ASTHMA : UNDERGRADUATE STUDENTS

Prof MOHMMAD EL DESOUKY ABOU Prof :MOHMMAD EL DESOUKY ABOU SHEHATA SHEHATA Prof .of Thoracic Thoracic Medicine Medicine Prof .of Mansoura University Mansoura University

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Definition of Asthma

A chronic Inflammatory disorder of the airways Many cells and cellular elements play a role Chronic inflammation leads to an increase in airway hyper responsiveness with recurrent episodes of wheezing , coughing , and shortness of breath Wide spread , variable .and often reversible airflow limitation
GINA 2009

Burden of Asthma

300 milion individuals are affected worldwide Global asthma prevalance 1% --18% Annual world deaths estimated at 250,000 / year
GINA 2oo7

Asthma Development And Expression

GENETIC FACTORS + ENVIRONMENTAL FACTORS

the mechanisms whereby they influence the development and expression of asthma are complex and interactive. Genes likely interact both with other genes and with environmental factors to determine asthma susceptibility

Genetics OF Asthma
Genes Linked To Pathogenesis

Production of allergen- specific igE antibodies Expression of airway hyper responsiveness Generation of inflammatory cytokines Determination of of ratio between Th1 and Th2 immunoresponse ( relevant to hyageine hypothesis)
Holloway JW, Beghe B, Holgate ST. The genetic basis of atopic asthma. Clin Exp Allergy 1999;29(8):1023-32.

Environmental Factors
Allergens Indoor: Domestic mites, furred animals (dogs, cats, mice), cockroach allergen, fungi, molds, yeasts Outdoor: Pollens, fungimolds, yeasts Infections (predominantly viral) Occupational sensitizers Tobacco smoke Passive smoking Active smoking Outdoor/Indoor Air Pollution Diet
GINA 201o

Pathogenesis : Th-cell cytokine profile determines antibody isotype

Predominant antibody response
IL-12

Biological role Defence against intracellular pathogens (e.g. viruses or bacteria) Defence against large extracellular pathogens and mediators of allergy

Th1cell

IL-2 IFN-g TNF-a TNF-b

IgG2a

Th0cell

IL-4

Th2cell

IL-4 IL-5 IL-10 IL-13

IgE, IgG1

Corry DB et al. Nature 1999

The IgE-mediated inflammatory response: type I hypersensitivity reaction

IgE FceRI B-cell Allergen

Mast cell IL-4

IL-13

Histamine Leukotrienes Prostaglandins Cytokines

Atopic disease

Th2-cell IL-5 Antigen-presenting cell Eosinophil

Holgate ST. QJM 1998

Inflammatory mediators result in early and late-phase asthmatic responses

Mast cell mediator release Neutrophil influx and mediator release

Eosinophil influx and mediator release

100 % predicted FEV1 80

60
40 20 0 0 Antigen 1 2 3 4 5
Histamine, prostaglandins, leukotrienes and thromboxanes mediate bronchospasm

Inflammation Persistent obstruction

6 7 8 24

Increased airway responsiveness

Time (hours)

Acute and chronic inflammation

Acute Inflammation

Chronic Inflammation

Airway Remodelling

HistopaPathology : Long-term consequences of

inflammation even in mild asthma

Normal lung

Patient with mild asthma

Asthma Pathology

Bronchoconstriction

Before allergen challenge

10 minutes after allergen challenge

P Howarth

Diagnosis of Asthma
Symptoms and signs

Wheeze History of any wheeze cough dyspnea tightnes of chest Symptoms occur or worsen at nights Symptoms occur or worsens in seasons Patient has eczema ; hay fever or family history of allergy

When We Suspect Asthma?

When symptoms occure or / worsen at night and awaking the patient When symptoms occur or worsens at season When there is associated eczema ; hay fever and or family history of asthma

When we suspect Asthma (cont )

Symptoms occur on exposure to

Animals with fur Aerosol chemicals Change of temperature Domestic dust mites Drugs Exercise Pollen Infection Smoke Strong emotions Symptoms responds to anti asthma therapy Patients cold go to the chest or take more than 10 days

Signs: Athma

In between attacks no signs are detected or minimal signs. During attacks: - Harsh vesicular breath sounds with prolonged expiration - Audible wheezes and rhonchi on auscultation. - There may be silent chest in severe cases. The course of asthma is characterized by its variability, periodicity and unpredictability; exacerbations vary from brief to sever ones.

Factors Influencing the Development and Expression of Asthma

Environmental Factors

Allergens Indoor: Domestic mites, furred animals (dogs, cats, mice), cockroach allergen, fungi, molds, yeasts Outdoor: Pollens, fungimolds, yeasts Infections (predominantly viral) Occupational sensitizers Tobacco smoke Passive smoking Active smoking Outdoor/Indoor Air Pollution Diet
GINA 201o

Diagnostic Challenge In Asthma Pseudo Asthma (cont)

When cough is not Asthma

Cystic fibrosis Primary Ciliary Dyskinesia Chronic purulent ( Bacterial ) bronchitis Tracheomalasia Habit cough syndrome

Diagnostic Challenge In Asthma Pseudo Asthma (cont)

When wheezing Is not Asthma

Vocal Cord Dysfunction Partial Aiway Obstruction ( COPD ) Foreign body Bronchomalasia

Diagnostic Challenge In Asthma Pseudo Asthma (cont)

When Dyspnea Is not Asthma

Hyperventilation Anaxiety Exertional Dyspnea

Investigation of Asthma
Lung Function

Spirometry

- Increase of FEV1> 12% or 200 ml after administration

- of bronchodilators Peak expiratory flow rate (PEF) - Improvement of 60 L / min or 20% of pre- bronchodilator administration - Diurnal variation more than 20% suggest a diagnosis of asthma Aiway hyper responsivenes ( when lung function is normal ) Metaccholine ; histamine and manitol Skin tests and Specific IgE in serum

Differential Diagnosis of Asthma

1. COPD (chronic bronchitis and emphysema). 2. Left sided heart failure (cardiac asthma). 3. Pulmonary embolism. 4. Mechanical obstruction of the airways by tumors or foreign body. 5. Drug induced cough e.g; angiotensin converting enzyme (ACE) inhibitors. 6. Vocal cord dysfunction (Factitious asthma).

Complications of Asthma

Respiratory failure may follow acute severe attacks. Chronic severe asthma with steroid resistance. Spontaneous Pneumothorax. Fractures of ribs and other complications of repeated cough may occur especially in old age. Segmental collapse due to plugging with mucus. Allergic bronchopulmonary aspergillosis. Psychological troubles.

Asthma Control ( Treatment )

Asthma education ( patient/ doctor relationship Identify and reduce risk factors Asses , Treat , and Monitor asthma Manage asthma exacerbation

Asthma Management And Prevention

1. 2. 3. 4. 5. Development of Patient/Doctor Partenership Identify and Reduce Risk Factors Assess ; Treat And Monitor Asthma Manage Asthma Exacerbation Special Consideration
GINA 2010

ASTHMA CONTROL
Assessing Asthma Control Treating to Achieve Control Monitoring to Maintain Control
GINA 2009

Component 4: Asthma Management and Prevention Program

Controller Medications

Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled 2-agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral 2-agonists Anti-IgE Systemic glucocorticosteroids

Component 4: Asthma Management and Prevention Program

Reliever Medications

Rapid-acting inhaled 2-agonists Anticholinergics Theophylline Short-acting oral 2-agonists

Levels of Asthma Control

Characteristic Daytime symptoms Limitations of activities Nocturnal symptoms / awakening Controlled Partly controlled
(Any present in any week)

Uncontrolled

None (2 or less / week)

None None

More than twice / week

Any Any 3 or more features of partly controlled asthma present in any week

Need for rescue / reliever treatment

Lung function (PEF or FEV1)

None (2 or less / week)

Normal

More than twice / week

< 80% predicted or personal best (if known) on any day

Exacerbation

None

One or more / year

1 in any week

LEVEL OF CONTROL
controlled partly controlled uncontrolled exacerbation

REDUCE

TREATMENT OF ACTION

maintain and find lowest controlling step consider stepping up to gain control INCREASE step up until controlled treat as exacerbation

REDUCE

INCREASE

TREATMENT STEPS
STEP STEP STEP STEP STEP

Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age

Drug
Beclomethasone Budesonide Budesonide-Neb Inhalation Suspension Ciclesonide Flunisolide Fluticasone 80 160 500-1000 100-250 Low Daily Dose (g) > 5 y Age < 5 y 200-500 200-600 100-200 100-200 250-500 80-160 500-750 100-200 >160-320 >1000-2000 >250-500 Medium Daily Dose (g) > 5 y Age < 5 y >500-1000 600-1000 >200-400 >200-400 >500-1000 >160-320 >750-1250 >200-500 >320-1280 >2000 >500 High Daily Dose (g) > 5 y Age < 5 y >1000 >1000 >400 >400 >1000 >320 >1250 >500

Mometasone furoate
Triamcinolone acetonide

200-400
400-1000

100-200
400-800

> 400-800
>1000-2000

>200-400
>800-1200

>800-1200
>2000

>400
>1200

Immunotherapy
Allergen immunotherapy indicated when
a. There is clear evidence of relationship between symptoms and exposure to allergen. b. Symptoms occur in major portion of the year. c. There is difficulty in controlling symptoms with pharmacological management.

Acute Severe Asthma

Symptom and Signs

Severe dyspnea Patient can,t talk few wards or short sentenses Silent Chest Diaphoresis Tachypnea R.R > 30/m Tachycadia pulse > 120/ m Pulsus paradoxus Cyanosis Hypoxemia and increased CO2 level (near fatal asthma)

Acute Severe Asthma

Investigations:

Peak flow meter < 60 liter/min. Decrease of PaO2 with normal PaCO2, Later on, with progression of the attack PaCO2 may increase
Treatment of Acute Severe Asthma: Oxygen therapy. Oxygen should be administered by nasal cannula or face mask.

Rapid-acting b2-agonistic are generally administered by nebulizer (Salbutamol on tubercului solution). Ipratropeum bromide: a combination of neublized b2-agonists and anticholenergic ipratropneium bromide may produce better bronchodilator effect than either drug alone.

Acute Severe Asthma

Theophylline: Loading dose: half the patient's body weight in kg x 10 in I.V. infusion over 30 min (e.g. for a 60 kg patient dose = 10 x 30 = 300 mg aminophylline). Maintenance dose: 0.5 mg/kg/hour I.V. Corticosteroids: Parenteral hydrocortisone in a dose up to 4 mg/kg which may be repeated. Effective within 4-6 hours. Hydration: plenty of oral and I.V fluids

Mechanical ventilation in Asthma

Indication of mechanical ventilation: Patients who are drowsy or comatosed. Patients who are exhausted with respiratory muscle fatigue. Paradoxical thoracoabdominal movement. Presence of cyanosis and hypercapnia. Previous history of mechanical ventilation in intensive care.