How Do We Achieve Optimal Asthma Control?

Role of Nebulised steroids in Management of Asthma

BY

MAYSA SHARAF ELDINPROFESSOR OF PULMONARY

MEDICINE

CAIRO UNIVERISITY

• Why do we care about asthma

control?

• What do we mean by asthma

control?

• Inhalation Therapy

Prof. Maysa Sharaf El Din

Why do we care about asthma control?

Prof. Maysa Sharaf El Din

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

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

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

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

What do we mean by asthma control?

Prof. Maysa Sharaf El Din

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 eventsAll of the above sustained for at least 7 out of 8 weeks* Minimal = twice or less per week

GINA 2011

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 eventsAll of the above sustained for at least 7 out of 8 weeks* Minimal = twice or less per week

How many of our patients

actually achieve this?

GINA 2011

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

What we know: Particle Size

2 – 5 Upper / central airways

Clinical effect

Subsequent absorption from lung

< 2Peripheral

airways / alveoli

Some local clinical effect

High systemic

absorption

> 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

Prof. Maysa Sharaf El Din

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

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 patientsProf. Maysa Sharaf El Din

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

Types of nebulizers

1. 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

Jet and Ultrasonic Nebulizers

JET• 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

New Generation Nebulizers:

Vibrating Mesh or Plate Nebulizers

Pari e-flowMicroAIR U22www.omron-healthcare.com

www.aerogen.com/theproducts.htm

www.eflow.pari.de/200/index.html

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

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

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

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

1. Well controlled

2. Partially uncontrolled

3. 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

1. Well controlled

2. Partially uncontrolled

3. Uncontrolled

Levels of Asthma Control

Characteristic Controlled(All of the following)

Partly controlled(Any present in any

week)Uncontrolled

Daytime symptomsNone (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

None Any

Need for rescue / “reliever” treatment

None (2 or less / week)

More than twice / week

Lung function (PEF or FEV1)

Normal< 80% predicted or

personal best (if known) on any day

Exacerbation None One or more / year 1 in any week

GINA 2011

What is your further management?

1. Increase dose of ICS

2. Add Theophylline

3. Start Antibiotics

4. Oral steroids

What is your further management?

1. Increase dose of ICS

2. Add Theophylline

3. Start Antibiotics

4. Oral steroids

(Evidence A) 2009

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.

1. Nebulised steroids

2. Oxygen therapy

3. IV Theophylline

4. Nebulized SAMA

5. All of above

6. None of the above

What is the required treatment for her in hospital?

1. Nebulised steroids

2. Oxygen therapy

3. IV Theophylline

4. Nebulized SAMA

5. All of above

6. None of the above

What is the required treatment for her in hospital?

1. Oral steroids

2. Nebulized steroids

3. ICS

4. 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 :

1. Oral steroids

2. Nebulized steroids

3. ICS

4. 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 :

1. Near-fatal asthma

2. Life threatening asthma

3. Acute severe asthma

4. Moderate asthma exacerbation

5. Brittle asthma

How do you classify her acute asthma?

How do you classify her acute asthma?

1. Near-fatal asthma

2. Life threatening asthma

3. Acute severe asthma

4. Moderate asthma exacerbation

5. Brittle asthma

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

NOTES

Prof. Maysa Sharaf El Din

Instructions for correct use of Nebulizer:1. Budisonide should be administered via Jet Nebulizer with a

mouthpiece or suitable facemask. Ultrasonic nebulizers are not suitable & therefore dis-recommended.

2.Nebulizer should be connected to an air compressor with an adequate airflow (5 – 8 l/min).

3.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

Cell Nucleus

GC-receptor

BudesonideBudesonide

Budesonide estersINACTIVE!

lipolysisesterifi-cation

Reactivated Esterification of budesonide

Miller-Larsson et al. 1998 and Wieslander et al. 1997

Prolonged duration of

action

Increasedairway

selectivity