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MOKGWANE EUTLWETSE SPARKS
4TH YEAR MED STUDENT
UWI, BAHAMAS CAMPUS
 DEFINITION
 EPIDEMIOLOGY
 PHYSIOLOGY
 PRESENTATION
 RISK FACTORS
 DIAGNOSIS
 MANAGEMENT
 REFERENCE
 Before considering asthma, it is important to
establish the diagnosis of asthma itself, since
confounding diseases may result in
misdiagnosis.
 Patients were found to be actually suffering
from bronchiectasis, COPD, anxiety or vocal
cord dysfunction, although real asthma may
coexist with these diagnosis .
 Severe asthma is often accompanied by
significant comorbidities such as
gastrooesophagel reflux, nasal polyps,
obesity and depression.
 The term applies to patients who remain
difficult to control despite extensive re-
evaluation of diagnosis and management over
an observation period of at least 6 months.
 2000, American Thoracic Society agreed that RA
should be defined on the basis of medication
requirements, asthma symptoms, frequency of
asthma exacerbations, and degree of airflow
limitation.
 Agreed on two major and seven minor criteria, with
RA being defined as one or both major criteria and at
least two minor criteria.
 Definition applicable only to patients in whom;
1. Other conditions have been excluded,
2. Exacerbating factors have been optimally treated,
and
3. Poor adherence does not appear to be a
confounding issue.
 Major Characteristics: In order to achieve
control to a level of mild-moderate persistent
asthma:
 1. Treatment with continuous or near continuous
( 50% of year) oral corticosteroids
 2. Requirement for treatment with high-dose
inhaled corticosteroids:
a. Beclomethasone dipropionate
b. Budesonide
c. Flunisolide
d. Fluticasone propionate
e. Triamcinolone acetonide
 Minor Characteristics
1. Requirement for daily treatment with a controller
medication in addition to inhaled corticosteroids,
e.g., long-acting -agonist, theophylline, or
leukotriene antagonist
2. Asthma symptoms requiring short-acting -agonist use
on a daily or near daily basis
3. Persistent airway obstruction (FEV1 < 80% predicted;
diurnal PEF variability > 20%)
4. One or more urgent care visits for asthma per year
5. Three or more oral steroid "bursts" per year
6. Prompt deterioration with 25% reduction in oral or
inhaled corticosteroid dose
7. Near fatal asthma event in the past
 Asthma affects 5-10% of the population or an
estimated 23.4 million persons, including 7
million children.
 It affects 5-7% of the population of North
America and Europe and the prevalence is
increasing.
 Most asthma is mild or moderate and well
controlled.
 Subgroup of patients with asthma (likely <5%)
have more troublesome disease.
 AIRFLOW LIMITATION
The fixed airflow of most patients with RA can be
defined as a postbronchodilator FEV1 of
<80%pred (in the presence of a reduced
FEV1/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 that
limit dynamic
responses, unknown elements of the obstructive
process & a
different disease process altogether.
 AIRWAY HYPERRESPONSIVENESS
It is known that airway responsiveness varies in
a temporal fashion, and this generally
thought to reflect changes in disease activity
and severity.
In RA, after intensive courses of anti-
inflammatory medications, patients will
continue to exhibit marked airway
hyperresponsiveness, failing to attain a
plateau in the dose-response curve occurs.
 VARIABLE AIRFLOW LIMITATION
Asthma is also distinguished by periodic and/or
reversible changes in airflow, such as
measured by the variability of PEF. Unlike
single measures of airflow, sequential
measures of PEF variability correlate with
increased airway responsiveness.
Patients with RA will have lower values of peak
flow, show less response to therapy, and have
wide diurnal swings in peak flow.
 The clinical presentation are basically both
the major and minor criteria used to define
Refractory Asthma.
1. Tobacco smoke
a. In utero
b. Environmental
2. Allergen sensitization
3. Viral infections
4. Occupational agents
5. Air pollutants
6. Stress
 In making diagnosis of RA, its important to consider
and exclude other diseases in the differential
diagnosis of wheeze, dyspnea, cough and
eosinophilia.
 Patients should be evaluated for diseases such as
COPD, bronchiectasis (including allergic
bronchopulmonary aspergillosis and cystic fibrosis),
vocal cord dysfunction.
 finally, in any person with RA, a thorough evaluation
for factors that could contribute to the severity of
the disease such as sinus disease, gastroesophageal
reflux, and compliance/adherences issues should be
performed.
 Thoroughly evaluated for their understanding of
asthma and their ability to use metered dose inhaler.
 The diagnostic workup of patients suspected of having chronic RA
should 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-trypsin
deficiency
 Allergy skin testing
 Specific IgE antibodies for aspergillus.
 Patients should be treated, as a starting point, as
outlined 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 to
three additional controller agents.
o No studies have evaluated the benefits of multiple
combinations of these alternative controllers.
o Clinician should carefully monitor clinical parameters
to assess the best combination of medications.
o CS pharmacokinetics can identify patients with
incomplete CS absorption, failure to convert inactive
form to active form, or rapid elimination.
 Patients who remain asymptomatic despite
optimal application of conventional therapy
and management of concomitant disorders,
anti-inflammatory and immunomodulating
drugs such as methotrexate, gold,
cyclosporine, iv gamma globulin and
macrolide antibiotics.
 Concurrent improvement in pulmonary
function is limited when using them and as
such their treatments has not been
impressive.
 IV gamma globulin may be effective in some
patients, its high cost prohibitive.
 Methotrexate- limited efficacy. SE; liver toxicity
and immunosuppressant
 Cyclosporine has been utilized only in a limited
study population. SE; risk of HTN.
 Oral gold, limited efficacy. SE; GI adverse
effects.
 None of them have demonstrated significant
improvement in airway hyperresponsiveness.
 More studies still needed to define their benefits
and risks, as well as which patients are mostly
likely to respond to the selected treatment.
http://ajrccm.atsjournals.org/cgi/content/full
/162/6/2341#B108
National Asthma Education and Prevention
Program Expert Panel. Report 2: Guidelines
for the diagnosis and management of
asthma. Washington DC: U.S. Government
Printing Office; 1997. NIH- NHLBI Publication
No. 97-4051.
Medscape eMedicine
Swiss Med Wkly 2009; 139(19-20): 274-277

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Refractory Asthma

  • 1. MOKGWANE EUTLWETSE SPARKS 4TH YEAR MED STUDENT UWI, BAHAMAS CAMPUS
  • 2.  DEFINITION  EPIDEMIOLOGY  PHYSIOLOGY  PRESENTATION  RISK FACTORS  DIAGNOSIS  MANAGEMENT  REFERENCE
  • 3.  Before considering asthma, it is important to establish the diagnosis of asthma itself, since confounding diseases may result in misdiagnosis.  Patients were found to be actually suffering from bronchiectasis, COPD, anxiety or vocal cord dysfunction, although real asthma may coexist with these diagnosis .  Severe asthma is often accompanied by significant comorbidities such as gastrooesophagel reflux, nasal polyps, obesity and depression.
  • 4.  The term applies to patients who remain difficult to control despite extensive re- evaluation of diagnosis and management over an observation period of at least 6 months.
  • 5.  2000, American Thoracic Society agreed that RA should be defined on the basis of medication requirements, asthma symptoms, frequency of asthma exacerbations, and degree of airflow limitation.  Agreed on two major and seven minor criteria, with RA being defined as one or both major criteria and at least two minor criteria.  Definition applicable only to patients in whom; 1. Other conditions have been excluded, 2. Exacerbating factors have been optimally treated, and 3. Poor adherence does not appear to be a confounding issue.
  • 6.  Major Characteristics: In order to achieve control to a level of mild-moderate persistent asthma:  1. Treatment with continuous or near continuous ( 50% of year) oral corticosteroids  2. Requirement for treatment with high-dose inhaled corticosteroids: a. Beclomethasone dipropionate b. Budesonide c. Flunisolide d. Fluticasone propionate e. Triamcinolone acetonide
  • 7.  Minor Characteristics 1. Requirement for daily treatment with a controller medication in addition to inhaled corticosteroids, e.g., long-acting -agonist, theophylline, or leukotriene antagonist 2. Asthma symptoms requiring short-acting -agonist use on a daily or near daily basis 3. Persistent airway obstruction (FEV1 < 80% predicted; diurnal PEF variability > 20%) 4. One or more urgent care visits for asthma per year 5. Three or more oral steroid "bursts" per year 6. Prompt deterioration with 25% reduction in oral or inhaled corticosteroid dose 7. Near fatal asthma event in the past
  • 8.  Asthma affects 5-10% of the population or an estimated 23.4 million persons, including 7 million children.  It affects 5-7% of the population of North America and Europe and the prevalence is increasing.  Most asthma is mild or moderate and well controlled.  Subgroup of patients with asthma (likely <5%) have more troublesome disease.
  • 9.  AIRFLOW LIMITATION The fixed airflow of most patients with RA can be defined as a postbronchodilator FEV1 of <80%pred (in the presence of a reduced FEV1/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 that limit dynamic responses, unknown elements of the obstructive process & a different disease process altogether.
  • 10.  AIRWAY HYPERRESPONSIVENESS It is known that airway responsiveness varies in a temporal fashion, and this generally thought to reflect changes in disease activity and severity. In RA, after intensive courses of anti- inflammatory medications, patients will continue to exhibit marked airway hyperresponsiveness, failing to attain a plateau in the dose-response curve occurs.
  • 11.  VARIABLE AIRFLOW LIMITATION Asthma is also distinguished by periodic and/or reversible changes in airflow, such as measured by the variability of PEF. Unlike single measures of airflow, sequential measures of PEF variability correlate with increased airway responsiveness. Patients with RA will have lower values of peak flow, show less response to therapy, and have wide diurnal swings in peak flow.
  • 12.  The clinical presentation are basically both the major and minor criteria used to define Refractory Asthma.
  • 13. 1. Tobacco smoke a. In utero b. Environmental 2. Allergen sensitization 3. Viral infections 4. Occupational agents 5. Air pollutants 6. Stress
  • 14.  In making diagnosis of RA, its important to consider and exclude other diseases in the differential diagnosis of wheeze, dyspnea, cough and eosinophilia.  Patients should be evaluated for diseases such as COPD, bronchiectasis (including allergic bronchopulmonary aspergillosis and cystic fibrosis), vocal cord dysfunction.  finally, in any person with RA, a thorough evaluation for factors that could contribute to the severity of the disease such as sinus disease, gastroesophageal reflux, and compliance/adherences issues should be performed.  Thoroughly evaluated for their understanding of asthma and their ability to use metered dose inhaler.
  • 15.  The diagnostic workup of patients suspected of having chronic RA should 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-trypsin deficiency  Allergy skin testing  Specific IgE antibodies for aspergillus.
  • 16.  Patients should be treated, as a starting point, as outlined 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 to three additional controller agents. o No studies have evaluated the benefits of multiple combinations of these alternative controllers. o Clinician should carefully monitor clinical parameters to assess the best combination of medications. o CS pharmacokinetics can identify patients with incomplete CS absorption, failure to convert inactive form to active form, or rapid elimination.
  • 17.  Patients who remain asymptomatic despite optimal application of conventional therapy and management of concomitant disorders, anti-inflammatory and immunomodulating drugs such as methotrexate, gold, cyclosporine, iv gamma globulin and macrolide antibiotics.  Concurrent improvement in pulmonary function is limited when using them and as such their treatments has not been impressive.
  • 18.  IV gamma globulin may be effective in some patients, its high cost prohibitive.  Methotrexate- limited efficacy. SE; liver toxicity and immunosuppressant  Cyclosporine has been utilized only in a limited study population. SE; risk of HTN.  Oral gold, limited efficacy. SE; GI adverse effects.  None of them have demonstrated significant improvement in airway hyperresponsiveness.  More studies still needed to define their benefits and risks, as well as which patients are mostly likely to respond to the selected treatment.
  • 19. http://ajrccm.atsjournals.org/cgi/content/full /162/6/2341#B108 National Asthma Education and Prevention Program Expert Panel. Report 2: Guidelines for the diagnosis and management of asthma. Washington DC: U.S. Government Printing Office; 1997. NIH- NHLBI Publication No. 97-4051. Medscape eMedicine Swiss Med Wkly 2009; 139(19-20): 274-277