bronchial
asthma
Introduction
Bronchial asthma is a chronic inflammatory condition
involving a variety of cells including eosinophils,mast
cells,T lymphocytes,neutrophils,and epithelial cells of
the airway,as well as cellular elements,which gives
rise to the increase of airway hyper-reactivity,Extensive
changeable and reversible ventilation restriction is
common and can cause recurrent tachypnea,feeling of
out of breath,and coughing,The symptoms are more
usually present and aggravated at night or early in the
morning,Remission might be achieved spontaneously or
following treatment,
etiology
The pathogenesis of asthma is complicated and is
affected by genetics and the environment,It is a
multigene disoder and closely related to atopy,Most
patients have prior history of eczema,allergic
rhinitis,food or drug allergy,and quite a few patients
have family history,The formation and attack of
asthma is also a consequence of the function of
multiple environmental factors such as inhalation of
allergens,respiratory tract infection,and coldness,
epidemiology
? 160 million patients in the word
? prevalence,1%--5%,1% in china
? Prevalence in male is similar to
that in female
? The onset is before 12 years of age in the majority
? Family history could be found in 20% patients
? Related to allergic rhinitis,eczema and nasal
polyp
etiology
? １, Genetic factors,multigene inheritance
heritability 70-80%
? ２, Predisposing factors,air pollution
1） inhalants,dust mites,pollen
2） infections
3） food
4） change of weather
5） mental factors
6） exercise运动
7） drugs
8） menstruation,pregnacy
Pathogenic mechanism
? Asthma is Characteristic of hyper-
reactivity of the airway
? Chronic （ allergic） inflammation is
the basic lesion of asthma
Allergic inflammation
Is divided into 3 subtypes according to the different
cytokines secreted by CD4 Th cell,
Th0,Th1 and Th2。 Investigations have shown that
allergic reactions like asthma are mediated by Th2 cells,
There is an increase or predominance of Th2 or its
cytokines,The resulting airway inflammation could be
classified into the following two types,
1,IgE mediated and T lymphocyte dependent pthway
2.NonIgE mediated and T lymphocyte dependent
pathway
Immunologic factors
the role of IgE mediation
? The combination of allergen with specific IgE
triggers the degranulation of the mast cells and
eosinophils,resulting in release of mediators
including leukotrienes C,D,E,and the subsequent
smooth muscle contraction,edema of the mucosa,
increase of secretion,and finally stenosis of the
bronchioles,which all contribute to asthma,Total
serum IgE or specific serum IgE titer increase is
seen in patients with asthma,indicating type I
allergic reactions might be present,
nonIgE mediated,T lymphocyte
dependent pathway
? In delayed type allergic reaction,Th2 cell
directly initiates imflammatory response by
activation and agglutination of various
inflammatory cells via the release of
multiple cytokines(IL-4,IL-13,IL-3、
IL-5）
Neuromental factors
The complicated autonomic innervation of the
bronchiopulmonary sysytem includes
cholinergic,adrenergic,nonadrenergic and
noncholinergic nerves,?-adrenergic receptor
malfunction and the increased tone of the
vagus,or with simultaneous increase of ?-
adrenergic reactivity,would promote
contraction of the smooth muscle and secretion
of the glands,resulting in attack of asthma
Neuromental factors
The inhibitory system of NANC is the major
nervous system that relaxes the smooth muscle of
the airway,Substance P,the transmitter of the
stimulative nervous system of NANC,is present
in the class C chemosensitive afferent fibers of the
vagus.when the class C afferent nerve ending is
exposed due to injury of the airway,local lesion
might be aggravated,Abrupt change of emotion
might induce asthma attack,especially in those
with refractory asthma,
Endocrine factors
Asthma disappears in puberty
in some patients;
aggravated in menstruation
period,during pregnancy,
and when there is
hyperthyroidism
Pathogenic mechanism
? IgE,mast cell smooth muscle contraction of the bronchiole allergen
allergen histamine,ECF immediate asthma reaction
?
? AAI ventilation disorder
?
?
? PAF
? ECF airway obstruction by exudation
? Late asthma
? reaction LTS microvascular transudation
? （ LAR） congestion and edema of the mucosa
? BHR
? PGS
? injury and exfoliation of the epithelial cells
? exposure of nerve ending neuropeptide,substance P
? inflammatory cells
? （ macrophage,eosinophils and neutrophils）
?
Hyper-reactivity of the airway
? Bronchial reactivity refers to the contractive reaction of the
airway to various stimuli including those chemical,physical
or pharmacologic in nature,Airway hyper-reactivity (AHR)
is defined as the excessive bronchial contraction in response
to the stumuli which do not elicit response or only cause
minor response under normal conditions,AHR is one of the
important characteristics of asthma,whilie airway
imflammation is one of the most important mechanisms that
contribute to AHR
Pathology
? The basic pathology of bronchial asthma includes
imflammation and remodeling of the airway,
? The basic pathological change of the inflammmation includes
infiltration of mast cells,macrophages,eosinophils,
lymphocytes and neutrophils; edema of the submucosa,
increase of the permeability of the microvasculature,
retention of the secretion within the bronchioles,spasm of the
bronchial smooth muscle,detachment of the cilated
epithelium,exposure of the basal membrane,poliferation of
goblet cells and increase of bronchial secretion,which
contribute to form the chronic剥脱性 eosinophilic bronchitis
Clinical manifestation
The typical onset of asthma is accompanied by
sneezing,nasal secretion,coughing and out of breath,
If timely treatment is not given,the bronchial
narrowing might get worse and cause dsypnea,In
severe cases,the patient is obliged to take the sitting
position which is refered to as othopnea,coughing
with or without large amount of whitish foamy sputum,
or even with cyanosis,
Clinical manifestation
Physical examination,
Increased anteroposterior diameter of the chest,
over-resonance on percussion,wheezing all
over the chest; when severe dyspnea exists,both
breathing sounds and wheezing could be
reduced or absent,No symptoms and sighns
might be present during the interval of attack,in
some cases,wheezing could be noted on
exersion
Clincal manifestation
Symptoms are more severe at night,and could
be relieved after medication or spontaneously,
When severe acute asthma attack could not be
mitigated within 24 hours by appropriate use
of adrenomimetics,the patient is in the state of
persistent asthma,The patient might be
struggling due to dyspnea before he becomes
weak and unable to cough,Blood pressure
might decline,cyanosis might appear,and the
patient might even die from acute respiratory
failure,
Lab
?Peripheral blood,eosinophils
increase,A false white cell count
increase might occur if adrenaline is
used,
?X-ray,over-inflation of the lung;
increased lung markings; small area
shadow might appear along the
bronhchioles if there is bronchial
pneumonitis or atelectasis
Lab
?Lung function test,decrease of airflow rate and
tidal volume,increase of reserve volume,Blood
gas test shows a decrease in PaO2; an initial
PaCO2 decline may be noted and an elevation
follows with progression,pH decreases in the late
stage.during the interval of attack,lung function is
usually normal except the reserve volume is
increased,Daily test of PEF and its variance is
helpful for the judgement of the existence of
subclinical asthma,
Lab
The suspected antigen is
used for skin test so as to
find out the allergen,The
skin prick test is quite
reliable
diagnosis
Diagnostic criteria for
asthma
Criteria for cough variant
asthma
Diagnotic criteria
1.recurrent breathlessness,wheezing,coughing,and tightness in the chest,Usually related to
contact of allergen,cold air,physical or chemical stimuli,upper respiratory tract
infection with virus,and exercise,ect.反复
2.diffuse or scattered expiratory wheezing could be heard during the attack,the expiratory
phase is lengthened,
3.the abve symptoms and signs might be remitted after treatment or spontaneously,
4.other causes of wheezing,short of breath,coughing and tightness in the chest are
excluded,
5.at least one of the following tests is positive,if the clinincal picture is （ eg no wheezing
or signs）：① positive bronchial or exercise challenge test② positive
bronchodilatator test［ FEV1 increase by more than 15%,and the increase of
absolute FEV1 volume>200ml］；③ daily PEF variance or 24 hour
fluctuation≥20% 。
when1~4or4,5 are met,bronchial asthma is diagnosed。
Differential diagnosis
? 1.Cardiac asthma Aminophylline,
morphine,epinephrine
? 2,喘息性慢性支气管炎
? 3,Bronchiogenic lung cancer
? 4,eosinophilic lung diseases
Staging
? Asthma could be classified into the
following 3 stages according to its
clinical picture,exacerbation phase,
persistent phase,and remission
phase,
Criteria for
cough variant asthma
? Also named allergic coughing,which is a
potential insidious form of asthma and occurs
at all age group,Its exclusive symptom is
chronic coughing with no positive signs,
Therefore it might be misdiagnosed as
bronchitis,However it is believed by most
physicians that its mechanism of pathogenesis
is identical to that of asthma,and treatment
is effective when medications for asthma are
indicated,
Criteria for
cough variant asthma
?Recurrent or persistent coughing for more
than 2 months without much sputum,which
occurs at night or in the early morning,and
got worse after exercise,No infection is
present or long term use of antibiotics
proves not effective,
?Bronchodilatators could reduce coughing
（ basic criterium）
?History of allergy or familial allergy，
airway is high responsive,positive allergen
skin prick test
Evaluation of
non-exacerbation phase
severe,frequent attack of symptoms,limited
capability,bad sleeping,PEF or FEV≤ 60％ of
predicted,PEF varience>30％
moderate, daily attacked,sleeping and
ability compromised,nocturnal asthma>once a
week,PEF or FEV1≤ 50％, <80％ of predicted，
PEFR>30％
Evaluation of
non-exacerbation phase
minor, symptoms≥once a week, but less
than once a day.ability and sleeping might
be affected.nocturnal asthma>twice a month，
PEF or FEV1≥ 80％, PEFR 20～ 30％
intermittent, symptoms appear
intermittently,<once a week,short duration
of attack （ hours ～ days ）,nocturnal
asthma≤twice amonth, pulmonary function
is normal,PEF or FEV1≥ 80％, PEFR<20％
Evaluation of the severity
for acute attack
Clinical feature minor moderate severe acute sleep apnea
breathlessness walking moving rest
position supine sitting bending forward
speech sentence phrases words unable to speak
irritation possible often often sleepiness confusion
sweating yes yes significant
Evaluation of the severity
for acute attack
Clinical feature minor moderate severe acute sleep apnea
Breath rate somewhat quickened markedly apnea
Motion of
accessory
respiatory no frequent frequent paradoxical
muscles and movement of the
three depressions chest and abdomen
Sign
Wheezing sound scattered diffuse diffuse weakened or absent
Pulse rate <100 100—120 >120 >120 or pulse rate
（ >12岁） slowed,irregular
Clinical feature minor moderate severe acute sleep apnea
PaCO2 <6 ≤6 >6possible respiratory failure
（ kPa）
SaO2 >95 91—95 ≤90
(％ )
pH decline
Evaluation of the severity
for acute attack
Goal of management for
asthma
⑴ to effectively control acute attack and
maintain minimal symtoms or no symptoms
⑵ to prevent aggravation；
⑶ to keep lung function around normal
level；
⑷ maintain the ability to exercice；
⑸ avoid the adverse reaction of the
medications for asthma,
Standards for asthma control
? ⑴ minimal (or no) chronic symptoms,including
symptoms at night,
? ⑵ minimal times of asthma attack；
? ⑶ no emergency room visit due to asthma
? ⑷ minimal use of ?2 antagnists；
? ⑸ no limitation of ability(including exercise),
? （ 6） 24 hour PEF variance<20％；
? (7)PEF noraml or almost normal；
? (8)minimal adverse reactions of medications
Elimination of etiology
Avoid allergen,appropriate treatment
of infection,eradicate exposure to the
predisposing factors(smoking,paint,
icecream,abrupt change of weather)
Asthma,Prevention
? Stop smoking
? Decrease ETS exposure
? Reduce exposure to biological dust
? Reduce exposure to pollution
? Reduce risk to respiratory viruses
? Dietary,Increase antioxidants and Omega 3s
? Decrease exposure to cow’s milk,dairy,nuts,soy,
wheat in infancy
Asthma,Treatment
? Remove the allergen
? Drug Therapy
– Bronchodilators (For acute responses)
– Adrenocorticol hormone,dangerous
side effects if used long term
? Psychosocial Techniques
– Stress Management
– Social Support
What’s New for Treating Asthma?
? Medications,
– long term or controller medications
– quick relief medications
? Stepped therapy,start high,back down
? Asthma monitoring and action plans
? Environmental controls
Overview of Medications
? Controller medications
– control inflammation
– long duration bronchodilation
– multiple new medications
? Quick relief medications
– for intermittent or breakthrough
symptoms
– Controversy,Use worsens asthma?
Marker of worsening asthma?
Controller Agents
? Inhaled corticosteroids
? Systemic corticosteroids
? Long acting ?2 agonists
? Cromolyn and derivatives
? Methylxanthines
? Leukotriene Modifiers
Inhaled Corticosteroids
? Control airway inflammation locally
? Ideal,control asthma (high local potency); no side
effects (low systemic effects)
? fluticasone,budesonide ****
? beclomethasone *
? (triamcinolone,flunisolide)
Systemic Corticosteroids
? May be needed initially
? Side effect profile well known
? Step down therapy
? Alternatives,high dose inhaled corticosteroids;
methotrexate; other immunosuppressive drugs
Long acting ? 2 Agonists
? Salmeterol
? prolonged
Quick Relief Medications
? ? 2 Agonists
? Anticholinergics
? Systemic corticosteroids
Managing Asthma Long term
? Prevent symptoms
? Maintain normal pulmonary function
? Maintain normal activity levels
? Prevent exacerbations,emergencies
? Optimize medical therapy
? Patient satisfaction (compliance)
Potential Treatments for Acute Asthma
? B-agonists
? Corticosteroids
? Oxygen
? Intubation &
Mechanical
Ventilation
? Methylxanthines
? Ipratropium Bromide
? BiPAP
? Heliox
? MgSO4 Infusion
? Mucolytics
? Chest Physical
Therapy
? Aggressive Hydration
? Antibiotics
? Inhalational
Anesthetics
? ECMO
? Inhalational
Furosemide
? Inhalational MgSO4
Methylxanthines (Theophylline)
? Used for over 50 years to treat asthma
? Poorly understood mechanism of action
? Physiologic effects thought to include
bronchodilation,stimulation of diaphragmatic
contractility,mucocilliary clearance,and possibly
some anti-inflammatory effect,
? Dose related toxicities include nausea,vomiting,
headache,CNS stimulation,seizure,hematemasis,
hyperglycemia,and hypokalemia
Ipratropium Bromide
? A synthetic anticholinergic compound
? Anticholinergic compounds are known to cause
bronchodilation
? Atropine has been used,but often limited due to
side effects such as tachycardia,dry mouth,
disturbances of visual accommodation,etc,
? Ipratropium thought to be relatively free of side
effects,but with preservation of bronchodilatory
properties