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