Optimum Therapy and QOL in Asthma Patient

Tamsil Syafiuddin
Department Pulmonology and Respiratory Medicine Faculty of Medicine Universitas Islam Sumatera Utara/Universitas Sumatera Utara Medan-Indonesia 2011

Levels of competence

Standar Kompetensi Dokter , Konsil Kedokteran Indonesia, 2006

Level of competence 4:
Mampu membuat diagnosis klinik berdasarkan
pemeriksaan fisik dan pemeriksaan tambahan yang diminta oleh dokter (misalnya: pemeriksaan laboratorum sederhana atau X-ray). Dokter dapat memutuskan dan mampu menangani

problem itu secara mandiri hingga tuntas.

Standar Kompetensi Dokter , Konsil Kedokteran Indonesia, 2006

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many chronic diseases
Philosophy of treat to target

Hypertension

: BP 140/90 mmHg or less

Diabetes : HbA1c 7% or less

Dyslipidaemia

: LDL-cholesterol <100 mg/dl

Asthma treatment is designed to meet specific targets and achieve CONTROL

Definition of asthma
Chronic inflammatory disease of airways (AW) Hyper responsiveness of tracheo bronchial tree Physiologic manifestation: AW narrowing relieved spontaneously or with BD Cster Clinical manifestations: a triad of paroxysms of cough, dyspnea and wheezing.
(GINA 2009)

Disease Pattern
Episodic --- acute exacerbations interspersed with symptom-free periods Chronic --- daily AW obstruction which may be mild, moderate or severe

superimposed acute exacerbations

Life-threatening--- slow-onset or fast-onset (fatal within 2 hours)
(GINA 2009)

Why inhalation therapy?

Oral Slow onset of action Large dosage used Inhaled route Rapid onset of action Less amount of drug used Better tolerated Treatment of choice in acute symptoms
(GINA 2009)

Greater side effects

Not useful in acute symptoms

assessed to establish: current treatment regimen, adherence to the current regimen, and level of asthma control.

Appropriate management

Optimum/Adequate management
(GINA 2009)

assessed to establish:
current treatment regimen, adherence to the current regimen, and level of asthma control.

Adequate management

(GINA 2009)

Guidelines on Asthma Management: Past and Current Trends

Severe persistent Old classification

Intermittent
Total control

Mild persistent
Partially control

Moderate persistent

Exacerbation
Uncontrol

New classification

GINA 2009

Inhalation of SABA
GINA 1998 (adapted) GINA 2009

ICS

Combination Therapy Combination Therapy

Stable condition

Asthma Pathology and Therapy Evolution

Adding LAA to ICS therapy Large use of short-acting 2-agonists 1975 Fear of short-acting 2-agonists
Kips et al, AJRCCM 2000 Pauwels et al, NEJM 1997 Greening et al, Lancet 1992

1980

Combination therapy

1985 1990
Bronchospasm Inflammation

2000

1995
Remodelling

(GINA 2009)

Interactions between corticosteroids and 2-agonists

Corticosteroid 2-agonist

Glucocorticoid receptor

2-adrenoceptor

Anti-inflammatory effect

Bronchodilatation

Effect of corticosteroids on 2-adrenoceptors Effect of 2-agonists on glucocorticoid receptors

Combine Agents give a positive and Strengthen Impact

Barnes PJ. Eur Respir J 2002;19:182191.

Gaining Optimal Asthma controL (GOAL) study

A 1-year, multicentre, randomised, double-blind, stratified, parallel-group, trial in adults and adolescents, comparing:

ICS + LABA ( seretide, salmeterol +fluticasone propionate) ICS alone (flixotide ,fluticasone propionate)
Dose stepped-up to achieve TOTAL CONTROL (or until maximum dose reached) Conducted between December 2000 and December 2002 Involving 326 sites in 44 countries across 6 continents

1. Bateman ED et al. Am J Respir Crit Care Med 2004; 170: 836844.

Control of asthma symptoms achieved faster with ICS+LABA compared with ICS alone
Weeks 112 (stratum 2)
Probability of week with guidelinedefined control

1.0 0.8

p=0.001
0.6 0.4
ICS+LABA /SFC

0.2
Week 2 Week 7

ICS alone/FP

10

11

12

13

Week in which guideline-defined control status first achieved SFC = Salmeterol/Fluticasone

Bateman ED et al. Am J Respir Crit Care Med 2004; 170: 836844.

Total Control
Time to achieve control
Probability of control
1.0 ICS alone (FP) ICS+ LABA (SFC) 0.8

0.6

0.4 Week 21 Week 45

0.2

0 0 4 8 12 16 20 24 28 32 36 40 44 48 52 Time to first Total Control week Patients previously on low-dose ICS (S2)
1. Bateman ED et al. Am J Respir Crit Care Med 2004; 170: 836844.

assessed to establish:
current treatment regimen, adherence to the current regimen, and level of asthma control.

Adequate management

(GINA 2009)

AHR continues to improve even after lung function has plateaued

110

FEV1 (% baseline)

100

AHR

FEV1

-1

95

-2

Baseline

6
Time (months)

12 1 month after treatment

Ward et al. Thorax 2002

Log10 PD20 (mg)

105

Inflammation can also be present during symptom-free periods

Rate of response of different measures of asthma control over 18 months of ICS treatment

% Reduction

AHR is a marker of inflammation AHR Night symptoms Rescue medication use Impaired FEV1 Impaired am PEF

Start of treatment

18

Months

Adapted from Woolcock A. Clin Exp Allergy Rev 2001; 1: 6264.

Treating ongoing inflammation

Rate of response of different measures of asthma control over 18 months of ICS treatment
AHR, airway hyperresponsiveness; FEV1, forced expiratory volume in 1 second; ICS, inhaled corticosteroid; PEF, peak expiratory flow

% Reduction

AHR is a marker of inflammation

AHR Rescue medication use Night symptoms Impaired FEV Impaired am PEF 1

Start of treatment (months)

18

Short term ACHIEVE CONTROL

Long term Maintain CONTROL

An ongoing requirement for rescue medication is a sign that the underlying inflammation is uncontrolled

Woolcock Clin Exp Allergy Rev 2001; GINA 2009

assessed to establish:
current treatment regimen, adherence to the current regimen, and level of asthma control.

Adequate management

(GINA 2009)

The goal of asthma treatment

(GINA 2009)

Treatment targets in common chronic diseases

Clear therapeutic targets exist for many chronic diseases Philosophy of treat to target
Diabetes Hypertension Dyslipidaemia HbA1c 7% or less BP 140/90 mmHg or less LDL-cholesterol <100 mg/dl

Asthma treatment is designed to meet specific targets and achieve CONTROL

Control Level Based on GINA 2009

Asthma Characteristics Classification
CONTROLLED
PARTLY CONTROLLED

UNCONTROLLED

Daytime symptoms Limitations of activities

Nocturnal symptoms / awakening

None (2 or less / week) None None

None (2 or less / week)

More than twice / week

Any Any
More than twice / week
< 80% predicted or personal best (if known) on any day

Need for rescue / reliever treatment

Lung function (PEF or FEV1) Exacerbation

3 or more features of partly controlled asthma present in any week

Normal
None

Once/more per year

One in any week

The goal of asthma treatment To achieve and maintain clinical control QoL

Control Level Based on GINA 2009

Asthma Characteristics Classification
CONTROLLED
PARTLY CONTROLLED

UNCONTROLLED

Daytime symptoms Limitations of activities

Nocturnal symptoms / awakening

None (2 or less / week) None None

None (2 or less / week)

More than twice / week

Any Any
More than twice / week
< 80% predicted or personal best (if known) on any day

QoL

Need for rescue / reliever treatment

Lung function (PEF or FEV1) Exacerbation

3 or more features of partly controlled asthma present in any week

Normal
None

Once/more per year

One in any week

Definition of Quality of life

Quality of life: An important consideration in medical care, quality of life refers to the patient's ability to enjoy normal life activities.

Evaluation of Control
Medical Outcomes Clinical Clinical
* Symptoms (frequency/severity) * Symptoms * Exercise tolerance (frequency/severity) * Medication usage * Exercise tolerance Quality of Life * Adverse events Biological * Medication usage * Life satisfaction * Inflammation markers * Adverse events * Skin PT * Social & role functioning Humanistic Outcomes of Life * Total/specific Quality IgE Biological ** Sense of community Life satisfaction Functional role functioning * Lung function * Social &markers * Inflammation * Spiritual fulfillement * PEF variability * Sense of community Spiritual fulfillement * * BHR Skin PT** Self-esteem * Self-esteem * Total/specific IgE Enjoyment ** Enjoyment * Pleasure Functional ** Pleasure Appreciation satisfaction * Lung function *Patient Appreciation * With asthma control * Cost-utility Economic Outcomes * PEF variability Cost-utility * With Quality of Life Patient satisfaction * Cost-benefit * Cost-benefit * BHR Cost-identification ** With asthma control * Cost-effectiveness * Cost-identification * With Quality of Life * Cost-effectiveness

Modified from BLAISS MS, JAMA 1997

Why aim for control?

Patients perspectives Clinicians perspectives Payers perspectives

PATIENTS PERSPECTIVES

Patients perspective What is your expectation if you are asthmatic?

More than 50% of the asthmatic patients want to have a normal life & free from exacerbation

CLINICIANS PERSPECTIVES

Cellular effects of corticosteroids

Inflammatory cells
Numbers (apoptosis) Eosinophil

Structural cells
Epithelial cell Cytokines Mediators

T-lymphocyte Cytokines Endothelial cell Mast cell Numbers Macrophage Cytokines Dendritic cell Numbers
Barnes PJ & Adcock IM. Ann Intern Med 2003;139:359370.

CORTICOSTEROIDS

Leak Airway smooth muscle

2-receptors
Mucus gland Mucus secretion

PAYERS PERSPECTIVES

Deaths and hospital days fall despite increase in patients eligible for asthma treatment

450 400 350 Value of the index 300

250
200 150 100 50 0

Finnish Asthma Programme 2005

Haahtela et al. Thorax 2006

Several composite control measures

(GINA 2009)

 Asthma Control Test Asthma Control Questionnaire

Asthma Therapy Assessment Questionnaire

Asthma Control Scoring System

Objective use of ACT

1.

ACT is a scored tool which allows numerical targets to be set. Simple to complete 5 questions with a 5 point rating scale (max: 25)
19 or less = Uncontrolled asthma 20-24 25 = = Well controlled Total Control

2.

Improves patient / physician communication. Clear and concise questions that engage patients in a more open, candid discussion Validated using spirometry and specialist assessment

3.

Terima Kasih