module 5: treatment of severe asthma an educational program of: updated: june 2011

Module 5:Treatment of Severe

Asthmaan educational program of:

Updated: June 2011

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Module 5:Treatment of Severe

AsthmaAuthors:Jean Bousquet, FranceRonald Dahl, Denmark

Michael A. Kaliner, USAConnie Katelaris, Australia

Contributer:Richard Lockey, USA

Severe asthma

•A shift in focus from severity to control

•How to control severe asthma

•Diagnosis and management of acute severe asthma

Section 1: Asthma Control

Lecture Objectives Section 1 – Asthma

ControlAt the end of this section participants

will be able to:• Diagnose severe asthma• Assess whether asthma is controlled • Outline appropriate treatment

strategies for optimal control of severe asthma

Definition of severe asthma

• Patients who need high dose inhaled CCS and long-acting ß2 agonists and:– are still uncontrolled – experience frequent acute exacerbations – and/or often require emergency treatment

and/or hospitalization

Diagnosis and classification of

asthmaAsthma severity is classified by:

• the presence of clinical features before treatment is started

• and/or by the amount of daily medication required for optimal treatment

GINA 2002

Intermittent

Classification of asthma: GINA 1998

Step 4>1000 BDP + LABA + other

Step 3200–1000 BDP

+ LABA

Step 2 <500 BDP

Step 1No controller

Current treatment step

Severe persistent

Severe persisten

t

Severe persisten

t

Severe persisten

t

Step 4

Symptoms daily

Frequent nocturnal symptoms

FEV1 <60% predicted

Severe persistent

Severe persisten

t

Severe persisten

t

Moderate persisten

t

Step 3

Symptoms daily

Nocturnal symptoms ≥1 x week

FEV1 60–80% predicted

Severe persistent

Severe persisten

t

Moderate persisten

t

Step 2

Symptoms >1 x week

Nocturnal symptoms <1 x week

Lung function normal between episodes

Severe persistent

Moderate persisten

t

Mild persisten

t

Step 1

Symptoms <1 x week

Nocturnal symptoms ≤2x month

Lung function normal between episodes

Clinical features

Mild persisten

t

Asthma management: from severity to control

There has been a shift in the paradigm for

asthma treatment; previousrecommendations for stepwise

implementation of pharmacotherapy were

based on disease severity, the focus is now on asthma control

GINA: goals of treatment 2006

GINA 2002

"The aim of asthma management should becontrol of the disease"

What is asthma control?

• To the patient– no symptoms which interfere with normal

lifestyle no exacerbations, normal quality-of-life

– particularly, no cough

• To carers (parents)– able to get to school, no night cough

• To the GP– no unscheduled visits, few exacerbations, no

admissions (sometimes maintenance of PEF)

• To the respiratory physician

– no night symptoms

– maintenance of lung function (FEV1)

– few exacerbations, no admissions

• To regulatory authorities

– improvement in a.m. PEF, FEV1

– improvement in symptom scores and quality of life

– enhanced cost effectiveness analyses

What is asthma control?

• Currently, single clinical endpoints, such as lung function, are often used to guide treatment

• Single endpoints may overestimate true asthma control1

• Other disease areas such as diabetes use a composite measure (HbA1c, blood pressure and cholesterol targets)2-4

A composite measure of control may help to improve

outcomes

1. Clark et al. Eur Respir J 2002 2. European Diabetes Policy Group 1999. Diabet Med 1999 3. Diabetes UK.Recommendations for the management of diabetes in primary care. 2nd ed. October 2000 4. Department of Health. NSF for Diabetes: Standards 5. British Thoracic Society/Scottish Intercollegiate Guidelines Network. British Guideline on the Management of Asthma. February 2003. 6. National Heart, Lung, and Blood Institute, World Health Organization. 1998

How can we assess control in practice?

We need simple tools that both healthcare providers and patients can use

– Asthma Control Questionnaire (ACQ)7-item questionnaire. Based upon day/night-time symptoms, daily activities, rescue bronchodilator

Juniper et al ERJ 1999; 14: 902-907

- Royal College of Physicians (RCP)3 questions based upon day/night-time symptoms and daily activities.

- Asthma Control Test (ACT)Validated instrument. 5 questions based upon day/night-time symptoms, rescue bronchodilator use and daily activities.

How can we assess control in practice ?

Br Med J 1990;301:651-653Nathan et al., J Allergy Clin Immun, 2004: 113(1): 59-65

Differences between scores

RCPrules

2ACQ ACT 30 sec

Night time symptoms

yes yes yes yes yes

Day time symptoms yes yes yes yes

Exercise, activities yes yes yes yes

Rescue medications (yes) yes yes yes yes

FEV1 or PEFR ACQ7

Duration of survey 1 wk or 1 mo

1 wk to

1 yr

1 wk 1 mo 1 wk to 3 mo

Levels of asthma control

CharacteristicControlled

(All of the following)

Partly controlled(Any present in any

week)Uncontrolled

Daytime symptomsNone (2 or less/ week)

More than twice/week

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

Limitations of activities None Any

Nocturnal symptoms/ awakening

None Any

Need for rescue/ “reliever” treatment

None (2 or less/ week)

More than twice/week

Lung function (PEF or FEV1)

Normal< 80% predicted or

personal best (if known) on any day

Exacerbation None One or more/year 1 in any week

Asthma Management and Prevention Program

Goals of long-term management

• Achieve and maintain control of symptoms• Maintain normal activity levels, including

exercise• Maintain pulmonary function as close to

normal levels as possible• Prevent asthma exacerbations• Avoid adverse effects from asthma

medications• Prevent asthma mortality

Severe asthma

• A shift in focus from severity to control

• How to control severe asthma• Diagnosis and management of

acute severe asthma

Asthma Management and Prevention Program

• Asthma can be effectively controlled in most patients by intervening to suppress and reverse inflammation as well as treating bronchoconstriction and related symptoms

• Early intervention to stop exposure to the risk factors that sensitized the airway may help improve the control of asthma and reduce medication needs

• Depending on level of asthma control, the patient is assigned to one of five treatment steps

• Treatment is adjusted in a continuous cycle driven by changes in asthma control status. The cycle involves:

- Assessing Asthma Control

- Treating to Achieve Control

- Monitoring to Maintain Control

Asthma Management and Prevention

Program Component 3: Assess, treat and monitor asthma

Assess asthma control

Maintain treatment

orStep down

Step up untilcontrolled

Management of asthma in adults and adolescents (GINA 2006 adapted)

Controlled Partially controlled Uncontrolled

No controllertreatment

Step 2

Controllertreatment

Step up

Exacerbation

Treat asexacerbation

Step 4 – Reliever medication plus two or more

controllers

• Selection of treatment at Step 4 depends on prior selections at Steps 2 and 3

• Where possible, patients not controlled on Step 3 treatments should be referred to a health professional with expertise in the management of asthma

Treating to achieve asthma control

Step 4 – Reliever medication plus two or more controllers

• Medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β2-agonist (Evidence A)

• Medium- or high-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A)

• Low-dose sustained-release theophylline added to medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β2-agonist (Evidence B)



Step 5 – Reliever medication plus additional

controller options

• Addition of oral glucocorticosteroids to other controller medications may be effective (Evidence D) but is associated with severe side effects (Evidence A)

• Addition of anti-IgE treatment to other controller medications improves control of allergic asthma when control has not been achieved on other medications (Evidence A)

Treating to maintain asthma control

• When control as been achieved, ongoing monitoring is essential to:

- maintain control

- establish lowest step/dose of treatment

• Asthma control should be monitored by the health care professional and by the patient


Stepping down treatment when asthma is controlled• When controlled on medium- to

high-dose inhaled glucocorticosteroids: 50% dose reduction at 3 month intervals (Evidence B)

• When controlled on low-dose inhaled glucocorticosteroids: switch to once-daily dosing (Evidence A)


Stepping down treatment when asthma is controlled• When controlled on combination inhaled

glucocorticosteroids and long-acting inhaled β2-agonist, reduce dose of inhaled glucocorticosteroid by 50% while continuing the long-acting β2-agonist (Evidence B)

• If control is maintained, reduce to low-dose inhaled glucocorticosteroids and stop long-acting β2-agonist (Evidence D)


Stepping up treatment in response to loss of control• Rapid-onset, short-acting or long-

acting inhaled β2-agonist bronchodilators provide temporary relief.

• Need for repeated dosing over more than one/two days signals need for possible increase in controller therapy


Stepping up treatment in response to loss of control• Use of a combination long-acting inhaled β2-

agonist (e.g., salmeterol, formoterol) and an inhaled glucocorticosteroid (e.g., fluticasone, budesonide) in a single inhaler both as a controller and reliever is effective in maintaining a high level of asthma control and reduces exacerbations (Evidence A)

• Doubling the dose of inhaled glucocorticosteroids is not effective, and is not recommended (Evidence A)


• When control as been achieved, ongoing monitoring is essential to:

- maintain control

- establish lowest step/dose of treatment

• Asthma control should be monitored by the health care professional and by the patient

Guided self-management plans GINA 2006 (adapted)

• Guided self management action plans enable patients with asthma to gain the knowledge, confidence and skills to assume a major role in the management of their asthma, reducing asthma morbidity in adults (Evidence A) and children (Evidence A).

Monitoring asthma: peak flow meters

Peak flow meters are useful to monitor asthma and prevent exacerbations:

• Inexpensive• Easy to use• Accurate• Provide “real life” measurements at worst and best times of the day• Provide objective measurement of pulmonary function• Detect early changes of asthma worsening

Patient “self management” based on peak flow

measurementIf personal best peak flow

measurements:

– Fall 10+%, double dose of inhaled CCS– Fall 20+%, use short-acting bronchodilator Q4 -6

hour, plus 2-4 x inhaled CCS– Call office, try to determine if infection is present– Fall 40 - 50%, add oral CCS– Fall greater than 50%, urgent visit to either

• Outpatient office • Emergency room

Kaliner In: Current Review of Asthma. Current Medicine, 2003

Use of inhaled corticosteroids

Rabe et al. Eur Respir J 2000;www.asthmainamerica.com;Lai et al. J Allergy Clin Immunol 2003;Data on file

Copyright permission for reproduction pending

Preventing exacerbations -underlying causes and patient

education Evaluate patient for :

– Allergy– Infection– Compliance– Inappropriate

concomitant medications– Social factors– Tobacco, drugs, irritants,

fumes– Psychiatric disordersInitiate or review patient education and self-management plan

Role of allergy in managing asthma

• 90% of asthmatics <16 years old are allergic• 70% of asthmatics 16-30 are allergic• 50% of adult asthmatics are allergic• Any asthmatic who wheezes 2 times/week

needs an allergy assessment• Allergy avoidance and allergy vaccination are

effective treatments for asthma (Evidence A)• Allergy treatment is both cost-effective and is

the only treatment capable of reducing asthma long-term

The main goal of the 10 year Finnish Asthma

Programme:

• To lessen the burden of asthma on individuals and society

Finnish Asthma Programme: Measures to achieve the

goals• Early diagnosis and active treatment• Guided self-management as the primary form of treatment• Reduction in respiratory irritants such as smoking and

environmental tobacco smoke• Implementation of patient education and rehabilitation

combined with normal treatment, planned individually and timed appropriately

• Increase in knowledge about asthma in key groups; and promotion of scientific research

• Appointment of one doctor, one nurse and one pharmacist responsible for asthma care in each clinic/region

Healthcare benefits from asthma intervention

Haahtela et al, Thorax 1998

Ast

hm

a I

ndic

es

(base

100 i

n 1

981) Reimbursement asthma

Hospitalization daysDeath rate

Year

350

300

250

200

150

100

50

0

1981 1983 1985 1987 1989 1991 1993 1995

Healthcare benefits from asthma intervention

Finnish Asthma Programme (1994-2004)

Haahtela et al, Thorax 2006

-80

-60

-40

-20

0

20

40

60%

ch

an

ge 1

993-2

00

3

asthmaprevalence

hospitaldays

disabilitypension

total costscost per ptper year

Summary• Asthma management in 2007 is focused on

control of the individual patient’s asthma symptoms, a paradigm shift from earlier recommendations of a step-wise increase in therapy based on asthma severity;

• Patient self-management plans play an important role in prevention of exacerbations;

• Successful asthma interventions lead to increased medication costs but decreased costs for hospitalization, and decreased death rates;

• Allergen exposure is an important contributory factor in exacerbations of IgE-mediated asthma.

Section 2: Acute Severe Asthma

Severe asthma

•A shift in focus from severity to control

•How to control severe asthma•Diagnosis and management of

acute severe asthma

Lecture objectives: Section 2

At the end of this section participants will be able to:

• Understand the risk factors for asthma exacerbations

• Understand the pathophysiology of acute severe asthma

• Identify the signs and symptoms of acute asthma

• Outline appropriate treatment strategies for optimal control of acute asthma exacerbations

Frequency of hospital and emergency room visits in

moderate-severe asthmatics; TENOR study

Rabe et al. Eur Respir J 2000;www.asthmainamerica.com;Lai et al. J Allergy Clin Immunol 2003;Adachi et al. Arerugi 2002;Data on file


Slight Moderate

Acute severe asthma monitoring

Severe

the cross-road of death

Slight Moderate

SevereNormo- ventilation

Hyper-ventilation

HypoventilationExhaustion

RHONCHI

Eur Respir J 1997; 10: 1359–1371


Bronchial Asthma

Spirometric abnormaliti

es

Central airway

narrowing

Bronchoconstriction

Gas exchange abnormalities

Distal airway narrowing

Airway Inflammation

Treatments must be directed towards these two components:

Smooth muscle spasm Inflammation, edema, plugs

Features of a severe asthma exacerbation

One or more present:• Use of accessory muscles of respiration• Pulsus paradoxicus >25 mm Hg• Pulse > 110 BPM• Inability to speak sentences• Respiratory rate >25 - 30 breaths/min• PEFR or FEV1 < 50% predicted• SaO2 <91- 92%

McFadden Am J Respir Crit Care Med 2003

Risk factors for fatal or near-fatal asthma attacks

• Previous episode of near-fatal asthma• Multiple prior ER visits or hospitalizations• Poor compliance with medical treatments• Adolescents or inner city asthmatics• (USA) African-Americans>Hispanics>Caucasians• Allergy to Alternaria• Recent use of oral corticosteroid (OCS)• Inadequate therapy:

– Excessive use of β-agonists– No inhaled corticosteroid (ICS)– Concomitant β-blockers

Ramirez and Lockey In: Asthma, American College of Physicians, 2002

Physical findings in severe asthma exacerbations

• Tachypnea• Tachycardia• Wheeze• Hyperinflation• Accessory muscle use• Pulsus paradoxicus• Diaphoresis (profuse sweating)• Cyanosis• Sweating• Obtundation (altered mental state)

Brenner, Tyndall and Crain In: Emergency Asthma. Marcel Dekker 1999

Causes of asthma exacerbations

• Lower or upper respiratory infections

• Cessation or reduction of medication

• Concomitant medication, e.g. β-blocker

• Allergen or pollutant exposure

Differential diagnosis

• COPD• Bronchitis• Bronchiectasis• Endobronchial

diseases• Foreign bodies• Extra- or intra-

thoracic tracheal obstruction

• Carcinoid syndrome

• Cardiogenic pulmonary edema

• Non-cardiogenic pulmonary edema

• Pneumonia• Pulmonary emboli• Chemical

pneumonitis• Hyperventilation

syndrome

Brenner, Tyndall, Crain In: Emergency Asthma. Marcel Dekker, 1999

Acute severe asthma – associations and differential

diagnoses• Hyperventilation syndrome• Vocal cord dysfunction• Vaso-vagal reaction• Anaphylactic reaction (urticaria, BP, pulse

rate, etc)• Aspiration - foreign body – pneumonia• Pneumothorax• Cardiac failure• Lung emboli

Stages of asthma exacerbations

Stage 1:Symptoms• Somewhat short of breath• Can lie down and sleep through the night• Cannot perform full physical activities without

shortness of breathSigns• Some wheezes on examination• Respiratory rate, 15 (normal <12)• Pulse 100• Peak flows and spirometry reduced by 10%


Stage 2:Symptoms• Less able to do physical activity due to shortness of

breath• Dyspnea on walking stairs• May wake up at night short of breath• Uncomfortable on lying down• Some use of accessory muscles of respiration

Signs• Wheezing• Respiratory rate 18• Pulse 111• Peak flows and spirometry reduced by 20+%


Stage 3:Symptoms• Unable to perform physical activity without

shortness of breath• Cannot lie down without dyspnea• Speaks in short sentences• Using accessory muscles

Signs• Wheezing• Respiratory rate 19 - 20• Pulse 120• Peak flows and spirometry reduced by 30+%


Stage 4:Symptoms• Sitting bent forward• Unable to ambulate without shortness of breath• Single word sentences• Mentally-oriented and alert• Use of accessory musclesSigns• Wheezing less pronounced than anticipated• Respiratory rate 20 - 25• Pulse 125+• Peak flows and spirometry reduced by 40+%• SaO2 91- 92%


Stage 5:Symptoms• Reduced consciousness• Dyspnea• Silent chest – no

wheezingSigns• Fast, superficial

respiration• Respiratory rate >25• Unable to perform peak

flows or spirometry• Pulse 130 - 150+ • SAO2 <90

Severity of asthma as graded by % predicted FEV1

FEV% predicted Severity• 70 - 100 Mild• 60 - 69 Moderate• 50 - 59 Moderately

severe• 35 - 49 Severe• < 35 Very severe:

(life-threatening)

Acute severe asthma - clinical assessment

• Respiratory frequency: (count)– Speech: sentences, single words

• Auxiliary respiratory muscle use• Posture: sitting, can patient lie down?• Airway patency: rhonchi, silent chest

(PEF)• Respiration: cyanosis (SaO2, blood gases) • General appearance, effort of

breathing: activity level (pulse rate)

Acute severe asthma - monitoring

• Clinical condition• PEF or FEV1 • PaO2 and PaCO2

ACUTE ASTHMA – MONITORING CHART Name: History: Birth date: Date: Time first seen:

Time

Pulse rate

Respiratory

rate

Use of accessory muscles

PEF

Pulse oximetry (SaO2)

Cyanosis

Exhaustion

Oxygen

flow

Treatment

_________

Neck Abdomen Arms

______ l/m

Short Acting Beta Agonist Dose: ____________ Delivery: Nebuliser/Spacer Oral steroid: ________ Inhaled steroid: ______

_________

Neck Abdomen Arms

______ l/m


_________

Neck Abdomen Arms

______ l/m


Acute severe asthma

Admission and close monitoring in hospital unit:

• Clinical stage 4• PEF or FEV1 < 30% of personal best (if unknown < 30% predicted)• PaCO2 > 6 kPa• PaO2 < 8 kPa• Poor response to initial treatment

Acute severe asthma treatment

Oxygen by nasal cannulae or mask

Inhaled broncodilator should be administered atregular Intervals (Evidence A): Nebulised ß2-agonist combined with anticholinergic each20 mins in the first hour, then hourly as necessary

Systemic steroid should be utilised in all but the Mildest Exacerbations (Evidence A):Oral (50-75mg prednisolone) or i.v. corticosteroid (80 mgMethylprednisolone); repeat after 12 hours; over the following

days 40 mg prednisolone or equivalent is usually maintained

Start inhaled high dose steroid as soon as possible


Dangerous, or at least ineffectiveDangerous: SedationIneffective: Mucolytics

PhysiotherapyAntihistamines


Consider:Infusion of Beta-2-agonist Infusion of theophylline Antibiotics – not all acute asthma exacerbations require antibioticsFluids

Acute severe asthma – treatment options

Standard treatment:Oxygen

Inhaled beta-2-agonist +/- anticholinergicSystemic corticosteroidAdditional options:

Systemic beta-2-agonist and/or theophylline, antibiotics, fluids

Nonstandard treatment:Antileukotrienes; Magnesium sulphate; Heliox; Bi-pap

Extreme intervention:Intubation and controlled hypoventilation/other

strategyAnesthesia-sedation; Bronchial lavage

Treatment of asthma exacerbations

oral corticosteroids• Oral corticosteroids are the most powerful

medications available to reduce airway inflammation

• Use until attack has completely abated:– PEFR and FEV1 at baseline levels– Symptoms gone

• Taper to QOD and determine if patient can remain well if corticosteroids are withdrawn completely

Acute severe asthma

• Treat the condition symptomatically• Determine what caused the

exacerbation:– inhalant allergen– food allergen– drug reaction (ASA, vaccination, etc)– infection– worsening of a chronic condition: - poor therapy compliance

- treatment needs adjustment

Prevention of relapse and recurrence of asthma

exacerbation - definitionRelapse: Reappearance of asthma symptoms that require unscheduled care within 3 weeks of an asthma exacerbation

Recurrence: Reappearance of asthma symptoms that require unscheduled care more than 3 weeks after the asthma exacerbation

Prevention of relapse and recurrence of asthma

exacerbationPatients treated for an asthmaexacerbation are at risk for subsequent severe attacks: (unscheduled doctor visits, Emergency Department visits,hospitalization, asthma death)

Proper asthma care can reduce this risk:a) Pharmacological

intervention with ICS b) Patient education –

knowledge and skillsc) Self management plans

and follow up

Prospective multicenter study of relapse after ED care of acute

severe asthma Relapse rate: 17%

Associations ORMultiple previous ED visits for asthma

1.3Use of home nebulizer 2.2Long duration of symptoms 2.5Report of multiple triggers (per trigger)

1.1

Emerman C et.al. Chest 1999; 115: 919-27

Comparison of short course of Inhaled CS and Oral CS for acute asthma

exacerbation in primary care

413 patient in 47 general practices.

Treatments: a) oral prednisolone 40mg daily for 16 days b) inhaled FP 1000mcg x 2 daily for16 days

Outcome was failure:Defined by symptoms and/or PEF

Levy ML et el. Thorax; 1996; 51: 1087-92

Comparison of short courses of OCS vs ICS in the treatment of

asthma exacerbation in primary care

Levy ML, et al. Thorax 1996; 51:1087-1092


Viral respiratory infection and asthma exacerbations

Studies using PCR techniques have shown that viral infection is a

common cause of asthma exacerbations.

Age n Setting %viral Reference _______ 19-46y 138 Outpatient 55 Nicholson BMJ 1993

9-11y 108 Outpatient 85 Johnston BMJ 1995

6m-12y 75 Hospitalized 82 Freymoth JCVirol 1999

2m-16y 70 ED 83 Rakes AJRCCM 1999

Antibiotics in asthma exacerbations

• Use antibiotics if any suspicion of bacterial

infection• If antibiotics are prescribed,

recommendation is for broad spectrum macrolide antibiotics that cover atypical bacteria (chlamydia, mycoplasma), eg, azithromycin, clarithromycin, erythromycin, roxithromycin, dirithromycin, amoxicillin + clavulan; moxifloxacin, cefuroxim

Delays in seeking help for acute asthma - the patient’s

perspective 95 patients explained their reasons for

delaying seeking professional care:• Uncertainty 74%• Disruption 86%• Minimization 90%• ”Self-reliance” 46%• Fear of steroids 31%

• To avoid ED 34%• Economic reasons 5%

Janson S. J Asthma 1998; 35: 427-35

Acute severe asthma

IS A RESPIRATORY ATTACK!

• Treat, Monitor and Follow-up

• Consider improved prophylaxis:

- allergen avoidance - allergen vaccination - pharmacological treatment update

- stop smoking - enhance compliance to recommendations by teaching and monitoring

World Allergy Organization (WAO)

For more information on the World Allergy Organization (WAO), please

visit www.worldallery.org or contact the:

WAO Secretariat555 East Wells Street, Suite 1100

Milwaukee, WI 53202United States

Tel: +1 414 276 1791Fax: +1 414 276 3349

Email: [email protected]

http://www.worldallery.org/

mailto:[email protected]

module 5: treatment of severe asthma an educational program of: updated: june 2011

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