Asthma

For HO studets
 Definition
• a syndrome characterized by airflow obstruction
that varies markedly
• relieved spontaneously or with BD ± Corticos-
teroids
• Chronic inflammatory disease of airways
• ↑ responsiveness ofCrz by
tracheobronchial tree to
wide range of trigger
• Physiologic manifestation: AW narrowing
which is usually reversible
• Clinical manifestations: a triad of paroxysms of
cough, dyspnea and wheezing
• Narrowing of the airways is usually reversible,
but in some patients with chronic asthma
there may be an element of Irreversible Air-
flow Obstruction.
 Disease Pattern
• Episodic --- acute exacerbations interspersed
with symptom-free periods
• Chronic --- daily AW obstruction which may be
mild, moderate or severe ± superimposed
acute exacerbations
• Life-threatening--- slow-onset or fast-onset
(fatal within 2 hours)
 Prevalence
• All ages, predominantly early life with peak
age of 3 years
• Adults: ~10–12% population
• Children: 15% population
• 2:1 male/female preponderance in childhood ;
equalize in adults
• Asthma is both common and frequently com-
plicated by the effects of smoking on the lungs
 Etiology
• Asthma is a heterogeneous disease with inter-
play between genetic and environmental fac-
tors.
Several risk factors have been implicated (Table 254-1).
 Etiology
• Allergic/atopic/early onset asthma---rhinitis,
urticaria, eczema, (+)skin tests, ↑IgE,(+) response to
provocation tests with aeroallergens , family history
of allergic disease.
• Idiosyncratic/non-atopic/intrinsic asthma/late onset
asthma--- no allergic diseases,(-)skin tests, normal
IgE, symptoms when upper resp infection, sx lasting
days or months and usually have more severe, persis-
tent asthma, have concomitant nasal polyps, and
may be aspirin-sensitive.
• Mixed group---usually onset later in life
Pathogenesis
Asthma is associated with a specific chronic inflammation
of the mucosa of the lower airways.

One of the main aims of treatment is to reduce this in-

flammation.
 1. Pathology
• The pathology of asthma has been revealed
through examining the lungs at autopsy of pa-
tients who have died of asthma and from
bronchial biopsies in patients with usually mild
asthma.

– The airway mucosa is infiltrated with activated

eosinophils and T lymphocytes, and there is acti-
vation of mucosal mast cells.
Histopathology of a small airway in fatal asthma .
The lumen is occluded with a mucous plug, there is goblet cell metaplasia,
and the airway wall is thickened, with an increase in basement membrane
thickness and airway smooth muscle.
 2. Inflammation
• There is inflammation in the respiratory mu-
cosa from the trachea to terminal bronchioles,
but with a predominance in the bronchi (carti-
laginous airways).

• Considerable research has identified the major

cellular components of inflammation, but it is
still uncertain how inflammatory cells interact
and how inflammation translates into the
symptoms of asthma (Fig. 254-2).
There is good evidence that the specific pattern of airway
inflammation in asthma is associated with airway hyperre-
sponsiveness (AHR), the physiologic abnormality of
asthma, which is correlated with variable airflow obstruc-
tion.

The pattern of inflammation in asthma is characteristic

of allergic diseases, with similar inflammatory cells seen
in the nasal mucosa in rhinitis.

However, an indistinguishable pattern of inflammation is

found in intrinsic asthma, and this may reflect local rather
than systemic IgE production.
The pathophysiology of asthma is complex with participation of several inter-
acting inflammatory cells, which result in acute and chronic inflammatory effects
on the airway.
 3. Inflammatory Mediators
• Many different mediators have been impli-
cated in asthma, and they may have a variety
of effects on the airways that could account
for the pathologic features of asthma (Fig. 254-4).

• Mediators such as Histamine, Prostaglandin

D2, and Cysteinyl-leukotrienes Contract air-
way smooth muscle, Increase microvascular
leakage, Increase airway mucus secretion, and
Attract other inflammatory cells.
 4. Effects of Inflammation
• The chronic inflammatory response has sev-
eral effects on the target cells of the airways,
resulting in the characteristic pathophysiologic
changes associated with asthma.

• Asthma may be regarded as a disease with

continuous inflammation and repair proceed-
ing simultaneously.
 Airway Epithelium
• Airway epithelial shedding may be important
in contributing to AHR and may explain how
several mechanisms, such as ozone exposure,
virus infections, chemical sensitizers, and al-
lergen exposure, can lead to its development,
as all of these stimuli may lead to epithelial
disruption.
 Fibrosis
• In all asthmatic patients, the basement mem-
brane is apparently thickened due to subep-
ithelial fibrosis with deposition of types III and
V collagen below the true basement mem-
brane and is associated with eosinophil infil-
tration, presumably through the release of
profibrotic mediators such as transforming
growth factor-B.
In asthmatic airways there is also a characteristic hypertro-
phy and hyperplasia of airway smooth muscle,

Which is presumably the result of stimulation of airway

smooth-muscle cells by various growth factors such as
platelet-derived growth factor (PDGF) or endothelin-1
released from inflammatory or epithelial cells.
 Vascular Responses
• There is increased airway mucosal blood flow
in asthma.

• The bronchial circulation may play an impor-

tant role in regulating airway caliber, since an
increase in the vascular volume may contrib-
ute to airway narrowing.

• Increased airway blood flow may be important

in removing inflammatory mediators from the
 Mucus Hypersecretion
• Increased mucus secretion contributes to the
viscid mucous plugs that occlude asthmatic
airways, particularly in fatal asthma.

– There is evidence for hyperplasia of submucosal

glands that are confined to large airways and of
increased numbers of epithelial goblet cells.

• IL-4 and IL-13 induce mucus hypersecretion in

experimental models of asthma.
 Neural Effects
• Various defects in autonomic neural control
may contribute to AHR in asthma, but these
are likely to be secondary to the disease,
rather than primary defects.

• Cholinergic pathways, through the release of

acetylcholine acting on muscarinic receptors,
cause bronchoconstriction and may be acti-
vated reflexly in asthma.
 Triggers of acute asthmatic episodes
• Allergens - pollen
• Pharmacologic stimuli
such as aspirin, NSAIDS, β-
adrenergic
blockers,preservatives,col
agent
• Environment pollutiono-
zone,SO2, NO2
• Occupational- metal salts,
•Infection- resp
viruses
•Exercise –IH cold
dry air →thermally-
induced hyperemia
and microvascular
engorgement
•Emotional stress
 Pathophysiology
• Reduction in AW diameter →↑AW resistance →
↓FeV and flow rates →hyperinflation →↑work of
breathing →altered respiratory muscle Fx and elastic
recoil →abnormal ventilation
• Vascular congestion and edema of bronchial walls
→abnormal perfusion
• V/P mismatch → altered blood gases →hypoxemia
and hypocapnia with respiratory alkalosis, but with
impending ventilatory failure → normocapnia and
later hypercapnia and respiratory acidosis
Limitation of airflow is due mainly to bronchoconstriction,
but Airway Edema, Vascular Congestion, and Luminal occlu-
sion with exudate may also contribute.

This results in a reduction in

1. Forced expiratory volume in 1 second (FEV1),
2. FEV1/forced vital capacity (FVC) ratio, and
3. Peak expiratory flow (PEF),
As well as an increase in airway resistance.
Early closure of peripheral airway results in lung hyperinfla-
tion, (air trapping) and increased residual volume, particu-
larly during Acute Exacerbations and in Severe Persistent
Asthma.

In more severe asthma, reduced ventilation and in-

creased pulmonary blood flow result in mismatching of
ventilation and perfusion and in bronchial hyperemia.

Ventilatory failure is very uncommon, even in patients

with severe asthma, and arterial Pco2 tends to be low
due to increased ventilation.
DIAGNOSIS : CLINICAL
• Asthma is a heterogeneous disease, usually
characterized by chronic airway inflammation.
It is defined by the history of respiratory
symptoms such as wheeze, shortness of
breath, chest tightness and cough that vary
over time and in intensity, together with vari-
able expiratory airflow limitation.
 . History of variable respiratory symp-
toms
Generally more than one type of respiratory symptom
(in adults, isolated cough is seldom due to asthma)
• Symptoms occur variably over time and vary in inten-
sity
• Symptoms are often worse at night or on waking
• Symptoms are often triggered by exercise, laughter, al-
lergens, cold air
• Symptoms often appear or worsen with viral infections
airflow limitation
Documented excessive vari-
ability in lung function* (one
or more of the tests below)
AND documented expiratory
airflow
limitation*
Positive bronchodilator (BD)
reversibility test* (more likely
to be positive if BD medica-
tion is withheld before test:
SABA ≥4 hours, LABA ≥15
hours)
ation is seen, the more confident the diagnosis
At a time when FEV1 is reduced, confirm that FEV1/FVC is re-
duced (it is
usually >0.75–0.80 in adults, >0.90 in children10)
Adults: increase in FEV1 of >12% and >200 mL from baseline,
10–15
minutes after 200–400 mcg salbutamol (albuterol) or equiva-
lent (greater
confidence if increase is >15% and >400 mL).
Children: increase in FEV1 of >12% predicted
Excessive variability in twice-daily PEF
over 2 weeks*
Significant increase in lung function af-
ter 4 weeks of anti-inflammatory
treatment
Positive exercise challenge test*
Adults: average daily diurnal PEF variability
>10%**
Children: average daily diurnal PEF variabil-
ity >13%**
Adults: increase in FEV1 by >12% and >200
mL (or PEF† by >20%) from
baseline after 4 weeks of treatment, outside
respiratory infections
Adults: fall in FEV1 of >10% and >200 mL
from baseline
Children: fall in FEV1 of >12% predicted, or
PEF >15%
Positive bronchial challenge test • Fall in FEV1 from baseline of ≥20%
with standard doses of metha-
(usually only performed in adults) choline
•
• or histamine, or ≥15% with stan-
dardized hyperventilation, hyper-
tonic
•
• saline or mannitol challenge

Excessive variation in lung function Adults: variation in FEV1 of >12% and

>200 mL between visits, outside of
between visits* (good specificity but
poor sensitivity) respiratory infections

Children: variation in FEV1 of >12% in

FEV1 or >15% in PEF† between

visits (may include respiratory infection

 DIAGNOSIS :
IMMUNOLOGIC

• Skin prick wheal and flare response.

• IgE and RAST.
• Eosinophil cationic protein (ECP).
• Peripheral blood and sputum eosinophilia.
 DIAGNOSIS : RADIOLOGY
• Chest XR may be normal between attacks.
• With attacks hyperinflation may be found.
• In complicated asthma segmental lobar col-
lapse (mucous plugs) and pneumothorax can
occur.
 DIFFERENTIAL DIAGNOSIS
1. Upper airway obstruction – glottic dysfunction.
2. Acute LV failure – pulmonary oedema.
3. Pulmonary embolism.
4. Endobronchial disease.
5. Chronic bronchitis.
6. Eosinophilic pneumonia.
7. Carcinoid syndrome.
8. Vasculitis.
 Classification of Severity
CLASSIFY SEVERITY
Clinical Features Before Treatment

Symptoms Nocturnal FEV1 or PEF

Symptoms
STEP 4 Continuous  60% predicted
Severe Per- Limited physical ac- Frequent Variability > 30%
sistent tivity

STEP 3 Daily 60 - 80% predicted

Attacks affect activity > 1 time week Variability > 30%
Moderate
Persistent
STEP 2  80% predicted
> 1 time a week > 2 times a month
Mild Per- Variability 20 - 30%
sistent but < 1 time a day

< 1 time a week

STEP 1  80% predicted
Asymptomatic and < 2 times a month
Mild normal PEF be- Variability < 20%
Intermittent tween attacks

The presence of one feature of severity is suffi-

cient to place patient in that category.
 MANAGEMENT
• Avoidance of allergen and triggers – may be impractical→ adjust
Rx.
 ICS-formoterol
ICS-formoterol isis the
the pre-
pre-
ferred
ferred reliever
reliever for
for patients
patients
prescribed
prescribed maintenance and
maintenance and
reliever
reliever therapy.
therapy. ForFor other
other
ICS-LABAs,
ICS-LABAs, thethe reliever
reliever
isis SABA
SABA

GINA 2020, Box 3-5A © Global Initiative for Asthma, www.ginasthma.org

GINA 2020, Box 3-4B © Global Initiative for Asthma, www.ginasthma.org
 Low, medium and high ICS doses:
adults/adolescents

This is NOT a table of equivalence. These are suggested total daily doses for the ‘low’,
‘medium’ and ‘high’ dose treatment options with different ICS.

DPI: dry powder inhaler; HFA: hydrofluoroalkane propellant; pMDI: pressurized metered dose inhaler (non-CFC); * see product information

GINA 2020, Box 3-6A

Chronic Obstructive Pulmonary
Disease (COPD)
 COPD
• Definition - a disease state characterized by airflow
limitation that is not fully reversible
COPD includes
• Emphysema - an anatomically defined condition
characterized by destruction and enlargement of the
lung alveoli
• Chronic bronchitis - a clinically defined condition
with chronic cough and phlegm
• Small airways disease - a condition in which small
bronchioles are narrowed
• COPD is present only if chronic airflow ob-
struction occurs; chronic bronchitis without
chronic airflow obstruction is not included
within COPD .
EPIDEIMOLOGY
• 3rd leading cause of death in US
• affects >10 million persons in US
 Risk Factors
• Cigarette Smoking
• Airway Responsiveness
• Respiratory Infections
• Occupational Exposures
• Ambient Air Pollution
• Passive, or Second-Hand, Smoking Exposure
• Genetic α1 Antitrypsin Deficiency
 Natural History
.The effects of cigarette smoking on pulmonary function
appear to depend on
• The intensity of smoking exposure
• Timing of smoking exposure during growth
• The baseline lung function of the individual
.Genetic factors likely contribute to the level of pul-
monary function achieved during growth and to the
rate of decline in response to smoking and poten-
tially to other environmental factors as well.
Pathogenesis
Airflow limitation, the major physiologic change in COPD,
can result from both small airway obstruction and emphy-
sema.
Small airways may become narrowed by cells, mucus, and
fibrosis, and extensive small airway destruction is hallmark
of advanced COPD.
Pathogenesis of emphysema is more clearly defined than
pathogenesis of small airway diseadse
Pulmonary vascular destruction occurs in concert with
above two
Pathogenesis
The dominant paradigm of the pathogenesis of emphy-
sema comprises four interrelated events (Fig. 260-3):
1. Chronic exposure to cigarette smoke may lead to in-
flammatory cell recruitment within the terminal air spa-
ces of the lung.
2. These inflammatory cells release elastolytic proteinases
that damage the extracellular matrix of the lung.
3. Structural cell death results from oxidant stress and loss
of matrix-cell attachment.
4. Ineffective repair of elastin and other extracellular ma-
trix components result in air space enlargement that de-
fines Pulmonary Emphysema.
Pathology
 Pathophysiology
• Airflow Obstruction
-Persistent reduction in forced expiratory flow
rates .reduced FEV1
.reduced ratio of FEV1/FVC
• Hyperinflation
-Increases in the residual volume and the resid-
ual volume/total lung capacity ratio
• Gas Exchange
-Non uniform distribution of ventilation -
Ventilation-perfusion mismatching
 1. Airflow Obstruction
• Airflow limitation, also known as airflow ob-
struction, is typically determined by spirome-
try, which involves forced expiratory maneu-
vers after the subject has inhaled to total lung
capacity.

• Key parameters obtained from spirometry in-

clude FEV1 and the total volume of air exhaled
during the entire spirometric maneuver
[forced vital capacity (FVC)].
Patients with airflow obstruction related to COPD have a
chronically reduced ratio of FEV1/FVC.

In contrast to asthma, the reduced FEV1 in COPD seldom

shows large responses to inhaled bronchodilators, al-
though improvements up to 15% are common.

Asthma patients can also develop chronic (not fully re-

versible) airflow obstruction.
Airflow during forced exhalation is the result of the balance
between the elastic recoil of the lungs promoting flow and
the resistance of the airways limiting flow.

In normal lungs, as well as in lungs affected by COPD,

maximal expiratory flow diminishes as the lungs empty
because the lung parenchyma provides progressively
less elastic recoil and because the cross-sectional area of
the airways falls, raising the resistance to airflow.
 2. Hyperinflation
• Lung volumes are also routinely assessed in
pulmonary function testing.

• In COPD there is often "air trapping" (in-

creased residual volume and increased ratio of
residual volume to total lung capacity) and
progressive hyperinflation (increased total
lung capacity) late in the disease.
Hyperinflation of the thorax during tidal breathing pre-
serves maximum expiratory airflow, because as lung volume
increases, elastic recoil pressure increases, and airways en-
large so that airway resistance decreases.
 Despite compensating for airway obstruction, hyperinfla-
tion can push the diaphragm into a flattened position with
a number of adverse effects.

1. First, by decreasing the zone of apposition between the di-

aphragm and the abdominal wall, positive abdominal pres-
sure during inspiration is not applied as effectively to the
chest wall, hindering rib cage movement and impairing in-
spiration.
2. Second, because the muscle fibers of the flattened di-
aphragm are shorter than those of a more normally curved
diaphragm, they are less capable of generating inspiratory
pressures than normal.

3. Third, the flattened diaphragm (with increased radius of

curvature, r) must generate greater tension (t) to develop
the transpulmonary pressure (p) required to produce tidal
breathing.

This follows from Laplace's law, p = 2t/r

 3. Gas Exchange
• Although there is considerable variability in
the relationships between the FEV1 and other
physiologic abnormalities in COPD, certain
generalizations may be made.

• The PaO2 usually remains near normal until the

FEV1 is decreased to ~50% of predicted, and
even much lower FEV1 values can be associ-
ated with a normal PaO2, at least at rest.
An elevation of arterial level of carbon dioxide (PaCO2) is not
expected until the FEV1 is <25% of predicted and even then
may not occur.

Pulmonary hypertension severe enough to cause cor pul-

monale and right ventricular failure due to COPD typically
occurs in individuals who have marked decreases in FEV1
(<25% of predicted) and chronic hypoxemia (PaO2 <55
mmHg);
However, recent evidence suggests that some patients
will develop significant pulmonary hypertension inde-
pendent of COPD severity.
Nonuniform ventilation and ventilation-perfusion mis-
matching are characteristic of COPD, reflecting the hetero-
geneous nature of the disease process within the airways
and lung parenchyma.

Physiologic studies are consistent with multiple

parenchymal compartments having different rates of
ventilation due to regional differences in compliance and
airway resistance.
Ventilation-perfusion Mismatching accounts for essentially
all of the reduction in PaO2 that occurs in COPD; shunting is
minimal.

This finding explains the effectiveness of modest eleva-

tions of inspired oxygen in treating hypoxemia due to
COPD and therefore the need to consider problems other
than COPD when hypoxemia is difficult to correct with
modest levels of supplemental oxygen in the patient with
COPD.
- Pulmonary hypertension
 Clinical Presentation
History
• Risk factors
• cough, sputum production, and exertional dyspnea
• symptoms for months or years before seeking medical atten-
tion
• Activities involving significant arm work, particularly at or
above shoulder level, are particularly difficult for patients with
COPD
• activities that allow the patient to brace the arms and use ac-
cessory muscles of respiration are better tolerated
• worsening dyspnea on exertion is the principal feature of ad-
vanced COPD
 Patients with features of asthma
and COPD

GINA 2020, Box 5-2

 Physical Findings
Early stages of COPD
• Normal physical examination
• Current smokers - signs of active smoking ( an
odor of smoke or nicotine staining of finger-
nails )
Because of the heterogeneity of COPD, patients may show a
range of phenotypic clinical pictures
severe disease
• prolonged expiratory phase and expiratory
wheezing
• signs of hyperinflation ( a barrel chest and en-
larged lung volumes with poor diaphragmatic
excursion)
• use of accessory muscles of respiration, sitting
in the characteristic "tripod"
Advanced disease
• systemic wasting - significant weight loss,
bitemporal wasting, and diffuse loss of subcu-
taneous adipose tissue
• paradoxical inward movement of the rib cage
with inspiration (Hoover's sign)
• Signs of overt right heart failure
• Clubbing of the digits is not a sign of COPD
 Laboratory Findings
• Arterial blood gases and oximetry
• Hematocrit – Secondary polycythemia
• Pulmonary function testing
-reduction in FEV1 and FEV1/FVC
-lung volumes may increase, resulting in an increase in total
lung capacity, functional residual capacity, and residual vol-
ume
Spirometry(V-T curves)
In patient with FV1/FVC < 70%

GOLD 1 mild FV1>/ 80% of predicted

2 moderate FVC1>/ 50 to 80

3 severe FVC1>/30 to 50

4 very severe FVC1</50

CXR
CT
ECG
 Cont…
• Echocardiography - rt ventricular hypertrophy
• Testing for α1AT deficiency
 Management
-Stable Phase COPD
Pharmacologic
• Smoking Cessation
• Bronchodilators
• Glucocorticoids
• Oxygen
• Others - α1AT augmentation therapy
Health benefits of smoking cessation

C-I lecture, Dr Elsah T., 11 Dec 2014

Non-pharmacologic
• General Medical Care
• Pulmonary Rehabilitation
• Lung Volume Reduction Surgery (LVRS)
• Lung Transplantation
Exacerbations of COPD
• Bronchodilators
• Antibiotics
• Glucocorticoids
• Oxygen
• Mechanical Ventilatory Support
Thank U for your attention