Asthma. Self study materials for medical students. Prepared in co-authorship with my dear colleague MD Zhuravka Natalia, assistant proffesor of Internal Medicine department, V.N. Karazin University.

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Asthma
Self study materials for students
6th year, Internal Medicine, Pulmonology circle
Topic 3-4. Management of patients with asthma
Dr. Natalia Zhuravka
Dr. Anton Litvin
Assistant professors
of Internal Medicine
V. N. Karazin Kharkiv
National University

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Definition
Asthma is a chronic inflammatory disease
of the airways which develops under the
allergens influence, associates with bronchial
hyperresponsiveness and reversible
obstruction and manifests with attacks of
dyspnea, breathlessness, cough, wheezing,
chest tightness and sibilant crackles more
expressed at expiration.

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Definition (GINA, 2011)
Asthma is a common and potentially
serious chronic disease that can be
controlled but not cured
Asthma causes symptoms such as
wheezing, shortness of breath, chest
tightness and cough that vary over time in
their occurrence, frequency and intensity

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Definition (GINA, 2011)
Symptoms are associated with variable
expiratory airflow,
i.e. difficulty breathing air out of the lungs
due to:
 Bronchoconstriction (airway narrowing)
 Airway wall thickening
 Increased mucus

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Definition (GINA, 2011)
Symptoms may be triggered or worsened
by factors such as viral infections,
allergens, tobacco smoke, exercise and
stress

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Epidemiology
• About 300 million people worldwide are affected
(1 - 18% of total population)
• 250,000 people die per year
• Low and middle income countries make up
more than 80% of the mortality
• It is more common in developed countries.
• Asthma is twice as common in boys as girls
• Asthma is more common in the young than the
old

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Epidemiology
http://www.asthmacure.com/wp-content/uploads/2010/11/asthma-prevalence3.jpg

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Etiology
• Genes
• Atopy
• Bronchial hyperresponsiveness

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Atopy
• Atopy is a predisposition
toward developing certain
allergic hypersensitivity reactions
by excessive production of
allergen-specific antibodies (Ig E).
• It is genetic origin.
• Atopy is the cause of eczema(atopic
dermatitis), allergic rhinitis (hay fever),
asthma, allergic conjunctivitis, eosinophilic
esophagitis, anaphylaxis.
http://www.biofronttech.com/images/ige.gif

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Bronchial hyperresponsiveness
• Bronchial hyperresponsiveness (or other
combinations with airway or hyperreactivity)
is a state characterised by easily
triggered bronchospasm.
• Bronchial hyperresponsiveness can be assessed
with a bronchial challenge test (post
bronchodilator test).

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Triggers
The most common triggers are:
• Allergens
• Air pollutants
• Smoking
• Viral respiratory infection
• Hyperventilation
• Physical exertion
• Emotional stress
• Adverse weather conditions

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Allergens
The allergens are divided into:
• communal
• industrial
• occupational
• natural
• pharmacological
• alimentary
http://sr.photos3.fotosearch.com/bthumb/CSP/CSP991/k12506213.jpg

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Communal allergens
Communal allergens are presented by:
• house-dust mites which live in carpets,
mattresses and upholstered furniture;
• spittle, excrements, desquamated epidermis,
hair and fur of domestic animals;
• vital products of domestic insects (e.g.,
cockroach);
• mycelial yeast-like fungi (molds);
• tobacco smoke during active or passive
smoking;
• various communal aerosols and synthetic
detergents.

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Industrial allergens
Main industrial allergen is industrial and
photochemical smog, which consists of:
• Nitric, carbonic, sulfuric oxides
• Formaldehyde
• Ozone
• Emissions of biotechnological industry

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Occupational allergens
The most important occupational allergen
is the dust of:
• Constructed buildings
• Mills, weaving-mills
• Book depositories
• Etc.
http://previews.123rf.com/images/jut/jut1005/jut100500018/7023592-
illustration-set-of-people-occupations-icons-Stock-Vector-cartoon-people-
face.jpg

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Natural allergens
• Plant pollen (especially ambrosia,
wormwood and goose-foot pollen)
• Respiratory (viral) infections
http://hdwallpaperspretty.com/wp-content/gallery/nature-clipart-
images/926-nature-clip-art-free.jpg

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Pharmacological allergens
• Enzymes
• Antibiotics
• Vaccines
• Serums
• Aspyrin
• Β-blockers
http://www.goldenlevel.com/images/stories/virtuemart/product/867745-medicines-1428708434-459-640x480.jpg

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Alimentary allergens
• Milk
• Eggs
• Wheat flour
• Fish
• Meat
• Stabilizers
• Nuts
• Genetically modified products
http://www.datamonitorconsumer.com/files/2014/01/Food1.jpg

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Pathogenesis
• Asthma pathogenesis is quite difficult and
insufficiently studied.
• In most cases the disease is based on 1 type
hypersensitivity reaction.
http://reflexions.ulg.ac.be/upload/docs/image/jpeg/2009-02/activation_proteases_fr.jpg

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Type 1 hypersensitivity reaction
• Type I hypersensitivity (or immediate
hypersensitivity) is an allergic reaction
provoked by reexposure to a specific type
of antigen referred to as an allergen.
• Exposure may be
by ingestion, inhalation, injection, or direct
contact.

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Type 1 hypersensitivity reaction
• Macrophage meets and absorbs the antigen.
• Presentation of antigen to CD4+ T-
helpers cells specific to the antigen that
stimulate B-cell production of IgE antibodies
also specific to the antigen.
• Normally IgA, IgG, or IgM being produced.
• IgE antibodies bind to receptors on the
surface of tissue mast cells and blood
basophils (sensibilisation).

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Type 1 hypersensitivity reaction
• Later exposure to the same allergen cross-
links the bound IgE on sensitised cells,
resulting in degranulation and the secretion of
pharmacologically active mediators such
as histamine, serotonin, chemotaxis
factors, heparin, proteases, thromboxane,
leukotrienes, prostaglandins that act on the
surrounding tissues.

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Type 1 hypersensitivity reaction
The principal effects of these products are:
• vasodilation
• smooth-muscle contraction
• hyperergic inflammation
• mucous edema
• glands hypersecretion
• viscous exudate formation
http://graphics8.nytimes.com/images/2007/08/01/health/adam/19346.jpg

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Type 1 hypersensitivity reaction
https://www.youtube.com
/watch?v=gafekFEbUg4

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Pathogenesis
https://upload.wikimedia.org/wikipedia/commons/4/4a/Asthma_attack-illustration_NIH.jpg

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Microscopic changes
• Bronchial wall infiltration with mast
cells, eosinophils, basophils and T-
lymphocytes
• Edema of mucous and submucous
tunics
• Destruction of bronchial epithelium
• Hypertrophy of bronchial smooth
muscles,
• Hyperplasy of submucous glands
• Microvessels dilation

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Classification
• Etiology:
▪ exogenous (atopic)
▪ endogenous (non-atopic)
• Clinical course:
▪ intermittent (beginning, early)
▪ persistent (chronic, late)
• Phase:
▪ remission
▪ exacerebration

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Classification
• Severity:
Clinical course,
severity
Daytime asthma
symptoms
Nighttime
awakenings
FEV1, PEF
Intermittent < 1 /week 2 and < /month >80% predicted.
Daily variability <
20%
Mild persistent
 1 /week but
not daily
> 2 /month
>80% predicted.
Daily variability –
20-30%
Moderate
persistent
Daily > 1 /week
> 60 but < 80%
predicted.
Variability>30%.
Severe
persistent
Persistent,
limits normal
activity
Daily
<60% predicted.
Variability >
30%.

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GINA classification
Asthma is classified by GINA on
the base of control assessment and
divided into:
• well-controlled
• partially controlled
• uncontrolled

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GINA classification
Asthma control is considered as:
• daytime symptoms  2 /week;
• ability to engage in normal daily activity;
• the absence of night-time awakenings as a
result of asthma symptoms;
• need in bronchodilators administration  2
/week;
• the absence of asthma exacerbations;
• normal or near normal lung function
parameters.

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Symptoms
Classic sighns of asthma are:
• Attacks of expiratory dyspnea
• Shortness of breath
• Cough
• Chest tightness
• Wheezing (high-pitched whistling
sounds at expiration)
• Sibilant crackles

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Exacerbration
It has 3 periods:
• Prodromal period
• Peak period
• Period of reverse changes.
http://www.juicingrecipesforeverything.com/juicing_for_a
sthma.jpg

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Prodromal period
• Vasomotoric nasal reaction with
profuse watery discharge
• Sneezing, dryness in nasopharynx
• Paroxysmal cough with viscous
sputum
• Emotional lability
• Excessive sweating
• Skin itch
• Other symptoms

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Peak period
• Expiratory dyspnea
• Forced position with arms support
• Poorly productive cough
• Cyanotic skin and mucous layers
• Hyperexpansion of thorax with use of all accessory
muscles at breathing
• Percussion: tympanitis, shifted downward lung borders
• Auscultation: diminished breath sounds, sibilant
crackles, prolonged expiration, tachycardia.
• Severe exacerbations: the signs of right-sided heart
failure (swollen neck veins, hepatomegalia), overload
of right heart chambers on ECG.

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Period of reverse changes
• Comes spontaneously or under
pharmacologic therapy
• Dyspnea and breathlessness relieve and
disappear
• Sputum becomes more liquid
• Productive cough
• Patient breathes easier
• Last from several minutes to hours

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Status asthmaticus
• Acute severe asthma (status
asthmaticus) is an acute exacerbation
of asthma that lasts for several hours and
does not respond to standard treatments
of bronchodilators (inhalers) and steroids.
• It is a life-threatening episode of airway
obstruction and is considered a medical
emergency.
• Complications include cardiac and/or
respiratory arrest.

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Status asthmaticus
• Progressive respiratory failure
• Hypoxemia
• Hypercapnia
• Respiratory acidosis
• Increased blood viscosity
• Blockade of bronchial β2-receptors

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Atypical forms
• Episodic appearance of wheezing
• Cough, heavy breathing occurring at night
• Cough, hoarseness after physical activity
• “Seasonal” cough, wheezing, chest tightness
(e.g., during pollen period of ambrosia)
• The same symptoms occurring during contact
with allergens, irritants
• Lingering course of acute respiratory
infections

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Complications
Persistent asthma:
• Fibrosing bronchitis
• Small bronchi deformation and obliteration
• Emphysema
• Pneumosclerosis
• Chronic respiratory failure
• Chronic cor pulmonale.

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Complications
Asthma exacerbations:
• Pneumothorax
• Lung atelectasis
• Pneumonia
• Acute or subacute cor pulmonale
• Asthmatic status.

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Lab diagnostics
• TBC - eosinophilia, moderate leucocytosis,
increased ESR.
• Immunological tests - increased serum
level of Ig E.
• Sputum microscopy - inflammatory cells,
Curschmann's spirals (viscous mucus
which copies small bronchi) and Charcot-
Leyden crystals (crystallized enzymes of
eosinophils and mast cells)

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X-ray
• Hyperlucency of lung
fields
• Low standing and
limited mobility of
diaphragm
• Eexpanded
intercostal spaces
• Horizontal rib
position
• => Emphysema

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Spirometry & Peakflowmetry
• Forced vital capacity (FVC) is the volume
of air that can forcibly be blown out after full
inspiration, measured in liters. FVC is the
most basic maneuver in spirometry tests.
• Forced expiratory volume in 1 second
(FEV1) is the volume of air that can forcibly
be blown out in one second, after full
inspiration.

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Spirometry & Peakflowmetry
• FEV1/FVC (FEV1%, Tiffeneau index) is
the ratio of FEV1 to FVC. In healthy adults
this should be approximately 75–80%.
• Peak expiratory flow (PEF) is the maximal
flow (or speed) achieved during the
maximally forced expiration initiated at full
inspiration, measured in liters per minute or
in liters per second.

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Spirometry & Peakflowmetry
https://www.youtube.com
/watch?v=M4C8EInOMOI

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Peakflow meters
https://www.nlm.nih.gov/medlineplus/ency/images/ency/fullsize/19367.jpg
http://www.woodleyequipment.com/images/clinical-trials/big/bg41275650293Peak%20Flow%20Meter.jpg.jpg

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Post bronchodilator test
• Post bronchodilator test – is a performing
of peakflowmetry for 2 times: before and
after inhaling bronchodilator.
• If the forced vital capacity
after inhaling (FVC2) is
15% > than FVC1
before inhaling
=> Ds: Asthma
http://www.dx-health.com/193-thickbox_default/berodual-n-aerosol.jpg

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Differential diagnosis
• In COPD there is permanent damage to the
airways. The narrowed airways are fixed,
and so symptoms are chronic (persistent).
Treatment to open up the airways, is
therefore limited.
• In asthma there is inflammation in the
airways which makes the muscles in the
airways constrict. This causes the airways
to narrow. The symptoms tend to come and
go, and vary in severity from time to time.
Treatment to reduce inflammation and to
open up the airways usually works well.

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Differential diagnosis
• COPD is more likely than asthma to cause
a chronic (ongoing) cough with sputum.
• Night time waking with breathlessness or
wheeze is common in asthma and
uncommon in COPD.
• COPD is rare before the age of 35 while
asthma is common in under-35.

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Key to diagnosis
• History
• Physical exam (resp. tract, skin,
chest)
• Spirometry to demonstrate
reversibility
• Additional studies
http://st.depositphotos.com/1776223/2032/i/950/depositphotos_20320029-an-old-doctor-showing-an-empty-medical-clipboard.jpg

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Acute exacerbation
https://www.youtube.com
/watch?v=EK8nzKzdnIM

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Management
1. Avoiding the contact with allergen. If it is
impossible, the specific hyposensitization with
standard allergens should be performed. It is rather
effective in case of monoallergy, in intermittent and
mild persistent asthma, in remission phase.
2. Elimination of trigger factors (rational job
placement, changing the residence, psychological
and physical adaptation, careful drug using) is the
second condition for successful asthma treatment.
3. Optimally selected medical care is the base of
asthma management.

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Drug therapy
Antiinflammatory drugs
(basic)
Bronchodilators
Hormone-containing
(corticosteroids)
Nonhormone-containing
(cromones, leukotriene
receptor antagonists)
Anticholinergic drugs
β2-agonists
Methylxanthines

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Drug therapy
https://commonchronicdiseases.files.wordpress.com/2015/05/medications_for_asthma-2.jpg

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Drug therapy

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Corticosteroids
The mechanism of action lays in:
• cell membrane stabilization
• inhibition of inflammatory mediators
• restoring the sensivity of β2-receptors.
http://www.allgen.nl/wp-content/uploads/ILL-PACKSHOT-BUDESONIDE-ORION-400-e1418041946580.jpg

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Corticosteroids
• Inhaled corticosteroids are the most effective
and safe and considered to be the first line
drugs for asthma treatment.
• Systemic are used during short courses,
mainly in case of severe persistent
asthma or asthmatic status.
http://www.hiwtc.com/photo/products/20/02/62/26282.jpg

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Inhaled steroids
Representatives:
• Fluticasone – Flovent, Diskus
• Budesonide - Pulmicort
• Mometasone – Asmanex, Twisthaler
• Beclomethasone - Qvar
• Ciclesonide - Alvesco
http://www.drsmartphonemd.com/wp-content/uploads/2013/04/inhaler.jpg

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• stabilize cell membranes
• used mainly in pediatric practice (in childhood)
• in case of intermittent or mild persistent asthma
Representatives:
• Cromolyn sodium – Intal
• Nedocromil – Tilade
Cromones
http://4nrx.ru/tilade-inhaler-nedocromil-sodium.jpg
http://kakzdravie.com/wp-content/uploads/2014/08/intal1.jpg

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Leukotriene receptor antagonists
• have the moderate intiinflammatory activity
• used in case of aspirin-induced asthma and
asthma of physical exertion.
Representatives:
• Montelukast - Singulair
• Zafirlukast – Accolate
• Zileuton - Zyflo
http://www.kernpharma.com/wp-content/uploads/2013/02/MONTE-10-mg-28-comp-459x363.jpg
http://mexmeds4you.com/image/cache/data/2124-500x500.jpg

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• β2-agonists - stimulate β2-adrenergic
receptors of bronchi
• Anticholinergic drugs - reduce tonus of
vagus
• Methylxanthines - inhibit phosphodiesterase
Bronchodilators
Smooth muscle relaxation

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They are the basic drug group among
bronchodilators.
• Short-acting (duration of action 5-6 h) β2-
agonists (SABAs) – Salbutamol, Fenoterol
- are used for quick relief of asthma
symptoms.
• Long-acting (> 12 h) β2-agonists (LABAs)
- Salmoterol, Farmoterol - for prevention of
asthma symptoms occurring.
Inhaled b2-agonists

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They are used predominantly in nighttime
asthma and in elderly patients because of the
least cardiotoxic effect.
Representatives:
• Ipratropium bromide
• Atrovent
• Troventol
Anticholinergic drugs
https://store.mcguff.com/Images/Images550/005553%20Ipratropium%20Bromide,%200.02%20Percent,%20Inhalation%20Solution,%202.5mL,%2025%20Vials%20per%20Tray%20McGuffMedical.com.jpg

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Combined inhaled drugs (corticosteroids with b2-
agonists) with use of delivery devices (nebulasers,
turbuhalers, spasers, spinhalers, sinchroners)
enhance the effectiveness of asthma therapy.
Representatives:
• Seretide
• Simbicort
Combined drugs
http://images.dokteronline.com/images/products/dokteronline-seretide-420-3-1352473202.jpg

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Management of asthmatic status
• Oxygen
• Systemic corticosteroids (Hydrocortisone 200mg or
Methylprednisolone 125mg every 6h or Prednisolone 50
mg/day per os)
• Inhalations of short-acting β2-agonists - Salbutamol
5mg or Fenoterol 2mg through nebulaser – 3 times at 1st
hour, then once an hour till distinct improvement of
patient’s condition is achieved; then 3-4 times a day.
• Inhaled anticholinergic drugs or Aminophylline IV.
• If ineffective - artificial lung ventilation.
http://www.vector-eps.com/wp-content/gallery/ambulances-vector-design/ambulance-vector-design1.jpg

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Types of inhalers
http://www.thuisarts.nl/sites/default/files/images/inhalers.png

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How to use inhaler?
https://www.youtube.com
/watch?v=Rdb3p9RZoR4

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Spacer
• Spacer is an add-on device used to increase the
ease of administering aerosolized medication from
a metered-dose inhaler (MDI).
• The spacer adds space in the form of a tube or
“chamber” between the canister of medication and the
patient’s mouth, allowing the patient to inhale the
medication by breathing in slowly and deeply for five
to 10 breaths.
http://www.asthma.ca/images/adults/treatment/spacer.gif

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How to use spacer?
https://www.youtube.com
/watch?v=uJy97bTdGzI

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Nebulizer
• Nebulizer is a drug delivery device used to administer
medication in the form of a mist inhaled into the lungs.
• Nebulizers are commonly used for the treatment
of cystic fibrosis, asthma, COPD and
other respiratory diseases.
• Nebulizers use oxygen, compressed
air or ultrasonic power to break up
medical solutions and suspensions
into small aerosol droplets (mist)
that can be directly inhaled from
the mouthpiece of the device.
http://img.medicalexpo.com/images_me/photo-g/electro-pneumatic-nebulizer-mask-compressor-69408-139473.jpg

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How to use nebulizer?
https://www.youtube.com
/watch?v=HGZSCe98CWU

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Prognosis
• In case of early detection and adequate
treatment the prognosis for the disease
is favourable.
• It becomes serious in
severe persistent and
poorly controlled
(insensitive for
corticosteroids)asthma.
http://allacart.com/wp-content/uploads/2015/03/future.png

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The examination of working capacity
• The patients with unfavorable for
the disease conditions of work need
the job replacement.
• Physical labours with severe
asthma are disable to work.
http://яркондер.рф/assets/img/worker.png

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Prophylaxis
• Preservation of the environment,
healthy life-style (smoking cessation,
physical training) – are the basis of
primary prophylaxis.
• These measures in combination
with adequate drug
therapy are effective
for secondary prophylaxis.
http://www.siddharthbharath.com/wp-content/uploads/2013/03/pay-attention-to-life-not-work0.jpg

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Thank you