ASTHMA : UNDERGRADUATE STUDENTS

BY

Prof MOHMMAD EL DESOUKY ABOU SHEHATA

Prof .of Thoracic MedicineMansoura University

BY

Prof :MOHMMAD EL DESOUKY ABOU SHEHATA

Prof .of Thoracic MedicineMansoura University

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

Th0-cell

IL-12

IL-4

IL-2IFN-TNF-TNF-

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

Predominantantibodyresponse

IgG2a

IgE, IgG1

Biological role

Defence againstintracellularpathogens (e.g.viruses or bacteria)

Defence againstlarge extracellularpathogens and mediators of allergy

Th1-cell

Th2-cell

Pathogenesis : Th-cell cytokine profile determines antibody isotype

Corry DB et al. Nature 1999

Th2-cellTh2-cell

B-cellB-cell

Eosinophil

IL-4

IL-13

Mast cell

FcRI

IgE

HistamineLeukotrienesProstaglandinsCytokines

Atopicdisease

IL-5

Antigen-presentingcell

Allergen

The IgE-mediated inflammatory response:type I hypersensitivity reaction

Holgate ST. QJM 1998

Mast cellmediator release

Inflammatory mediators result in early and late-phase asthmatic responses

24

Time (hours)Antigen

% p

red

icte

d F

EV

1

0 1 2 3 4 5 6 7 8

100

80

60

40

20

0

Eosinophil influx and mediator release

Neutrophil influxand mediator release

Histamine, prostaglandins, leukotrienesand thromboxanesmediate bronchospasm

• Inflammation

• Persistent obstruction

• Increased airway responsiveness

AcuteInflammation

AirwayRemodelling

ChronicInflammation

Acute and chronic inflammation

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 Patient’s 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 Developmentand 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 AsthmaPseudo – Asthma (cont)

When cough is not Asthma

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

Diagnostic Challenge In AsthmaPseudo – Asthma (cont)

When wheezing Is not Asthma

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

Diagnostic Challenge In AsthmaPseudo – 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. Development of Patient/Doctor Partenership

2. Identify and Reduce Risk Factors

3. Assess ; Treat And Monitor Asthma

4. Manage Asthma Exacerbation

5. 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 MedicationsComponent 4: Asthma Management and Prevention Program

Controller Medications

Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β2-agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral β2-agonists Anti-IgE Systemic glucocorticosteroids

Inhaled glucocorticosteroids Leukotriene modifiers Long-acting inhaled β2-agonists Systemic glucocorticosteroids Theophylline Cromones Long-acting oral β2-agonists Anti-IgE Systemic glucocorticosteroids

Component 4: Asthma Management and Prevention Program

Reliever MedicationsComponent 4: Asthma Management and Prevention Program

Reliever Medications

• Rapid-acting inhaled β2-agonists

• Anticholinergics

• Theophylline

• Short-acting oral β2-agonists

• Rapid-acting inhaled β2-agonists

• Anticholinergics

• Theophylline

• Short-acting oral β2-agonists

Levels of Asthma Control

Characteristic ControlledPartly controlled(Any present in any

week)Uncontrolled

Daytime symptomsNone (2 or less /

week)More than

twice / week

3 or more features of

partly controlled

asthma present in any week

Limitations of activities

None Any

Nocturnal symptoms / awakening

None Any

Need for rescue / “reliever” treatment

None (2 or less / week)

More than twice / week

Lung function (PEF or FEV1)

Normal <80% predicted or

personal best (if known) on any day

Exacerbation None One or more / year 1 in any week

controlled

partly controlled

uncontrolled

exacerbation

LEVEL OF CONTROLLEVEL OF CONTROL

maintain and find lowest controlling step

consider stepping up to gain control

step up until controlled

treat as exacerbation

TREATMENT OF ACTIONTREATMENT OF ACTION

TREATMENT STEPSREDUCE INCREASE

STEP

1STEP

2STEP

3STEP

4STEP

5

RE

DU

CE

INC

RE

AS

E

Estimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by AgeEstimate Comparative Daily Dosages for Inhaled Glucocorticosteroids by Age

Drug Low Daily Dose (g) Medium Daily Dose (g) High Daily Dose (g)

> 5 y Age < 5 y > 5 y Age < 5 y > 5 y Age < 5 y

Drug Low Daily Dose (g) Medium Daily Dose (g) High Daily Dose (g)

> 5 y Age < 5 y > 5 y Age < 5 y > 5 y Age < 5 y

Beclomethasone 200-500 100-200 > 500-1000> 200-400 > 1000> 400

Budesonide 200-600 100-200 600-1000> 200-400 >1000> 400

Budesonide-Neb Inhalation Suspension

250-500 > 500-1000 > 1000

Ciclesonide 80 – 160 80-160 > 160-320> 160-320 >320-1280> 320

Flunisolide 500-1000 500-750 >1000-2000> 750-1250 > 2000> 1250

Fluticasone 100-250 100-200 > 250-500> 200-500 > 500> 500

Mometasone furoate 200-400 100-200

< 400-800< 200-400 <800-1200< 400

Triamcinolone acetonide 400-1000 400-800 >1000-2000> 800-1200 >2000> 1200

Immunotherapy

Allergen immunotherapy indicated whena. 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 2-agonistic are generally administered by nebulizer (Salbutamol on tubercului solution).

Ipratropeum bromide: a combination of neublized 2-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.