Respiratory system
Asthma
definition
• The Global Initiative for Asthma (GINA) provides a practical asthma
definition
Asthma is a complex disorder and has been defined as “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 variable expiratory airflow limitation.
Etiology
• Asthma results from a complex interaction of genetic and
environmental factors.
• There appears to be an inherited component because the presence of
asthma in a parent is a strong risk factor for developing asthma in a
child.
• Environmental exposure also appears to be an important etiologic
factor. Although asthma occurs early in life for most patients, those
with occupational asthma develop the disease later upon exposure to
specific allergens in the workplace.
• Environmental risk factors for the development of asthma include
1. socioeconomic status,
2. family size,
3. Exposure to secondhand tobacco smoke in infancy, and in utero,
4. allergen exposure, ambient air pollution, urbanization,
5. viral respiratory infections including respiratory syncytial virus (RSV)
and rhinovirus,
6. and decreased exposure to common childhood infectious agents. ??
-:Hygiene theory
• The timing of, and exposure to, certain environmental factors during
early childhood in genetically susceptible individuals is thought to
predispose to the development of allergies and asthma by allowing
the allergic immunologic system (T-helper cell type 2 [Th2] [Th2]high
asthma lymphocytes) to develop instead of the system to fight
infections (T-helper type 1[Th1] [Th2] low asthma] lymphocytes).
• The first 2 years of life appear to be most important for the exposures
to produce an alteration in the immune response system.
• Exposure to secondhand smoke after birth increases the risk of
childhood asthma.
• Adult-onset asthma may be related to atopy, nasal polyps, aspirin
sensitivity, occupational exposure, or recurrence of childhood asthma
PATHOPHYSIOLOGY
• Asthma is characterized by airway narrowing and inflammation
primarily in medium-sized bronchi.
• A key feature of the pathophysiology is airway hyperresponsiveness,
which is exaggerated narrowing of the airways in response to a trigger
or allergen such as cold air, strong odors, pollen, or dust.
• Airway narrowing results from contraction of airway smooth muscle,
increased mucus secretion, airway edema, and remodeling.
Early phase allergic reaction:-
• Inhaled allergens cause an early-phase allergic reaction characterized
by activation of cells bearing allergen-specific immunoglobulin E (IgE)
antibodies.
• There is rapid activation of airway mast cells and macrophages, which
release proinflammatory mediators such as histamine and eicosanoids
that induce contraction of airway smooth muscle, mucus secretion,
vasodilation, and exudation of plasma in the airways.
• Plasma protein leakage induces a thickened, engorged, edematous
airway wall and a narrowing of the airway lumen with reduced mucus
clearance.
Late-phase inflammatory reaction
occurs 6 to 9 hours after allergen provocation and involves recruitment
and activation of eosinophils, T lymphocytes, basophils, neutrophils,
and macrophages.
Inflammatory Cells
Epithelial Cells
• Bronchial epithelial cells participate in mucociliary clearance and
removal of noxious agents;
• however, they also enhance inflammation by releasing eicosanoids,
peptidases, matrix proteins, cytokines, chemokines, and nitric oxide
(NO)
• Epithelial cells can be activated by IgE-dependent mechanisms,
viruses, pollutants, or histamine.
Eosinophils
• Eosinophils play an effector role in asthma by releasing
proinflammatory mediators, cytotoxic mediators, and cytokines.
• On activation, eosinophils release inflammatory mediators such as
leukotrienes (LTs) and granule proteins to injure airway tissue.
T-lymphocyte
• T-lymphocyte activation leads to release of cytokines from type 2 T-
helper (TH2) cells that mediate allergic inflammation (interleukin [IL]-
4, IL-5, and IL-13).
• Conversely, type 1 T-helper (TH1) cells produce IL-2 and interferonγ
that are essential for cellular defense mechanisms.
• Allergic asthmatic inflammation may result from an imbalance
between TH1 and TH2 cells.
Mast cell
• Mast cell degranulation in response to allergens results in release of
mediators such as histamine; eosinophil, and neutrophil chemotactic
factors; leukotrienes C4, D4, and E4; prostaglandins; and platelet-
activating factor (PAF).
Histamine is capable of inducing smooth muscle constriction and
bronchospasm and may play a role in mucosal edema and mucus
secretion.
Macrophages
• Alveolar macrophages release a number of inflammatory mediators,
including PAF and leukotrienes B4, C4, and D4.
• Production of neutrophil chemotactic factor and eosinophil
chemotactic factor furthers the inflammatory process.
Neutrophils
• Neutrophils are also a source of mediators (PAFs, prostaglandins,
thromboxanes, and leukotrienes) that contribute to BHR and airway
inflammation
The 5-lipoxygenase pathway
and Aspirin-induced asthma
The 5-lipoxygenase pathway
and Aspirin-induced asthma
• The 5-lipoxygenase pathway of arachidonic acid metabolism is
responsible for production of cysteinyl leukotrienes.
• Leukotrienes C4, D4, and E4 are released during inflammatory
processes in the lung and produce bronchospasm, mucus secretion,
microvascular permeability, and airway edema
Innervation of bronchial smooth
muscle
• Bronchial smooth muscle tone depends on a complex balance
between different bronchoconstrictor and bronchodilator influences;
the autonomic nervous system is an important regulator of smooth
muscle tone in the airways.
DIAGNOSIS AND CLINICAL
PRESENTATION
• The diagnosis of asthma is made primarily by a history of recurrent
episodes of coughing, wheezing, chest tightness, or shortness of
breath and confirmatory spirometry.
•The patient may have a family history of allergy or asthma or have
symptoms of allergic rhinitis. A history of exercise or cold air
precipitating dyspnea or increased symptoms during specific allergen
seasons also suggests asthma.
• Spirometry demonstrates obstruction
CLINICAL PRESENTATION
• CHRONIC ASTHMA
Classic asthma is characterized by episodic dyspnea associated with
wheezing, but the clinical presentation of asthma is diverse.
Patients may also complain of episodes of dyspnea, chest tightness,
coughing (particularly at night), wheezing, or a whistling sound when
breathing. These often occur with exercise but may occur
spontaneously or in association with known allergens
• The severity is determined by lung function, symptoms, nighttime
awakenings, and interference with normal activity prior to therapy.
• Patients can present with mild intermittent symptoms that require no
medications or only occasional use of short-acting inhaled β 2-
agonists to severe chronic asthma symptoms despite receiving
multiple medications
Acute asthma
• Patients may be anxious in acute distress and complain of severe
dyspnea, shortness of breath, chest tightness, or burning.
• They may be able to say only a few words with each breath.
Symptoms are unresponsive to usual measures.
• Signs include expiratory and inspiratory wheezing on auscultation, dry
hacking cough, tachypnea, tachycardia, pallor or cyanosis,
Pharmacology of asthma
