2. ASTHMA
• Asthma is a chronic inflammatory disorder of
the airways that causes recurrent episodes of
wheezing, breathlessness, chest tightness, and
cough, particularly at night and/or early in the
morning. The hallmarks of the disease are
intermittent and reversible airway
obstruction, chronic bronchial inflammation
with eosinophils, bronchial smooth muscle
cell hypertrophy and hyperreactivity, and
increased mucus secretion.
3.
4. PREVALENCE
• Asthma is one of the most common chronic
diseases globally and currently affects ~300
million people. The prevalence of asthma has
risen in affluent countries over the past 30
years but now appears to have stabilized, with
~10–12% of adults and 15% of children
affected by the disease.
5. ETIOLOGY
• Asthma is a heterogeneous disease with
interplay between genetic and environmental
factors. Several risk factors have been
implicated.
6.
7. ETIOLOGY
• ATOPY;
• INTRINSIC ASTHMA (more severe, persistent asthma);
• INFECTIONS (Mycoplasma and Chlamydia spp?);
• GENETICS;
• ENVIRONMENTAL FACTORS (hygiene, diet, Air pollution,
allergens, occupational Exposure).
• Several other factors have been implicated in the cause of
asthma, including lower maternal age, duration of
breastfeeding, prematurity and low birth weight, and
inactivity, but are unlikely to contribute to the recent global
increase in asthma prevalence. There is also an association
with acetaminophen (paracetamol) consumption, which
remains unexplained.
8. PATHOGENESIS
• Asthma is associated with a specific chronic inflammation of the mucosa of the
lower airways.
• PATHOLOGY
• The pathology of asthma is remarkably uniform in different types of asthma,
• including atopic, nonatopic, occupational, aspirin-sensitive, and pediatric asthma.
• The airway mucosa is infiltrated with activated eosinophils and T lymphocytes,
and there is activation of mucosal mast cells.
• A characteristic finding is thickening of the basement membrane caused by
subepithelial collagen deposition.
• There is also vasodilatation and increased numbers of blood vessels
(angiogenesis).
• the airways may be narrowed, reddened, and edematous.
• These pathologic changes are found in all airways but do not extend to the lung
parenchyma; small airway inflammation is found particularly in patients with
severe asthma. The involvement of airways may be patchy, and this is consistent
with bronchographic findings of uneven narrowing of the airways.
9. Histopathology of a small
airway in fatal
asthma.
The lumen is occluded with
a mucus plug, goblet cell
metaplasia is present, and
the airway wall is
thickened, with an
increase
in basement membrane
thickness and airway
smooth muscle.
10. PATHOGENESIS
• INFLAMMATION
• Many inflammatory cells are known to be
involved in asthma, with no predominant key cell:
• Mast Cells;
• Macrophages and Dendritic Cells;
• Eosinophils;
• Neutrophils;
• T Lymphocytes;
• Structural Cells.
11. Inflammation in the
airways of asthmatic
patients
Inflammation in the
airways of asthmatic
patients leads to
airway
hyperresponsiveness
and symptoms.
12. The pathophysiology
of asthma is complex
The pathophysiology
of asthma is complex,
with participation o
several interacting
inflammatory cells,
resulting in acute and
chronic inflammatory
effects on the airway.
13. PATHOGENESIS
• INFLAMMATORY MEDIATORS
• Many different mediators have been
implicated in asthma, and they may have a
variety of effects on the airways that could
account for the pathologic features of asthma
16. Chemokines in
asthma.
Chemokines in asthma.
Tumor necrosis factor α (TNF
α) and other triggers of
airway epithelial cells release
thymus and activation-
regulated chemokine (TARC,
CCL17) an macrophage-
derived chemokine (MDC,
CCL22) from epitheliar cells,
which attract TH2 cells via
activation of their CCR4
Receptors. These promote
eosinophilic inflammation
directly through the release of
interleukin 5 (IL-5) and
indirectly via the release of IL-
4 and IL-13, which induce
eotaxin (CCL11) formation in
airway epithelial cells.
18. PATHOGENESIS
• AIRWAY REMODELING
• Several changes in the structure of the airway are
characteristically found in asthma, and these may
lead to irreversible narrowing of the airways.
• Population studies have shown a greater decline
in lung function over time than in normal
subjects;
• However, most patients with asthma preserve
normal or near-normal lung function throughout
life if appropriately treated.
20. PATHOPHYSIOLOGY
• Limitation of airflow is mainly caused by
bronchoconstriction, airway edema, vascular
congestion, and luminal occlusion with exudate may
also contribute.
• This results in a reduction in forced expiratory volume
in 1 s (FEV1), FEV1/forced vital capacity (FVC) ratio, and
peak expiratory flow (PEF).
• AIRWAY HYPERRESPONSIVENESS (AHR) is the
characteristic physiologic abnormality of asthma and
describes the excessive bronchoconstrictor response to
multiple inhaled triggers that would have no effect on
normal airways.
21. CLINICAL FEATURES AND DIAGNOSIS
• The characteristic symptoms of asthma are wheezing,
dyspnea, and coughing.
• Symptoms may be worse at night, and patients typically
awake in the early morning hours.
• There is increased mucus production in some patients, with
typically tenacious mucus that is difficult to expectorate.
• There may be increased ventilation and use of accessory
muscles of ventilation.
• Typical physical signs are inspiratory, and to a great extent
expiratory, rhonchi throughout the chest, and there may be
hyperinflation.
• There may be no abnormal physical findings when asthma
is under control.
22. DIAGNOSIS
• Lung Function Tests (reduced FEV1, FEV1/FVC
ratio, and PEF. Reversibility is demonstrated by a
>12% and 200-mL increase in FEV1 15 min after
an inhaled short-acting β2-agonist.
• The increased AIRWAY HYPERRESPONSIVENESS
(AHR) is normally measured by methacholine or
histamine challenge with calculation of the
provocative concentration that reduces FEV1 by
20% (PC20).
23. DIAGNOSIS
• Hematologic Tests and Imaging are not
usually helpful.
• Skin prick tests to common inhalant allergens
are positive in allergic asthma and negative in
intrinsic asthma but are not helpful in
diagnosis.
24. DIAGNOSIS
• DIFFERENTIAL DIAGNOSIS It is usually not
difficult to differentiate asthma from other
conditions that cause wheezing and dyspnea:
• Upper airway obstruction by a tumor or
laryngeal edema;
• Eosinophilic pneumonias;
• Systemic vasculitis;
• Chronic obstructive pulmonary disease
(COPD).
30. • Alternative Therapies (Nonpharmacologic
treatments, including hypnosis, acupuncture,
chiropraxy, breathing control, yoga, and
speleotherapy);
• Future Therapies It has proven very difficult to
discover novel pharmaceutical therapies,
particularly because current therapy with
corticosteroids and β2- agonists is so effective
in the majority of patients.
ASTHMA TREATMENT
31. • MANAGEMENT OF CHRONIC ASTHMA
• Stepwise Therapy For patients with mild,
intermittent asthma, a short-acting β2-agonist
is all that is required.
ASTHMA TREATMENT
32. Step-wise approach to asthma therapy according to th severity of asthma
and ability to control symptoms. ICS- inhaled corticosteroid; LABA- long-
acting 2-agonist; OCS -oral corticosteroid.
33.
34. • Education
• Patients with asthma need to understand how to
use their medications and the difference between
reliever and controller therapies.
• Education may improve compliance, particularly
with ICSs.
• All patients should be taught how to use their
inhalers correctly. In particular, they need to
understand how to recognize worsening of
asthma and how to step up therapy.
ASTHMA TREATMENT
35. ACUTE SEVERE ASTHMA
• Exacerbations of asthma are feared by patients and may be life
threatening. One of the main aims of controller therapy is to
prevent exacerbations; in this respect, ICS and combination inhalers
are very effective.
• TREATMENT
• A high concentration of oxygen should be given by face mask to
achieve oxygen saturation of above 90%.
• The mainstay of treatment is high doses of short-acting inhaled
β2-agonists that are given either by nebulizer or via a metered dose
inhaler with a spacer.
• In severely ill patients with impending respiratory failure, IV β2-
agonists may be given.
• In patients who are refractory to inhaled therapies, a slow infusion
of aminophylline may be effective.
36. • Although asthma is easily controlled in most
patients with appropriate medication, the
disease is difficult to control in a small
proportion of patients (∼5% of asthmatics)
despite maximal inhaled therapy.
REFRACTORY ASTHMA
37. • MECHANISMS
• The most common reason for poor control of
asthma is noncompliance with medication,
particularly ICS.
• Compliance with ICS is difficult to monitor
because there are no useful plasma
measurements that can be made. Compliance
may be improved by giving the ICS as a
combination with a LABA that gives symptom
relief.
REFRACTORY ASTHMA
38. • CORTICOSTEROID-RESISTANT ASTHMA
• A few patients with asthma show a poor
response to corticosteroid therapy and may
have various molecular abnormalities that
impair the anti-inflammatory action of
corticosteroids.
• Complete resistance to corticosteroids is
extremely uncommon and affects fewer than
one in 1000 patients.
REFRACTORY ASTHMA
39. REFRACTORY ASTHMA
• BRITTLE ASTHMA
• Some patients show chaotic variations in lung
function despite taking appropriate therapy.
Some show a persistent pattern of variability and
may require oral corticosteroids or, at times,
continuous infusion of β2-agonists (type I brittle
asthma), and others have generally normal or
near-normal lung function but precipitous,
unpredictable decreases in lung function that
may result in death (type 2 brittle asthma).
40. • REFRACTORY ASTHMA
• It is important to check compliance and the
correct use of inhalers and to identify and
eliminate any underlying triggers.
• Low doses of theophylline may be helpful in
some patients, and theophylline withdrawal has
been found to worsen many patients’ symptoms.
• There is some evidence that anti-TNF therapy
may be effective, but this is controversial and
very expensive.
ASTHMA TREATMENT
