Asthma

Front 1

Ventilation

Back 1

Movement of air from atmosphere into and out of the lungs.

Must be taken through the upper airway passages, comprising the nose, nasal passages, mouth, pharynx and larynx.

The air then processes from there into the lower airway, consisting the trachea, bronchi and bronchioles of the lungs.

Front 2

Inspiration

Back 2

The process of taking air in.

Front 3

Perfusion

Back 3

The movement of blood through the lungs.

Front 4

Diffusion

Back 4

The movement of gases between alveoli (air-filled sacs) and the capillary (supply the alveoli).

Gas moves across the alveolar capillary membrane. Oxygen moves from the air that is in the alveoli into the blood, flowing through the pulmonary capillary.

Carbon dioxide passes from the blood into the alveoli.

Front 5

Asthma

Back 5

Chronic reactive airway disorder, characterized by increase resistance to air flow due to airway obstruction.

Involves:

Ø Inflammation of the air way

Ø Bronchospasm

Ø Increased mucus secretion

Ø Injury to mucosal lining

Usual onset in childhood or adolescence. Arises from complex interaction b/w heredity and environmental factors and manifest as acute attacks.

Front 6

Extrinsic (Atopic) Asthma

Back 6

- It is initiated by type 1 hypersensitivity response to the extrinsic antigen

- An antigen bind to the mast cell and cause the mast cell degranulation with release of histamine, leukotriene, interleukin and prostaglandin resulting in inflammation and bronchospasm

- This airway inflammation in turn produce the airway edema, epithelial injury and impair mucociliary function

Front 7

Intrinsic (nonatopic) Asthma

Back 7

It is initiated by diverse non-immune mechanism, overlapping symptoms

Triggered by:

§ Irritant receptors

§ Vagal reflex

§ Viral infection

§ Inhaled irritants

§ NSAIDs

§ Sulfites

§ Emotional stress

Front 8

Early Phase

Back 8

· Occurs within 10 – 20 minutes of triggering stimuli and can last up to 2 hrs

· Allergen binds to preformed IgE on sensitized mast cells on mucosal surface of airways

· Mast cell activation result in the release of preformed granules, inflammatory mediators

§ Histamine, chemotactic chemokine

§ Interleukins and tumor necrosis factor alpha, prostaglandin D2, and platelet activating factor

· Cause infiltration of inflammatory cells, opening of mucosal intercellular junctions allowing access to submucosal mast cell which result in

Ø Further inflammation as well as increased mucus secretion, increased vascular permeability and bronchoconstriction.

Dendritic Cells may receive antigen which will be processed later in late phase response to naive T lymphocytes in lymph nodes.

Front 9

Late Phase

Back 9

· Occurs 4-8 hrs after triggering stimuli and may persist for days or even weeks

· Release of inflammatory mediators causes recruitment and persistent activation of

- Neutrophil, eosinophil, basophil, T lymphocyte (TH2)

o Triggered earlier by chemotactic factors and up-regulation of endothelial adhesion molecules.

· These inflammatory cells cause epithelial injury and edema, increased mucus, changes in mucociliary function resulting in

- Accumulation of mucus and increased airway responsiveness and bronchospasm

· Epithelial damage and impaired mucociliary function is caused because of direct toxic effects of cellular products, specifically from eosinophil such as major basic protein.

Macrophages are also activated in the last phase.

Front 10

Treatment

Back 10

1. Control of factors contributing to asthma severity

2. Pharmacologic treatment

- Corticosteroid

- Bronchodilators

- Mast cell stabilizers

- Beta-agonists

- Anticholinergic drug

Front 11

Prevalence in Canada

Back 11

Prevalence of asthma of off-reserve Aboriginal people >12 y.o is higher than that of the general population.

The prevalence of asthma has decreased from 51% (1995/96) to 39% (2000/01).

· Higher prevalence in boys and women. Rates are steadily increasing around the world. Mortality has decreased.

Front 12

Etiology - Childhood

Back 12

Family history of allergy and allergic disorder including hay fever, asthma and eczema.

High exposure to airborne allergens such as pets, house dust mites, cockroaches and mold.

Exposure to tobacco smoke in utero or early in life.

Low birth weight and respiratory distress syndrome.

No relationship b/w household income and childhood asthma was found

A difference in the prevalence of asthma b/w urban and rural areas was not in Canada

Front 13

Etiology - Adult

Back 13

Occupational exposures to low molecular weight sensitizer.

· Exposure to infectious agents, allergens or pollution

- Although, atmospheric pollution itself is unlikely to be the primary cause of asthma in the absence of other risk factors

For women – smoking, obesity, hormonal influences may also be risk factor

Front 14

Definition of Asthma

Back 14

Asthma is characterized by paroxysmal or persistent symptoms, such as dyspnea, chest tightness, wheezing, sputum production and cough associated with variable airflow limitation and airway hyper-responsiveness to endogenous or exogenous stimuli. Inflammation and its resultant effects on airway structure are considered the main mechanism leading to the development and persistence of asthma.

Mild, moderate, severe.

Transient, intermittent or persistent.

Front 15

Pathophysiology

Back 15

· Inflammation

· Bronchospasm

· Increased mucus production

· Airway remodeling

· Extrinsic vs. intrinsic asthma

· Early and late phases

Front 16

Extrinsic Triggers

Back 16

Type I hyper-sensitivity reaction

Exposure to an extrinsic allergen/antigen.

Front 17

Intrinsic triggers

Back 17

- Respiratory tract infections (viral)

- Exercise

- Cold air, weather changes

- Drugs & chemicals

- Irritants

- Hormonal changes & emotional upsets

- Airborne pollutants

- GERD

Bronchospasm by way of parasympathetic stimulation through vagal pathways may initiate an exacerbation of asthma and asthma symptom for triggers such as inhaled irritants, emotional factors and hormonal changes

Front 18

Mast Cells

Back 18

· Mast cells are cellular bags of granules found in large numbers in the skin and linings of the GI and respiratory tract.

· They are activated by physical injury, chemical agents, immunologic and infectious means

· They degranulate releasing:

§ Histamine, Chemotactic factors and Cytokines

· The activated mast cell also begins synthesizing inflammatory mediators derived from plasma membrane lipids such as:

§ Platelet activating factor, prostaglandin D2, leukotriene, cytokine and growth factors

Front 19

Histamine

Back 19

· Potent vasodilator that causes increased vascular permeability through retraction of endothelial cells

· Histamine also causes smooth muscle to contract causing bronchoconstriction when stimulated in the bronchi.

Front 20

Leukotriene

Back 20

· Their functions are similar and complementary to histamine

· They are more potent and stimulate slower and more prolonged effects compared to histamine

Cysteinyl leukotriene (LTC4; LTD4 & LTE4) cause slow and sustained constriction of the bronchioles

Front 21

Prostaglandin D2

Back 21

· They causes vasodilation, increased vascular permeability and bronchoconstriction

Front 22

Chemotactic Chemokine

Back 22

· They are cytokines that attract immune and inflammatory cells.

· They primarily function to attract leukocytes

Front 23

Cytokines

Back 23

· TNF – alpha increase the activation and migration of inflammatory cells (eosinophils and neutrophils) and contributes to airway remodeling.

o TNF – alpha also causes endothelial cells to express adhesion molecules.

· TNF – alpha and IL – 1 alter muscarinic receptor function resulting in increased levels of acetylcholine which causes bronchial smooth muscle contraction and mucus secretion

· IL – 4, 5, 8 and 13 are T – helper 2 cytokines

· IL – 4 stimulate activation, proliferation and production of antigen – specific, IgE by B cells.

· IL – 5 activates and promotes eosinophil activity

· IL – 8 causes a more exaggerated inflammatory response through activation of basophils, neutrophils and eosinophil.

· IL – 13 impair the clearance of mucus; contribute to bronchoconstriction and increases fibroblast secretion.

Front 24

Platelet Activating Factor (PAF)

Back 24

· Includes platelet aggregation, increases vascular permeability, increases vascular permeability through endothelial cell retraction, activates neutrophil and is a potent eosinophil chemoa-attractant

· In the respiratory system, PAF causes bronchospasm, eosinophil infiltration and nonspecific bronchial hyper-reactivity

Front 25

Cysteinyl Leukotriene

Back 25

Cysteinyl leukotriene which are mostly produced by mast cells, eosinophil and basophil are the leukotriene.

They were initially called “slow reacting substance of anaphylaxis” due to their effect on bronchial smooth muscle of slow and prolonged contraction and hence bronchoconstriction

Front 26

T Lymphocyte (TH2)

Back 26

· TH2 lymphocytes act as growth factors for mast cells as well as recruiting and activating eosinophil by stimulating the differentiation of B cells into IgE – producing plasma cells.

· T- cell differentiation is skewed towards TH2 phenotype cells

Front 27

Leukocytes

Back 27

· Neutrophil, eosinophil and basophil are also known as “granulocytes”.

· Neutrophil are first on scene and the predominant phagocytes in the early inflammatory phase.·

Eosinophils have an important role by controlling the release of specific mediators from mast cells.

· Like mast cells, basophil binds to IgE which is secreted by plasma cells and release histamine and mediators of inflammation such as 1L – 4

· Lymphocytes are T & B cells

Macrophages arrive after neutrophil which they arrive in the late phase.

Front 28

Bronchospasm

Back 28

· It is the result of the action of several mediators:

§ Histamine (early phage)

§ Leukotriene (late phase)

§ PAF

§ Prostaglandin

· The parasympathetic control of airway function appears to not function appropriately due to heightened responsiveness to cholinergic mediators.

Ø This is caused by an alteration of muscarinic receptor function by TNF – alpha and IL – 1 leading to an increase in acetylcholine, which causes bronchial smooth muscle contraction and further mucus secretion.

Front 29

Mucus Hyper-Secretion

Back 29

Sub-mucosal glands and goblet cells produce mucus in the airway.

· Mucus secretion triggered by the inflammatory response

· Leukotriene stimulate increased mucus production

· Interleukin – 9 and 13 are the two most relevant cytokines that up-regulate mucus secretion

· Other mediators that may have a role in mucus hyper-secretion are TNF – alpha, IL – 1 beta and ligands of the epidermal growth factor receptor.

è The most damaging effect of mucus hyper-secretion is airway obstruction by mucus plugs which is caused by mucus hyper-secretion and increased plasma exudation

Front 30

Airway Remodelling

Back 30

§ More inflammation = more airway remodeling

Airway remodeling begins early on in the disease

· Declining lung function which is attributed to airway remodeling is found in young children as well as new asthmatics

· Change to the airway due to inflammation may include sub-mucosal infiltration which activated lymphocytes and eosinophil, mast cell activation, epithelial changes and basement membrane thickening

· In more severe asthma goblet cell hyperplasia and smooth muscle hypertrophy/hyperplasia along with mucus plugging are common

Front 31

Clinical Signs

Back 31

Objective findings assessed or measured.

· Physical assessment finding

· Lab results

· Radiological findings

· Pulmonary function tests

· Peak flow monitoring

Front 32

Clinical Symptoms

Back 32

Subjective in nature and reported by patient.

Dyspnea is the result of an inability to adequately ventilate and abnormal ventilation – perfusion relationship

· Chest tightness results from air trapping and resultant hyper-inflation of the lungs

Cough results as the asthmatic pt tries to clear his or her airway of mucus.

· Wheezing is the result of the passing of air through narrowed airways

"Noisy Breathing" = expiratory as the obstruction is in the lower airways.

Front 33

Clinical Manifestations

Back 33

Asthma attack are related to narrowed airway because of lower airway obstruction due to bronchospasm, edema of the bronchial mucosa and mucus hyper-secretion

Lungs become hyper-inflated putting respiration muscles at a disadvantage.

As hyperinflation progresses, alveolar hypoventilation occur as gas exchange is impeded by increasing intra-pleural and alveolar gas pressure casing ventilation perfusion mismatch.

Mucus also inhibits alveolar ventilation.

Hyperventilation is triggered by lung receptors responding to increasing lung volume and alveolar hypoxia

This hypoxia cause vasoconstriction, which in turn decreases vascular perfusion contributing to the ventilation – perfusion mismatch

Hyperventilation causes a decrease in serum carbon dioxide resulting in respiratory alkalosis usually accompanied with hypoxemia

Work of breathing increases

Front 34

Physical Assessment Findings

Back 34

§ In the clinical setting, percussion is often not done in a respiratory assessment

§ Palpation maybe done to assess perfusion of the skin by determining skim temperature and capillary refill or assessing for pain, masses or crepitus of the chest

§ Inspection -> increased work of breathing, use of accessory muscles, prolonged expiration, wheezing, cough and an inability to maintain a conversion

§ Auscultation -> wheezing, distant breathing sounds, other adventitious breath sounds such as crackles which may be related to an infection

- Vital signs = tachypnea, tachycardia and hypoxemia

Front 35

Lab Values

Back 35

o Normal values:

pH 7.35 – 7.45; pC02 35 – 45; HC03 22-26; p02 80 – 100

§ Clinical ABGs:

pH 7.50 (H - alkalosis) ; pC02 29 (L); HC03 22 (N); p02 76 (L – hypoxemia)

Ø Respiratory alkalosis with hypoxemia

pH 7.32 (L – acidosis) ; pC02 49 (H); HC03 27 (N); p02 70 (L – hypoxemia)

Ø Respiratory acidosis with hypoxemia

Front 36

Chest X-ray

Back 36

· Hyperinflation +/- flattening of the hemi-diaphragms are common radiological finding on chest X-ray.

Ø If a bacteria infection is suspected or confirmed, antibiotic are warranted

Ø If a viral respiratory infection is suspected or confirmed, antibiotic are not warranted.

Front 37

Pulmonary Function Tests

Back 37

· “Spirometry offers the single most objective measurement of lung function available”

Bronchial provocation tests use histamine, methacholine or exposure to a non-pharmacologic agent like cold air to cause bronchoconstriction

· Airway obstruction is assessed flowing bronchial provocation using baseline and post B-agonist measurements of forced vital capacity (FVC), forced expiratory volume in 1 second, (FEV 1), ratio of forced expiratory volume in 1 sec and forced vital capacity (FEVI/FVC) and forced expiratory volume 25 – 75% (FEV 25 – 75%)

Front 38

Peak Flow Monitoring

Back 38

Green zone: PEF > 80% of personal best -> asthma is well controlled

Yellow zone: PEF 50-80% of personal best -> caution should be taken

Red zone: PEF <50% of personal best -> indicates medical alert

*use short-acting bronchodilator*

Front 39

Patient Teaching

Back 39

Avoid triggers and recognize signs of impending asthma attack.

· Use peak flow monitoring

· Take their meds as prescribed

· Use proper inhaler technique and use appropriate med delivery device

Front 40

Long-Acting Control Medication

Back 40

They address inflammation and airway obstruction.

- Inhaled corticosteroids

i.e. Fluticasone (Flovent)

(the med of choice for all individuals with persistent asthma)

- Long – acting beta 2 agonist

i.e. Salmetrol (sevevent)

(function in the same ways as short – acting beta 2 agonist meds but last longer)

- Leukotriene modifiers

i.e. Montelukast (Singulair)

(interfere with leukotriene action)

- Systemic corticosteroids

i.e. Prednisone

(Ø Corticosteroid meds block the cyclooxygenase and lipoxygenase pathways in the inflammatory process)

- Mast cell stabilizers

i.e. Cromolyn (Intal)

(stabilize the membrane of a sensitized mast cell after an antigen – IgE interation preventing the release of inflammatory mediator)

- Monoclonal antibody

i.e. Omalizumab (Xolair)

(anti – IgE antibody that prevents bidning of IgE to basophils and mast cells)

Front 41

Quick Relied Medication

Back 41

They reverse acute airflow obstruction.

Bronchodilators

(inhalation)

Beta 2 agonist

i.e. Albuterol (Ventolin)

(act on beta 2 pulmonary receptor increasing level s of cyclic adenosine monophosphate (cAMP) and relaxing smooth muscle. They can affect beta 1 receptor in heart causing tachycardia.)

Anticholinergic

i.e. Ipratropium (Atrovent)

(inhibit muscarinic cholinergic receptors reducing vagal tone of the airways which results in bronchodilation)

Systemic corticosteroids

i.e. Prenisone

(decrease inflammation by suppression of polymorpho-nuclear leukocyte leukocytes and fibroblasts as well as reducing capillary permeability)