Download ABNORMAL NEURAL CONTROL OF AIRWAYS

DEFINITION OF ASTHMA
ASTHMA
is a chronic inflammatory disorder of the
airways in which many cells, in particular
mast cells, eosinophils, and T lymphocytes, and their
products (mediators, cytokines) play a role;
The inflammation causes
 an increase in airway
responsiveness to a variety
of stimuli
 widespread but variable airflow limitation that is
at least partially reversible either spontaneously
or with treatment.
Clinical
symptoms: recurrent episodes of wheezing,
breathlessness, chest tightness, and cough particulary at
night and/or in the early morning.
.
A.Bręborowicz-2006
The reasons for the increase in the prevalence of ASTHMA



changes in indoor environment
– higher exposure to HDM
– high quantities of cockroaches
– increasing humidity (prevention of heat loss)
changes in outdoor environment
– urbazniztion
– heavy pollution
‘Hygenic hypothesis’ of asthma/atopy development - less infections
(hygenic style of life, vaccination) lead to decrease stimulation of
TH1 population of lymphocytes and predominance of TH2
population; this population responsible for overproduction of IgE
and atopic background
A.Bręborowicz-2006
PATHOGENESIS OF ASTHMA
AIRWAY INFLAMMATION
ABNORMAL NEURAL CONTROL
HORMONAL IMBALANCE
PSYCHOLOGICAL DISTURBANCES
TYPES OF ASTHMA

ALLERGIC = ATOPIC = EXTRINSIC ASTHMA
IgE - DEPENDENT
Th2 LYMPHOCYTE DEPENDENT MECHANISMS

NONALLERGIC = NONATOPIC = INTRINSIC ASTHMA
IgE - INDEPENDENT
Th2 LYMPHOCYTE DEPENDENT MECHANISMS
A.Bręborowicz-2006
AIRWAY INFLAMMATION IN
ASTHMA

A pivotal role in the generation of an immune response is
activation of T lymphocytes by antigen presented by APC
(dendritic cells, macrophages,
B lymphocytes).

T lymphocytes initiate immunological cascade.
Their products - CYTOKINES - modulate the function of
large number of target cells. Cytokines are responsible for
differentiation, migration, accumulation and activation of
inflammatory cells such as:
eosinophils, mast cells, neutrophils, B lymphocytes.

Cells activated by cytokines release mediators and other
cytokines. Mediators contributes to the development of the
characteristic pathological events that occur in asthma.
A.Bręborowicz-2006
PATHOLOGICAL CHANGES
IN ASTHMA




SWELLING OF THE AIRWAY WALL
– OEDEMA
– CELLULAR INFILTRATION
CONTRACTION OF SMOOTH MUSCLE
MUCUS PLUG FORMATION
– EPITHELIAL CELL DAMAGE AND SHEDDING
(CELL DEBRIS)
– INCREASED MUCUS SECRETION
– EXUDED SERUM PROTEINS
AIRWAY WALL REMODELLING
- increase in smooth muscle
- vascular proliferation
- collagen deposition
- increase in bronchial glands
A.Bręborowicz-2006
ABNORMAL NEURAL CONTROL
OF AIRWAYS




autonomic nerves influence the tone of the airway
smooth muscle, airway secretion, blood flow, mikrovascular permeability and the migration and release
of inflammatory cells
the autonomic nervous system consists of:
sympathetic, parasympathetic and non-adrenergic non-cholinergic
(NANC) nervous system
several nonspecific stimuli provoke reflex bronchoconstriction by
activating the sensory receptors;
in asthmatic patients the airway response develops at lower level of
stimulation and the intensity of the
airflow limitation response is more severe
A.Bręborowicz-2006
ASTHMA DEVELOPMENT
Environmental
factors
Genetic
background
FACTORS THAT EXACERBATE ASTHMA TRIGGERS

ALLERGENS

RESPIRATORY INFECTIONS

EXERCISE AND HYPERVENTILATION

WEATHER

SULFUR DIOXIDE

FOODS, ADDITIVES, DRUGS
A.Bręborowicz-2006
CLINICAL MANIFESTATION
Natural history of asthma
ASTHMA EXACERBATION
ASTHMA FREE PERIOD
REMISSION
SYMPTOMS
dry cough
feeling of chest tightness
audible musical wheezing followed by dyspnoea
(patient describes dyspnoea as both expiratory and inspiratory)
increased work of breathing
difficulties in walking, even talking
duration - minutes, hours, days
the expectoration of viscous sputum
A.Bręborowicz-2006
 ONSET: acute or insidious
 SIGNS
sitting position, leaning forward using the arms
 paleness, cyanosis
 sweat
 hyperinflation of the chest
 tachypnoe, tachycardia
 pulsus paradoxus - reduction in pulse volume during inspiration
 use of accessory muscles of respiration
 increased percussion note
 auscultation: prolonged expiration, wheezing, rhonchi, silent
lung
 barrel chest deformity, Harrison sulci, clubbing of the fingers

A.Bręborowicz-2006
ASTHMA EQUIVALENT
– COUGH VARIANT ASTHMA - the cough at
night or induced by exercise, cold air or
laughter
– COUGH PREDOMINANT ASTHMA
– WHEEZY BRONCHITIS
A.Bręborowicz-2006
ASTHMA IN EARLY LIFE
INFANTILE ASTHMA

significant number of asthmatic children
demonstrates first obstructive episodes
early in life
– 30% < 1yr of age
– 50-55% < 2 yr of age
– 80% < 5 yr of age
A.Bręborowicz-2006
ASTHMA IN EARLY LIFE
INFANTILE ASTHMA

wheezing - associated lower respiratory tract
illnesses in infants and young children are extremly
common;

a large number of anatomical and physiological
factors predisposes to obstruction but only part of
infants develops recurrent symptoms;

there are many causes of recurrent and
persistent wheezing but their prevalence is low;
however before asthma diagnosis is establish other
alternative diagnoses should be excluded.
A.Bręborowicz-2006
Infantile asthma - criteria of diagnosis



3 wheezy episodes
(independent of atopy)
2 wheezy episodes with
atopic background
(positive family or
individual history)
1 wheezy episode
induced by exposure to
allergen
A.Bręborowicz-2006
GINA recommendation
 recurrent wheezing
(wheezy bronchitis)
other causes excluded
positive response to therapy
DIAGNOSIS
OF ASTHMA
A.Bręborowicz-2006
1. Case history










characteristics of asthma episode, frequency, duration,
severity
types of triggers (precipitating, agravating)
the onset of the disease
atopic history
environmental history
previous and current therapy
response to medication
impact of disease on child, family, school attendence
psychosocial evaluation of patient/family
general medical history of child
2. Physical examination
A.Bręborowicz-2006
3. lung function tests

considerable (more than 20%) variabilty of peak flow
rate or FEV1 over short period of time
daily variability=
PEF evening - PEF morning
1/2 (PEF even. + PEF morn.)
x 100
response to bronchodilator when obstruction
(improvement of at least 15-20% in PEF or FEV1)
 measurement of bronchial hyperresponsiveness
(decreasing of at least 15-20% in PEF or FEV1 after
non-specific provocation)
 basic spirometry - assessment of degree of obstruction

A.Bręborowicz-2006
4. assessment of allergy
 SERUM IgE
 measure of the allergy predisposition and their
degree
 the concentration is age dependent
 total concentration
 specific IgE level - against specific antigens; not
more sensitive than skin test, results
independent of therapy, skin lesions,
dermographism, no risk of excessive
(allergic/anaphylactic) reaction
 normal values does not exclude allergy
A.Bręborowicz-2006
4. assessment of allergy

SKIN TESTS
 background
- recovery of IgE on the surface of
patient mast cells; interaction between allergen and
IgE leads to releasing of histamine and other
mediators, which acts on specific receptors in small
vessels, causing increasing permeability and
dilatation and axon reflex stimulation
 technique:
prick/puncture or intradermal, small
quantity of allergenic extract is introduced into the
skin
A.Bręborowicz-2006
4. assessment of allergy

SKIN TESTS

two control tests should be always performed:
negative control - for exclusion of nonspecific
reaction on pricking or solution used in
production of extracts;
positive control - for assessment of skin reactivity

size of skin weal recorded after 15 min. - measuring the
mean diameter, positive test - a wheal at least 3 mm
greater than negative control
A.Bręborowicz-2006
Allergen SPECIFIC IgE

The advantages:
safety
- high degree of
precision
- standardization
- lack of dependence on the
skin reactivity and medication

The disadvantages:
- lack of immediately
available results
- high costs
•Supplement to skin testing when the clinical significance of result is
doubt
•If immunotherapy is considered and lack of convincing history to
confirm positive skin prick tests (concerns mites and moulds)
A.Bręborowicz-2006
5. other tests
 CHEST X - ray  normal in asymptomatic asthma, necessary
to exclude other diseases
 acute asthma - hyperinflation and
diagnosis of complication
 BLOOD EOSINOPHIL COUNT  increased count in about 50% of astma
patients
 predictive for responsiveness to therapy
measure of the severity, indicates steroid
requirement
 SPUTUM EOSINOPHILIA
 positive > 20% of the total leucocytes
 usually present in symptomatic asthma
A.Bręborowicz-2006
5. other tests
 DIFFERENTIAL DIAGNOSIS
A.Bręborowicz-2006
Classification of asthma severity


Intermittent asthma
– intermittent symptoms < 1 time a week
– brief exacerbation
– nightime asthma symptoms 1- 2 times a month
– asymptpmatic and normal lung function between
exacerbation: PEF variability < 20%
FEV1 > 80% predicted
Mild persistent asthma
– symptoms 1 time a week or more, but < 1 time per day
– exacerbation may affect activity and sleep
– nightime asthma symptoms > 2 times a month
– PEF variability 20-30%, FEV1 > 80% predicted
A.Bręborowicz-2006
Classification of asthma severity
Moderate persistent asthma
– symptoms daily
– exacerbations affect activity and sleep
– nightime asthma symptoms >1 time a week
– PEF variability > 30%, FEV1 60 - 80% predicted
 Severe persistent asthma
– continous symptoms
– frequent exacerbations
– frequent nightime asthma symptoms
– PEF variability > 30%, FEV1 <60% predicted

A.Bręborowicz-2006
Asthma management program
Educate patients to develop partnership in asthma
management
 Assess and monitor asthma severity with both
symptoms reports and measurements of lung function
 Avoid and control asthma triggers
 Establish individual medication plans for long term
management
 Establish plans for managing exacerbation
 Provide regular follow up care

A.Bręborowicz-2006
Goals for successful
management of asthma
Achieve nad maintain control of symptoms
 Prevent asthma exacerbations
 Maintain pulmonary function as close to normal level
possible
 Maintain normal activity levels, including exercise
 Avoid adverse effects from asthma medications
 Prevent development of irreversible airflow limitation
 Prevent asthma mortality

A.Bręborowicz-2006
General principles of long
term asthma therapy
Chronic therapy
 Dependence of intensity of therapy on
severity of asthma
 Priority of anti-inflammatory drugs
 Short acting bronchodilators as first line
rescue medication
 Long acting bronchodlators associated with
anti-inflamatory therapy in moderate and
severe asthma

A.Bręborowicz-2006
General principles of long
term asthma therapy

Priority of inhaled medication

Establishment of individual therapy

Written instruction

Complementary function of antihistamines
A.Bręborowicz-2006
Asthma medication –
preventers

Inhaled corticosteroids

(potential side effects in high doses)
Sodium cromoglycate
(very safe but only weakly antiinflammatory)

Nedocromil sodium
A.Bręborowicz-2006
Asthma medication controllers
 Leukotriene antagonists
(good safety profile, responders and nonresponders)
 Slow
release theophylline
(narrow therapeutic window)
 Long
acting inhaled (or oral) beta2
agonists ?????????
(not antiinflammatory, but steroid sparing)
A.Bręborowicz-2006
Asthma medication - relievers
 Short acting beta
2 agonists
 Muscarinic receptor antagonists anticholinergics
 Systemic corticosteroids
 Rapid
release teophylline (short acting)
A.Bręborowicz-2006
GINA NHLBI/WHO Report 2002
Choice of therapy
EPISODIC asthma


b2 agonist as needed
*
prevention of EIA cromones
GKS ih
b2 agonists
Anti- leukotriens
A.Bręborowicz-2006
GINA NHLBI/WHO Report 2002
Choice of therapy
MILD asthma


b2 agonist as needed *
chronic antiinflammatory therapy
budezonid up to 400ug
Cromones
Slow released
theophylline
Anti-leukotriens
A.Bręborowicz-2006
Choice of therapy
MODERATE asthma


b2 agonists as needed
*
budezonid 400 - 800ug
+
Long acting
b2 agonists
Anti - leukotriens

or
budezonid > 800 ug
A.Bręborowicz-2006
Slow released
theophylline
Choice of therapy
SEVERE Asthma

b2 agonists as needed

*
budezonid > 800 ug
+
Slow-released
theophylline
+
+
A.Bręborowicz-2006
Long acting
b2 agonists
GKS systemic
+
+
Anti-leukotriens
Asthma exacerbation
 Short acting beta
2 agonists
 Systemic corticosteroids
 Muscarinic receptor antagonists
 Theophylline
 Monitoring
 Oxygen
 Hydratation
A.Bręborowicz-2006