Outcomes of Asthma

A. Sonia Buist M.D.A. Sonia Buist M.D.

Oregon Health & Oregon Health & Science University, Science University, Portland, OregonPortland, Oregon

OUTCOMES Markers of success or failure in managing

a disease, focused on the important characteristics that influence the course and consequences of that disease for patients and society Meaningful correlation with benefit Outcome must be measurable Outcome must be amenable/sensitive to

change Valid reflections of the process of care

Asthma outcomes

Mortality Prevalence Hospital admissions & re-admissions Heath resource utilisation & costs Severity - Control Morbidity

Time lost from school, work Treatment impact Doctor visits QOL Exacerbations

Asthma Control as New Outcome for Asthma FEV1 infrequently measured and

doesn’t correlate well with health status

Adherence to peak flow monitoring poor

Need for a simple, inexpensive instrument that can be used in clinical practice and clinical research

Goals of Asthma Management

Maintain “near normal” pulmonary function

Prevent chronic and troubling symptoms

Maintain normal activity levels

Prevent recurrent exacerbations

Minimal or no adverse effects of treatment

National Asthma Education and Prevention Program Expert Panel (NAEPP) Report 2: Guidelines for the Diagnosis and Management of Asthma. Update on selected topics. Allergy Clin Immunol 2002;110(5 pt 2):S141-219.

NAEPP Severity Symptoms Nighttime Sx Lung Function

Severe Persistent

Continual symptoms Limited phys activity Freq exacerbations

Frequent FEV1<60% pred PEF var >30%

Moderate Persistent

Daily symptoms Daily BA use Exac > 2/week

> once/week FEV1 60-80% pred PEF var > 30%

Mild Persistent

Sx > 2-6 days/week Exac may affect activity

> twice/month FEV1 >80% pred PEF var 20-30%

Mild intermittent

Sx < 2 days/week Asympt between exac Exac are brief

< 2 times/month FEV1 > 80% pred PEF var < 20%

NAEPP Severity Symptoms Nighttime Sx Lung Function

Severe Persistent

Continual symptoms Limited phys activity Freq exacerbations

Frequent FEV1<60% pred PEF var >30%

Moderate Persistent

Daily symptoms Daily BA use Exac > 2/week

> once/week FEV1 60-80% pred PEF var > 30%

Mild Persistent

Sx > 2-6 days/week Exac may affect activity

> twice/month FEV1 >80% pred PEF var 20-30%

Mild intermittent

Sx < 2 days/week Asympt between exac Exac are brief

< 2 times/month FEV1 > 80% pred PEF var < 20%

Stepwise Approach to Asthma Therapy - Adults

Reliever: Rapid-acting inhaled β2-agonist prn

Controller: Daily inhaled corticosteroid

Controller: Daily inhaled

corticosteroid Daily long-

acting inhaled β2-agonist

Controller: Daily inhaled

corticosteroid Daily long –

acting inhaled β2-agonist

plus (if needed)

When asthma is controlled, reduce therapy

Monitor

STEP 1:Intermittent

STEP 1:Intermittent

STEP 2:Mild Persistent

STEP 3:STEP 3: Moderate Moderate PersistentPersistent

STEP 4:STEP 4:Severe Severe

PersistentPersistent

STEP DownSTEP DownSTEP DownSTEP Down

Outcome: Asthma Control Outcome: Best Possible Results

Alternative controller and reliever medications may be considered

Controller:None

-Theophylline-SR -Leukotriene modifier -Oral corticosteroid

Problems with Using Guideline-Defined Severity Spirometry often not done Patients are already on asthma meds

(guidelines say “pre-drug”) ICS affect lung function so hard to assess

severity accurately Lung function is measured at one point in

time (not a composite measurement) Severity is often underestimated

What is Severity?

Depends on your perspective

To a ClinicianTo a Clinician:: a patient who needs: several different kinds of asthma

medications who goes to the ED frequently who has low lung function that

doesn’t reverse completely with short-acting bronchodilators

What is Severity?

To a Patient:To a Patient: asthma that seriously interferes with their life:

wakes them at night needs several medications involves a complicated management

regimen interferes with school/work prevents them from doing what they

would like to do

What is Severity?

To a Healthcare Manager:To a Healthcare Manager: a patient who uses healthcare that is costly:

frequent ED visits/hospitalizations needs a specialist needs costly medications

What is Severity?

To a pathologist:To a pathologist: very severe chronic inflammatory changes in the airways, probably with remodeling.

To a physiologistTo a physiologist: a patient with severe airflow limitation that is largely (but not necessarily entirely) reversible.

What is Severity?

Why is Severity Important?

Closely linked to cost-of-care

Enables targeted interventions

clinical trials guidelines implementation

Environmentalexposures

Self-management

Globalseverity

Medicalmanagement

Other personal

factors

Level ofcontrol

• HCU• QOL• Factual

status

Health outcomes

Alternative to Management Algorithm Use asthma control as a guide

rather than asthma severity

Severity

Control

Interplay of Asthma Severity, Management and Control

Asthma managementAsthma managementGood Poor

good control

poor control

Sev

erit

yS

ever

ity

Mild

SevereSevere

Severe

Red Flags That Asthma Is Not Well Controlled Frequent use of short-acting beta-

agonists Use of >1 canister of SABA/month or

>8 puffs/day Need for unscheduled care (ED or

hospitalization) Missed school or work

What Is Good Control? Virtually no use of short-acting -

agonist (<2x/week) Isn’t woken at night by asthma No unscheduled health care

utilization (ED visits/hospitalization) No lost work or school No exacerbations

Why is Level of Control Important?

Reflects patients current health status

Reflects outcome of care

Typically a very patient-oriented measure

Depends on your perspectiveDepends on your perspective

Individual clinician: level of control is key

FDA/pharmaceutical industry

Health plan manager

Epidemiologist/ outcomes researcher

Which is More Important: Severity or Level of Control?

Level of control is outcome, severity is a confounder

Control Instruments Available ATAQ (Asthma Therapy Assessment

Questionnaire). Cross-sectional & prospective validation 4 dimensions

ACQ (Asthma Control Questionnaire). Juniper 7 questions

ACT (Asthma Control Test—QualityMetric Inc) 5 dimensions

Development & Validation of AAsthma TTherapy AAssessment Questionnaire

We developed a simple 4-question instrument to assess asthma control

Scored as 0-4 (control problems) Validated the instrument in a large

health management organization (cross-sectional validation)

Prospectively validated the instrument over 12 months

Vollmer et al, Am J Resp Crit Care Med 1999;160:1647-1652

Asthma Therapy Control Questionnaire (ATAQ) In the past 4 weeks, did you feel that

your asthma was well controlled? In the past 4 weeks, did you miss any

work, school or normal activity because of your asthma?

In the past 4 weeks, did your asthma wake you up at night?

In the past 4 weeks, what was the highest # of puffs a day you took of your quick relief inhaler?

Score is 0-4Score is 0-4Vollmer et al, Am J Resp Crit Care Med 1999;160:1647-1652

ATAQ Asthma Control Index

In the past four weeks (12 months):

Has your asthma been well-controlled?

Score 1 point if “no” or “unsure”

ATAQ Asthma Control Index

In the past four weeks (12 months):

Has your asthma been waking you up at night?

Score 1 point if “yes” or “unsure”

ATAQ Asthma Control Index

In the past four weeks (12 months):

Has your asthma been interfering

with your usual activities?

Score 1 point if “yes” or “unsure”

ATAQ Asthma Control Index

In the past four weeks (12 months):

What is the highest number of puffs of your reliever

medication on any single day?

Score 1 point if more than 12

Cross-sectional validation of ATAQ

ATAQ mailed to 5,181 adult members of large health maintenance organization (HMO) in Pacific Northwest of U.S.(K.P.)

Quality of life instruments (generic [SF-36] and asthma-specific [Juniper]) also sent to one-quarter.

Vollmer et al, Am J Resp Crit Care Med 1999;160:1647-1652

Distribution of ATAQ Control Index

0%10%20%30%40%50%60%70%80%90%

100%

None One Two Three Four

Ref: Vollmer et al., AJRCCM 1999

ATAQ Validation

Within last Within last 4 weeks year

Self-perception of asthma control 30% - -Missed activities 27% 47%Nocturnal awakening 40% 66%Overuse of rescue meds 8% 15%At least one problem 52% - -

Vollmer WM, et al. Am J Respir Crit Care Med. 1999;160:1647-1652.

Retrospective Validation of ATAQ

Vollmer et al. Am J Respir Crit Care Med. 1999;160:1647-1652.

Relation Between Control of Problems During Previous4 Weeks & Health Care Utilization During Previous Year

asthma

01234

Within each control group, p<0.001

# of Problems with Asthma

Control

0

10

20

30

40

50

60

70

80

≥2 Visits worsening ≥1 Urgent visit ≥1 Hospitalization

Pat

ien

ts (

%)

None One Two Three Four P-value

SF-36 Scales Physical Mental

66 71

58 65

50 59

36 47

35 45

<.001 <.001

Asthma QOL Overall

St. George’s Resp Quest

5.7

4.9

4.3

3.1

2.9

<.001

Overall 30 40 46 56 63 <.001

Number of Control Problems in Past 4 Weeks

Mean Quality of Life Scores by Number of Control Problems

Vollmer et al, Am J Resp Crit Care Med 1999;160:1647-52

Prospectively validated control instrument (ATAQ)

Studied HCU over subsequent 12 months

Association of Asthma Control with Health Care Utilization: A Prospective Evaluation

Vollmer et al, AJRCCM 2002; 165: 195-99

Prospective Validation of ATAQ

Vollmer et al. Am J Respir Crit Care Med. 2002;165:195-199.

4795 Subjects with Asthma Who Completed ATAQ Followed Prospectively for 1 Year

# of Problems with Asthma

Control

0123 or 4

0

200

400

600

800

1000

1200

1400

1600

Routine Visits Acute Visits ED Visits Hospitalizations

Rat

e p

er 1

000

Pa

tie

nt

Yea

rs

0

25

50

75

100

125

150

175

200

Conclusions from ATAQ Validation The majority of asthma patients are

probably not in optimal control

Asthma control as assessed by the ATAQ can predict past & future health care utilization

ATAQ is simple to use & can be self-administered

Assessing Outcomes of Care

Level of control can be viewed as a legitimate outcome in its own right

Can also be used to predict more traditional outcomes of care, such as health care utilization and quality of life

Asthma Control : a worthy outcome?

Ideal asthma controlIdeal asthma control Absent or minimal

symptoms Absent or minimal

rescue medication No nocturnal or early

am symptoms Absent morbidity Lung function normal

or best

Professor Ann Woolcock

Time course of asthma control

No night No night symptomssymptoms

DaysDays

% i

mp

rove

men

t

100 am PEFam PEFFEV1

AHRAHR

YearsYearsMonthsMonthsWeeksWeeks

No SABA useNo SABA use

0

Woolcock AJ Clin Exp Allergy Rev, 2001. 1(2): p. 62-4.

Gaining Optimal Asthma Control (GOAL) Study

Background:“to date no studies have assessed the

benefits of aiming for complete, comprehensive, and sustained clinical control in a controlled study that allows for dose escalation, as necessary, to achieve this”

Gaining Optimal Asthma Control (GOAL) Study 1-yr RCT with 3,421 pts aged 12-80 yrs

from 44 countries with uncontrolled asthma

2 arms: fluticasone + salmeterol and fluticasone alone

Treatment was stepped up until total control was reached (or 500µg CS bid)

Control assessed over 8wks before visits at 12,24,36 52 months

Bateman et al AJRCCM 2004; 170: 836-44

Gaining Optimal Asthma Control (GOAL) Study 2 control definitions used: “totally

controlled” and “well controlled”. If neither, “uncontrolled”

Control definitions were composite measures that included: PEF, rescue med use, symptoms, night-time wakenings, exacerbations, ED visits, adverse events

Bateman et al AJRCCM 2004; 170: 836-44

Bateman et al, Am J Resp Crit Care Med 2004;170:836-844.

Outcomes of GOAL Study Proportion of pts who achieved well-

controlled asthma with the combo compared to fluticasone alone in phase 1

Many secondary outcomes

Bateman et al AJRCCM 2004; 170: 836-44

Gaining Optimal Asthma Control (GOAL) Study

Phase 1: Dose escalation. Regimen stepped up every 12 weeks until total control achieved or max dose

Phase 2: Maintenance control dose or max dose for 1 year (double blind)

Bateman et al AJRCCM 2004; 170: 836-44

Bateman et al, Am J Resp Crit Care Med 2004;170:836-844.

Proportion of patients achieving a well-controlled week

GOAL Study

Conclusions of GOAL Study The majority of patients with uncontrolled

asthma across a wide range of severities, comprehensive guideline-defined control can be achieved & maintained

The combo of ICS & LABA allows better control The combo of ICS & LABA allows better control than ICS alonethan ICS alone

Exacerbations were virtually eliminated if total Exacerbations were virtually eliminated if total control was achieved control was achieved

QOL was near normal in most with total controlQOL was near normal in most with total control

Bateman et al AJRCCM 2004; 170: 836-44

Questions that GOAL Raises When should stepping down occur? How far can we generalize the

findings? To kids <12 years? To clinical practice?

Is “total control” the right goal to shoot for?

Does aiming at total control over-treat?

Conclusions Asthma severity & control are different

although related metrics. Both are important

There are now several validated instruments for assessing asthma control

An algorithm for asthma management based on asthma control has the advantage of simplicity & is easy for patient & provider to understand & apply

Asthma control is a good outcome for RCTs

Rule of 2’s

Rescue inhaler not needed more than: 2 days / week 2 nights/month

Patients can understand this easily and apply it

Unanswered Questions Will an algorithm based on asthma

control lead to better adherence in asthma?

Will stressing asthma control lead to even fewer asthma patients receiving spirometry?

Study OutcomesPrimary

Adherence to asthma anti-inflammatory and other controller medications

Asthma-related quality of life

Acute asthma health care utilization

Secondary Asthma control Use of reliever medications Symptom-free days; lung

function Satisfaction with asthma care Preferences, values, &

attitudes towards adherence Asthma-related health care

costs Total asthma health care

utilization

Summary Asthma control is a feasible clinical

outcome

Future asthma guidelines will probably use control to guide therapy rather than severity