ASTHMA
Barte, Anne Bernadette B.
What is Asthma?
Asthma syndrome characterized by airflow
obstruction that varies markedly, both spontaneously & with treatment
Narrowing of airways is usually reversible; in
contrast with chronic asthma w/c is irreversible airflow obstruction
EPIDEMIOLOGY
Asthma is one of the most common chronic
diseases globally
Currently affects 300 million people
Present at any age w/ a peak age of 3
Childhood: males > females
Adulthood: sex ratio has equalized
Asthmatic children became asymptomatic during
adolescence/until they reach age 40, however returns in some during adult life
Death are uncommon & have been steadily
declining in many affluent countries over the last decade
(ICSs) in pxs w/ persistent asthma is responsible for the decrease in mortality in recent years
Widespread use of inhaled corticosteroids
ETIOLOGY
Heterogeneous disease w/ interplay bet.
genetic & environmental factors; these are the ff:
Atopy Intrinsic Asthma Infections Environmental Factors: hygiene hypothesis, diet, air pollution, allergerns, occupational exposure Other Factors
PATHOGENESIS
Pathology
Inflammation Inflammatory Mediators: cytokines, chemokines, oxidative stress, nitric
oxide, transcription factors
Effects of Inflammation: airway epithelium, fibrosis, airway smooth
muscle, vascular responses, mucus hypersecretion, neural effects
Airway remodeling Asthma triggers: allergens, virus infections, pharmacologic agents,
exercise, physical factors, food, air pollution, occupational factors, hormonal factors, gastroesophageal reflux, stress
Pathology
airway mucosa is infiltrated with activated eosinophils and T
lymphocytes, and there is activation of mucosal mast cells
inflammation is reduced by treatment with ICSs 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.
Inflammation
there is inflammation in the respiratory mucosa from trachea to terminal
bronchioles, but with a predominance in the bronchi (cartilaginous airways).
Inflammatory Mediators
Mediators such as histamine, prostaglandins, and cysteinyl-leukotrienes
contract airway smooth muscle, increase microvascular leakage, increase airway mucus secretion, and attract other inflammatory cells.
Because each mediator has many effects, the role of individual mediators
in the pathophysiology of asthma is not yet clear.
Effects of Inflammation
Airway epithelium: damage may contribute to airway
hyperresponsiveness, including loss of its barrier function to allow penetration of allergens; loss of enzymes (such as neutral endopeptidase); loss of a relaxant factor (so called epithelial-derived relaxant factor); and exposure of sensory nerves, which may lead to reflex neural effects on the airway subepithelial fibrosis with deposition of types III and V collagen below the true basement membrane, and it is associated with eosinophil infiltration be secondary to the chronic inflammatory process
Fibrosis: basement membrane is apparently thickened due to
Airway smooth muscle: still debate about the role of abnormalities; may
Vascular responses: microvascular leakage from postcapillary venules in
response to inflammatory mediators is observed in asthma, resulting in airway edema and plasma exudation into the airway lumen viscid mucus plugs that occlude asthmatic airways, particularly in fatal asthma cause bronchoconstriction and may be activated reflexly in asthma
Mucus hypersecretion: increased mucus secretion contributes to the
Neural effects: release of acetylcholine acting on muscarinic receptors,
Airway remodeling
observation suggests that the accelerated decline in lung function occurs
in a smaller proportion of asthmatics, and these are usually patients with more severe disease
may lead to irreversible narrowing of the airways
Asthma triggers
Allergens virus infections pharmacologic agents exercise, physical factors Food
air pollution occupational factors hormonal factors gastroesophageal reflux stress
PATHOPHYSIOLOGY
Limitation of airflow is due mainly to bronchoconstriction, but airway
edema, vascular congestion, and luminal occlusion with exudate may also contribute. trapping), and increased residual volume, particularly during acute exacerbations.
Early closure of peripheral airway results in lung hyperinflation (air
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.
important aim of therapy is to reduce AHR
TREATMENT
Bronchodilators and Controllers
Bronchodilator Therapies: B2-agonists (5), Anti-cholinergics,
Theophylline (2),
Controller Therapies: Inhaled corticosteroids (3), Systemic
corticosteroids, Antileukotrienes, Cromones, Steroid-sparing Therapies, Anti-IgE, Immunotherapy, Alternative therapies, Future therapies
The main drugs for asthma can be divided into two:
Bronchodilator Therapies: B2-agonists Anti-cholinergics Theophylline Controller Therapies: Inhaled corticosteroids Systemic corticosteroids Antileukotrienes Cromones Steroid-sparing Therapies Anti-IgE Immunotherapy Alternative therapies
Bronchodilator Therapies
B2-agonists
relax airway smooth-muscle cells of all airways, where they act as
functional antagonists, reversing and preventing contraction of airway smooth-muscle cells by all known bronchoconstrictors
given by inhalation
rapid onset of bronchodilation and are therefore used as needed for
symptom relief
short-acting 2-agonists (SABAs), such as albuterol and terbutaline, have a
duration of action of 36 hours
Anti-cholinergics
used as an additional bronchodilator in patients with asthma that is not
controlled on other inhaled medications
most common side effect is dry mouth; in elderly patients, urinary
retention and glaucoma may also be observed
Theophylline
Inexpensive
lower doses has anti-inflammatory effects, and these are likely to be
mediated through different molecular mechanisms phosphodiesterase inhibition
most common side effectsnausea, vomiting, and headachesare due to
Controller Therapies
Inhaled corticosteroids
ICSs are the most effective anti-inflammatory agents used in asthma
therapy, reducing the number of inflammatory cells and their activation in the airways
reduce eosinophils in the airways and sputum, and numbers of activated T
lymphocytes and surface mast cells in the airway mucosa
local side effects include hoarseness (dysphonia) and oral candidiasis
Systemic corticosteroids
used intravenously (hydrocortisone or methylprednisolone) for the
treatment of acute severe asthma, although several studies now show that oral corticosteroids are as effective and easier to administer
Antileukotrienes
Cysteinyl-leukotrienes are potent bronchoconstrictors, cause
microvascular leakage, and increase eosinophilic inflammation through the activation of cys-LT1-receptors
given orally once or twice daily and are well tolerated
Cromones
Cromolyn sodium and nedocromil sodium are asthma controller drugs
that appear to inhibit mast cell and sensory nerve activation
relatively little benefit in the long-term control of asthma due to their
short duration of action (at least 4 times daily by inhalation).
Steroid-sparing Therapies
Methotrexate, cyclosporine, azathioprine, gold, and intravenous gamma
globulin have all been used as steroid-sparing therapies, but none of these treatments has any long-term benefit and each is associated with a relatively high risk of side effects
Anti-IgE
Omalizumab is a blocking antibody that neutralizes circulating IgE
without binding to cell-bound IgE; it thus inhibits IgE-mediated reactions may improve asthma control
reduce the number of exacerbations in patients with severe asthma and
Immunotherapy
injected extracts of pollens or house dust mite has not been very effective
in controlling asthma and may cause anaphylaxis evidence of clinical efficacy
not recommended in most asthma treatment guidelines because of lack of
Alternative therapies
Nonpharmacologic treatments, including hypnosis, acupuncture,
chiropraxy, breathing control, yoga, and speleotherapy, may be popular with some patients
Acute Severe Asthma
Clinical Features & Treatment
Patients are aware of increasing chest tightness, wheezing, and dyspnea
that are often not or poorly relieved by their usual reliever inhaler
Treatment: The mainstay of treatment is high doses of short-acting
inhaled 2-agonists that are given either by nebulizer or via a metered dose inhaler with a spacer; patients may benefit from an anesthetic, such as halothane, if they have not responded to conventional bronchodilators
OT Management
Relaxation Techniques
Energy Conservation Program Education Group therapy
