INHALATION THERAPY FOR ASTHMA AND COPD ORIGIN AND PROGRESS DR SUNDEEP SALVI MD, DNB, PhD(UK) Director Chest Research Foundation Pune
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
INHALATION OF FUMES FROM DATURA PLANT (Asthma Bidis / Cigarettes) 2000 BC INDIA Datura Stramonium
ROMAN HOT WATER SPRINGS Healing effects of water and steam inhalation for various respiratory illness A Roman Hot Water Spring Temple, UK
ARABS - Water-Seal SMOKING PIPES
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.
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
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.
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
Deposition pattern of drugs DEVICE AEROSOL FORMULATION PATIENT FACTORS AND TECHNIQUE
Particle size and airway deposition > 5 m 2-5 m <2 m
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
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
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)
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: 317-320) Specifically recommended in Problems with coordination Children High dose inhaled steroids(>800 mcg/day) Acute asthma using high dose bronchodilators
ACE Spacer Inspirease Spacer Aerochamber EZ Spacers
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
NEOHALER
DRY POWDER INHALERS Single dose Multi-dose - Reservoir - Singlet Handihaler Rotahaler Single dose Multi-dose - Reservoir - Singlet Turbohaler Diskhaler Accuhaler
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
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
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.
PATIENT RELATED EFFECTS Optimal inspiratory flow Full inspiration from functional residual capacity Breath hold for at least 6 seconds
(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): 623-635)
WHICH IS THE BEST INHALER DEVICE?
ASK THE PATIENT Assess the inhaler technique Prime importance to correct inhaler technique
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
DO MEDICAL PERSONNEL KNOW HOW TO USE INHALER DEVICES CURRENTLY?
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: 111-116)
Resp Therapists Nurses Doctors (Hanania NA et al, Chest 1994; 105: 111-116)
%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: 221-225)
WHAT IS IN THE FUTURE?
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
PREVIEW – LOOKING INTO THE FUTURE - II Antibiotics Inhaled Insulin for management of Diabetes Morphine Growth factors Vasopressin
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
Amount of Salbutamol smaller than 5m aerodynamic diameter from different spacer devices Eur Resp J; 1997, 10: 1345-48