ASTHMA
DEFINITION
Asthma is a chronic inflammatory disorder of the airways in which many cells and cellular
elements play a role. In susceptible individuals, inflammation causes recurrent episodes of
wheezing, breathlessness, chest tightness, and coughing. These episodes are usually
associated with airflow obstruction that is often reversible either spontaneously or with
treatment. The inflammation also causes an increase in bronchial hyperresponsiveness (BHR)
to a variety of stimuli.
PATHOPHYSIOLOGY
• The major characteristics of asthma include a variable degree of airflow obstruction (related
to bronchospasm, edema, and hypersecretion), BHR, and airway inflammation.
• 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.
• The 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.
• Eosinophils migrate to the airways and release inflammatory mediators (leukotrienes and
granule proteins), cytotoxic mediators, and cytokines.
• 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 interferon- γ that are essential for cellular defense
mechanisms. Allergic asthmatic inflammation may result from an imbalance between TH1
and TH2 cells.
• 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.
• 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 are also a source of mediators (PAFs, prostaglandins, thromboxanes, and
leukotrienes) that contribute to BHR and airway inflammation.
•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.
• Bronchial epithelial cells participate in inflammation by releasing eicosanoids, peptidases,
matrix proteins, cytokines, and nitric oxide. Epithelial shedding results in heightened airway
responsiveness, altered permeability of the airway mucosa, depletion of epithelial-derived
relaxant factors, and loss of enzymes responsible for degrading inflammatory neuropeptides.
• The exudative inflammatory process and sloughing of epithelial cells into the airway lumen
impair mucociliary transport. The bronchial glands are increased in size, and the goblet cells
are increased in size and number. Expectorated mucus from patients with asthma tends to
have high viscosity.
• The airway is innervated by parasympathetic, sympathetic, and nonadrenergic inhibitory
nerves. The normal resting tone of airway smooth muscle is maintained by vagal efferent
activity, and bronchoconstriction can be mediated by vagal stimulation in the small bronchi.
Airway smooth muscle contains noninnervated β2-adrenergic receptors that produce
bronchodilation. The nonadrenergic, noncholinergic nervous system in the trachea and
bronchi may amplify inflammation in asthma by releasing nitric oxide.
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.
• Signs include expiratory wheezing on auscultation, dry hacking cough, or signs of atopy
(e.g., allergic rhinitis or eczema).
• Asthma can vary from chronic daily symptoms to only intermittent symptoms. The intervals
between symptoms may be days, weeks, months, or years.
• 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 β2-
agonists to severe chronic asthma symptoms despite receiving multiple medications.
SEVERE ACUTE ASTHMA
• Uncontrolled asthma can progress to an acute state where inflammation, airway edema,
excessive mucus accumulation, and severe bronchospasm result in profound airway
narrowing that is poorly responsive to usual bronchodilator therapy.
• 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, and hyperinflated chest with intercostal and
supraclavicular retractions. Breath sounds may be diminished with very severe obstruction.
DIAGNOSIS
CHRONIC ASTHMA
• 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 (forced expiratory volume in 1 second [FEV1]/forced
vital capacity less than 80%) with reversibility after inhaled β2-agonist administration (at
least a 12% improvement in FEV1). Failure of pulmonary function to improve acutely does
not necessarily rule out asthma. If baseline spirometry is normal, challenge testing with
exercise, histamine, or methacholine can be used to elicit BHR.
ACUTE SEVERE ASTHMA
• Peak expiratory flow (PEF) and FEV1 are less than 50% of normal predicted values. Pulse
oximetry reveals decreased arterial oxygen and O2 saturations. The best predictor of outcome
is early response to treatment as measured by improvement in FEV1 at 30 minutes after
inhaled β2-agonists.
• Arterial blood gases may reveal metabolic acidosis and a low PaO2.
• The history and physical examination should be obtained while initial therapy is being
provided. A history of previous asthma exacerbations (e.g., hospitalizations, intubations) and
complicating illnesses (e.g., cardiac disease, diabetes) should be obtained. The patient should
be examined to assess hydration status; use of accessory muscles of respiration; and the
presence of cyanosis, pneumonia, pneumothorax, pneumomediastinum, and upper airway
obstruction. A complete blood count may be appropriate for patients with fever or purulent
sputum.
