GINA 16 – Management & Treatment of Asthma

GINA 16 – Management &

Treatment of Asthma

Raphael Northoff - PTA (pharmaceutical &technical assistant),

Observer Clínica Universidad de La Sabana

Structure

Short explanations

What is GINA?

What is asthma ?

How is asthma evaluated?

Symptoms

Exacerbation

Treating Asthma

General management

Drugs

About GINA

Asthma specialist from over 50 different nations

Launched in 1993

Semiannual meetings

Publish guidelines

With the participation of WHO and NIH

Non profit organization

How GINA defines asthma

“Asthma is a heterogeneous disease, usually

characterized by chronic airway inflammation. It is

defined by the history of respiratory symptoms

such as wheeze, shortness of breath, chest

tightness and cough that vary over time and in

intensity, together with variable expiratory airflow

limitation.”

GINA objectives

• Increase awareness of asthma and its public health consequences.

• Promote identification of reasons for the increased prevalence of

asthma.

• Promote study of the association between asthma and the

environment.

• Reduce asthma morbidity and mortality.

• Improve management of asthma.

• Improve availability and accessibility of effective asthma therapy.

GINA 16 Key changes in

Stepwise treatment (details later)

Low-resource settings

still up to 50% asthma undiagnosed, up to 34% over-

diagnosed

Prevention of asthma

Other changes

remediate dampness or mold in homes reduces asthma

symptoms and medication use in adults (Evidence A)

Vitamin D not associated with improvement in asthma

symptom control or reduction in exacerbations

Levels of symptom controlLevel of asthma symptoms control

In the last 4 weeks, has

the patient had

Well controlled Partly controlled Uncontrolled

Daytime asthma symptoms

more than twice a week?

Yes/No

None of these 1-2 of these 3-4 of these

Any night waking due to

asthma? Yes/No

Reliever needed for

symptoms* more than

twice a week? Yes/No

Any activity limitation due

to asthma?

Yes/No

* Includes reliever taken before exercise (many people do this routinely)

FIGURE 1: GINA 2016 teaching-slide-set

Evaluating asthma severity

Is assessed retrospectively from the level of treatment which is required to control

symptoms and exacerbations

Assess asthma severity after several month controller treatment

Severity is not statistic – it may change over month or years or as different

treatments become available

• Well-controlled with Steps 1or 2

• As-needed SABA or low-dose ICSMild asthma

• Well-controlled with Step 3

• Low-dose ICS/LABAModerate asthma

• Requires Step 4/5

• Moderate or high ICS/ LABA + add onSevere asthma

Treating asthma to control symptoms and

minimize risk

Symptom RiskC

ON

TR

OL

RE

DU

CT

ION

three categories of long-term treatment

Reliever

Taken as necessary

in case of exacerbation/

prevention of exercise

Induced bronchoconstriction

Controller

Taken regularly - reduces inflammation and exacerbation risk and controls symptoms

Add-on

Severe asthma,

persistent symptoms

Some abbreviations in common use

ICS inhaled corticosteroids

OCS oral corticosteroids

LTRA leukotriene receptor antagonists (oral)

SABA short-acting−𝛽2-agonists (inhaled)

LABA long-acting-𝛽2-agonists (inhaled)

FEV1 forced expiratory volume in one second (value for diagnosis and control of asthma, should be > 0.7)

Process of managing asthma


Don’t forget

• *Not for children <12 years

• **For children 6-11 years, the preferred Step 3 treatment is medium

dose ICS

• # For patients prescribed BDP/formoterol or BUD/ formoterol

maintenance and reliever therapy

• Tiotropium by mist inhaler is an add-on treatment for patients ≥12

years with a history of exacerbations


update

When stepping down and when stepping

up?

Considering stepping up asthma treatment

When asthma poor controlled for at least 2-3 month

Important: first check for common causes (incorrect inhaler technique, poor adherence,

symptoms not due to asthma)

Short-term step up (increase doses)

For 1-2 weeks, e.g. viral infection

Considering stepping down asthma treatment

After well-controlled asthma symptoms maintained for 3 month

Find each patient´s minimum effective dose, that control both symptoms and

exacerbations

What´s new in the stepwise treatment?

Updates in higher lever care or add-on therapy

Phenotype-guided treatment

Severe allergic asthma: add-on omalizumab (anti-IgE)

Severe eosinophilic asthma: add-on mepolizumab (anti-IL5)

Sputum-guided treatment to reduce exacerbations and/or steroid dose

examine sputum (bronchial secrete) for eosinophils, which are prevenient to an exacerbation

reduces exacerbations and/or corticosteroid dose

Aspirin-exacerbated respiratory disease: consider add-on LTRA

phenotypes may be overlapping in specific patients and may change over time

Preferred option is referral for specialist investigation

and consideration of add-on treatment


TO KEEP IN MIND !

Role in therapy - controllers

Inhaled corticosteroids (ICS)

Most recommend therapy

Anti-inflammatory, anti-allergic, immunosuppressive (effect local)

demonstrate best anti-inflammatory efficacy to treat prolonged (allergic) asthma (more effective when dosed twice daily)

Most benefits achieved with low-dose ICS

higher-dose ICS may realize little further benefits but increase risk of side effects

ICS are as first line most recommended and well evaluated treatment

Also in combination with LABA

adverse effects of ICS

Oropharyngealcandidiasis

Some contain lactose

(do flush out after use)

Inflammation of the throat &hoarseness

Coughing from upper airway irritation

Headache

Predominantly local side-effects like

Systemic side-effects are less general


long-acting−𝜷𝟐-agonists (LABA)

Inhaled

Selective stimulation of adrenergic receptors bronchial musculature

Effect:

Spasmolytic in bronchial tubes

Bronchodilator effect

Should only be used in combination with ICS

LABA don’t have that important anti-inflammatory aspect

E.g.: salmeterol, formoterol (formotorol has an early effect access)

effect for 12 to 24

hours

Adverse effects of LABA

Tachycardia,

Arrhythmia,

Angina pectoris

Tremor, restlessness

Adverse effects appear particularly in use of high-doses

Also a stimulation of 𝛽1- receptor (heart/ CNS)


Combination of ICS and LABA

As dry powder inhaler

“Adding LABA reduces symptoms and exacerbations and increases FEV1, while

allowing lower dose of ICS”

“In at-risk patients, maintenance and reliever regimen significantly reduces

exacerbations with similar level of symptom control and lower ICS doses

compared with other regimens”

Using same inhaler as controller and reliever increases adherence !

Only approved for:

low-dose beclomethasone/formoterol and low-dose budesonide/ formoterol

1 + 2 = 4

Role in therapy – reliever Short-acting-beta 2-agonists (SABA)

Selective stimulation of adrenergic receptors bronchial musculature

Effect:

Spasmolytic in bronchial tubes

Bronchodilator effect

onset of action 1 - 5 min relief for 3 - 6 hours

Taken as necessary in case of exacerbation, strong symptoms

prevention of exercise Induced bronchoconstriction

Should be used in lowest possible dose

Frequent use is part of uncontrolled asthma

Most important: Salbutamol, fenoterol, terbutaline

Role in therapy - controllers (sec. line/ add on)

Leukotriene receptor antagonists (LKRA)

oral administration

Leukotriene: strong inflammations mediators

they cause a constriction and swelling of airways in the lungs

increase secretion of mucus

Less effective than low dose ICS

May be used for some patients with both asthma and allergic rhinitis or if patient

will not use ICS

More common in pediatrics (no need to inhale)

e.g. : Montelukast

adverse effects of LKRA

Nausea, diarrhea, emesis

Skin rash,

Infection of the upper airways

Rarely Liver inflammation

(monitoring of liver values)

Some neuropsychological disturbances like

depression, hallucination, peevishness are reported

LKRA are generally well tolerated

Role in therapy – controllers (sec. line/ add-on)

Theophylline

Oral

Unspecific adenosine-receptor agonist, antagonizing equally

A2b (A3) responsible for release of inflammatory mediators

Unspecific Inhibition of phosphodiesterase (PDE)

Bronchodilation

Second line medication!

As add-on (Step 3/ 4) when patient don’t achieve relief from ICS/ LABA

but less effective then increasing the ICS/ LABA doses

Low therapeutic range and unspecific action

Xanthine derivative

Adverse effects of theophylline

Potential for significant side effects, which due to the unspecific action of

theophylline (effect also on A1 and A2a)

In low serum concentration side effect occur similar to those of caffeine

Over dose more than 20 mcg/ ml

Can be reduced by close monitoring and adequate doses

Nausea and vomit

insomnia Tachycardia, arrhythmia, tremor and convulsing

Role in therapy - controllers (sec. line/ add on)

Tiotropium

Inhaled (mist inhaler)

inhibition of muscarinic Ach-receptors (anticholinergic)

Bronchodilator effect by inhaling

Reduces significantly exacerbations (and asthma symptoms )

to prevent wheezing, shortness of breath, coughing and chest tightness

May be used as add-on therapy for patients with history of exacerbations

can improve outcomes for patients with asthma who remain symptomatic despite

the use of ICS/LABA maintenance therapy

disadvantage of non anti-inflammatory aspect

Adverse effects of tiotropium

As consequence of inhibiting the muscarine-receptors there can appear

Dry mouthand bitter

taste

Indigestion, Constipation

and stomache

pain

Muscle pain

Role in therapy – controllers (sec. line/ add-on)

Monoclonal Anti-IgE antibody omalizumab

injected once in six month (s.c.)

It binds the IgE molecule

in so doing it prevents the union from IgE with cell-surface receptors

As adjustment the inflammatory reaction is likely to be stabilized, that means

Less release of inflammation mediators, production of anti-gens and IgE-syntesis

For patients with:

severe allergic asthma uncontrolled with high-dose ICS/ LABA

exalted serum concentration of IgE (phenotype treatment)

Could be an option to prevent side-effects of instead taken OCS

IgE blood levels should measured when medicating with omalizumab

High treatment costs

FIGURE 5: N Engl J Med 2006;354:2689-95

Adverse effects of omalizumab

risks of the development of cancer

Omalizumab 0,5% and Placebo 0.2%¹

Risk of the development of

anaphylaxis

Omalizumab is intended to prevent anaphylaxis but in

clinical trials 3 persons (<0.01%) had anaphylaxis¹

Rash, nausea, diarrhea, vomit,

Epistaxis and injection side effects

¹FDA, Center for Biologics Evaluation and Research. BLA STN 103976/0, review of clinical safe-ty data: original BLS

submitted on June 2, 2000 and response to complete review let-ter submitted on December 18, 2002. Rock-ville, Md.:

Department of Health and Human Services, 2003.

Role in therapy – controllers (sec. line/add-on)

Monoklonal Anti-IL5 antibody

injected monthly (s.c.)

Anti-IL5 binds with high affinity to free IL5 – inhibition of

IL5 plays a key role in eosinophil proliferation, differentiation, maturation, migration

to tissue sites and survival

Eosinophils are noted for increasing the possibility of exacerbations

Effect:

reduces exacerbations

no improvement in symptoms, lung function or airway hyperesponsivness

Indicated for severe eosinophilic asthma (phenotype) when

persistent sputum eosinophilia

despite high doses of inhaled corticosteroids

update

Mepolizumab

binds IL5

Role in therapy – controllers (sec. line/add-on)

Monoklonal Anti-IL5 antibody

injected monthly (s.c.)

Mepolizumab is the most studied anti-IL5 in the treatment of severe asthma

For others like reslizumab or benralizumab not sufficient evidence

Adverse effects of mepolizumab

Because of the recent use of mepolizumab adverse effects are mostly documented

in studies

Headacheand dorsal

pain

Injection sideeffects like

pain, rush orswelling

Role in therapy – controllers (sec. line)

Oral corticosteroids (OCS)

Anti-inflammatory , anti-allergic, immunosupprressive (systemic effect)

Only local effects are needed

ICS should always be preferred before OCS!

high risk for adverse effects

Low dose OCS (≤7.5mg/day prednisone equivalent)

Is used for severe asthma if other options aren´t efficient enough

Short-term treatment after exacerbation

Asses and monitor for osteoporosis

Adverse effects of OCS

Short-term use of OCS (after exacerbation) is less likely for occurrence of adverse

effects

Treatment by long-term OCS increases significantly the risk of heavy adverse

effects

Osteoporosis

Obesity

Skin thinning

arterial hypertension

Glaucoma

Diabetes

Slow wound heeling

Emotional disturbances

Muscle weakness

GINA 16 – Management & Treatment of Asthma

Health & Medicine

Transcript of GINA 16 – Management & Treatment of Asthma