Management of Severe Refractory Asthma

Sumardi
Pulmonology Division Internal Medicine Departement GMU / Sardjito Hospital

INTRODUCTION

Asthma is a heterogeneous disease in which adequate asthma control cannot be achieved in a substantial proportion despite currently available treatment possibilities subgroup has been defined as severe refractory asthma classification into distinct phenotypes is ongoing to target the right treatment to the right patient therapeutic targeted treatment options are currently to provide possible targets to improve disease state, symptoms and quality of life

DEFINITION

The WHO (2010) distinguished three subtypes of severe asthma:

1) severe untreated asthma,

2) difficult-to-control severe asthma, and 3) severe refractory asthma

Identified phenotypes of severe refractory asthma (ATS/ERS 2013):

Early onset severe allergic asthma Late onset non-atopic, inflammation predominant asthma with fixed airflow limitation Late onset obese female preponderant asthma

WHAT CAN I DO?

patients labelled as severe refractory asthma remain a challenge for the treating clinician.

Severe refractory asthma that do not respond to current standard therapy, i.e. high doses of inhaled glucocorticosteroids in combination with long-acting 2-agonists (LABA)

Wener RRL and Bel EH 2013 Severe refractory asthma: an update Eur Respir Rev 22: 227 235

CURRENT TREATMENT

According to current guidelines (Global Initiative for Asthma, National Asthma Education and Prevention Programme and the British Thoracic Society) the treatment of patients with severe asthma:

constitutes of high-dose inhaled or oral/systemic glucocorticosteroids, in combination with

LABAs, and/or
Anticholinergic

THERAPY IN SEVERE REFRACTORY ASTHMA

Wener RRL and Bel EH 2013 Severe refractory asthma: an update Eur Respir Rev 22: 227235

High dose continuous nebulizer :

Steroid

Budesonide > 2000 mcg, or Fluticasone > 2000 mcg Salbutamol > 5 mg, or Terbutaline > 5 mg

Beta2-agonis :

Anti-cholinergic ipatrium bromide > 5 mg

Systemic corticosteroid methylprednisolon 125 mg 500 mg/day iv, or Pulse dose 500 mg/12 hours iv, 3 days

MAINTENANCE IN SEVERE REFRACTORY ASTHMA

Wener RRL and Bel EH 2013 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 160 960 mcg/day for 2- 3 months

Salmeterol 50 100 mcg/day for 2-3 months

Indacaterol, carmoterol, olodaterol, vilanterol, once/day

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 and pulmonary 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 future therapy. J Allergy Clin Immunol 129: 4859

OTHERS BRONCHODILATOR

Phosphodiesterase 3/4 inhibitors

Vasoactive intestinal peptide analogues and

Potassium channel openers

Barnes PJ. 2012 Severe asthma: advances in current management and future therapy. J Allergy Clin Immunol 129: 4859

Nonpharmacological targeted treatment

Bronchial thermoplasty Preliminary investigations with radiofrequency ablation of airway smooth muscle have 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 in the treatment of severe asthma: a multicenter, randomized, double-blind, sham-controlled clinical trial. Am J Respir Crit Care Med 181: 116124.

SUMMARY

Severe refractory asthma do not respond to high doses of inhaled glucocorticosteroids in combination with LABA

Specific treatment with more highdose steroid inhaler and steroid systemic
High dose LABA may improve fixed airflow limitation

Some targeted therapy may improve lung function and quality of life
Bronchial thermoplasty may improve :

pulmonary function testing airway hyperresponsiveness asthma-related quality of life and symptom scores