asthma. self study materials for medical students. (in collaboration with zhuravka n.v.)
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AsthmaSelf study materials for students
6th year, Internal Medicine, Pulmonology circleTopic 3-4. Management of patients with asthma
Dr. Natalia ZhuravkaDr. Anton Litvin
Assistant professorsof 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
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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
activityDaily
<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 classificationAsthma 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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SymptomsClassic 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_asthma.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
http://www.mypacs.net/repos/mpv3_repo/viz/full/0/59/3/61869396.jpg
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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.jpghttp://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) is15% > 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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Management1. 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 therapyAntiinflammatory 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
www.anti-asthma.ir/images/content/5195931304364867729.jpg
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CorticosteroidsThe 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.
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Inhaled steroidsRepresentatives:
• 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.jpghttp://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.jpghttp://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.
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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.
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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.
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Thank you