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
There are number of factors that affect drug deposition in the the airways.
These include:
Geometry of the respiratory tract
Airflow
Particle diameter and size
Time in the airway (breath hold)
Prof. Maysa Sharaf El Din 9

10. What we know: Particle Size
> 5
Particle size (microns)
Regional deposition
Efficacy
Safety
Mouth / oesophageal region
No clinical effect
Absorption from GIT if swallowed
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
2 – 5
Upper / central airways
Clinical effect
Subsequent absorption from lung
< 2
Peripheral airways / alveoli
Some local clinical effect
High systemic absorption
Prof. Maysa Sharaf El Din 10

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 12

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 13

14. Types of nebulizers Jet nebulizer 2. Ultrasonic 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
Cools during operation
Small aerosol particle size
Less expensive
More noise
ULTRASONIC
Heats up during operation
Larger aerosol particle
More expensive
Less noise
Prof. Maysa Sharaf El Din 15

16. New Generation Nebulizers: Vibrating Mesh or Plate Nebulizers
MicroAIR U22
Pari e-flow 16

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 17

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 18

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 19

20. Partially uncontrolled Uncontrolled
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. Partially uncontrolled Uncontrolled
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
Characteristic
Controlled
(All of the following)
Partly controlled (Any present in any week)
Uncontrolled
Daytime symptoms
None (2 or less / week)
More than twice / week
3 or more features of partly controlled asthma present in any week
Limitations of activities
None
Any
Nocturnal symptoms / awakening
Need for rescue / “reliever” treatment
More than twice / week
Lung function (PEF or FEV1)
Normal
< 80% predicted or personal best (if known) on any day
Exacerbation
One or more / year
1 in any week
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. Step 4 – Reliever medication plus two or more controllers
Selection of treatment at Step 4 depends on prior selections at Steps 2 and 3
Where possible, patients not controlled on Step 3 treatments should be referred to a health professional with expertise in the management of asthma
Medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β2-agonist (Evidence A)
Medium- or high-dose inhaled glucocorticosteroid combined with leukotriene modifiers (Evidence A)
Low-dose sustained-release theophylline added to medium- or high-dose inhaled glucocorticosteroid combined with a long-acting inhaled β2-agonist (Evidence B)
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. Oral steroids Nebulized steroids ICS No steroids
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. Oral steroids Nebulized steroids ICS No steroids
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. Management of Acute Asthma (Evidence-Based)
Instructions for correct use of Nebulizer:
Budisonide should be administered via Jet Nebulizer with 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 with 0.9% 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
Cell
Nucleus
GC-receptor
Budesonide
Budesonide
Prolonged duration of action
esterifi-
cation
lipolysis
Increased airway selectivity
Budesonide esters
INACTIVE!
12. Intracellular esterification of budesonide.
After entering the cell, inhaled budesonide (like other GCSs) binds to the glucocorticosteroid (GC) receptor, and the resulting complex translocates to the cell nucleus. However, surplus budesonide also forms esters with long-chain fatty acids, resulting in the formation of a depot of budesonide esters within the cell (Miller-Larsson et al, 1998; Thorsson et al, 1998). These conjugates are inactive, but as the concentration of free budesonide in the cell decreases, free budesonide is released from them under the influence of lipases (Miller-Larsson et al, 1998; Wieslander et al, 1997).
Miller-Larsson et al and Wieslander et al. 1997

37. Thank You

38. Disadvantages of Jet Nebulizers
Bulky, expensive (equipment/medication)
Require A/C for compressor (lack of portability)
Require frequent cleaning
Time consuming to dispense medication
Wide variability in output characteristics
Nebulizer brand
Fill volume
Flow rate of compressed gas 38