Asthma

By Ass. Prof. Dr. Abdul Hameed Al Qaseer

Asthma is a chronic inflammatory disease of airways that is characterized by increased responsiveness of the tracheobronchial tree to a multiplicity of stimuli . It is manifested physiologically by a widespread narrowing of the air passages , which may be relieved spontaneously or as a result of therapy, & clinically by paroxysms of dyspnea , cough , & wheezing .

Prevalence of Asthma

Asthma is a very common disease . Current estimates suggest that 300 millions people world-wide suffer from asthma & additional 100 millions may be diagnosed with asthma by 2025 . The prevalence of asthma is rising in many parts of the world e.g. in US the prevalence increased from 4-5% to ~ 10-12% of adult & 15% of children. The prevalence of asthma in UK ~ 7% in adults . There is no study to estimate the real prevalence in IRAQ !!

Prevalence ( cont.):

The mean prevalence of asthma in Middle East is about 5.8% .In Kuwait 8.5% ; Iran 5.5% ; Turkey 7.4% ; Saudi Arabia 5.6% .Asthma more common in children , about One –half of cases develop before age 10.Another 1\ 3 occur before 40 .

Etiology Of Asthma

Asthma is a heterogeneous disease, genetic & environmental factors play a role . Environmental factors , such as viruses , occupational exposure , & allergens contribute to its initiation & continuance.

Aetiology

Classification Of Asthma
Allergic asthma ( atopic)( extrinsic) It is often associated with a personal &\or family history of allergic disease + increased level of IgE in serum &\ or positive response to provocation test .It is usually early –onset & typically episodic .2. Idiosyncratic asthma (non- atopic ) (intrinsic):3. Many patients have disease not fit clearly into either of the above ( mixed group).

Intrinsic Asthma

30% of asthma cases between the age18-66 ys Non-allergic, may be auto-allergy or auto-immunity triggered by infection History of respiratory virus infection No clinical or family history of atopy Normal IgE level, no specific IgE antibodies detected against common allergens Often more severe clinical course Associated with nasal polyps and aspirin sensitivity May be a sensitization to an as-yet undetected allergen

Pathogenesis Of Asthma

Asthma results from a state of persistent subacute inflam - mation of the airways. The airways are edematous & infiltrated with eosinophils( which seems to play an important role), neutrophils , & lymphocytes . Physiologic & clinical features of asthma derive from an interaction among the resident & infiltrating cells in the air- ways.

macrophage

Antigen
phagocytosis
B Lymphocytes
Cell to cell contact
Antibodies
Interleukin-1
Growth of specific Lymphocytes
Mast cell
binding
IgE IgA IgG IgD IgM
Eosinophils Mediators -Histamine -PAF -Leukortriense -Protaglandins


Mucus hypersecretion Hyperplasia
Eosinophil
Mast cell
Allergen
T cell
Vasodilatation New vessels
Plasma leak Oedema
Neutrophil
Mucus plug
Macrophage/ dendritic cell
Bronchoconstriction Hypertrophy / hyperplasia
Cholinergic reflex
Epithelial shedding
Subepithelial fibrosis
Sensory nerve activation
Nerve activation
Inflammation and tissue damage in Asthma
Barnes PJ

Pathophsiology

Major cells are :Mast cells ; Eosinophils ; Lymphocytes ; & Epithelial cells Less important cells :Neutrophils ; macrophages ; basophils . …..Each of the major cells types can produce mediators & Cytokines to initiate & amplify both acute inflammatory & The long- term effects.

Mediators Histamine Leukotrienes Prostaglandins Thromboxane PAF Bradykinins Tachykinins Endothelins & Others

Mediators released produce an intense , immediate inflammatory reaction involving :

Bronchoconstruction Vascular congestion Edema formation Increased mucus production Impaired mucociliary transport. Structural changes ( fibrosis , sm hyper- plasia , angiogenesis ,mucus hyperplasia)

Stimuli That Incite Asthma

Allergens: Pharmacologic Stimuli : Environment & Air Pollution : Occupational Factors : Infections : Exercise: Emotional : Coexisting conditions that can aggravate asthma like : 1. Rhinitis 2. sinusitis 3. GERD .

Allergens :

Most of the allergens that provoke asthma are airborne. Immune mechanisms appear to be causally Related to the development of asthma in 25- 35% of all cases & contributory in ~ another 1\ 3 . Important allergen such as house dusts mites, cat's allergen & pets ,cockroach allergen. Smoking increase the risk of asthma (~ 4 x).

Aspirin-sensitive asthma

Aspirin & other NSAID can result in asthma exacerbation in Some (~10%) patients .Most of such patients have severe Asthma & nasal polyps. The affected patients develop rhinorrhea & nasal congestion . They may benefit from leukotriene modifying agents. Other drugs e.g. B- blockers .


Exercise – induced Asthma Exercise is common precipitant of acute episodes of asthma.Typically the attacks follow exertion & do not occur during it.Short sprints are more likely to induce the episodes .The challenge test consist of a short ( 6-8 min) exercise ,&Spirometry is checked before & at 0,5,10,15, 20, or 30 min.After exercise. A 20% decrease in FEV1 confirms the Dx.Approximately 10% of the athletes on U.S. Olympic teams in recent years had exercise- induced asthma.It dose not evoke any long – term squeal ,nor dose it incr -ease airway reactivity.


Infections :
Respiratory infections are the most common stimuli that evoke acute exacerbations of asthma Viruses & not bacteria are the major stimuli. In children RCV & parainfluenza virus are most important . In older children & adult , rhinovirus & influenza virus are the commonest .

Clinical Presentation Of Asthma

Triad of cough + dyspnea + wheezing usually episodic . Dry cough . Exertional syspnea. Asymptomatic

Clinical features in adults that influence the probability of asthma ( from BTS 2008)

MORE THAN ONE OF THE FOLLOWING SYMPTOMS : Wheeze , breathlessness , chest tightness , & cough , particularly if : * symptoms worse at night\ early morning * symptoms in response to exercise , allergens & cold air . * symptoms after taking aspirin or B-blockers.


History of atopic disorders . Family history of asthma or atopic disorders. Widespread wheeze on auscultation . Otherwise unexplained low FEV1 or PEF . Otherwise unexplained peripheral eosinophilia .

Making a diagnosis of asthma-----------------------------------------------

Compatible clinical history + ether \ or . FEV1 >\= 15% ( & 200 ml) increase following bronchodilator \ trial of corticosteroids . > 20% diurnal variation on > 3 days in a week for 2 weeks on PEF diary . FEV1 >\= 15 % decrease after 6 min of exercise ---------------------------------------------------------------- GINA accepts an increased FEV1 12%

Peak flow(PEFR) measurement

The fastest flow rate of air during a forced expiration PEFR = 600L/min in healthy adult male = 450L /min in healthy female & children AM-PM variation in healthy person < 20% PEFM, easy to use, repeatable, inexpensive

Importance of long term peak flow measurements

To establish diagnosis and treatment To assess severity of an exacerbation To assess response to treatment To evaluate how well asthma is controlled To alert patient to need for possible change in treatment


Other Diagnostic methods
Enhanced bronchoconstriction( AHR) to a variety of direct Or indirect stimuli e.g. Exercise Cold air Dusts , smoke ,& chemicals. Histamine & methacholine ( provocative test). Challenge test using adenosine ( may be more specific).

Other investigations:

Eosinophilia( sputum or blood) IgE ( total or specific). Skin tests Pulmonary function test ( for Dx & evaluations) CXR ABG.

Differential Diagnosis Of Asthma

COMMON : Acute bronchitis Aspiration( foreign body) Bronchial stenosis Cardiac failure Chronic bronchitis Cystic fibrosis Eosinophilic pneumonias

D. Dx ( cont.)

Uncommon : Airway obstruction e.g. external or internal Carcinoid syndrome Pulmonary embolism Systemic vasculitis Endobronchial sarcoid Systemic mastocytosis.

What are the deference between asthma & COPD(ch.bronchitis)?

ASTHMA
COPD
ONSET
Mainly childhood
mid-late adult life
smoking
Usually nonsmoker
almost invariably smoker
Chronic cough & sputum
Absent
Frequent
Dyspnea on effort
Variable & reversible
constant , poorly reversible
Nocturnal symptoms
Relatively common
Uncommon
Airflow limitation
Diurnal variability
Normal
Response to bronchodilator
Good
poor

Ancillary tests in the D. Dx. between stable asthma & COPD

TEST
ASTHMA
COPD
Reversibility to bronchodilator & /or corticosteroids
Usually present
usually absent
TLV + RV
usually normal
Increase
DLco
normal

AHR

might be increase

allergy test
Often +
often -
CXR
usually normal
usually abnormal
sputum
eosinophilia
neutrophilia
Exhaled NO
increase
usually normal

Management Of Asthma

1. Patients education :: T he patient & his parents ( child ) should be educated for : 1. The nature of the disease 2. the deference between reliever & controller . 3. proper using of the inhaler . 4. the uses of a peak flow meter . 5. about corticosteroids

s

2. Avoidance of precipitating factors:

Desensitization : There is little evidence of its benefit in asthma , & there is attendant risk .

Management of chronic Asthma

Step 1 :In patients with mild to moderate asthma ( occasional use of inhaled short –acting B2 agonist (ISABA) . e.g. salbutamol ; terbutalineStep 2 :When the pat. use ISABA more than once daily .ISABA used as required + regular inhaled steroids (ICS). e.g. beclomethasone ; budesonide ( up to 800 ug\d) or fluticasone ( up to 400 ug \ d ).

Step 3 :

a. High dose of ICS ( 800-2000 ug|d) + ISABA or b. Low dose of ICS + long – acting B2 – agonist e.g. salmeterol ; formoterol Step 4 : Like step 3 plus one or more of : a. Leukotriene receptor antagonist. b. Inhaled ipratropium bromide or oxitropium….. c. Long –acting oral B2 – agonist . d. Sodium cromoglycate or nedocromil

Step 5 :

When a patient in exacerbations of asthma . Short courses of `rescue` oral corticosteroids (30-60mg\d of prednisolone ) often required . Indications for `rescue` courses include: Symptoms & PEF progressively worsening day by day PEF < 60% Onset or worsening of sleep disturbance. Persistence of morning until midday. Symptoms severe enough to require nebulised or injected bronchodilators


TREATMENT
Avoid or control triggers
STEP 1: INTERMITTENT
Avoid or control triggers
STEP 2: MILD PERSISTENT
Avoid or control triggers
STEP 3: MODERATE PERSISTENT
Avoid or control triggers
STEP 4: SEVERE PERSISTENT
CONTROLLER: daily medications Inhaled steroid Or possibly cromone, SR theophylline or anti-leukotriene

CONTROLLER: none

Step upif not controlled (after check on inhaler technique and compliance)
Step down when controlled
Patient education essential at every step Reduce therapy if controlled for at least3 months Continue monitoring

Characteristic

Controlled (All of the following)
Partly controlled(Any present in any week)
Uncontrolled
Daytime symptoms
None (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



Why don’t patients comply with treatment? Difficulties with inhaler devices Too complex regimen e.g multiple doses or multiple drugs Side effects Cost of medication Dislike of medication(taste, odour or shape) Distant health services and pharmacies
Misunderstanding or lack of instructions Dissatisfaction with health care professionals Poor supervision, training or follow-up Inappropriate expectations underestimation of severity Cultural issues Fear of addiction Attitude toward ill health religious issues
Drug factors
Non drug factors

Management of acute severe asthma :

Features of acute severe asthma: PEF 33-50 % of predicted ( < 200 l\ min) Respiratory rate > 25 \ min Heart rate > 110 \ min Inability to complete sentences in one breath.

Features of Life- threatening asthma :

PEF < 100 L\min SaO2 < 92% or PaO2 < 8 Kpa ( 60 mmHg ) Normal PaCO2 Silent chest . Cyanosis Feeble respiratory effort Bradycadia or arrhythmias Hypotension Exhaustion Confusion Coma Near- fatal Asthma Raised PaCO2 &\or requiring mechanical ventilation

Treatment of acute severe Asthma

Oxygen therapy : High concentration to maintain SaO2 > 92% 2. Inhaled bronchodilators: (high dose) a. short- acting B2 –agonist ( metered dose inhaler through a spacer or nebuliser e.g. salbutamide b. Ipratropium bromide ( provide additional effect)

3. Systemic corticosteroids : Oral prednisolone 30-60 mg \d or I.V. Hydrocortisone 200mg initially 4. Other : I.V. Fluids ( if the pat dehydrated ) potassium supplementation Subsequent management : 1. I.V. magnesium 1.2- 2.0 g \ 20 min 2. I.V. aminophylline 3. I.V. leukotriene receptor antagonist

Monitoring of the patients

PEF every 15-30 min Pulse oximetry Arterial blood gases (ABG) CXR


Indications for assisted ventilation
Coma Respiratory arrest Deterioration of ABG PaO2 < 8 Kpa Pa CO2 > 6 kpa low PH 4. Exhaustion ; confusion ; drowsiness

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