The Saudi Initiative for Asthma Guidelines for the Diagnosis and Management of Asthma in Adults and Children Out-patient Management of Asthma in Adults On behalf of the SINA panel Mohamed S. Al-Moamary, FRCP (Edin) FCCP Dep. of Medicine, King Abdulaziz Medical City-Riyadh King Saud bin Abdulaziz University for Health Sciences

Enter presenter name Enter the presenter’s institute Out-patient Management of Asthma in Adults Enter presenter name Enter the presenter’s institute

What is SINA? SINA is developed by a task force originated from the Saudi Initiative for Asthma Group under the umbrella of the Saudi Thoracic Society SINA is a practical approach for a comprehensive management of asthma in adults and children and when to refer to a specialist. International recommendations were customized to the local setting for asthma diagnosis and management Directed to HCW dealing with asthma who are not specialists in the field.

Purpose of SINA To provide a document that is easy to follow, simple to understand yet totally updated and carefully prepared for use by non-asthma specialist including primary care doctors and general practice physicians

The SINA guidelines booklet is available at: www.sinagroup.org Where do you find SINA? The SINA guideline was published in the Annals of Thoracic Medicine (www.thoracicmedicine.org): Al-Moamary MS, Alhaider SA, Al-Hajjaj MS, Al-Ghobain MO, Idrees MM, Zeitouni MO, Al-Harbi AS, Al Dabbagh MM, Al-Matar H, Alorainy HS. The Saudi initiative for asthma - 2012 update: Guidelines for the diagnosis and management of asthma in adults and children. Ann Thorac Med 2012;7:175-204 The SINA guidelines booklet is available at: www.sinagroup.org

Saudi Thoracic Society commitment The STS is committed to improve the care of asthma by a long term plan: Periodic scientific meetings Annual asthma meeting (since 2001) Frequent asthma courses Educational brochures Publishing new and updated asthma guidelines

What is new in SINA-2012 Comprehensive revision with the addition of new 125 references Addition of charts and algorithms for asthma diagnosis and management Updating asthma management Rewritten “asthma in children” section New section on “difficult to treat asthma”

SINA Panel Mohamed S. Al-Moamary (Chairman), King Saud bin Abdulaziz University for Health Sciences, Riyadh Sami Alhaider, King Faisal Specialist Hospital and Research Center, Riyadh Mohamed S. Al-Hajjaj, King Saud University, Riyadh Mohammed O. AlGhobain, King Saud bin Abdulaziz University for Health Sciences, Riyadh Majdy M. Idrees, Military Hospital, Riyadh Mohamed O. Zeitouni, King Faisal Specialist Hospital and Research Center, Riyadh Adel S. Alharbi, Military Hospital, Riyadh  Hussain Al-Matar, Imam Abdulrahman Al Faisal, Dammam Maha M. Al Dabbagh, King Fahd Armed Forces Hospital, Jeddah  Hassan S Alorainy, King Faisal Specialist Hospital and Research Center, Riyadh

Acknowledgment The SINA panel would like to thank the following reviewers : Prof. J. Mark FitzGerald from the University of British Columbia, Vancouver, BC, Canada Prof. Qutayba Hamid from the Meakins-Christie Laboratories, and the Montreal Chest Research Institute Prof. Sheldon Spier, the University of British Columbia, Vancouver, Canada Prof. Eric Bateman from the University of Cape Town Lung Institute, Cape Town, South Africa (SINA 2009) Prof. Ronald Olivenstein from the Meakins-Christie Laboratories and the Montreal Chest Research Institute, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada. (SINA 2009)

SINA Documents Published manuscript Booklet Electronic version Slides kit Flyers Website: www.sinagroup.org

Sections of SINA Epidemiology Pathophysiology Diagnosis Medications Approach to Management Treatment Steps Special Situations Acute Asthma

Prevalence of asthma has increased between 1986 – 1995 Alfrayyah et al. Ann Allergy Asthma Immunol 2001;86:292–296

Burden of Asthma Asthma is among the most common chronic illnesses in Saudi Arabia 53% had missed school or work (AIRKSA-2007) 35% attempted Unconventional therapy (Al Moamary, ATM 2008) 46% were controlled in Riyadh (AIRKSA-2007) 36% were controlled in 5 tertiary care centers in Riyadh (Aljahdali SMJ-2008) 48% were controlled in one center (Al Moamary, ATM 2008)

AIRKSA report (Ministry of Health) 78 % of adults & 84% of kids reported acute asthma over 12 months (AIRKSA) 54 % of adults & 80% of kids reported ER over 12 months (AIRKSA) 45-68% of adults & 37-56% of kids reported limitation of activity over 12 months (AIRKSA) 76 % of adults & 78% of kids never had spirometry(AIRKSA)

The prevalence of wheeze and associated symptoms in the study group Al-Ghobain et al, NBC Pulm Med 2012;12:39

Pattern of asthma treatment Al-Shimemeri, Ann Thorac Med 2006;1:20-5

Airway Hyper-responsiveness Pathology of Asthma Inflammation Airway Hyper-responsiveness Airway Obstruction Symptoms of Asthma

Pathophysiology

Inflammation  Remodeling Airway Hypersecretion Subepithelial fibrosis Angiogenesis

Diagnosis - History Episodic attacks: Cough Breathlessness Wheezing Nocturnal symptoms Patient could be asymptomatic between attacks co-existent conditions: GERD, rhinosinusitis.

Relevant Questions Does the patient or his/her family have a history of asthma or other atopic conditions, such as eczema or allergic rhinitis? Does the patient have recurrent attacks of wheezing? Does the patient have a troublesome cough at night? Does the patient wheeze or cough after exercise? Does the patient experience wheezing, chest tightness, or cough after exposure to pollens, dust, feathered or furry animals, exercise, viral infection, or environmental smoke?

Relevant Questions Does the patient experience worsening of symptoms after taking aspirin/nonsteroidal inflammatory medication or use of B-blockers? Does the patient's cold “go to the chest” or take more than 10 days to clear up? Are symptoms improved by appropriate asthma treatment? Are there any features suggestive of occupational asthma

Physical Examination Normal between attacks Bilateral expiratory wheezing Examination of the upper airways Other allergic manifestations: e.g., atopic dermatitis/eczema Consider alternative Dx when there is localized wheeze, crackles, stridor, clubbing

Measurements of lung function: Investigations Measurements of lung function: Spirometry Peak expiratory flow (PEF) Normal Spirometry does not role out asthma Spirometry is superior to PEF

Bronchodilator response Proper instructions on how to perform the forced expiratory maneuver must be given to patients, and the highest value of three readings taken. The degree of significant reversibility is defined as an improvement in FEV1 ≥12% and ≥200 ml from the pre-bronchodilator value.

Clinical Assessment Measurements of allergic status to identify risk factors (if indicated) Chest X-ray is not routinely recommended Routine blood tests are not routinely recommended IgE measurement is indicated in severe cases

Assessment of Asthma Control

Asthma Control Test Level of Control: Total: 25 Control: 20-24 Partial control: 16-19 Uncontrolled: < 16

Differential Diagnosis Upper airway diseases Allergic rhinitis and sinusitis Obstructions involving large airways Foreign body in trachea or bronchus Vocal cord dysfunction Vascular rings or laryngeal webs Laryngotracheomalacia, tracheal stenosis, or bronchostenosis Enlarged lymph nodes or tumor Obstructions involving small airways Viral bronchiolitis or obliterative bronchiolitis Cystic fibrosis Bronchopulmonary dysplasia Heart disease Other causes Recurrent cough not due to asthma Aspiration from swallowing mechanism dysfunction or GERD

Differential Diagnosis COPD (e.g., chronic bronchitis or emphysema) Congestive heart failure Pulmonary embolism Mechanical obstruction of the airways (benign and malignant tumors) Pulmonary infiltration with eosinophilia Cough secondary to drugs (e.g., angiotensin-converting enzyme (ACE) inhibitors) Vocal cord dysfunction

Management

Patient/Dr Partnership Enhance the chance of disease control Agreed goals of management Guided self-management plan

Asthma Education Creation of partnership between patient and healthcare worker Understanding clinical presentation of asthma and diagnosis Ability to differentiate between “relievers” and “controllers” medications and their appropriate indications Recognition of potential side effects of medications and the appropriate action to minimize them Performance of the proper technique of devices Identification of symptoms and signs that suggest worsening of asthma control and the appropriate action to be taken Understanding the approach for monitoring asthma control Recognition of the situations that need urgent medical attention Ability to use a written self-management plan

Non-Adherence Drugs: Non-drugs Poor technique of inhaler devices. Regimen with multiple drugs. Occurrence of Side effects from the drugs. Cost of medications. Non-drugs Lack of knowledge about asthma. Lack of partnership in the management. Inappropriate expectations. Underestimation of severity. Cultural issues.

Precipitating Factors Indoor Allergens and Air Pollutants Outdoor Allergens Occupational Exposure Food and Drugs www.tnfos.com

Self-management plan

Self-management plan www.tnfos.com لكل مريض خطة علاجية ذاتية خاصة به توضع تحت إشراف الطبيب المختص حسب حالته الإجراء الواجب إتباعه : الإستمرار على الأدوية المعطاة : إستخدام البخاخ الموسع للشعب الهوائية_____ بخة كل ____ ساعات عند الضرورة وقبل التمارين ارياضية ب 15 – 30 دقيقة . إستخدام البخاخ الواقي _____ بخة ______ مرة يومياً و بشكل منتظم لمدة ( ) . أدوية أخرى : 1- الحالة المستقرة : ممارسة الحياة بشكل طبيعي (لعب ، نوم ، دراسة) إختفاء أعراض الربو في الليل . ندرة إستخدام البخاخ في الموسع للشعب الهوائية (أقل من 3 مرات أسبوعياً) سرعة تدفق الهواء أكثر من 80% من الحد الطبيعي الإجراء الواجب إتخاذه : زيادة جرعة البخاخ الواقي ______إلى ______بخة _____مرة يومياً لمدة 10أيام ثم الرجوع إلى الجرعة السابقة إستخدام البخاخ الموسع للشعب الهوائية ( ) ( ) بخة كل ____ ساعات بإنتظام لمدة _____أيام أو حتى تتحسن الحالة إستشارة الطبيب في أقرب وقت ممكن . 2 - الحالة المتوسطة الإستقرار (أزمة ربو على وشك الحدوث) : إستخدام البخاخ الموسع للشعب الهوائية أكثر من 3 مرات يومياً . الإستيقاظ في الليل بسبب (كحة ، كتمة ، صفير في الصدر) وجود أعراض نزلة برد فيروسية . القدرة على نفخ الهواء بين 60 – 80 % من الحد الطبيعي . الإجراء الواجب إتخاذه : إستخدام البخاخ الموسع للشعب الهوائية ___بخة كل ____ ساعات طلب الإستشارة الطبية بصفة عاجلة . زيادة جرعة البخاخ الواقي ____)إلى ______بخة ____)مرة يومياً لمدة 10أيام ثم الرجوع إلى الجرعة السابقة عمل ما يلي : 3 - الحالة المتأزمة الحادة (سارع بطلب المساعدة الطبية) إذا لم تحدث استجابة لما سبق أو حدث : زيادة أعراض أزمة الربو . عدم القدرة على إتمام كلمتين في نفس واحد . عودة أعراض الربو بعد أقل من نصف ساعة من إستخدام البخاخ الموسع للشعب الهوائية . القدرة على نفخ الهواء أقل 50% من الحد الطبيعي . لابد من التوجه لقسم الطوارئ فوراً . (توجه للطوارئ أو أطلب الإسعاف) : إذا تدهورت أزمة الربو على الرغم من الإجراءات السابقة ، أو حدث إزرقاق فيالأطراف أو تدهور في مستوى الوعى ، أو تدني في سرعة تدفق الهواء لأقل من 50 % من المعدل الطبيعي www.tnfos.com

Asthma Medications Controllers are medications taken daily on a long-term basis to keep asthma under clinical control chiefly through their anti-inflammatory effects. Relievers are medications used on an as-needed basis that act quickly to reverse bronchoconstriction and relieve symptoms.

Controller Medications Inhaled glucocorticosteroids Long-acting inhaled B2-agonists Leukotriene modifiers Long-acting anticholinergics Theophylline Anti-IgE Systemic glucocorticosteroids

Inhaled Corticosteroids The most effective antiinflammatory medications for asthma treatment Benefits of ICS: reduce symptoms improve quality of life improve lung function decrease airway hyperresponsiveness control airway inflammation reduce frequency and severity of exacerbations, and reduce mortality.

Inhaled Corticosteroids When ICS discontinued, deterioration of clinical control may follow within weeks Most of the benefits from ICS are achieved in adults at relatively low doses Increasing to higher doses may provide further benefits in terms of asthma control but increases the risk of side effects Tobacco smoking reduces the responsiveness to ICS

Inhaled Corticosteroids To reach control, add-on therapy with another class of controller is preferred to increasing the dose of ICS ICS are generally safe and well-tolerated Though low-medium dose of ICS may affect growth velocity, this effect is clinically insignificant and may be reversible.

Inhaled Corticosteroids Local adverse effects: oropharyngeal candidiasis dysphonia – may be e reduced by using MDI with spacer devices and mouth washing Systemic side effects are occasionally reported with high doses and long-term treatment

Inhaled Corticosteroids

Leukotriene modifiers (LTRA) LTRA reduces airway inflammation, improve asthma symptoms and lung function It has less consistent effect on exacerbations when compared to ICS. Alternative treatment to ICS for patients with mild asthma, especially in those who have clinical rhinitis Some patients with aspirin-sensitive asthma respond well to the LTRA

Leukotriene modifiers (LTRA) Available as montelokast in Saudi Arabia Their effects are generally less than that of low dose ICS When added to ICS, LTRA may reduce the dose of ICS required by patients with uncontrolled asthma, and may improve asthma control LTRA are generally well-tolerated. There is no clinical data to support their use under the age of six months.

LABA LABA: (formoterol and salmeterol) Should not be used as monotherapy Combination with ICS lead to: improves symptoms decreases nocturnal asthma improves lung function decreases the use of rapid-onset inhaled B2-agonists reduces the number of exacerbations achieves clinical control of asthma in more patients, more rapidly, and at a lower dose of ICS

Dual Pathways of Inflammation Steroid-sensitive mediators play a key role in asthmatic inflammation CysLTs play a key role in asthmatic inflammation Montelukast Inhaled steroids blocks the effects of CysLTs block steroid- sensitive mediators DUAL PATHWAY The slide represents an artistic rendition. Adapted from Peters-Golden M, Sampson AP J Allergy Clin Immunol 2003;111(1 suppl):S37-S42; Bisgaard H Allergy 2001;56(suppl 66):7-11.

Long acting anti-chlenergics It was superior to a doubling of the dose of an inhaled glucocorticoid for patients at step 3 It was non-inferior to LABA It improves lung function in patients with severe uncontrolled asthma It is effective as add-on therapy to combination devices at step 4 Daily home peak expiratory flow measurements were higher with tiotropium doses Peters et al. N Engl J Med 2010; 363:1715-1726

Sympicort turbohaler: Seretide: Combination devices Sympicort turbohaler: Combination of budesonide/formeterol: 160/4.5 Seretide: Combination of fluticasone/salmeterol Evohaler: 50/25 125/25 250/25 Diskus: 100/50 250/50 500/50

Theophylline Weak bronchodilator with modest anti-inflammatory properties It may provide benefit as add-on therapy in patients who do not achieve control on ICS alone Less effective than LABA and LTR. Side effects: gastrointestinal symptoms cardiac arrhythmias seizures, and even death drug interaction

Omalizumab (Xolair) indication: Anti-IgE Omalizumab (Xolair) indication: Uncontrolled severe allergic asthma on high dose ICS and other controllers. Needs specialist consultation. Side effects: Pain and bruising at injection site and very rarely anaphylaxis (0.1%).

Oral glucocorticosteroids Long-term oral glucocorticosteroid therapy may be required for uncontrolled asthma despite maximum standard therapy. It is limited by the risk of significant adverse effects. Side effects: Osteoporosis, hypertension, diabetes, adrenal insufficiency, obesity, cataracts, glaucoma, skin thinning, and muscle weakness. Withdrawal can elicit adrenal failure. In patients prescribed long-term systemic glucocorticosteroids, prophylactic treatment for osteoporosis should be considered.

Reliever Medications Short-acting inhaled B2-agonists Anticholinergics Theophylline

Short-acting B2-agonists The medications of choice for symptoms relief Pretreatment for exercise-induced bronchoconstriction. Formoterol is used for symptom relief because of its rapid onset of action. Increased use, especially daily use, is a warning of deterioration of asthma control Side effects: B2-agonists are associated with adverse systemic effects such as tremor and tachycardia.

Short-Acting Anticholinergics Less effective than SABA. Used in combination with SABA in acute asthma. An alternative bronchodilator for patients with adverse effects from rapid acting B2agonists. Side effects: can cause a dryness of the mouth and a bitter taste.

Asthma control Control asthma symptoms Minimal use (≤2 days a week) of reliever therapy Maintain (near) normal pulmonary function Maintain normal exercise and physical activity levels Prevent recurrent exacerbations of asthma Minimize the need for ER visits or hospitalizations Optimize control with the minimal dose of medications Reduce mortality Optimize quality of life

Principles of management The principles of asthma management in adults will follow 3 stages: Initiation Adjustment Maintenance

Initiation based on SINA approach The consensus among SINA panel is to simplify the approach to initiate asthma therapy by using ACT score ACT Score ≥ 20  Step 1 ACT Score 16–19  Step 2 ACT Score 16  Step 3 Al-Moamary et al, BMC Pulm Med 2012;12

Initiation based on GINA approach Step 1  SABA on as needed bases Step 2  For patients who are not currently taking long-term controller medications. Step 3  If the initial symptoms are more frequent.

SINA v.s. GINA approaches Al-Moamary et al, BMC Pulm Med 2012;12

Adults Patients with Asthma

Adjustment of treatment Clinical Assessment Obtain ACT score and perform PFM Based on ACT, Adjust treatment: ACT = 20-25: Controlled  Maintain treatment ACT = 16-19: Partial control Step up ACT < 16: Uncontrolled Step up  Introduce self-management plan

Approach to Asthma Treatment in Adults and children > 5 years

Principles of Asthma Treatment Daily long-term controller medication is the corner stone of treatment ICS are considered as the most effective controller Relievers or rescue medications must be available to all patients at any step SABA should be taken as needed to relieve symptoms Increasing use of reliever treatment is an early sign of worsening asthma control

Principles of Asthma Treatment Treat patients who may have seasonal asthma as having uncontrolled asthma during the season, then at step 1 for the rest of the year Patients who had two or more exacerbations requiring oral corticosteroids or hospital admissions in the past year, should be treated as patients with uncontrolled asthma

Step 1 - Recommendations Mild and infrequent symptoms Initial ACT 20 – 25 Consider rapid onset B2-agonist to be taken “as needed” to treat symptoms Patient experiencing sudden, severe, or life-threatening exacerbations  treat flare-up accordingly

Step 2 - Recommendations Daily ICS at a low dose (< 500 μg of beclomethasone equivalent/day or equivalent) Alternative treatment isLTRA (montelukast)

Step 3 – Recommendations Add a LABA to a low-medium dose ICS for patients whose asthma is not controlled on a low dose ICS alone, such as: Fluticasone/Salmeterol (Seretide) Budesonide/Formoterol (Symbicort) Use a maintenance dose of the combination drugs twice daily Use the rapid onset B2-agonist as a reliever treatment.

Step 3 - GOAL study GOAL study has shown that an escalating dose of combination of Fluticasone/ Salmeterol (Seretide) achieves Well controlled asthma in 85% of patients Totally controlled asthma in 30% of patients

Step 3 - S.M.A.R.T® approach S.M.A.R.T® approach: Use of Formoterol/Budesonide for both rescue and maintenance Maintenance dose single inhaler (1–2 puff 160/4.5 BID) plus extra puffs from the same inhaler up to a total of 12 puffs per day. Those patients who require such high dose should seek medical advice to step up therapy that may include use of short course of oral prednisone.

Step 3 – Alternative therapy Adding LTRA to ICS, especially those with concomitant rhinitis or Increasing ICS dose to the medium to high dose range as a monotherapy or Adding sustained release theophylline or Adding long acting anti-cholinergic Consultation with a specialist is recommended for patients whenever there is a difficulty in achieving control

Step 4 – Recommendations Maximizing treatment is recommended by combining high-dose ICS with LABA or Adding LTRA, tiotropium, or theophylline to high-dose ICS and LABA or Omalizumab may be considered: Allergic asthma (as determined by skin test or RAST study) and still uncontrolled. Special knowledge about the drug Consultation is recommended

Step 5 - Recommendations Omalizumab to be considered for patients who have allergic asthma and persistent symptoms despite the maximum therapy mentioned above lowest possible dose of long-term oral corticosteroids for patient who: Does not have allergic asthma Omalizumab is not available or not adequately controlling the disease

Step 5 – long term steroids Long-term systemic corticosteroids: lowest possible dose to maintain control Monitor for the development of side effects Continue attempts to reduce the dose Maintaining high-dose of ICS therapy Strongly consider concurrent treatments with calcium supplements and vitamin D Consultation is mandatory

Obtain ACT score and perform PFM Based on ACT score, adjust treatment: Maintaining Control Clinical Assessment Obtain ACT score and perform PFM Based on ACT score, adjust treatment: ACT= 20-25: well controlled Maintain treatment with lowest ICS dose (may step down) ACT= 16-19: Partial control Step up ACT < 16: uncontrolled  Step up Follow-up at 1 to 3 month intervals

Allergen-specific immunotherapy (AIT) Gradual administration of increasing quantities of an allergen product to an individual with IgE-mediated allergic disease administered either subcutaneously or sublingually induces clinical and immunologic tolerance, has long term efficacy, and may prevent the progression of allergic disease, may improves the quality of life

Allergen-specific immunotherapy (AIT) more effective in seasonal asthma than in perennial asthma, particularly when used against a single allergen. may be considered if strict environmental avoidance and comprehensive pharmacologic It has been a controversial treatment for asthma; however, beneficial clinical effects have been demonstrated concerns regarding safety and cost, there was no demonstrated consistent effect on lung function

Special Situations

Asthma and pregnancy - 1 Unpredictable course: one third will have worsening of their of asthma control Maintaining adequate control of asthma during pregnancy is essential for the health and well-being of the mother and her baby. Identifying and avoiding triggering factors should be the first step of therapy for asthma during pregnancy

Asthma and pregnancy - 2 Same stepwise approach as in non-pregnant patient. Salbutamol is the preferred SABA ICSs are the preferred controllers Use of ICS, theophylline, antihistamines, B2-agonists, and LTRA is generally safe Acute exacerbations of asthma during pregnancy should be treated on the same outlines as in non-pregnant patients

Asthma and pregnancy - 3 Continuous fetal monitoring in severe asthma exacerbation If anesthesia is required during labor, regional anesthesia is recommended whenever possible The use of prostaglandin F2α may be associated with severe bronchospasm

Cough is the main symptom Cough-variant asthma Cough is the main symptom It is common in children, and is often more problematic at night Other diagnoses to be considered are: Drug-induced cough caused by angiotensin-converting-enzyme inhibitors GERD Postnasal drip and chronic sinusitis Treatment is similar to long-term management of asthma

Exercise-induced Asthma Bronchoconstriction peaks within 10 to 15 minutes after completing the exercise and resolves within 60 minutes. Prevention: SABA before exercise Warm-up period before exercise Some patients may need maintenance therapy Regular use of LTRA may help in this condition especially in children

Aspirin/NSAID induced Asthma Occurs in 10–20% of adults with asthma The majority experience first symptoms during the third to fourth decade. Once aspirin or NSAID hypersensitivity develops, it is present for life. Within 1-2 hours following ingestion of aspirin, an acute, severe attack may develop, and is usually accompanied by rhinorrhea, nasal obstruction, conjunctival irritation, and scarlet flush of the head and neck

Aspirin/NSAID induced Asthma Prevention by avoidance of aspirin/NSAID Patients for whom aspirin is considered essential, they should be referred to an allergy specialist for aspirin desensitization Aspirin and NSAID can be used in asthmatic patients who do not have aspirin induced asthma

GERD is more prevalent in asthmatics GERD triggered asthma GERD is more prevalent in asthmatics Mechanisms of GERD triggered asthma: vagal mediated reflex reflux of micro-aspiration of gastric contents into the upper airways If GERD symptoms presents, a trial of GERD therapy for 6–8 weeks wit lifestyle modifications Asymptomatic patients with uncontrolled asthma may not benefit from GERD therapy

Difficult to treat asthma (DTA) - 1 It is also called chronic severe asthma, steroid-dependent asthma, difficult-to-control asthma, and refractory asthma Defined as asthma in patients who require very high doses of inhaled steroids with other controller agents, or near continuous oral steroid treatment to maintain asthma control. Accounts for 5-10 % of adult asthma, but the health cost is disproportionally high Morbidity and mortality are also higher than in regular asthma

Difficult to treat asthma (DTA) - 2 Prior to labeling a patient to have DTA: Ensure patient is adherent to medications with good technique Misdiagnosis e.g. bronchiectasis, endo-bronchial tumors, and vocal cord dysfunction Control other diseases preciptatnts, e.g. chronic sinusitis, gastro-esophageal disease, sleep apnea syndrome, obesity, and congestive heart failure (CHF) Confounding factors, e.g. non-adherence with treatment, the presence of allergens at home

Difficult to treat asthma (DTA) - 3 Some patients may have the "pseudo-steroid" resistance in patients with persistent symptoms despite high doses of ICS and other "non-steroidal" asthma therapy The aim is to reach the best possible outcome as it may be difficult to achieve full control Patients should be at maximum therapy is given (Step 5 therapy) Anti-IgE treatment (Omalizumab) is given if the patients fulfill the criteria for this treatment

Difficult to treat asthma (DTA) - 4 There are New modalities that may help to control DTA e.g.,: Mepolizumab has been shown to reduce exacerbations and improves asthma control in patients with refractory eosinophilic asthma Bronchial thermoplasty that utilizes radiofrequency energy to alter the smooth muscles of the airways. In severe persistent asthma, it leads to improvements in various measures of asthma, including FEV1, quality of life, asthma control, and use of rescue medications