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Management of severe asthma an update 2014


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Management of severe asthma an update 2014

  1. 1. Management of Severe Asthma An Update M.Moin M.D Professor of Allergy & Clinical Immunology Immunology, Asthma & Allergy Research Institute IAARI Children's Medical Center Tehran University of Medical Sciense 1392 2014
  2. 2. Severe Asthma : Many Clinical phenotypes! Subgroups :  Severe Asthma / Refractory Asthma  Difficult to control asthma  Poorly controlled asthma  Steroid-dependent & /or Steroid resistant asthma  Brittle asthma  Irreversible asthma  Fatal or Near-fatal asthma ATS & ERS joint workshop consensus Am J Respir Care Med,162:2341-51,2000
  3. 3. Diagnostic Criteria for Severe Asthma ATS – ERS Joint Workshop Consensus -2000 Diagnosis : One or both major criteria & Two minor criteria Major criteria In order to achieve control(mild-mod , persistent asthma) : 1. Rx with continuous or near continuous(≥50% of the year) 1. Rx with high dose I.C.S(1000ug Fluticasone/BDP) ATS & ERS joint workshop consensus Am J Respir Care Med,162:2341-51,2000
  4. 4. Diagnostic Criteria for Severe Asthma ATS – ERS Joint Workshop Consensus -2000 Minor criteria 1. Daily Rx with ICS + LABA , theophylline or LA 2. Daily SABA(Rescue medication) 3. Persistent daily FEV1<80% & diurnal PEF variab. >20% ATS & ERS joint workshop consensus Am J Respir Care Med,162:2341-51,2000
  5. 5. Diagnostic Criteria for Severe Asthma ATS – ERS Joint Workshop Consensus -2000 Minor criteria,Cot'd 4. ≥1 ED visist/year 5. ≥3 OCS/year 6. Prompt deterioration with ≤25% ↓ICS/OCS 7. Near-fatal asthma in the past. ATS & ERS joint workshop consensus Am J Respir Care Med,162:2341-51,2000
  6. 6. WHO Definition of Severe Asthma 1- Asthma for which control is not achieved despite the highest level of recommended treatment: refractory asthma and corticosteroidresistant asthma 2- Asthma for which control can be maintained only with the highest level of recommended treatment. • Severe asthma includes 3groups: - Untreated severe asthma - Difficult-to-treat severe asthma - Treatment-resistant severe asthma –Bousquet J, Mantzouranis E, Cruz AA, Ait-Khaled N, Baena-Cagnani CE, Bleek ER, et alUniform definition of asthma severity, control, and exacerbation: document presented for the World Health Organization Consultation on Severe Asthma. J Allergy Clin Immunol 2010;126:926-38. –Desai D, Brightling C, Cytokine and anti- Cytokine therapy in asthma: ready for the chinic? Clin Exp Immunol 2009;158:10-9
  7. 7. Severe Asthma Phynotypes in Childhood Well controlled with maximal therapy Poorly controlled with maximal therapy Difficult-to-threat asthma Severe therapyresponsive asthma Untreated severe asthma Severe, therapyresistant asthma The WHO definition of severe asthma
  8. 8. Classification of Asthma Severity Night Symp. Daytime Symp. < 2 times/mth. < 1 time/wk Intermittent > 2 times/mth. > 1 time/ wk Mild Persistent > 1 time/week Continuous Daily Continuous Moderate Persistent Severe Persistent
  9. 9. Levels of Asthma Control (Assess patient impairment) Characteristic Controlled Partly controlled (All of the following) (Any present in any week) Daytime symptoms Twice or less per week More than twice per week Limitations of activities None Any Nocturnal symptoms / awakening None Any Need for rescue / “reliever” treatment Twice or less per week More than twice per week Normal Uncontrolled < 80% predicted or personal best (if known) on any day Lung function (PEF or FEV1) 3 or more features of partly controlled asthma present in any week Assessment of Future Risk (risk of exacerbations, instability, rapid decline in lung function, side effects)
  10. 10. Stepwise Management of Asthma by severity : *At all levels patient should have a SABA prn Step 5: Severe Persistent High-dose ICS + LABA + Oral CS Step 4 : Severe Persistent Medium dose ICS + LABA Step 3: Moderate Persistent Low -dose ICS+ LABA Step 2: Mild Persistent Low -dose ICS , LTAs 2nd line Step 1: Intermittent No daily medicines , SABA p.r.n. Pharmacological management. Thorax 2003; 58 (Suppl I): i1-i92
  11. 11. GINA 2006: Asthma education Asthma treatment steps Environmental control as needed rapidacting β2-agonist Oral glucocorticosteroid (lowest dose) *in children <6yrs: moderate-dose ICS anti-IgE antibodies
  12. 12. Diagnostic Assessment of Severe Asthma • Is the diagnosis correct or is there an alternative diagnosis? • Is the patient compliant with treatment and is the technique correct? • Are there trigger factors e.g. Allergens, Irritants, ETS, Drugs? • Are there co- morbidities? e.g. Rhinosinusitis, GERD etc.
  13. 13. Diagnostic Assessment of Severe Asthma  Alternative diagnoses?        Cystic fibrosis Bronchiectasis Recurrent aspiration COPD CHF Obstructive bronchiolitis Bronchial amyloidosis
  14. 14. Diagnostic Assessment of Severe Asthma  Alternative diagnosis?       ABPA Eosinophilic syndromes Laryngotracheal tumours Inhalation of foreign body Tracheomalacia Tracheobronchial malformations
  15. 15. Education and removal of triggering factors Compliance & technique ?  Educate about adherence and proper technique  Systematic reviws showed that education about selfmanagement significantly improved health outcomes  Educational material used should be at appropriate health literacy level
  16. 16. Education and removal of triggering factors Trigger factors ?  Implement strict environmental control  Advise about the negative effects of smoking and obesity on asthma control  Smoking reduces the effects of ICS
  17. 17. Diagnostic Assessment of Severe Asthma  Comorbid conditions ? - Upper airway obstruction (VCD, Tracheal stenosis) - Hyperventilation syndrome - Gastro esophageal reflux (Does treatment improve asthma?) - Rhinosinusitis - Hyperthyroidism - Bronchiectasis - Depression
  18. 18. Diagnostic Approach of Severe Asthma  Complete history and clinical examination critical in making an accurate diagnosis  Pre- and post- bronchodilator spirometry for diagnosing reversible airway obstruction.  Flow- volume loops helpful to R/O upper airway obstruction.
  19. 19. Diagnostic Assessment of Severe Asthma  Methacholine challenge test to evaluate bronchial hyperresponsiveness  Skin prick test, RAST  Laryngoscopy to evaluate upper airway dysfunction  CXR and HRCT of chest when indicated  Investigate appropriately for other diseases PRN (CBC & Diff, Sweat test & CF-genotype, Ig,s, Ig Subclasses, …)
  20. 20. Treatment Approach  Guidelines recommend stepwise Rx according to severity for control of the disease at all times  No clear internationally accepted regimens for uncontrolled asthma despite treatment at the highest point at each step  This is due to paucity of studies and different definition used in the available studies
  21. 21. Treatment Approach • Aim of treatment should be to obtain the best possible results when there is failure of optimal control • Also aim to have the fewest undesirable effects • Have a practical & good treatment plan
  22. 22. Intensive initial therapy to achieve control of symptoms  High does ICS + LABA BD and a short course of OCS 40mg/day prednisolone for 15 days  Introduce a strategy of reducing dosage  If deterioration on withdrawal of OCS introduce other drugs e.g. antileukotrienes, theophyllins etc while giving low does OCS  Trial and error done with monitoring of functional parameters and inflammation
  23. 23. Deficient Response to OCS possible causes :  Incompete absorotion may be due to GIT disorder  Failure to covert prednisone to prednisolone due to enzymatic alterations  Rapid elimination due to drug interaction eg rifampicin, phenytoin etc.  Corticosteroid resistance : Confirmed when FEV1 is < 70% of predicted after treatment with 40mg OCS for 2weeks but responds to a bronchodilator test
  24. 24. Deficient response to OCS (Cont.)  If no response double dose for another 2 weeks  Those responding to the higher doses have altered response to OCS  Some may respond to IM ateroids e.g. triamcinolone 40mg every 10 days. (Level C)  Always use prednisolone in case of conversion failure
  25. 25. Treatment Approach Cont,d  Omalizumab has shown a reduction of 50% of steroids dose in atopic asthma with high IGE levels  Safety profile require long term evaluation  Administered every 2 or 4 weeks at a dose of 150375mg.
  26. 26. Follow-up and written action plan Omalizumab  Close monitoring essential  2 to 3 visits per month in the first 2 months until best results are achieved  Then monitor 3 monthly  Self treatment plan needed to avoid lifethreatening attacks
  27. 27. C.S. Sparing Agents (Evidence- based)  Chloroquine, methotrexate, cyclosporine, gold salts have been widely used  They have modulatory effects on inflammation  They also have side effects that need monitoring
  28. 28. C.S. Sparing Agents (Not Evidence- based)  Insufficient data to justify use of the following drugs as corticosteroid sparing agents: colchicine, chlorquine, dapsone(level C evide for all 3)  Intravenous immunoglobulins and azathioprine (level B evidence)  Oral or parenteral gold salts and cyclosporin not recommended for routine use (level B evidence)
  29. 29. From Phenotype to Endotype! Asthma: defining of the persistent adult phenotypes Sally E Wenzel The Lancet 2006, 368 : 804-13
  30. 30. From Phenotype to Endotype! Phenotype:Observable characteristics often with no direct relationship to disease process. Endotype:Biological mechanisms that underlie a distinct disease entity present within a phenotype. Phenotyping the severe asthma Personalized Strategy in Treatment Endotyping The right Rx. to the right patient
  31. 31. From Phenotype to Endotype! Inflammatory Phenotypes in Stable Persistent Asthma, on ICS Pauci – granulocytic Eosinophilic 31% Eosinophilic Eosinophilic 41% 59% Neutrophilic 28% Simpson J et al, Respirology 2006;11:54-61 Neutrophilic Non- eosinophilic Paucigranulocytic
  32. 32. Treatment of Severe Asthma with Eosinophilic Bronchitis • • • • ICS/LABA :adherence !! OCS: trial LTRA: add on montelukast Maintenance OCS: dose adjustment by sputum eos, [adherence !!!] • Itraconazole for ABPA • Oral gold/ methotrexate • Parenteral steroid From Phenotype to Endotype! & Personalized Rx.
  33. 33. Treatment of Severe Asthma with Noneosinophilic Bronchitis • ICS/LABA • Triggers: – smoking – infection • Macrolide • ? Theophylline • ?TNFa From Phenotype to Endotype! & Personalized Rx.
  34. 34. Treatment Plan in Children Licensed therapeutic approches : High- dose inhaled steroids Symbiocort maintenance and reliever therapy (SMART) Anti- IgE Rx. (→ 50% ↓ CS dose)
  35. 35. Treatment Plan in Children Unlicensed treatments: Methotrexate Azathioprine Ciclosporin Subcutaneous terbutaline ? Cytokine- specific monoclonal antibody (Anti-IL5, Anti-IL13, …) ? Bronchial thermoplasty
  36. 36. Severe Asthma- Differential diagnosis and management Exclude an alternative diagnosis Exclude comorbidities “Not asthma at all”, e.g.vocal cord dysfunction. Foreign body aspiration, CF “Asthma plus”, e.g.GERD, allergic rhinitis, chronic sinusitis, food allergy, OSA, vitamin D deficiency Severe Asthma Differential diagnosis and management If asthma treatment is not working, check DAT: Diagnosis, Adherence, Technique Therapeutic approaches Difficult asthma Improves when basic management is corrected: -Adherence -Inhaler technique 25% of asthma exacerbations are due to ICS nonadherence Therapy- resistant asthma Licensed treatments (FDA-approved) -high-dose inhaled steroid (ICS) and LABA -Single-inhaler maintenance and reliever therapy (SMART) (ICS/formoterol) -Anti-IgE therapy, omalizumab (Xolair) - Bronchial thermoplasty Unlicensed treatments Methotrexate, azathioprine, cyclosporin, terbutaline infusion SC Still symptomatic even when basic management issues resolved DDx. With Difficult asthma
  37. 37. References 1. Assembly on asthma of the Spanish Society of Pulmonology and Thoracic Surgery.Guidelines for the Diagnosis and Management of difficult-to-control Asthma.Arch Brononeumol 2005:41(9) :513-523 2. Fitzgerald JM,Shahidi N , Achieving asthma control in patients with moderate disease .J Allergy Clin immunnol 2010;125:307-311. 3. Ayres JG et al.Brittle asthma .Paed Resp Reviews.2004;5:40-44 4. Wenzel S, Szefler SJ, Managing severe asthma , J Allrgy Clin Immunol 2006;117:505-511. 5.Moin M et al. Risk Factors Leading to Hospital Admission in Iranian Asthmatic Children .Int Arch Allergy Immunol 2008;145:244-248 6.Moin et al Acta Medica; Risk Factors For Asthmatic Children Requiring Hospitalization2001:39(1):14-16 6. Fanta CH , Steroid Dependent Asthma , Asthma Grand Rounds Bulletin 2005;1-7. 7.Moin M et al. A systemic review of recent asthma surveys in Iranian children Chron Resp Dis.2009:6(2):109-14 6. Spahn JD , Bratton DL , Refractory Childhood Asthma : New insights into the Pathogenesis ,Diagnosis , and Management in :Leung DYM , Sampson HA . Pediatric Allergy : Principles and Practice ;2003,Mosby :444-464
  38. 38. THANKS