The role of guidelines in asthma treatment: From past to date

The role of guidelines in asthma The role of guidelines in asthma treatment: From past to datetreatment: From past to date

Prof Dr Füsun YıldızKocaeli University School of Medicine

Chest Diseases Department

Turkish Thoracic Society 10th Annual Congress 25-29 April 2007

Lecture planLecture plan

1-Definition of guideline, why and how should the guidelines be prepared?

2-Why do we need asthma guidelines?3-The history of asthma guidelines from

past to date4-Are patients and physicians compliant

to prepared guidelines?

Definition of a guidelineDefinition of a guideline

The systematically developed definitions which help the physicians and their patients to select the most suitable health services on certain clinical circumstances

The types of guidelinesThe types of guidelines

Specialists consensus basedEvidence basedConclusion based (metaanalysis,

cost efectiveness, decision analysis)

Preference based (evidence based+ patient preference)

Why and how should the Why and how should the guidelines be prepared?guidelines be prepared?

The development of a guideline should be based on critical analysis of the diagnostic and/or therapeutic options available for a particular problem

Ideally the risks and benefits of the diagnostic and/or theurapeutic alternatives should be tested and their efficacy demonstrated

The information required to utilize a guideline should be easily acquired without unusual cost or risk to patient

Campbell JA Clin Med and Research 2004;2:145-146

Why and how should the Why and how should the guidelines be prepared?guidelines be prepared?

Guidelines should be developed for a specific group of users

Those that are appropiate for the clinician may not be suitable for the patient

Guidelines may give general recommendations and should not be interpreted as standarts of care

Guidelines should be concise and be based on readily available clinical information

Guidelines need constant updating in order to follow the scientific evidence

Campbell JA Clin Med and Research 2004;2:145-146



2-Why do we need asthma guidelines?

3-The history of asthma guidelines from past to date

4-Are patients and physicians compliant to prepared guidelines

Why do we need asthma guidelines?

• Asthma is a common disease in developed countries (5-12% of population), and increasing in prevalence in the developing world

• Random-dialing telephone surveys show that burden of asthma is great, that patients are rarely assessed by objective measures, and that effective treatments are under-prescribed and under-used

• In the U.S. 5,000 deaths from asthma occur each year; most are preventable

• In Europe and North America, 70% of patients with asthma seek care from a primary care physician, not from a specialist

There are 300 million asthma patients all over the world There are 300 million asthma patients all over the world 100 million is expected increase in 2025100 million is expected increase in 2025

2.5 – 5.0

0 – 2.5

No standart results

>10.1

7.6 – 10.0

5.1 – 7.5

AstAsthma may cause deathshma may cause deaths

180 000 deaths related to asthma in 2000

WHO Factsheet 206 January 2000

255 000 asthma related deaths in 2005

World Health Organisation. The World Health report

Among 250 deaths 1 related to asthma all around the world

Masoli M, et al. Allergy 2004

Economic burden of asthmaEconomic burden of asthma

GINA, 1995

Sweden

1,400

0

USAAustria

1,000

200

600

Expense per patient Expense per patient ((ABDABD$)$)

400

800

1,200

Totalexpenses

England

348.3 billion $6.4 billion $457 million $ 1.79 billion $

1,315 $

640 $

326 $

522 $

86 asthmatic children, treatment with inhaled corticosteroid (mean duration~ 6 months)

Mean expense per month (£)

Asthma expenses decrease with appropiate treatment

Perera BJC. Arch Dis Child 1995; 72: 312-316.

40

30

20

10

0PL Inhaled Steroid

36,33

6,16



2-Why do we need asthma guidelines?3-The history of asthma guidelines

from past to date4-Are patients and physicians compliant

to prepared guidelines

First line treatment Uncontrolled asthma

1980-1985 Short acting ß2 agonist Add ICS

1985-1990 ICS Add short acting ß2 agonist

1989-1994 ICS Increase ICS dose

1994-1997 ICS Increase ICS dose consider adding LA ß2 agonist

1997-1999 ICS Add LA ß2 agonist if needed increase ICS and/or add LTRA

2000- ICS if ICS naiveICS+ LA ß2 agonist if ICS treated

Add LA ß2 (or LTRA)

Increase ICS dose and/or add LTRA

Evolution of concepts for the asthma treatmentEvolution of concepts for the asthma treatment

Bousquet J etal Allergy 2007;62.102-112

Guidelines ?

Development of guidelinesDevelopment of guidelines

Guidelines

Opinion-based

Implementation of guidelines by adequatetrials and surveillance

studies

Evidence-based

1985-1998

1998-

Development of asthma guidelinesDevelopment of asthma guidelines Guidelines prepared in Australia and New

Zeland were among the first guidelines probably because of the asthma death epidemic of 1980s

Sears MR etal Arch Dis Child 1986;61:6-10

These guidelines were based on the opinion of experts and their goal was to reduce asthma deaths and morbidity

Woolcock A etal Med J Austr 1989;151:650-652

It is interesting to note that they were also published in nurse journals

Old Nurse 1990;9:19-20

Guidelines ?

19952002 r2004 r2006

19911997 r2002 r2007

2000

GINA NHBLI TTS NATIONAL

Development of asthma guidelines: From Development of asthma guidelines: From opinion-based to evidence-based opinion-based to evidence-based

guidelinesguidelines

• In U.S., National Asthma Education and Prevention Program initiated by Office of Prevention and Education, Division of Lung Disease, NHLBI

• Early recognition of need for Consensus Guidelines for Diagnosis and Management of Asthma

• National Asthma Expert Panel appointed in 1990, with representatives from Pulmonary and Allergy Societies, Emergency Medicine Society, Association of Respiratory Care Members included Primary Care Physicians, but not as official representatives of Primary Care Societies

Expert Panel Report 1Expert Panel Report 1

• The report in 1991 focused on the role of the patient education and use of objective measures of lung function including home PEF monitoring

• It also recognised the role of inflammation in the pathogenesis of asthma and recommended anti-inflammatory medications for patients with moderate-severe asthma

• 1991 Guidelines organized around four topics

-Assessment and Monitoring

- Identification and control of factors contributing to severity

- Pharmacology

- Patient Education

Symptoms Nighttime Symptoms Lung Function

Continual symptoms Frequent FEV1 or PEF ≤60%

Limited physical activity PEF variability >30%Frequent exacerbations

Symptoms on most days >2 time a week FEV1 60%-80% predicted

Use of inhaled PEF variability >30%short-acting beta2-agoniston most days

Exacerbations affect activityExacerbations ≥2 times a week;may last days

Symptoms on <3 days/week <2 times/month FEV1 or PEF >80%PEF variability 20% - 30%

Exacerbations brief, (from a few hours to a few days); intensity may

affect activity.

Asymptomatic and normal PEFbetween exacerbations

Classify Severity of AsthmaClassify Severity of Asthma

Reference: National Asthma Education and Prevention Program. Expert Panel Report 1: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md: National Heart, Lung, and Blood Institute, National Institutes of Health; April 1992.

Step 3Severe

Step 2Moderate

Step 1Mild

NHLBI Treatment Guidelines (EPR 1)

Step 1 - Mild Asthma -No daily medication

Step 3 - Moderate Asthma -ICS (preferred)-Or theophylline, cromolyn, or leukotriene

antagonist

Step 4 - Severe Asthma -High dose ICS -+ oral corticosteroid

NAEPP Expert Panel Report 1, NHLBI, NIH 1992

Controversies about EPR 1

1-Place of Leukotriene receptor antagonists?

-Many studies show LTRA’s to be less effective than ICS therapy

2-Concern over possible harm from chronic use of inhaled ß2-agonist?

- NIH-funded study showed that in mild asthma, regular use of albuterol is associated with neither benefit nor harm


3-Place of long-acting ß2-agonists?

-Studies show greater benefit of addition of long- acting ß2-agonist to ICS vs doubling dose of ICS

-NIH study shows monotherapy with LABA no better than placebo in preventing exacerbations

4-Increased awareness of some asthma progressing to severe, irreversible airflow obstruction?

-Pathologic studies show evidence of “remodeling” in even mild asthma. Presumed to reflect consequence of inflammation


5-Reports of loss of benefit of ICS therapy if treatment is delayed?

-Supported by retrospective studies; fit with concept that unregulated inflammation results in poorly reversible changes in airway structure

6-Skepticism over importance of PEF monitoring for action plan?

Symptoms Nighttime Symptoms Lung Function

Continual symptoms Frequent FEV1 or PEF ≤60%

Limited physical activity PEF variability >30%Frequent exacerbations

Daily symptoms >1 time a week FEV1 60%-80% predicted

Daily use of inhaled PEF 60%-80% predictedshort-acting beta2-agonist

Exacerbations affect activity PEF variability >30% Exacerbations ≥2 times a week;may last days

Symptoms >2 times a week but ≥2 times a month FEV1 or PEF >80%<1 time a dayExacerbations affect activity PEF variability 20% - 30%

Symptoms ≤2 times a week <2 times a month FEV1 or PEF ≥80%Asymptomatic and normal PEF PEF variability 20% - 30%between exacerbationsExacerbations brief (from a fewhours to a few days); intensity may vary

EPR-2 Reclassification of Asthma SeverityEPR-2 Reclassification of Asthma Severity

Reference: National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the Diagnosis and Management of Asthma. Bethesda, Md: National Heart, Lung, and Blood Institute, National Institutes of Health; April 1997. NIH publication 97-4051.

Step 4SeverePersistent

Step 3ModeratePersistent

Step 2MildPersistent

Step 1MildIntermittent

Expert Panel Report 2 (EPR 2): Treatment Revision

Step 1 - Mild Intermittent Asthma – No daily medication

Step 2 - Mild Persistent Asthma – Low dose ICS or Cromolyn/nedocromil– (or Leukotriene antagonist or theophylline)

Step 3 - Moderate Persistent Asthma – Medium dose ICS or– Low-medium dose ICS + long-acting bronchodilator:

long-acting inhaled ß2-agonist– (or theophylline or oral long-acting ß2-agonist)

Step 4 - Severe Persistent Asthma – High dose ICS + long-acting bronchodilator: long-acting

inhaled ß2-agonist– (or theophylline or oral long-acting ß2-agonist)– + oral corticosteroid

NAEPP Expert Panel Report 2, NHLBI, NIH 1997

Controversies about EPR-2

1-Does addition of another long term control agent improve outcomes who are receiving IKS over 5 who have moderate or severe persistent asthma?

-Combination therapy that is adding long-acting ß2 agonists to IKS is more effective than simply increasing the dose of IKS for patients over 5 who have moderate or severe persistent asthma

2-Are long term use of IKS in children effect vertical growth, bone mineral density, ocular toxicity and supression of HPA?

- Studies includes 6 years of observation low-to-medium doses of IKS have no adverse effect on growth velocity, bone mineral density, ocular toxicity and supression of HPA

Controversies about EPR-2

3-Does adding antibiotics to standart care improve outcomes of treatment for acute exacerbations of asthma?

-Antibiotics are not recommended for the treatment of acute asthma exacerbations except as needed for comorbid conditions

4-Does early intervention with long term therapy prevent progression of asthma as indicated by changes in lung function and severity of symptoms?

-Evidence is insufficient to permit conclusions on the benefits of early treatment of asthma in preventing the progression of disease

Revision of Expert Panel Report 2 (up 2002)

The guidelines that were first published in 1991, revised in 1997, were revised in 2002 in the way that reflected the latest scientific advances

The update stressed that IKS are preferred for controling and preventing asthma symptoms and for improving lung function and quality of life

New data provide reassuring evidence on the safety of IKS use at appropriate doses in children

NAEPP Expert Panel Report 2, NHLBI, NIH 2002(update)

Asthma Guidelines: Recent Asthma Guidelines: Recent discussionsdiscussions

1-Distinction between “Severity” and “Control”

2-Concern over possible harm from chronic use of inhaled ß2-agonist in subgroups (by genotype, race, or some unknown interacting feature)

3-Alternatives to addition of long-acting ß2-agonists to ICS treatment (LTRA, theophylline)

4-Variations among asthmatic patients in responsiveness to different treatments

5-Challenge to central role of eosinophil in pathogenesis of remodeling

6-Place of expensive, anti-IgE monoclonal antibody treatment

No daytime symptoms

No nocturnal symptoms

Morning PEF ≥ 80%

Normal daily activities

No exacerbation

No emergency visit

Lowest drug dose with minimum adverse

effect

GINA 1995-2005 : Goals of therapyGINA 1995-2005 : Goals of therapy

GINA 2005GINA 2005: Stepwise Treatment : Stepwise Treatment

Notreatment

1st stepIntermittant Low dose

IKS(theophylline,

lökotriene antagonist, chromoline)

2nd StepMild persistent

Low-moderate dose IKS +

LABA (theophylline,

lökotriene antagonist,

oral 2-agonist)

3rd stpModerate persistent

High dose IKS + LABA+ If needed

• Anti-IgE• Lökotriene

antagonist• Oral 2-agonist• Oral

corticosteroid• theophylline-SR

4th Severe persistent

End-point: asthma controlEnd-point:

possible best point

GINA Workshop Report 2005.IKS = inhaled corticosteroid; LABA = long acting β2-agonist

SEVERITY

Severity and Control Severity and Control ConceptsConcepts

Severity and Control Severity and Control ConceptsConcepts

CONTROL

1991 2006

Response to treatment

If trere is response to treatment then you can control the disease

The step of disease tells both severity and response to treatment

Stoloff SW. et al. J Allergy Clin Immunol 2006; 117: 544-8

Problems in assessing the severityProblems in assessing the severity

To assess the severity cause problem in patients who are still under treatment

The run of asthma is variable, it is difficult to assess the severity in one visit, the severity of disease may change over time

The symptoms are not parallel with the severity of disease all the time

Response to treatment changes, the response may not be like in all patients with same severity

Li JT, JACI 2005; 116: S3-11

GINA 2006GINA 2006Asthma Control CriteriaAsthma Control Criteria

GINA 2006GINA 2006Asthma Control CriteriaAsthma Control Criteria

Criteria Controlled (all)

Partly controlled(any measure present in any week)

Uncontrolled

Daytime symptoms

None (twice or less / week)

More than twice/ week

Three or more features of

partly controlled

asthma present in any

week

Limitations of activities

None Any

Nocturnal symptoms

None Any

Need for reliever NoneMore than twice/ week

PFT (PEF. FEV1) Normal <%80 (predicted or personal best)

Exacerbations None One or more / year

GINA 2006:Treatment with control GINA 2006:Treatment with control criteriacriteria

CONTROL LEVEL TREATMENT PLAN

Controlled Find the lowest step

Partly controlled Consider step up till the control

Uncontrolled Consider step up till the control

Exacerbation Treat the patient

decre

as

ein

crease



2-Why do we need asthma guidelines?3-The history of asthma guidelines from

past to date4-Are patients and physicians

compliant to prepared guidelines

How is the compliance to the How is the compliance to the prepared guidelines? prepared guidelines?

Problems related to guidelines -Classification with severity -Ignorance of personal differences -Not suitable for daily practice -The discordance of reference studies with real life Lack of concordance of physicians to the

proposals of guidelines Inconsistency of patients to prescribed treatments Problems related with policy makers and

regulatory authorities

EPR-2 emphasized the role of inflammation in the pathogenesis of asthma

The report also presented basic recommendations for the diagnosis and management of asthma that will help the clinicans and patients make appropriate decisions about asthma care

Although the NHBLI asthma guidelines have been in existence for nearly a decade they have not been widely utilized by health care providers

Asthma Guidelines: An assessment of Asthma Guidelines: An assessment of physician understanding and practicephysician understanding and practice

Doerschug KC et al Am J Respir Crit Care Med 1999;159:1735-Doerschug KC et al Am J Respir Crit Care Med 1999;159:1735-17411741

Hypothesis: Not all components of the updated guidelines are well understood by the physicians who care for asthmatics

Material-methods: Based upon 1997 prepared NHLBI guideline, a multiple-choice test of asthma knowledge distributed to physicians at a University Hospital

20 asthma specialists, 11 asthma speciality fellow, 11 General Medicine faculty, 5 Family medicine faculty, 51 Internal medicine residents and 5 Family medicine residents completed the questionnaires

Results of questionnaire on asthma knowledge

Doerschug KC et al Am J Respir Crit Care Med 1999;159:1735-1741Doerschug KC et al Am J Respir Crit Care Med 1999;159:1735-1741

The comparison of percentage of correct answers among all physicians



Performance of all physicians in the estimation of disease severity

Compliance with National Compliance with National Asthma Management guidelines Asthma Management guidelines

Asthmatics receiving care in different physicians noted that 72% of respondents with severe disease reported having a steroid inhaler whom 54% used it daily

In addition although 26 % of respondents reported having a peak flowmeter, only 16% used it on a daily basis

Logoreta AP etal Arch Intern Med 1998;158:457-

464

Physician guideline knowledge

31% use guidelines every time

48% use guidelines time to time

11% have no knowledge about guidelines

Use of spirometry

%70 use spirometry for diagnosis and follow up

%35 spirometry offered patients had spirometry in the last 1 year

Use of PEF meter

83% of physicians offer PEF meter use to their patients

62% of patients say that they heard about PEF meter

28% of patients had PEF meter in their house

Only 9% of patients use PEF meter

Use of antiinflammatory treatment

92% of physicians think that persistant asthmatics must use anti inflammatory treatment

86% of physicians prescript anti inflammatory treatment

9% of patients use IKS in the last 1 month

Acute attack action plan

70% of physicians offer an action plan to their patients

27% of patients say that they heve no knowledge about action plan

‘‘Asthma in America’ survey results: Asthma in America’ survey results: 2509 adult asthmatics or asthmatic children parents, 512 physicians were included in the study

Rickard KA etal J Allergy Immmunol 1999;103:S171

RESULTRESULT

• There have been a significant role of guidelines that were prepared for diagnosis and treatment of asthma in the last 15 years

• But recent studies have shown that there are still serious problems to achieve the control in asthmatic patients

• Updated guidelines (GINA 2006, NHLBI/NIH 2007) suggest to use control criterias in place of disease severity in the adjustment of treatment

• In order to evaluate the control, utilization of symptoms and physiologic parameters seems to be the most realistic way

What does the Cochrane review say?

It would appear that further research is needed.

We are looking forward to seeing you!

World Asthma Meeting 2007 (WAM)

22-25 June 2007 İstanbul

The role of guidelines in asthma treatment: From past to date

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