Asthma

What are current trends in the prevalence and mortality rate of asthma?

Prevalence of asthma is increasing while mortality rates of asthma is decreasing due to effective treatment and management strategies for asthma, allowing more people to survive and live with the condition

Which sex has higher prevalence rates of asthma?

Children - boys

Adults - women

Which provinces have higher and lower rates of asthma?

Higher in Ontario and Nova Scotia

Lower in Northwest Territories, Yukon, and Nunavut

What are common risk factors of asthma onset during childhood?

-Family history of allergies and allergic disorders

-Exposure to airborne allergens during early childhood (pets, dust mites, cockroaches)

-Exposure to tobacco smoke during early childhood or in utero

-Low birth weight

-Hx of Respiratory distress syndrome

What is the relationship between asthma prevalence and SDOHs? (Income, Rural/Urban)

Asthma prevalence is not associated with household income

In Canada, asthma prevalence is not associated with living in rural or urban communities, but in other countries, such as the states, asthma is more prevalent in urban communities

Which genes are commonly involved with the prevalence of asthma?

*ADAM 33 gene - associated with asthma and bronchial hyperresponsiveness

Other genes include those involved with production of Il4, IL5, IL13, IgE antibodies, eosinophils, mat cells, adrenergic receptors, leukotrienes, and bronchial hyperresponsiveness

What are common risk factors of asthma onset during adulthood?

-Occupational exposure to low molecular weight sensitizers (isocyanates)

-Exposure to infectious agents, allergens, or pollution

-Smoking, Obesity, and hormonal influences in women

What are two common periods when asthma attacks most commonly occur during the year?

September epidemic - Children and adults

Christmas epidemic - Adults

What is a potential cause of the "September epidemic" of asthma attacks?

Occurs in children and adult populations

Thought to be associated with increased exposure to viruses, sensitizing allergens, and stress - which are common sources of asthma attacks

What is a potential cause of the "December epidemic" of asthma attacks?

Occurs in adult populations

Thought to be associated with exposure to infections and viral infections (such as the flu), especially as children return home for the winter break

What is the definition of asthma?

A chronic inflammatory disorder of the airways, characterized by dyspnea, chest tightness, wheezing, sputum production, and coughing - associated with airflow limitation and airway hyperresponsiveness. Inflammation is thought to be the main mechanism of the condition. Airway obstruction and exacerbations are usually reversible.

What are different classifications of asthma?

Mild

Moderate

Severe

Transient

Intermittent

Persistent

What are the 4 main pathophysiological processes involved in asthma?

1. Inflammation

2. Bronchospasm/Bronchoconstriction

3. Increased mucus production

4. Airway remodeling

What is extrinsic vs intrinsic asthma?

Extrinsic Asthma - Asthma caused by exposure to allergen, which binds to and activates IgE antibodies

Intrinsic Asthma - Asthma not caused by exposure to allergen

Both often have same immune cell involvement, and individuals often experience a combination of extrinsic and intrinsic asthma

What is extrinsic asthma?

aka atopic asthma, an allergic reaction caused by an exposure to an extrinsic allergen, resulting in activation of IgE antibodies

What is intrinsic asthma?

aka non-atopic asthma, asthma that results from a variety of triggers other than an extrinsic allergen.

Triggers can include

-Viral respiratory tract infections

-Hyperventilation

-Cold air/Weather changes

-Drugs

-Irritants

-Hormonal Changes and emotional upsets

-Airborne pollutants

-Gastroesophageal reflux disease

What is a theory as to how intrinsic triggers can result in an asthma attack?

Non-atopic triggers, such as inhaled irritants, emotional factors, and hormonal changes can cause parasymapthic stimulation through vagal pathways and initiate an asthma attack.

What occurs in the early phase response in asthma?

Allergens bind to IgE receptors on mast cells, resulting in mast cell degranulation and synthesis, releasing inflammatory mediators.

These inflammatory mediators open up mucosal intracellular junctions, allowing allergens to access submucosal mast cells, resulting in further inflammation

Allergens also bind to dendritic cells, which act as antigen presenting cells to activate naive T cells or TH2 cells, resulting in further immune activation

The overall result is inflammation, increased vascular permeability, increased mucus secretion, and bronchoconstriction

When does the early phase response occur in asthma?

Usually 10 to 20 minutes after triggering stimuli and can last up to 2 hours

What inflammatory mediators are released by mast cell degranulation during an asthma attack?

Mostly involved in the early phase response

Mast cell degranulation causes release of histamine, chemokines, and cytokines

What inflammatory mediators are released by mast cell synthesis during an asthma attack?

Mostly involved in late phase response

Mast cell synthesis causes production of leukotrienes (especially cysteinyl leukotrienes), cytokines, prostaglandin D2, and platelet activating factors

What is the role of the dendritic cell in the early phase response?

Binds to allergens once intracellular junctions open, presents allergens to naive T cells and TH2 cells to further activate immune cells during the late phase response

What causes mucosal intracellular junctions to open during the early phase response?

Inflammatory mediators released by mast cell degranulation (histamine, chemokines, interleukins, TNFa) result in opening of intracellular junctions, which allows allergens to access submucosal mast cells and bind to them, causing increased inflammation, vascular permeability, mucous secretion, and bronchoconstriction

What is the role of submucosal mast cells in the asthma response?

Mast cells located below the mucosal layer.

In the context of the asthma response, submucosal mast cells are activated when mucosal intercellular junctions open, allowing entry of antigens to bind to the submucosal mast cells and activate them.

This results in increased inflammation, vascular permeability, mucus secretion, and bronchoconstriction.

What are the physiological results of the processes that occur during the early phase asthma response?

Increased inflammation

Increased vascular permeability

Increased mucus secretion

Increased bronchoconstriction

What occurs in the late phase response in asthma?

Inflammatory mediators released during the early phase response results in expression of adhesion molecules and chemotaxis, causing activation of leukocytes, primarily eosinophils, basophils, neutrophils, TH2 lymphocytes, and macrophages

These leukocytes cause epithelial damage, edema, and mucociliary function, resulting in mucus accumulation, increased airway responsiveness, and bronchoconstriction

What leukocytes are activated during the late phase response in asthma?

Eosinophils (major basic protein -> epithelial damage and impaired mucociliary function)

Basophils (release of histamine and inflammatory mediators - IL4)

Neutrophils (acute inflammation response)

TH2 Lymphocytes (release of mast cell growth factors and activation of eosinophils

Macrophages (late inflammation response)

What causes epithelial injury and impaired mucociliary function in the late phase response in asthma?

Toxic byproducts released by eosinophils, such as major basic protein, results in epithelial injury and impaired mucociliary function, leading to stimulation of parasympathetic nerves that causes bronchoconstriction and increased mucus production

What is the role of major basic protein in asthma?

Released by eosinophils during the late phase asthma response, causes endothelial damage and changes to mucociliary function, resulting in parasympathetic stimulation that cause bronchoconstriction and increased mucus production

What are the physiological results of the processes that occur during the late phase response in asthma?

Endothelial damage

Bronchoconstriction

Increased airway responsiveness

Increased mucus production

Increased vascular permeability

What is the role of mast cells in the asthma response?

Mast cells are immune cells that contain granules and are activated by injury, chemicals, and during an immune response

In the context of asthma, mast cells are sensitized by binding of antigen specific IgE antibodies (from activation of TH2 cells which release IL4),

Once an antigen binds to the sensitized mast cell, the mast cell degranulates, resulting in the release of inflammatory mediators (primarily histamine), and synthesis, which results in the production of more inflammatory mediators (primarily leukotrienes, prostaglandins, and platelet activating factors).

These inflammatory mediators contribute to the inflammatory processes in an asthma attack

What is the role of histamine in an asthma response?

Vasodilation

Increased vascular permeability

Bronchoconstriction

Released by mast cell degranulation

What is the role of leukotrienes in an asthma response?

Vasodilation

Increased vascular permeability

Bronchoconstriction

Synthesized by mast cells

Effects are similar and complement histamine, however, the effects are more potent and prolonged compared to histamine

What is the role of chemokines in an asthma response?

Attracts leukocytes for the late phase asthma response (eosinophils, neutrophils, basophils, TH2 lymphocytes, macrophages)

What is the role of prostaglandin d2 in an asthma response?

Vasodilation

Increased vascular permeability

Bronchoconstriction

Synthesized by mast cells

What is the role of cysteinyl leukotrienes in the asthma response?

Especially involved in an asthma response

Synthesized by mast cells, eosinophils, and basophils

Causes slow and sustained bronchoconstriction and airway remodeling

Which type of leukotriene is most involved in the asthma response?

Cysteinyl leukotrienes - causes slow and sustained bronchoconstriction and airway remodeling

What is the role of platelet activating factors in the asthma response?

Platelet aggregation

Increased vascular permeability

Neutrophil activation

Eosinophil attraction

Bronchoconstriction

What is the role of TH2 lymphocytes in the asthma response?

Produce cytokines that act as growth factors for mast cells

Activates eosinophils, basophils, and mast cells by stimulating differentiation of B cells into IgE antibodies

What is the role of neutrophils in the asthma response?

First leukocytes present during an inflammation reaction

What is the role of eosinophils in the asthma response?

Regulates release of specific inflammatory mediators from mast cells

Role in endothelial damage and changes to mucociliary function in late phase asthma response, resulting in PNS stimulation -> bronchoconstriction and increased mucus production

What is the role of basophils in the asthma response?

Releases histamine and inflammatory mediators (IL-4) once activated via IgE

Which cytokines are involved in the asthma response which are mentioned in the web module?

TNF-a (Leukocyte activation, Airway Remodeling, Mucus Secretion, Bronchoconstriction)

IL1 (Bronchoconstriction, Mucus Secretion)

IL4 (Production and differentiation of B cells into IgE receptors)

IL5 (Eosinophils activation)

IL8 (Basophils, Neutrophils, and Eosinophil activation)

IL9 (Mucus Secretion)

IL13 (Mucus Secretion, Impaired Mucus Clearance, Bronchoconstriction)

What is the role of TNF-a in the asthma response?

Activates eosinophils

Activates neutrophils

Airway remodeling

Expression of adhesion molecules

Bronchconstriction via muscarinic stimulation

Increased mucus secretion via muscarinic stimulation

What is the role of IL-1 in the asthma response?

Bronchoconstriction via muscarinic stimulation

Increased mucus secretion via muscarinic stimulation

What is the role of IL-4 in the asthma response?

Stimulates activation, proliferation of production of antigen specific IgE antibodies from B cells

What is the role of IL-5 in the asthma response?

Activates eosinophils

What is the role of IL-8 in the asthma response?

Activates basophils, neutrophils, and eosinophils

Causes a more exaggerated inflammatory response through activation of these leukocytes

What is the role of IL-9 in the asthma response?

Increases mucus secretion

What is the role of IL-13 in the asthma response?

Increases mucus secretion

Impairs mucus clearance

Bronchoconstriction

Which inflammatory mediators cause bronchoconstriction in the asthma response?

Histamine (early phase)

Leukotrienes (late phase)

Platelet activating factor

Prostaglandins

Cytokines

>TNF-a*

>IL-1*

>IL-13

How does bronchoconstriction occur as a pathophysiological process of asthma?

Release of inflammatory mediators (histamine, leukotrienes, PAF, prostaglandins) causes bronchoconstriction)

In addition, autonomic nervous system dysregulation, caused by TNF-a and IL-1, results in stimulation of muscarinic receptors, resulting in increased mucus secretion and bronchoconstriction

What is autonomic nervous system dysregulation in asthma?

IL1 and TNFa alter parasympathetic input to the airways by increasing Ach levels and stimulating muscarinic receptors, resulting in bronchoconstriction and increased mucus secretion

What inflammatory mediators cause mucus hypersecretion in the asthma response?

Leukotrienes

Cytokines

>IL-9*

>IL-13*

>TNF-a

>IL-1B

>Epidermal growth factor receptor ligand

How does mucus hypersecretion occur as a pathophysiological process of asthma?

Inflammation, specifically from leukotrienes, IL-9, and IL-13, causes submucosal hyperplasia and goblet cell hypertrophy, resulting in increased mucus hypersecretion.

This results in increased airway responsiveness and creates mucus plugs that cause airway obstruction

Impaired mucociliary function inhibits the ability for the mucus to be cleared, resulting in more accumulation

What two processes cause airway obstruction in the asthma response?

Bronchoconstriction (TNF-a, IL-1, histamine, leukotrienes, PAF, prostaglandins)

Mucus hypersecretion (IL-9, IL-13, Leukotrienes)

What are goblet cells?

Responsible for producing mucus in the GI and respiratory tract.

In the asthma response, it is stimulated by leukotrienes, IL-9, and IL-13 to produce more mucus, resulting in goblet cell hypertrophy and increased mucus hypersecretion

How does airway remodeling occurs as a pathophysiological process of asthma?

Increased inflammation via infiltration of lymphocytes, eosinophils, mast cells, along with epithelial changes and basement membrane thickening, results in increased airway remodeling.

Airway remodeling involves increased goblet cells (increased mucus secretion), smooth muscle hypertrophy (thickened smooth muscle layer), and increased deposition of collagen in the airway (thickened lamina reticularis)

What is airway remodelling?

An increase in goblet cells, hyperplasia and hypertrophy of smooth muscle cells leading to a thickened smooth muscle cell layer, and increased airway deposition of collagen and other proteins resulting in thickening of the lamina reticularis with subepithelial fibrosis and increased vascularity in the airway wall.

Which inflammatory cells/mediators are major contributors to airway remodelling?

>TNF-a

>Cysteinyl leukotrienes

>Eosinophils

What is the end pathway of the asthma response?

Bronchial hyperresponsiveness

Airway obstruction

What are 5 assessments to diagnose/monitor asthma?

>Physical assessment Findings

>Lab results

>Radiological Findings

>Pulmonary Function Tests

>Peak Flow Monitoring

What are 4 key symptoms of an asthma attack?

Dyspnea (caused by low V/Q ratio)

Chest tightness (caused by air trapping and lung hyperventilation)

Cough (attempt to clear airway mucus - usually non productive)

Wheezing (passing of air through narrowed airways, usually expiratory)

What causes wheezing as a symptom of an asthma attack?

Mucosal hypersecretion and bronchoconstriction causes the airways to be narrowed, resulting in air being trapped. The wheeze is often expiratory as air is unable to exit the lungs

What causes dyspnea as a symptom of an asthma attack?

Mucosal hypersecretion and bronchoconstriction causes the airways to be narrowed, resulting in air being trapped. This causes the lungs to be hyperinflated, resulting in increased intrapleural and alveolar gas pressure. In addition, the narrowed airways causes air to flow to wider passages, resulting in uneven ventilation in the alveoli. Both of these lead to alveolar hypoventilation ->dyspnea as more work is needed to breath.

What causes dry coughing as a symptom of an asthma attack?

Mucosal hypersecretion results in accumulation in the airways. Coughing is used to try to expel the excess mucus out of the airways, however, coughing becomes less productive as air is trapped in the lungs and as the patient is breathing at higher residual lung volumes (close to maximum)

What causes chest tightening as a symptom of an asthma attack?

Mucosal hypersecretion and bronchoconstriction causes the airways of the lungs to be narrowed. This causes air trapping and leads to the lungs being hyperinflated, resulting in chest tightening

What causes initial respiratory alkalosis during an asthma attack?

Mucosal hypersecretion and bronchoconstriction causes airways to be narrowed, resulting in air trapping and uneven ventilation as the air flows to wider passages. Along with the ensuing lung hyperinflation, alveolar hypoventilation develops.

This results in a low V/Q ratio, where there is low ventilation compared to higher perfusion.

The high perfusion is compensated by vasoconstriction.

The low ventilation is compensated by hyperventilation, which can lead to initial respiratory alkalosis as more CO2 is expelled from the lungs.

What causes respiratory acidosis during a prolonged asthma attack?

Mucosal hypersecretion and bronchoconstriction causes airways to be narrowed, resulting in air trapping and uneven ventilation as the air flows to wider passages. Along with the ensuing lung hyperinflation, alveolar hypoventilation develops.

This results in a low V/Q ratio, where there is low ventilation compared to higher perfusion.

The high perfusion is compensated by vasoconstriction.

The low ventilation is compensated by hyperventilation, which can lead to initial respiratory alkalosis as more CO2 is expelled from the lungs.

As the attack progresses and the patient breaths closer to their functional residual capacity, they are unable to compensate for the low V/Q mismatch. This results in an accumulation of CO2 as the patient is unable to expel it form the lungs, and consequently respiratory acidosis

What is the normal ABG blood pH range?

pH 7.35-7.45

What is the normal ABG pCO2 range?

pCO2 (partial pressure of CO2) 35-45

What is the normal ABG HCO range?

HCO (bicarbonate) 22-26

What is the normal ABG pO2 range?

pO2 (partial pressure of O2) 80-100

What are typical ABG results initially during an asthma attack?

Usually respiratory alkalosis, hypoxemia may or may not be present

pH >7.35

pCO2 <35

pO2 norm or <80

What are typical ABG results during a prolonged asthma attack?

Usually respiratory acidosis with hypoxemia

pH <7.35

pCO2 >45

pO2 <80

What are typical physical assessment for a patient presenting with an asthma attack?

Inspection

->Increased work of breathing

->Use of accessory muscles

->Prolonged Expiration

->Wheezing

->Coughing

->Inability to maintain a conversation

Auscultation

->Wheezing (some air movement)

->Distant/Quiet breath sounds (air not moving, medical emergency)

->Crackles (infection)

Palpitation

->Skin perfusion

->Skin temp

->Capillary refill

->Pain

->Masses

->Crepitus, indicating rubbing of tissues or air where it is not supposed to be

VS

Tachypnea (Compensation for low ventilation)

Hypoxemia (Low oxygen due to low ventilation)

Tachycardia (Due to stress, anxiety, or adverse effects of medications -B2 agonists)

What assessments should be performed during the inspection phase of a physical assessment with a patient presenting with an asthma attack?

->Increased work of breathing

->Use of accessory muscles

->Prolonged Expiration

->Wheezing

->Coughing

->Inability to maintain a conversation

What assessments should be preformed during the auscultation phase of a physical assessment with a patient presenting with an asthma attack?

Assess for breath sounds

->Wheezing (some air movement)

->Distant/Quiet breath sounds (air not moving, medical emergency)

->Crackles (infection)

What assessments should be preformed during the palpitation phase of a physical assessment with a patient presenting with an asthma attack?

->Skin perfusion

->Skin temp

->Capillary refill

->Pain

->Masses

->Crepitus, indicating rubbing of tissues or air where it is not supposed to be

What are common vital signs for a patient presenting with an asthma attack?

Tachypnea (Compensation for low ventilation)

Hypoxemia (Low oxygen due to low ventilation)

Tachycardia (Due to stress, anxiety, or adverse effects of medications -B2 agonists)

What are common findings on a chest x-ray for a patient presenting with an asthma attack?

Hyperinflation of the lungs

Flattening of the hemidiaphragms may or may not be present

Note for any infections (viral or bacterial)

What is the most objective measurement tool that can be used to measure lung function?

Spirometry

What are 4 values measured by spirometry to assess for asthma?

FVC - Forced vital capacity

FEV1 - Forced expiratory volume in 1 second

FEV1/FVC - Ratio between FEV1 and FVC

FEF (25-75%) - Forced mid expiratory flow between 25-75% of forced vital capacity

These are all values measured by a spirometer

What is a bronchial provocation test?

A patient is given histamine, methacholine (PANS stimulation), or cold air to artificially stimulate bronchoconstriction.

A spirometry is used to measure the patient's lung function to assess for narrowed airways.

A key finding is also reversible airway obstruction, where there is a 12% improvement in FEV1 or FVC after the induced bronchoconstriction, indicating reversible airway obstruction, which is characteristic of asthma (compared to COPD)

What is a positive diagnosis of asthma in a bronchial provocation test?

Lowered lung function during provocation

12% improvement in FEV1 or FVC post challenge, indicating reversible airway obstruction

What is peak flow monitoring?

A monitoring tool used for patients with asthma that measures how quickly a patient can exhale, and comparing that value to the patient's personal best to assess how well their asthma is being controlled (similar to a CBG for patients with diabetes)

What is the green zone in peak flow monitoring?

PEF >80% of personal best

Indicates that asthma is being well controlled

What is the yellow zone in peak flow monitoring?

PEF 50-80% of personal best

Indicates that asthma is not being well controlled

Patient should use a short acting bronchodilator and contact their health care professional if it is ineffective

What is the red zone in peak flow monitoring?

PEF < 50% of personal best

Constitutes a medical emergency, patient should contact emergency services, use a short acting bronchodilator, and increase the dosage if necessary

What are pharmacological therapies for long-term control/maintenance of asthma?

1. Inhaled corticosteroids (Fluticasone)

2.Systemic corticosteroids (Prednisone)

3. Long acting b2 agonist (Salmetrol)

4. Leukotriene modifiers (Montelukast)

5. Mast cell stabilizers (Cromolyn)

6. Monoclonal antibody (Omalizumab)

What are pharmacological therapies for quick relief of an asthma attack?

1. Short acting b2 agonist (Albuterol)

2. Short acting anticholinergics (Ipratropium)

3. Systemic corticosteroids (Prednisone)

What is the best practice for pharmacological therapies for quick relief of an asthma attack?

Use of beta 2 agonist

Anticholinergics as add on therapy

What is the best practice for pharmacological therapies for control/maintenance of an asthma attack

Use of inhaled corticosteriods

What is the mechanism of action of beta 2 agonists?

Acts on adrenergic receptors (SNS) to increase cAMP and promote bronchodilation. Binds selectively to receptors on the lungs, however, can still cause tachycardia if it binds to the heart

What is the mechanism of action of anticholinergics?

Inhibits muscarinic receptors (PANS), causing bronchodilation

What is the mechanism of action of corticosteriods?

Blocks production of inflammatory mediators from COX (prostaglandin, thromboxane) and lipoxygenase (leukotrienes) pathways, suppressing leukocytes and reducing capillary permeability. Overall, reduces/inhibits the inflammatory response in asthma

What is the mechanism of action of leukotriene modifiers?

Inhibits leukotrienes, reducing/inhibiting the inflammatory response in asthma

What is the mechanism of action of mast cell stabilizers?

Inhibits mast cell degranulation and release of inflammatory mediators when an antigen is bound

What is the mechanism of action of monoclonal antibodies?

Inactivates endogenous IgE antibodies to prevent basophil and mast cell sensitization and activation during an asthma attack

What are patient teaching topics for a patient with asthma?

-Avoid triggers and recognize signs of an impending asthma attack

-Make a written action plan that includes medication titration and symptom management

-Peak flow monitoring

-Medication adherence

-Proper inhaling technique and use of medication delivery devices (inhalers, spacers, etc.)