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