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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