DIFFICULT TO TREAT ASTHMA By 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 asthma according 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.

 Severe refractory asthma  Difficult to control asthma  Brittle asthma  difficult asthma  Severe asthma  Therapy-resistant asthma  Steroid-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

Diagnosis of Asthma excluded and discharged Control Achieved and Discharged Control Achieved and Discharged 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?

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

41% 28% 31% Simpson J et al, Respirology 2006;11: % 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.

 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

 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 12 years, the licensed indication is a IgE up to 1500 IU/ml.

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

 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.

 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.

 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.

Thank you