1. INHALATION THERAPY FOR ASTHMA AND COPD
ORIGIN AND PROGRESS
DR SUNDEEP SALVI MD, DNB, PhD(UK)
Director
Chest Research Foundation
Pune

2. AEROSOL THERAPY DURING THE ANCIENT TIMES
3000 BC until 400 BC (Egyptian period)
Asthma caused by
Demons, spirits, foreign gods
Treatment
Prayers, Sacrifices
Offerings to Gods, spells
Burning incense to please Gods

3. INHALATION OF FUMES FROM DATURA PLANT (Asthma Bidis / Cigarettes)
2000 BC INDIA
Datura Stramonium

4. ROMAN HOT WATER SPRINGS
Healing effects of water and steam inhalation for various respiratory illness
A Roman Hot Water Spring Temple, UK

5. ARABS - Water-Seal SMOKING PIPES

6. DISCOVERY OF THE PRESSURIZED METERED DOSE INHALER
March 1955
SUSIE MASON, 13 year old asthmatic
‘Why can’t they put my asthma medication in a spray can like they do for my mothers hair sprays?’
Dr Maison who worked with Riker Labs (now 3M) ran to Irving, a Chemist with this idea.
- Coca Cola bottle
- Meshberg Valve
- Freon Propellant - ice cream freezer
- Ascorbic Acid
First clinical trial – 1956 by Carr at Veterans Hospital in California. Launched in March 1956 (Medihaler-Epi, Medihaler-Iso).
Today – more than 800 million pMDIs are sold every year.

7. The first inhaler in India was the Autohaler (Isoprenaline) in 1972
Tiotropium,
Levosalbutamol
Formoterol+Budesonide
Formoterol
Salmeterol+Fluticasone
Fluticasone
Ipratropium
Budesonide
Beclomethasone
Salbutamol
Isoprenaline
YEARS
1972
1976
1984
1993
1994
1995
2000
2000
2001
2003/4

8. ADVANTAGE OF AEROSOL THERAPY IN ASTHMA
Deposition of the drug directly at the local site
Faster onset of action
Lower dose of medication required
Lower side effects
E.g.: Salbutamol by oral route vs aerosol route
342 mg (170 tablets) Salbutamol excess over a period of one month.

9. Aerosol Therapy for asthma and COPD
The success of therapy using aerosolized medicine depends on the ability to deliver adequate amounts of drug to the lungs with few side effects

10. Deposition pattern of drugs
DEVICE
AEROSOL
FORMULATION
PATIENT FACTORS
AND TECHNIQUE

11. Particle size and airway deposition
> 5 m
2-5 m
<2 m

12. AEROSOL GENERATION SYSTEMS
Jet and Ultrasonic nebulizers
Pressurized metered dose inhalers (pMDIs), with or without spacers (static and non static)
Dry powder inhalers (DPIs): Unit dose and Multidose

13. Pressurized METERED DOSE INHALER
ADVANTAGES:
Easy to use if technique proper
Convenient – multiple doses in a small canister
Cheap – relatively cheaper to manufacture
DISADVANTAGES:
Co-ordination problems
Cold Freon effect
Increased oropharyngeal deposition
CFC propellant – harms environment
Pressurized METERED DOSE INHALER

14. pMDI can cause thermal / chemical burns
11 year old boy with chronic asthma
Repeatedly firing his Salbutamol MDI with the noozle placed directly against the skin – firing up to 10 times at one time
(Patel R et al, Arch Dis Childhood 2004; 89: 1129)
                                                                                                                                                                                                                                                   
                                                                                                                                                                                                                                                   
                                                                                                                                                                                                                                                   

15. Use of a spacer device
Chamber reservoir where the actuated aerosol can be held prior to inhalation
First developed by Newman et al as a device that reduced oropharyngeal deposition in 1981 (Newman et al, Am Rev Respir Dis 1981; 124: )
Specifically recommended in
Problems with coordination
Children
High dose inhaled steroids(>800 mcg/day)
Acute asthma using high dose bronchodilators

16. ACE Spacer
Inspirease Spacer
Aerochamber
EZ Spacers

17. Salbutamol with Non-static Spacer versus Static Spacer
Fine particle dose at variable flow rates
Asthalin Inhaler
Derihaler Inhaler 90
76.94 80 70
66.07
57.51 60
54.84 50
45.09
Fine particle Dose (mcg)
41.95 40
26.2 30
23.5 20 10
Inhaler at 28.3
Inhaler with
Inhaler at 60
Inhaler with
l/min
Spacer at 28.3
l/min
Spacer at 60
l/min
l/min

18. NEOHALER

19. DRY POWDER INHALERS Single dose Multi-dose - Reservoir - Singlet
Handihaler
Rotahaler
Single dose
Multi-dose
- Reservoir
- Singlet
Turbohaler
Diskhaler
Accuhaler

20. DRY POWDER INHALERS ADVANTAGES:
Breath actuated – no co-ordination skills required
Easy and convenient to use
No propellant – environmentally friendly
DISADVANTAGES:
Requires a good inspiratory effort
Carries a single dose at a time
Capsule and drug life reduced by moisture and humidity
Reservoir multi-dose DPIs: Pure drug Cohesion and static forces can reduce dose uniformity
DRY POWDER INHALERS

21. Creates a fine mist of the drug which can be inhaled
ADVANTAGES:
Creates a fine mist of the drug which can be inhaled
Does not require co-ordination or a minimum inspiratory pressure
DISADVANTAGES:
Unpredictable lung dose
Inefficient lung deposition
Bulky
Expensive
NEBULIZERS
Ultrasonic
Jet

22. BDP Deposition in Healthy Subjects
AEROSOL FORMULATION AS A DETERMINANT OF DRUG DEPOSITION
BDP Deposition in Healthy Subjects
CFC-BDP
HFA-BDP
Reprinted with permission from Leach CL. Resp Med. 1998;92(suppl A):3-8.

23. PATIENT RELATED EFFECTS
Optimal inspiratory flow
Full inspiration from functional residual capacity
Breath hold for at least 6 seconds

24. (Fink JB, Respir Care 2000; 45(6): 623-635)
(2,500 mcg)
(200 mcg)
(200 mcg)
(200 mcg)
(Fink JB, Respir Care 2000; 45(6): )

25. WHICH IS THE BEST INHALER DEVICE?

26. ASK THE PATIENT
Assess the inhaler technique
Prime importance to correct inhaler technique

27. AGE AS A DETERMINING FACTOR
Children < 2 years - nebuliser
Children 2-5 years - MDI with spacer with face mask
Children > 5 years - DPI, MDI with spacer
Children > 12 years - MDI alone (if suitable), DPI
Very old people - DPI or breath actuated MDI

28. DO MEDICAL PERSONNEL KNOW HOW TO USE INHALER DEVICES CURRENTLY?

29. Medical personnel’s knowledge of and ability to use inhaling devices
Medical personnel’s knowledge of and ability to use inhaling devices. (University of Toronto, Canada)
- Respiratory therapists (n = 30)
- Nurses (n = 30)
- Doctors (n = 30)
Knowledge scores
Demonstration scores
- pMDI, DPI, Spacers
(Hanania NA et al, Chest 1994; 105: )

30. Resp Therapists
Nurses
Doctors
(Hanania NA et al, Chest 1994; 105: )

31. %age of medical housemen who could use pMDI correctly
73%
13% 5%
At start
After Lecture / Demo
After one-to-one practical demo
(Lee-Wong et al, Postgrad Med J 2003; 79: )

32. WHAT IS IN THE FUTURE?

33. PREVIEW – LOOKING INTO THE FUTURE - I
Monodisperse particles – equal lung deposition at half the delivered dose
Liquid-based systems for use in pMDI – achieve lung doses in excess of 70% of the nominal dose.
Metered dose inhalers with complex electronics control delivery
Battery-powered fans to create an aerosol for reliable drug delivery.
Developing drug particles with no inherent charge

34. PREVIEW – LOOKING INTO THE FUTURE - II
Antibiotics
Inhaled Insulin for management of Diabetes
Morphine
Growth factors
Vasopressin

35. AEROSOL THERAPY FOR ASTHMA IN INDIA
Asthma – grossly under-diagnosed in India
Amongst diagnosed asthmatics - < 10% use inhaler therapy
Misconceptions about inhaler therapy
- Addictive
- Very strong medicine
Both physicians and patients to be made more aware

36. Amount of Salbutamol smaller than 5m aerodynamic diameter from different spacer devices
Eur Resp J; 1997, 10: