Refractory Asthma


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Refractory Asthma

  3. 3.  Before considering asthma, it is important toestablish the diagnosis of asthma itself, sinceconfounding diseases may result inmisdiagnosis. Patients were found to be actually sufferingfrom bronchiectasis, COPD, anxiety or vocalcord dysfunction, although real asthma maycoexist with these diagnosis . Severe asthma is often accompanied bysignificant comorbidities such asgastrooesophagel reflux, nasal polyps,obesity and depression.
  4. 4.  The term applies to patients who remaindifficult to control despite extensive re-evaluation of diagnosis and management overan observation period of at least 6 months.
  5. 5.  2000, American Thoracic Society agreed that RAshould be defined on the basis of medicationrequirements, asthma symptoms, frequency ofasthma exacerbations, and degree of airflowlimitation. Agreed on two major and seven minor criteria, withRA being defined as one or both major criteria and atleast two minor criteria. Definition applicable only to patients in whom;1. Other conditions have been excluded,2. Exacerbating factors have been optimally treated,and3. Poor adherence does not appear to be aconfounding issue.
  6. 6.  Major Characteristics: In order to achievecontrol to a level of mild-moderate persistentasthma: 1. Treatment with continuous or near continuous( 50% of year) oral corticosteroids 2. Requirement for treatment with high-doseinhaled corticosteroids:a. Beclomethasone dipropionateb. Budesonidec. Flunisolided. Fluticasone propionatee. Triamcinolone acetonide
  7. 7.  Minor Characteristics1. Requirement for daily treatment with a controllermedication in addition to inhaled corticosteroids,e.g., long-acting -agonist, theophylline, orleukotriene antagonist2. Asthma symptoms requiring short-acting -agonist useon a daily or near daily basis3. Persistent airway obstruction (FEV1 < 80% predicted;diurnal PEF variability > 20%)4. One or more urgent care visits for asthma per year5. Three or more oral steroid "bursts" per year6. Prompt deterioration with 25% reduction in oral orinhaled corticosteroid dose7. Near fatal asthma event in the past
  8. 8.  Asthma affects 5-10% of the population or anestimated 23.4 million persons, including 7million children. It affects 5-7% of the population of NorthAmerica and Europe and the prevalence isincreasing. Most asthma is mild or moderate and wellcontrolled. Subgroup of patients with asthma (likely <5%)have more troublesome disease.
  9. 9.  AIRFLOW LIMITATIONThe fixed airflow of most patients with RA can bedefined as a postbronchodilator FEV1 of<80%pred (in the presence of a reducedFEV1/FVC) after 7-14 day course of oral CS.Explanations:mucous plugging, smooth muscle hypertrophy/hyperplasia & edema formation.Unresponsiveness to beta agonists:downregulation of beta receptors, fibrosis thatlimit dynamicresponses, unknown elements of the obstructiveprocess & adifferent disease process altogether.
  10. 10.  AIRWAY HYPERRESPONSIVENESSIt is known that airway responsiveness varies ina temporal fashion, and this generallythought to reflect changes in disease activityand severity.In RA, after intensive courses of anti-inflammatory medications, patients willcontinue to exhibit marked airwayhyperresponsiveness, failing to attain aplateau in the dose-response curve occurs.
  11. 11.  VARIABLE AIRFLOW LIMITATIONAsthma is also distinguished by periodic and/orreversible changes in airflow, such asmeasured by the variability of PEF. Unlikesingle measures of airflow, sequentialmeasures of PEF variability correlate withincreased airway responsiveness.Patients with RA will have lower values of peakflow, show less response to therapy, and havewide diurnal swings in peak flow.
  12. 12.  The clinical presentation are basically boththe major and minor criteria used to defineRefractory Asthma.
  13. 13. 1. Tobacco smokea. In uterob. Environmental2. Allergen sensitization3. Viral infections4. Occupational agents5. Air pollutants6. Stress
  14. 14.  In making diagnosis of RA, its important to considerand exclude other diseases in the differentialdiagnosis of wheeze, dyspnea, cough andeosinophilia. Patients should be evaluated for diseases such asCOPD, bronchiectasis (including allergicbronchopulmonary aspergillosis and cystic fibrosis),vocal cord dysfunction. finally, in any person with RA, a thorough evaluationfor factors that could contribute to the severity ofthe disease such as sinus disease, gastroesophagealreflux, and compliance/adherences issues should beperformed. Thoroughly evaluated for their understanding ofasthma and their ability to use metered dose inhaler.
  15. 15.  The diagnostic workup of patients suspected of having chronic RAshould consist of full pulmonary function tests including: Spirometry with a flow-volume curve Total lung capacity Residual volume Diffusion capacity Daily peak flow monitoring Serum Ig E levels Serum eosinophil levels Further testing could include: High-resolution CT scans Genetic testing for cystic fibrosis or alpha1 anti-trypsindeficiency Allergy skin testing Specific IgE antibodies for aspergillus.
  16. 16.  Patients should be treated, as a starting point, asoutlined in the Expert Panel 2 report. High dose/high potency inhaled CS (budesonide,fluticasone propionate, mometasone). Oral CS at as low a low dose as possible, and one tothree additional controller agents.o No studies have evaluated the benefits of multiplecombinations of these alternative controllers.o Clinician should carefully monitor clinical parametersto assess the best combination of medications.o CS pharmacokinetics can identify patients withincomplete CS absorption, failure to convert inactiveform to active form, or rapid elimination.
  17. 17.  Patients who remain asymptomatic despiteoptimal application of conventional therapyand management of concomitant disorders,anti-inflammatory and immunomodulatingdrugs such as methotrexate, gold,cyclosporine, iv gamma globulin andmacrolide antibiotics. Concurrent improvement in pulmonaryfunction is limited when using them and assuch their treatments has not beenimpressive.
  18. 18.  IV gamma globulin may be effective in somepatients, its high cost prohibitive. Methotrexate- limited efficacy. SE; liver toxicityand immunosuppressant Cyclosporine has been utilized only in a limitedstudy population. SE; risk of HTN. Oral gold, limited efficacy. SE; GI adverseeffects. None of them have demonstrated significantimprovement in airway hyperresponsiveness. More studies still needed to define their benefitsand risks, as well as which patients are mostlylikely to respond to the selected treatment.
  19. 19. Asthma Education and PreventionProgram Expert Panel. Report 2: Guidelinesfor the diagnosis and management ofasthma. Washington DC: U.S. GovernmentPrinting Office; 1997. NIH- NHLBI PublicationNo. 97-4051.Medscape eMedicineSwiss Med Wkly 2009; 139(19-20): 274-277