Asthma

ASTHMA

Ass. Prof .Dr: MUHAMMED WAHEEB AL,OBAIDY
CONSULTANT CHEST PHYSCIAN
MEDICAL COLLEGE – BAGHDAD UNIVERSITY.

Objective

Provide a clear definition of asthma
Recognise the burden of asthma at a global level
Recognise the burden of asthma in our country or region
Describe the pathogenesis of asthma
Differentiate the pathogeneses of asthma and COPD
Identify the major host and environmental causes of asthma

Objective

Recognise the key signs and symptoms of asthma
Differentiate the diagnosis of asthma with that of other major respiratory diseases, including COPD, bronchiolitis, bronchiectasis and tuberculosis
Understand the diagnostic role of spirometry and peak expiratory flow (PEF) measurements
Recognise the diagnostic challenges of asthma
Identify the goals of asthma treatment
Understand each of the four components of asthma management
Understand the asthma ‘step up/step down’ treatment sequence
Assess and manage severe asthma attacks


The Definition
Asthma is a chronic inflammatory disease of the airways characterized by hyper-responsiveness of the tracheo-bronchial tree to a multiplicity of stimuli.
Asthma is manifested physiologically by widespread narrowing of the air passages which may be reversed spontaneously or in response to treatment.
Clinically asthma is manifested by paroxysms of dyspneoa, cough, & wheezing.
Harrison Text book of Internal Medicine

Prevalence of Asthma

Asthma is a very common disease.
Current estimates suggest that 300 million people world-wide suffer from asthma and an additional 100 million may be diagnosed by 2025.
The prevalence of Asthma is rising in many parts of the world, e.g. in the USA prevalence increased from 3-4% to about 10-12% of adults and about 15% of children.
In the U.K. the prevalence is around 7%
There are no studies demonstrating the prevalence of Asthma in Iraq.

GINA Guidelines 2004

Prevalence continued
In the middle east the prevalence is about 5.8%.
In Kuwait 8.5%, Iran5.5%, Turkey 7.4%, Saudi Arabia 5.6%.
Asthma is more common in children, about half the cases develop before the age of 10 years, another third before the age of 40.

GINA Guidelines 2004

Prevalence of clinical asthma

• GINA 2004

In this report an arbitrary figure of 50% of the prevalence of ‘current wheezing’ in children (self-reported wheezing in the previous 12-month period in 13- to 14-year old children) has been used as the prevalence of "clinical asthma’. The prevalence rates for ‘clinical asthma’ reported in this report represent a conservative estimate. Data from: International Study of Asthma and Allergies in Childhood (ISAAC) and the European Community Respiratory Health Survey (ECRHS).

Prevalence of asthma

%
• GINA 2004
In this report an arbitrary figure of 50% of the prevalence of ‘current wheezing’ in children (self-reported wheezing in the previous 12-month period in 13- to 14-year old children) has been used as the prevalence of ‘clinical asthma’. The prevalence rates for ‘clinical asthma’ reported in this report represent a conservative estimate. Data from: International Study of Asthma and Allergies in Childhood (ISAAC) and the European Community Respiratory Health Survey (ECRHS).

Etiology of Asthma

Asthma is a heterogeneous disease with genetic and environmental factors playing a role.
Environmental factors include viruses, occupational exposure and allergens playing a role in both the initiation and continuation of the disease.
Henry Salter in 1860 suggested “distinct traces of inheritance are seen in 2 cases out of 5.
Many studies now suggest that first degree relatives have a 20-25% chance of developing Asthma.

Harrison Text Book of Internal Medicine

Aetiology

Classification Of Asthma

• 1.Allergic Asthma ( atopic)( extrinsic)
• It is often associated with a personal \family history of
• allergic disease + increased level of IgE in serum \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).
Harrison Text book of Internal Medicine

Intrinsic Asthma

30% of asthma cases between the age18-66 years.
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 sub-acute inflammation 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 airways.

Asthma mechanism- role of inflammatory cells

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
GINA 2004

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

Major cells are :

Mast cells ; Eosinophils ; Lymphocytes ; & Epithelial cells

Less important cells :
Neutrophils ; macrophages ; basophiles . …..

Each of the major cells types can produce mediators &

Cytokines to initiate & amplify both acute inflammatory &
The long- term effects.

Mediators

Histamine
Leukotriens
Prostaglandins
Thromboxane
PAF
Bradykinins
Tachykinins
Endothelins and others.


Mediators released produce an intense , immediate inflammatory reaction involving :
• Bronchoconstruction
• Vascular congestion
• Edema formation
• Increased mucus production
• Impaired mucociliary transport.
• Structural changes ( fibrosis , smooth muscle hyperplasia , angiogenesis ,mucus hyperplasia)

Changes in the airway

Davidson Text book of Internal Medicine

Stimuli That Incite Asthma
• 1.Allergens.
• 2.Pharmacologic Stimuli.
• 3.Environment & Air Pollution..
• 4.Occupational Factors.
• 5.Infections.
• 6.Exercise..
• 7.Emotional.
• Coexisting conditions that can aggravate asthma :
• 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 third.
Important allergen such as house dusts mites, cat's allergen & pets ,cockroach allergen.
Smoking increase the risk of asthma by about 4 times.

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 and 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 minutes after exercise.
A 20% decrease in FEV1 confirms the diagnosis.
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 increase 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 & par influenza virus are most important.
In older children & adult , rhinovirus & influenza virus are the commonest .

Occupational asthma

Occupational asthma is the most common form of occupational respiratory disorders & should be considered in all adult asthmatics .
It is especially important from to enquire whether symptoms improve during time away from work , e.g. Weekends or holidays .
Atopic individuals & smokers at high risk .
The diagnosis can be reached by performing 2- hourly peak flow recording ; skin prick tests or the measurement of specific IgE may confirm the diagnosis .
Bronchial provocative tests with the suspected agent may be necessary .
Workplace visit to identify & rectify exposure , & to trigger screening of other employees.

Workers most commonly reported to occupational asthma schemes .

* Paint sprays * Bakers & pastry-makers
* Welders * Food processing
* Chemical workers * Animal handlers
* Timber workers * Nurses


Most frequent reported causative agents

*Isocyanates * Flour& grain dust
* Colophony & fluxes * Latex
* Animals * Aldehydes
* Wood dust

Nocturnal asthma

Occurrence of asthma symptoms at night or early morning
Circadian rhythm
Exposure to triggers at day time leads to broncho-spasm at night
Sleep Apnea?
Sinusitis ?
GERD ?
Increase venous return?

Clinical Presentation Of Asthma

• Triad of cough + dyspnea + wheezing ( in up to90%)
• usually episodic .
• Dry cough : It may be the sole presentation ( cough-variant asthma ) , as many as 30-50% in children who complaint from chronic cough will developed wheeze (75%) in the next 5-7 years & 13% of adult >50 years .
• Exertional dyspnea.
• Asymptomatic .
Davidson Text book of Internal Medicine


GINA 2004

DIAGNOSIS OF ASTHMA

Clinical features in adults that influence the probability of asthma
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.
From BTS 2008

Clinical features cont.

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 .

From BTS 2008

Making a diagnosis of asthma
Compatible clinical history + either \ 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%
GINA 2004

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

Typical Spirometric (FEV1) Tracings

1
Time (sec)
2
3
4
5
FEV1
Volume
Normal Subject
Asthmatic (After Bronchodilator)
Asthmatic (Before Bronchodilator)


Note: Each FEV1 curve represents the highest of three repeat measurements
GINA 2004

Increased loss of FEV1 in asthma

Lange P et al, NEJM 1998
No asthma (n = 5480)
Asthma (n = 314)
Age (years)
Height-adjusted FEV1 (L)
Male non-smokers
p <0.001
Epidemiology / pathology

Measuring Airway Responsiveness

GINA 2004

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(Chronic 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
Davidson Text book of Internal Medicine


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


Davidson Text book of Internal Medicine

Management Of Asthma

• 1. Patients education :
• Patients & their parents (children)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

Education changes patient expectations

Satisfaction with control (% of patients)
Before
After

0
10
20
30
40
50
60
70
Being shown GINA guidelines
• 25%
• drop
• Haughney et al. Prim Care Respir J 2004


Management cont.
2. Avoidance of precipitating factors:

Desensitization :

There is little evidence of its benefit in asthma ,

& there is attendant risk .
Davidson Text Book of Internal Medicine

Classification of Asthma Severity

CLASSIFY SEVERITY
Clinical Features Before Treatment

Symptoms

Nighttime
Symptoms
PEF
STEP 4
Severe Persistent
STEP 3
Moderate Persistent
STEP 2
Mild Persistent
STEP 1
Intermittent
Continuous
Limited physical activity
Daily
Use b2-agents daily
Attacks affect activity
> 1 time a week but < 1 time a day
< 1 time a week
Asymptomatic and normal PEF between attacks
Frequent
>1 time week
>2 times a months
< 2 times a month
< 60% predicted
Variability >30%
> 60% - <80% predicted
Variability >30%
<80% predicted
Variability 20-30%
³ 80% predicted
Variability <20%
The presence of one of the features of severity is sufficient to place a patient in that category.
GINA 2004


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, terbutaline
Step 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 mcg\d) or fluticasone ( up to 400 mcg \ d ).
- Or leukotriene modifier .
Davidson’s Text Book of Internal Medicine

Management cont.

• Step 3:
• 1-Medium- high dose of ICS ( 800-2000 mcg|d) + ISABA or
• 2-Low dose of ICS + long – acting B2 – agonist e.g. salmeterol ; formoterol or
• 3-Low dose of ICS + leukotriene modifier .
• 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 nedocromili.
Davidson’s Text Book of Internal Medicine


Management cont.
• 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
Davidson’s Text Book of Internal Medicine

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
• Rapid-acting Inhaled ß2-agents as needed (max. 3-4 times/day)
• CONTROLLER: daily medications
• Inhaled steroid plus long-acting inhaled ß2-agents
• Consider adding, SR theophylline, ICS at higher doses or anti-leukotriene
• Rapid-acting Inhaled ß2-agents as needed (max. 3-4 times/day)
• Rapid-acting Inhaled ß2-agents as needed (max. 3-4 times/day)
• Rapid-acting Inhaled ß2-agents as needed (max. 3-4 times/day)
• CONTROLLER: daily multiple medications
• Inhaled steroid plus long-acting inhaled ß2-agents plus either
• Oral steroid, SR theophylline or LTRA
• 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
GINA 2004

GINA 2004

Levels of Asthma Control
• 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

GINA 2004

Clinical Control of Asthma
No (or minimal)* daytime symptoms
No limitations of activity
No nocturnal symptoms
No (or minimal) need for rescue medication
Close to Normal lung function
No exacerbations
_________
* Minimal = twice or less per week
GINA 2004


Deaths and hospital days fell despite increase in patients eligible for asthma treatment
• Haahtela et al. Thorax 2006

450
400
350
300
250
200
150
100
50
0
1981
1983
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
Value of the index
Share of asthmatics
Drug cost per patient
Deaths
Number of hospital days


Finnish Asthma Programme 2005

Asthma care can be improved at no additional overall cost

• Haahtela et al. Thorax 2006

Finnish Asthma Program 2005

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
• Bradycardia or arrhythmias
• Hypotension
• Exhaustion
• Confusion
• Coma
• Near- fatal Asthma
• Raised PaCO2 &\or requiring mechanical ventilation
GINA 2004


Treatment of acute severe Asthma
• 1. 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 nebulizer e.g. salbutamol.
• b. Ipratropium bromide ( provide additional effect)
Davidson’s Text Book of Internal Medicine

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
Davidson’s Text Book of Internal Medicine

Conclusions

Asthma is common and has a big impact – worldwide
Impact of asthma can be reduced
Global asthma severity assessments are unreliable
Physicians underestimate severity
Patients overestimate control
Asthma control instruments have predictive validity
Poor asthma-control score is associated with:
Big impact on patient’s life
Increased exacerbations, admissions, doctor visits


Monitoring of the patients
• PEF every 15-30 min
• Pulse oximetry
• Arterial blood gases (ABG)
• CXR

Indications for assisted ventilation

• 1. Coma
• 2. Respiratory arrest
• 3. Deterioration of ABG
• PaO2 < 8 Kpa
• Pa CO2 > 6 kpa
• low PH
• 4. Exhaustion ; confusion ; drowsiness

Asthma in pregnancy

* Asthma during pregnancy has unpredictable course:
1\3 improve ; 1\3 worsen.
* It represents the greater danger to the fetus :
- intrauterine growth restriction & low birth weight.
- preterm birth .
- high perinatal mortality.
- neonatal hypoxia .
Uncontrolled asthma associated with more maternal :
Hypertension ; hyperemesis ; pre-eclampsia ; vaginal bleeding ; complicated labour .
Davidson’s Text Book of Internal Medicine


Asthma in pregnancy (cont):
Good safety for:
B2- agonist; inhaled steroids; theophyllines; oral prednisolone & chromones .
Oral leukotriene receptor antagonist should not be stopped in women have previously controlled before pregnancy .
Women on prednisolone > 7.5 mg / d should receive hydrocortisone 100 mg 6-8 h during labour.
Davidson’s Text Book of Internal Medicine

Asthma in pregnancy (cont):

* Prostaglandin F2 alpha may induce bronchospasm !!

* During breastfeeding medication can be used normally.
Davidson’s Text Book of Internal Medicine

Thank You