet (mg)	Oral solution (mg)
3.1.1 Adrenoceptor stimulants
Bambuterol			20
Formoterol		24
Fenoterol	600			4
Reproterol	4000
Salbutamol	800	800	16	10
Salmeterol		100
Terbutaline	2000	2000	15	20
Tulobuterol			4
Ephedrine			50	50
Orciprenaline sulphate		6000	60
3.1.2 Antimuscarinic bronchodilators
Ipratropium bromide	120			0.3
Oxitropium bromide	600			4
3.1.3 Theophylline
Aminophylline			600	600
Aminophylline hydrate			600	600
Choline theophyllinate			600	600
Theophylline			400	400
3.1.4 Compound bronchodilator preparations
Fenoterol/ipratropium*	600/240			5/2
Ipratropium/salbutamol*	160/800			2/10
3.2.0 Corticosteroids (respiratory)
Beclometasone diproprionate inhaler	800	800		1.5
Budenoside inhaler	800	800		1.5
Fluticasone propionate Diskhaler	600	600
3.3.0 Cromoglycate and related treatment
Ketotifen			2	2
Nedocromil	8000	8000
Sodium cromoglicate	40000	80000		80

Pirbuterol and rimiterol are discontinued
*Doses not DDDs.

Table 4 shows the reimbursed cost and volume of drugs used for reversible airways disease. There are several caveats to the calculated volume of use. Firstly, some of the drugs are used variously to treat other conditions: b₂ agonists for chronic airways obstruction; cromoglycate for food allergy. Secondly, a proportion of prescriptions are for children and adolescents, who may receive lower doses. Thirdly, the defined daily doses are at the top of the range recommended by the BNF; many patients will be managed on lower doses. All forms of drug are included in the estimate of volume of use except intravenous preparations, which are a tiny proportion of the total.
 

Table 4 Reimbursement and use of pharmaceuticals for reversible airways disease: England 1997

 

BNF  Section	Drug group	Total cost (£ millions)	Volume/1000 person years thousands)	Cost per  person year
3.1.1	Adrenoceptor stimulants	157.65	2006	78.59
3.1.2	Antimuscarinic bronchodilators	23.66	323	73.17
3.1.3	Theophylline	7.95	156	51.08
3.1.4	Compound bronchodilator preparations	13.43	93	144.16
3.2.0	Corticosteroids (respiratory)	253.53	1330	190.68
3.3.0	Cromoglycate and related treatment	8.88	27	324.30
	Total	465.10	3935	118.19

Dividing reimbursed cost by volume of use, it is possible to calculate a crude cost per year of treatment for each drug, reflecting the mix of brands, forms, and doses currently prescribed. These estimates do not include other associated costs of asthma treatment (for example, admission to hospital), which may vary by prescribed drug, neither do they reflect differences in outcome between treatments.

The average figures shown in table 4 are weighted by the current mix of drugs, forms, and delivery methods prescribed in primary care.  However, they conceal considerable variation between drugs and between delivery devices. The most commonly used drugs are shown in table 5, disaggregated by form. In the absence of any differences in therapeutic effect, potentially large savings could be achieved by substitution of the cheapest form when the patient’s circumstances permit.
 

Table 5 Drugs prescribed for asthma in primary care, England 1997

 

	% of volume prescribed	Cost (£) per person  year at DDD
3.1.1 Adrenoceptor stimulants
Salbutamol
Aerosol MDI	74.6	28
Aerosol other*	14.2	111
Powder	2.1	73
Solution	3.5	236
Tablet	0.5	151
Oral liquid	5.2	44
All forms	100	50
Salmeterol
Aerosol MDI	71.8	348
Powder	28.2	377
All forms	100	356
Terbutaline
Aerosol MDI	48.1	52
Powder	48.5	116
Solution	1.3	259
Tablet	1.6	50
Oral liquid	0.5	194
All forms	100	89
3.2.0 Corticosteroids (respiratory)
Beclometasone
Aerosol MDI	79.6	137
Aerosol other	8.2	130
Powder	12.2	229
All forms	100	148
Budenoside
Aerosol MDI	39.6	138
Powder	53.7	270
Solution	6.7	1342
All forms	100	290
Fluticasone
Aerosol MDI	68.6	295
Powder	31.4	354
All forms	100	313

MDI: Metered dose inhaler.

*Includes vortex and breath-actuated delivery devices.

+Annual data estimated from data available for three quarters of 1997.

Scope of the guideline

The areas covered by the guideline are:

· Drug treatment (including devices)

· Exacerbations of asthma

· Complementary therapies

· Allergen avoidance, smoking cessation, patient education, and self management

· Referral

All recommendations are for primary healthcare professionals and apply to adult patients attending general practice with asthma. The development group assumes that healthcare professionals will use general medical knowledge and clinical judgment in applying the general practice principles and specific recommendations of this document to the management of individual patients. Decisions to adopt any particular recommendation must be made by the practitioner in the light of available resources and circumstances presented by individual patients.

Aims of treatment

We adopted the aims of treatment in the British Thoracic Society guidelines:

· The least possible symptoms

· The least possible need for relieving bronchodilators

· The least possible limitation of activity

· The least possible circadian variation in peak flow

· The best peak flow possible

· The least possible adverse effects from medicine

A further general statement from the British Thoracic Society guidelines that is relevant at this point is that it is preferable to adjust treatment to cover exposure to day to day triggers, such as exercise and cold air, because avoidance imposes inappropriate restrictions on lifestyle. Specific comments about the adjustment of the dosages of drugs are made within the relevant sections on drug treatment.

• Brad Cheek: last updated Dec 2006
• Home
• Doctors
• Training
• IT
• Links
• Latest
• Search