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Management
of Severe Refractory Asthma
Sumardi
Pulmonology DivisionInternal Medicine Departement GMU /
Sardjito Hospital
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INTRODUCTION
Asthma is a heterogeneous disease in which adequateasthma control cannot be achievedin a substantialproportion despite currently available treatmentpossibilities
subgroup has been defined as severe refractoryasthma
classification into distinct phenotypes is ongoing totarget the right treatment to the right patient
therapeutic targeted treatment options are currently toprovide possible targets toimprove disease state,symptoms and quality of life
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DEFINITION
The WHO (2010) distinguished three subtypes of severeasthma:
1) severe untreated asthma,
2) difficult-to-control severe asthma, and
3) severe refractory asthma
Identified phenotypes of severe refractory asthma(ATS/ERS2013):
Early onset severe allergic asthma
Late onset non-atopic, inflammation predominantasthma with fixed airflow limitation
Late onset obese female preponderant asthma
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WHAT CAN I DO?
patients labelled assevere refractory asthmaremain achallenge for the treating clinician.
Severe refractory asthma that do not respondto current
standard therapy, i.e.high doses of inhaledglucocorticosteroids in combination with long-acting2-agonists (LABA)
Wener RRL and Bel EH2013 Severe refractory asthma: an update Eur Respir Rev 22: 227
235
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CURRENT TREATMENT
According to current guidelines (Global Initiative forAsthma, National Asthma Education and PreventionProgramme and the British Thoracic Society) the
treatment of patients with severe asthma: constitutes ofhigh-dose inhaled or
oral/systemicglucocorticosteroids, incombination with
LABAs, and/orAnticholinergic
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THERAPY IN SEVERE REFRACTORY
ASTHMAWener RRL and Bel EH2013 Severe refractory asthma: an update Eur Resp ir Rev 22: 227235
High dose continuous nebulizer:
Steroid
Budesonide > 2000 mcg, or
Fluticasone > 2000 mcg
Beta2-agonis:
Salbutamol > 5 mg, or
Terbutaline > 5 mg
Anti-cholinergicipatrium bromide > 5 mg
Systemic corticosteroid methylprednisolon
125 mg 500 mg/day iv, or
Pulse dose 500 mg/12 hours iv, 3 days
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MAINTENANCE IN SEVERE
REFRACTORY ASTHMA
Wener RRL and Bel EH2013 Severe refractory asthma: an update Eur Respir Rev 22: 227235
Oral highdose methylprednisolone 1.5-2 mg/kgBW/day
Tappering to optimal dose of methylprednisolone after
asthma controlled (2-4 weeks) Highdose steroid inhaler 2000-6000 mcg/day 2-3 devide
dose, for 2-3 months, and tappering to optimal dose
LABA inhaler : Formoterol 160960 mcg/day for 2- 3 months
Salmeterol 50100 mcg/day for 2-3 months
Indacaterol, carmoterol, olodaterol, vilanterol, once/day
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Targeted therapy
Omalizumab(Anti-IgE) Reduced exacerbation rate
Mepolizumab(Anti-IL5) Reduced exacerbation rate &Reduced eosinophilia
Golimumab(Anti-TNF-a) No improvement in pulmonary function
Etanercept(Anti-TNF-a) Improvement in pulmonary function
Daclizumab(Anti-IL2R chain)Improved asthma control andpulmonary function
Lebrikizumab(Anti-IL13) Improvement in pulmonary function
Tralokinumab(Anti-IL13) Improvement in pulmonary function
Barnes PJ. 2012 Severe asthma: advances in current management and futuretherapy. J Allergy Clin Immunol 129: 4859
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OTHERS BRONCHODI LATOR
Phosphodiesterase 3/4 inhibitors
Vasoactive intestinal peptide analogues and
Potassium channel openers
Barnes PJ. 2012 Severe asthma: advances in current management and futuretherapy. J Allergy Clin Immunol 129: 4859
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Nonpharmacological targeted treatment
Bronchial thermoplasty
Preliminary investigations with radiofrequency ablation ofairway smooth musclehave offered a novel promising
treatment option in severe refractory asthma . Several studies showed improved:
pulmonary function testing
airway hyperresponsiveness
asthma-related quality of life and symptom scores
Castro M, Rubin AS, Laviolette M,et al. 2010 Effectiveness and safety of bronchial thermoplasty inthe treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinicaltrial.Am J Respir Crit Care Med 181: 116124.
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SUMMARY
Severe refractory asthma do not respondto high doses ofinhaled glucocorticosteroids in combination with LABA
Specific treatment with more highdose steroid inhaler andsteroid systemic
High dose LABA may improve fixed airflow limitation
Some targeted therapy may improve lung function and qualityof life
Bronchial thermoplasty may improve :
pulmonary function testing
airway hyperresponsiveness
asthma-related quality of life and symptom scores