GINA is an international group of asthma specialists that publishes guidelines for asthma management and treatment. Asthma is defined as a chronic lung disease characterized by inflammation and variable airflow obstruction. GINA outlines approaches for evaluating asthma severity and control, treating asthma with a stepwise approach using controllers like inhaled corticosteroids and relievers. New guidelines address low-resource settings, prevention strategies, and add-on biologic treatments for phenotypes like severe allergic or eosinophilic asthma.

1. GINA 16 – Management &
Treatment of Asthma
Raphael Northoff - PTA (pharmaceutical &technical assistant),
Observer Clínica Universidad de La Sabana

2. Structure
 Short explanations
 What is GINA?
 What is asthma ?
 How is asthma evaluated?
 Symptoms
 Exacerbation
 Treating Asthma
 General management
 Drugs

3. 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

4. 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.”

5. 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.

6. 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

7. Levels of symptom control
Level 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

9. 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

10. Treating asthma to control symptoms and
minimize risk
Symptom Risk
CONTROL
REDUCTION

11. 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

12. 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)

13. Process of managing asthma
FIGURE 2: GINA 2016 teaching-slide-set
Don’t forget

14. • *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
FIGURE 3: GINA 2016 teaching-slide-set
update

15. 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

16. 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

17. FIGURE 4: GINA 2016 teaching-slide-set
TO KEEP IN MIND !

18. 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

19. new

20. adverse effects of ICS
Oropharyngeal
candidiasis
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

21. Role in therapy - controllers
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

22. 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)

23. Role in therapy - controllers
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

24. 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

25. 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

26. 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

27. 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

28. 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

29. 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

30. Adverse effects of tiotropium
 As consequence of inhibiting the muscarine-receptors there can appear
Dry mouth
and bitter
taste
Indigestion,
Constipation
and
stomache
pain
Muscle pain

31. 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

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

33. 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.

34. 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

35. Mepolizumab
binds IL5

36. 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

37. Adverse effects of mepolizumab
 Because of the recent use of mepolizumab adverse effects are mostly documented
in studies
Headache
and dorsal
pain
Injection side
effects like
pain, rush or
swelling

38. 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

39. 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