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DIFFICULT TO TREAT ASTHMABy
PROF. RAMADAN M. NAFAE
PROFESSOR AND HEAD OF CHEST DEPARTMENT FACULTY OF MEDICINE ZAGAZIG UNIVERSITY
Worldwide, 300 million people have asthma, and the frequency of this disease has increased greatly since the 1980s
Stepwise approach to the treatment of asthmaaccording to the Global Initiative for Asthma (GINA) guidelines.
Asthma control test
Level of asthma control
Difficult to treat asthma definition
Asthma that doesn’t reach an acceptable level of control at step 4 of therapy and usually has an element of poor glucocorticoid responsiveness and requires high doses of inhaled glucocorticoids .
Names for Difficult to control asthma
Severe refractory asthmaDifficult to control asthmaBrittle asthmadifficult asthmaSevere asthmaTherapy-resistant asthmaSteroid-dependent asthma
Epidemiology of difficult to treat asthma
It represent about 5 to 10 % of all asthma patients.
It is more common in females ( about 75 % of all difficult to treat asthma patients ).
Severe asthma phenotypes
Difficult Asthma Clinic
Tria l A d d on Th erap ies123
O p tim ise A s th m a M an ag em en t S k ills
Id en tify an d M an ag e A g g rava tin g F ac to rs
C on firm D iag n os is
R efe rred to D A CDiagnosis of Asthma excluded
and discharge
dControl
Achieved and
Discharged
Control Achieved
and Discharge
d Control Achieved
and Discharge
d or remain
under DAC
Control NOT
Achieved and
remain under the
care of DAC
Systematic approach to difficult-to-treat asthma
key questions must be considered:
Do they really have asthma?
Are patients taking their treatment?
Do coexisting conditions exacerbate the asthma?
What aggravating factors might be considered?
Has the patient fits into a recognized asthma phenotype?
Do they really have asthma?
Do they really have asthma?
Do they really have asthma?
Investigations used in systematic
assessment for severe asthma.
Are patients taking their treatment?
despite persistent symptoms, many patients choose not to take their prescribed treatment.
Do coexisting conditions exacerbate the asthma?
coexisting disorders with
asthma-like symptoms were
found in 19% to 34% of patients
with difficult asthma.
Vocal cord dysfunction
(paradoxical adduction during
inspiration) is an important
disorder that can mimic or
coexist with asthma.
Psychological factors.
Upper airway disease.
Gastro-oesophageal reflux disease.
Adverse drug effects.
Allergy.
Occupational factors.
Cigarette smoking.
Obesity
What aggravating factors might be considered?
Has the patient fits into a recognized asthma
phenotype?
Management of sever asthma
Inflammatory Phenotypes in Stable Persistent Asthma, on ICS
Eosinophilic
Neutrophilic
Paucigranulocytic
41%
28%
31%
Simpson J et al, Respirology 2006;11:54-61
59% Non eosinophilic
Current treatments for severe asthma
patients with severe asthma are at Step 4 or Step 5, requiring a
high dose of ICS with or without OCS and the addition of other
controller medications including LABAs, leukotriene modifiers and
theophyllines.
Difficult 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
Difficult asthma with noneosinophilic bronchitis ICS/LABA Triggers:
◦ smoking◦ infection
Macrolide ? Theophylline ?TNFa
Anti-immunoglobulin E
Omalizumab is a humanised monoclonal antibody that can be
given subcutaneously; its dose is determined by baseline IgE
and body weight.
the total IgE must be <1300 IU/ml for children over 6 years of
age. In adults and children >12 years, the licensed indication
is a IgE up to 1500 IU/ml .
What new approaches are available?
Other biological treatments
etanercept (a tumour necrosis factor antagonist).
gomilumab (a humanised monoclonal antibody
against tumour necrosis factor).
Antiinterleukin 13 antibody or anti-neutrophilic
strategies such as anti-CXCR1/R2.
These are under trials
What new approaches are available?
Various drugs such as ciclosporin, methotrexate,
gold, and subcutaneous terbutaline have been
tried with various degrees of success in difficult
asthma. These agents are not in widespread use
but may be considered under specialist
supervision.
Other drugs
Bronchial thermoplasty—where controlled
thermal energy is delivered to the airway wall
during several bronchoscopy procedures—results in
prolonged reduction of smooth muscle mass.
This procedure reduces symptoms, use of relievers,
and exacerbations, and it improves quality of life
and lung function.
Bronchial thermoplasty
Managing asthma that is refractory to usual
treatment requires a systematic approach to
ensure a correct diagnosis, identify coexisting
disorders, tailor treatment, and evaluate
adherence.
Conclusions
Thank you