How Do We Achieve Optimal Asthma Control? Role of Nebulised steroids in Management of Asthma

1. How Do We Achieve Optimal Asthma Control? Role of Nebulised steroids in Management of Asthma BY MAYSA SHARAF ELDIN PROFESSOR OF PULMONARY MEDICINE CAIRO UNIVERISITY

2. Why do we care about asthma control? • What do we mean by asthma control? • Inhalation Therapy Prof. Maysa Sharaf El Din

3. Why do we care about asthma control? Prof. Maysa Sharaf El Din

4. Burden of Asthma • Asthma is one of the most common chronic diseases worldwide with an estimated 300 million affected individuals • Prevalence increasing in many countries, especially in children • A major cause of school/work absence GINA 2010

5. Burden of Asthma • Health care expenditures very high • Developed economies might expect to spend 1-2 percent of total health care expenditures on asthma. • Developing economies likely to face increased demand • Poorly controlled asthma is expensive; investment in prevention medication likely to yield cost savings in emergency care GINA 2011

6. What do we mean by asthma control? Prof. Maysa Sharaf El Din

7. Clinical Control of Asthma • No (or minimal)* daytime symptoms • No limitations of activity • No nocturnal symptoms • No (or minimal) need for rescue medication • Normal lung function • No exacerbations • No emergency visits • No treatment-related adverse events • All of the above sustained for at least • 7 out of 8 weeks * Minimal = twice or less per week GINA 2011

8. Clinical Control of Asthma How many of our patients actually achieve this? • No (or minimal)* daytime symptoms • No limitations of activity • No nocturnal symptoms • No (or minimal) need for rescue medication • Normal lung function • No exacerbations • No emergency visits • No treatment-related adverse events • All of the above sustained for at least • 7 out of 8 weeks * Minimal = twice or less per week Asthma without Asthma GINA 2011

9. Factors Affecting Inhaled Drug Delivery and Deposition - Geometry of the respiratory tract - Inspiratory flow - Time in the airway (breath hold) - Particle diameter and density Prof. Maysa Sharaf El Din

10. What we know: Particle Size Regional deposition Particle size (microns) Efficacy Safety Absorption from GIT if swallowed Mouth / oesophageal region > 5 No clinical effect Subsequent absorption from lung 2 – 5 Upper / central airways Clinical effect Some local clinical effect High systemic absorption < 2 Peripheral airways / alveoli • All inhaled methods ( MDI & DPI ) • Compliance, adequate technique • 75% - 93% of patients on traditional press-and-breathe inhalers use improper technique • Even after retraining, up to 50% revert to incorrect techniques Prof. Maysa Sharaf El Din

11. Factors affecting drug delivery with nebulised therapy • 1. Device-related factors • Airflow • Droplet size • Nebulisation time and volume • 2. Drug-related factors • The shape and size of drug particles • water solubility • The viscosity and surface tension of the formulation • 3.Patient-related factors • Breathing patterns • inspiratory flow rate Prof. Maysa Sharaf El Din

12. Clinical Profile: Who Are the Ideal Patients for Nebulized Therapy? Patients inadequately controlled and unable to achieve symptomatic relief with MDI/DPI therapy Patients with cognitive impairment Patients unable to use MDI/DPI devices appropriately (eg, patients with arthritis, peripheral neuropathy) Home health care patients Prof. Maysa Sharaf El Din

13. Advantages of Nebulizers Any age Easy to teach and use Patient coordination not required preferred inhalation device in infants and for acute Rx in ERs and hospital High drug doses possible Can be used with supplemental oxygen No propellant required Prof. Maysa Sharaf El Din

14. Types of nebulizers • Jet nebulizer Driven by compressed air. The smaller droplets leave the nebuliser as a fine mist.The larger droplets fall by gravity and returned to the reservoir 2. Ultrasonic nebulizer The aerosol is created by a rapid vibrations. Ultrasonic nebulisers should not be used to deliver suspensions 3. Mesh nebulizer Liquid or drug suspension is pushed through a fine static mesh. There is no recycling into the reservoir of inappropriately sized droplets Prof. Maysa Sharaf El Din

15. Jet and Ultrasonic Nebulizers ULTRASONIC Heats up during operation Larger aerosol particle More expensive Less noise JET • Cools during operation • Small aerosol particle size • Less expensive • More noise Prof. Maysa Sharaf El Din

16. New Generation Nebulizers: Vibrating Mesh or Plate Nebulizers MicroAIR U22 Pari e-flow www.aerogen.com/theproducts.htm www.omron-healthcare.com www.eflow.pari.de/200/index.html

17. Advantages of New Vibrating Mesh or Plate Nebulizers • Simple, compact, silent • Do not require propellants or a compressor system • Portable, battery operated, designed for use by ambulatory patients • High fine particle fraction • Highly efficient delivery of aerosols to lower respiratory tract • Only negligible volume of drug solution left in device • Low aerosol velocity  throat deposition Prof. Maysa Sharaf El Din

18. Limitations of Vibrating Plate/Mesh Devices Cost higher than jet nebulizers Need for regular cleaning to prevent blockage of minute apertures with drug particles (especially with suspensions) Batteries need to be replaced periodically Need to reduce drug dose/volume of solution because of higher efficiency of drug delivery in order to prevent “overdosing” Prof. Maysa Sharaf El Din

19. Adaptive Aerosol Delivery (AAD)“Smart nebulizers” • Principle: delivery of precise and reproducible amounts of drug • adapted to the breathing pattern • during part of inspiration • Benefit • - improvement of efficacy and compliance Prodose AAD System

20. Hoda is 45 years old female patient. • She has long-term asthma. She is known case of Diabetes.Her current treatment is ICS+LABA plus SABA when needed. She has symptoms which impair ability to sleep and perform daily activities with persistent cough, wheezing and chest tightness several days each week • Q: Is her asthma • Well controlled • Partially uncontrolled • Uncontrolled

21. Hoda is 45 years old female patient. • She has long-term asthma. She is known case of Diabetes.Her current treatment is ICS+LABA plus SABA when needed. She has symptoms which impair ability to sleep and perform daily activities with persistent cough, wheezing and chest tightness several days each week • Q: Is her asthma • Well controlled • Partially uncontrolled • Uncontrolled

22. Levels of Asthma Control GINA 2011

23. What is your further management? • Increase dose of ICS • Add Theophylline • Start Antibiotics • Oral steroids

24. What is your further management? • Increase dose of ICS • Add Theophylline • Start Antibiotics • Oral steroids

25. 2009 (Evidence A)

26. She increased her inhaled steroid from 2 to 4 inhalations twice daily, but noted no improvement. She found herself needing to use her ventolin inhaler 4-5 times per day. After a sleepless night of cough and chest congestion, she sought help at her local hospital In the ED she appeared in moderate distress. She had laboured breathing at 28 breaths/min, with a markedly prolonged expiratory phase. She was using her accessory muscles of respiration. Her blood pressure was 120/70 mm Hg with 20 mm Hg paradoxical pulse. Her heart rate was 112 beats/minute. Chest examination revealed musical inspiratory and expiratory wheezes throughout all lung fields.

27. What is the required treatment for her in hospital? • Nebulised steroids • Oxygen therapy • IV Theophylline • Nebulized SAMA • All of above • None of the above

28. What is the required treatment for her in hospital? • Nebulised steroids • Oxygen therapy • IV Theophylline • Nebulized SAMA • All of above • None of the above

29. Over the next 2-3 days she progressively improved, and is now ready for home discharge.To prevent relapse after hospital or ER discharge , would you recommend : • Oral steroids • Nebulized steroids • ICS • No steroids

30. Over the next 2-3 days she progressively improved, and is now ready for discharge home.To prevent relapse after hospital or ER discharge , would you recommend : • Oral steroids • Nebulized steroids • ICS • No steroids

31. How do you classify her acute asthma? • Near-fatal asthma • Life threatening asthma • Acute severe asthma • Moderate asthma exacerbation • Brittle asthma

32. How do you classify her acute asthma? • Near-fatal asthma • Life threatening asthma • Acute severe asthma • Moderate asthma exacerbation • Brittle asthma

33. Levels of severity of acute asthma • Life threatening asthma :altered conscious level, Exhaustion, Arrhythmia Hypotension, Cyanosis, Silent chest, Poor respiratory effort. • Near-fatal asthma : Hypoxemia SpO2 <92%, PaO2<60 mmHg and/or Raised PaCO2 requiring MV with raised inflation pressures. • Acute Severe Asthma : Any one of: unable to complete 1 sentences in 1 breath, respiratory rate ≥25/min, heart rate ≥110/min, PEF 33-50% best or predicted • Moderate asthma exacerbation: Increasing symptoms, PEF >50-75% best or predicted no features of acute severe asthma • Brittle Asthma : • Type 1: wide PEF variability despite intense therapy (>40% diurnal variation for >50% of time over a period >150 days) • Type 2: sudden severe attacks on a background of apparently well controlled asthma British Thoracic Society Guidelines (BTS) 2009

34. NOTES Prof. Maysa Sharaf El Din

35. Instructions for correct use of Nebulizer: Budisonide should be administered via Jet Nebulizerwith a mouthpiece or suitable facemask. Ultrasonic nebulizers are not suitable & therefore dis-recommended. Nebulizer should be connected to an air compressor with an adequate airflow (5 – 8 l/min). Fill volume should be 2 – 4 ml. • Instructions for correct use of Nebulizer: • 4. Budisonide Nebulising Suspension can be mixed with0.9% saline& nebulizer solutions of: • Terbutaline • Salbutamol • Sodium Cromoglycate • Ipratropium • Fenoterol • Acetylcysteine Management of Acute Asthma (Evidence-Based) • Regular bronchodilators including ipratropium bromide. (Level A). • Oxygen (Controlled) (Level A). • Corticosteroids (Level A). • No role for routine antibiotics, rehydration (Level A). • Magnesium for more severe attacks (Level A). Prof. Maysa Sharaf El Din

36. Reactivated Esterification of budesonide Increasedairway selectivity Prolonged duration of action Cell Nucleus GC-receptor Budesonide Budesonide esterifi- cation lipolysis Budesonide esters INACTIVE! Miller-Larsson et al. 1998 and Wieslander et al. 1997

37. Thank You