Respiratory Emergencies - Asthma Class Notes

Topic: ====== - Pathophysiology and management of reactive airway disease - Respiratory pharmacology Objectives: =========== 1. Review airway physiology. 2. Explain the inflammatory process and how it contributes to bronchoconstriction. 3. List asthma triggers. 4. Describe the cli...

Topic: ====== - Pathophysiology and management of reactive airway disease - Respiratory pharmacology Objectives: =========== 1. Review airway physiology. 2. Explain the inflammatory process and how it contributes to bronchoconstriction. 3. List asthma triggers. 4. Describe the clinical presentation of an asthma patient. 5. Explain how end tidal monitoring is beneficial in monitoring a patient suffering from an asthma attack. 6. Differentiate between asthma and status asthma. 7. Explain the best evidenced based treatment for asthma including the roles of beta ~2~ agonists, anticholinergics, steroids and sympathomimetics. NOCP: ===== 4.3.e -- Conduct respiratory system assessment and interpret findings. 4.5.a -- Conduct oximetry testing and interpret findings. 4.5.b -- Conduct end tidal carbon dioxide monitoring and interpret findings. 5.8.b -- Follow safe process for responsible medication administration. 5.8.m -- Administer medication via inhalation. 6.1.c -- Provide care to patients experiencing signs & symptoms involving respiratory system. Physiology of Airway Disease -- Asthma ====================================== Review of Airway Physiology =========================== - Air moves through upper airways (mouth, nose) into pulmonary airways (trachea, bronchioles, alveoli). As we move down respiratory tract, cartilaginous structures in trachea and upper bronchi give way to smooth muscle. Results in airways having the ability to contract & relax. - Alveoli are the site of gas exchange. Air must get to alveoli & alveoli must work. - Airways are innervated by autonomic nervous system. - Parasympathetic stimulation through the vagus nerve and cholinergic receptors causes bronchoconstriction. - Sympathetic stimulation through Beta 2 adrenergic receptors increases bronchodilation. - Normally parasympathetic overrides sympathetic a bit so always in a state of slight bronchoconstriction. - With need for increased airflow (exercise) vagal mediated bronchoconstrictor tone is inhibited and bronchodilator effects of sympathetic nervous system increase. - Bronchial smooth muscle also responds to inflammatory mediators to produce bronchoconstriction. **Inflammatory Mediators:** A chemical that is released by a mast cell that causes inflammation. **Mast Cell:** -------------- Mast cells, also known as mastocytes or labrocytes, are a type of white blood cell that play a crucial role in the immune system. [They are found in various tissues throughout the body, particularly around blood vessels, nerves, and near surfaces exposed to the external environment, such as the skin, lungs, and digestive tract](https://en.wikipedia.org/wiki/Mast_cell). **Key Functions of Mast Cells:** 1. **Allergic Reactions**: Mast cells are well-known for their role in allergic reactions. [They contain granules rich in histamine and heparin, which are released during allergic responses, leading to symptoms like itching, swelling, and redness^1^](https://en.wikipedia.org/wiki/Mast_cell). 2. **Immune Defense**: They act as sentinels, detecting and responding to pathogens like bacteria, viruses, and parasites. [When they recognize a threat, they release various chemicals to alert and recruit other immune cells](https://my.clevelandclinic.org/health/body/mast-cells). 3. **Wound Healing and Tissue Repair**: Mast cells contribute to wound healing and the formation of new blood vessels (angiogenesis).  4. [**Regulation of Blood Flow**: By releasing histamine, mast cells can increase blood flow to specific areas, which is crucial during immune responses and healing processes](https://my.clevelandclinic.org/health/body/mast-cells). **Clinical Significance:** - **Mast Cell Activation Syndrome (MCAS)**: This condition occurs when mast cells release too many chemicals, leading to chronic allergic symptoms and other systemic issues. - [**Anaphylaxis**: A severe, potentially life-threatening allergic reaction that involves widespread mast cell activation and massive histamine release](https://my.clevelandclinic.org/health/body/mast-cells) Mast cells play a significant role in the pathogenesis of asthma, particularly allergic asthma. Here's how they are involved: **Key Roles of Mast Cells in Asthma:** 1. **Release of Mediators**: Mast cells release various chemical mediators such as histamine, leukotrienes, and prostaglandins when they encounter allergens. [These mediators cause inflammation, bronchoconstriction (narrowing of the airways), and increased mucus production](https://erj.ersjournals.com/content/56/1/2001337). 2. **Bronchoconstriction**: Histamine and other mediators released by mast cells lead to the contraction of airway smooth muscles, resulting in bronchoconstriction. [This is a hallmark of asthma, causing difficulty in breathing](https://www.mdpi.com/1422-0067/20/7/1733). 3. **Inflammatory Response**: Mast cells contribute to both the early-phase and late-phase inflammatory responses in asthma. [The early-phase response occurs within minutes of allergen exposure, while the late-phase response can occur hours later, leading to sustained inflammation and airway hyperresponsiveness](https://erj.ersjournals.com/content/56/1/2001337). 4. **Recruitment of Other Immune Cells**: Mast cells release cytokines and chemokines that attract other immune cells, such as eosinophils and T cells, to the site of inflammation. [This amplifies the inflammatory response and contributes to chronic asthma symptoms](https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00821/full). **Immunoglobulin** ------------------ - Immunoglobulins, are also known as antibodies --------------------------------------------- - They are proteins produced by white blood cell in response to exposure to an antigen -- viruses, bacteria, environmental antigens (pollen), tumor antigens. ----------------------------------------------------------------------------------------------------------------------------------------------------------- There are several types of immunoglobulins, each with a specific function: -------------------------------------------------------------------------- - Immunoglobulin A (IgA): Found in mucous membranes, such as the lining of the respiratory and digestive tracts, as well as in saliva and tears. ---------------------------------------------------------------------------------------------------------------------------------------------- - Immunoglobulin G (IgG): The most common type, found in all body fluids. It protects against bacterial and viral infections. --------------------------------------------------------------------------------------------------------------------------- - Immunoglobulin M (IgM): The first antibody produced in response to an infection, providing initial defense. ----------------------------------------------------------------------------------------------------------- - Immunoglobulin E (IgE): Associated with allergic reactions and found in the lungs, skin, and mucous membrane. ------------------------------------------------------------------------------------------------------------- **The Pathogenesis of Asthma** ------------------------------ The pathogenesis of asthma from an immunological perspective involves a complex interplay of immune cells and mediators in response to antigen exposure. -------------------------------------------------------------------------------------------------------------------------------------------------------- 1. Antigen Exposure: When an individual with asthma is exposed to an allergen (antigen), such as pollen, dust mites, or pet dander, the immune system recognizes these substances as harmful. ------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------ 2. Dendritic Cells and Antigen Presentation: Dendritic cells in the airway epithelium capture the antigen and process it. These cells then migrate to the lymph nodes, where they present the antigen to naïve T-helper (Th) cells. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 3. Th2 Cell Differentiation: In individuals with asthma, there is a skewing towards a Th2 immune response. The naïve Th cells differentiate into Th2 cells, which are central to the allergic response. Th2 cells release cytokines called interleukin --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 4. IgE Production: Interleukin tells B cells to produce immunoglobulin E (IgE) antibodies specific to the allergen. These IgE antibodies bind to high-affinity receptors on the surface of mast cells and basophils. This sensitizes the mast cell to these specific antigens. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 5. Mast Cell Activation: Upon subsequent exposure to the same allergen, the allergen cross-links the IgE antibodies on mast cells, leading to their activation and degranulation. This releases a variety of mediators, including histamine, leukotrienes, and prostaglandins, which contribute to bronchoconstriction, increased mucus production, and vascular permeability. --------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 6. Eosinophil Recruitment and Activation: The activation of eosinophils to the site of inflammation causes them to release cytokines that further damage the airway epithelium and perpetuate inflammation. -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- 7. Chronic Inflammation and Airway Remodeling: The ongoing inflammation leads to structural changes in the airways, known as airway remodeling. This includes thickening of the airway walls, increased smooth muscle mass, and fibrosis, which contribute to the chronic nature of asthma and its symptoms -------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------------- **Asthma -- Intrinsic vs. Extrinsic** Intrinsic and extrinsic asthma are two subtypes of asthma that differ primarily in their triggers and underlying mechanisms. **Extrinsic Asthma (Allergic Asthma):** - Onset in childhood and adolescence - Often includes a family history. - Often have other associated allergic disorders (hay fever, eczema) - Attacks are related to exposure to specific allergens. - [**Triggers**: Caused by external allergens such as pollen, dust mites, pet dander, mold, and certain foods](https://asthma.net/living/extrinsic-vs-intrinsic). - **I**[**mmune Response:** Involves an immune response where the body produces IgE antibodies in reaction to allergens](https://asthma.net/living/extrinsic-vs-intrinsic). - [**Commonality**: It is the most common form of asthma, affecting 60-90% of people with asthma](https://www.medicalnewstoday.com/articles/325536). - [**Symptoms**: Symptoms include wheezing, coughing, chest tightness, and shortness of breath, typically triggered by exposure to allergens](https://www.medicalnewstoday.com/articles/325536). **Extrinsic -- Early Stage** - Occurs within minutes of exposure to an allergen. - **Mechanism:** When an allergen is inhaled, it binds to IgE antibodies on mast cells in the airways. This triggers the release of inflammatory mediators such as histamine, leukotrienes, and prostaglandins. - **Symptoms:** These mediators cause immediate bronchoconstriction, leading to symptoms like wheezing, coughing, shortness of breath, and chest tightness **Extrinsic -- Late Stage** - Late phase response occurs within 4-8 hours of exposure. - **Mechanism**: The late phase is characterized by a second wave of inflammation. This involves the recruitment of additional inflammatory cells, such as eosinophils, neutrophils, and T-lymphocytes, to the airways. - **Symptoms:** The inflammation during this phase can cause prolonged bronchoconstriction, increased mucus production, and further airway hyperresponsiveness. Symptoms can be more severe and persistent compared to the early phase. Epithelial cell injury occurs with changes in mucociliary function, reduced clearance of secretions, increased vascular permeability, edema, bronchospasm and continued heightened airway responsiveness. **Intrinsic Asthma (Non-Allergic Asthma):** - [**Triggers**: Triggered by non-allergic factors such as respiratory infections, stress, exercise, cold air, smoke, and pollution](https://www.medicalnewstoday.com/articles/325536). Depending on the trigger, the physiological mechanism that induces symptoms of asthma can vary. - Respiratory Infections: Viral infections can damage the epithelial cells lining the airways, leading to an inflammatory response. This inflammation increases airway sensitivity and can cause bronchoconstriction, where the muscles around the airways tighten1. - Exercise: Physical activity, especially in cold or dry air, can lead to loss of heat and moisture in the airways. This can cause the airways to narrow and trigger an asthma attack. The exact mechanism involves the release of inflammatory mediators like histamine and leukotrienes. - Air Pollutants: Pollutants such as smoke and smog can irritate the airways, leading to oxidative stress and inflammation. This inflammation can cause the airways to become hyperresponsive, leading to bronchoconstriction. - Weather Conditions: Cold air can cause the airways to constrict, while sudden changes in weather can trigger inflammation and bronchospasm. The cold air can also dry out the airways, leading to irritation and increased mucus production. - Stress: Emotional stress can lead to the release of stress hormones like cortisol and adrenaline. These hormones can cause changes in breathing patterns and increase airway reactivity, leading to asthma symptoms. - - [**Immune Response**: Does not involve an allergic reaction or the production of IgE antibodies](https://www.verywellhealth.com/intrinsic-asthma-5201485). - **Commonality**: Less common than extrinsic asthma, occurring in 10-40% of people with asthma. [It is more prevalent in adults and often develops later in life](https://asthma.net/living/extrinsic-vs-intrinsic)[^2^](https://www.medicalnewstoday.com/articles/325536). - [**Symptoms**: Like extrinsic asthma, including wheezing, coughing, chest tightness, and shortness of breath, but triggered by non-allergic factors](https://www.medicalnewstoday.com/articles/325536). A small population of patient may experience an asthma attack in response to ASA or NSAID use. - Believed to be an abnormality in the metabolism of arachidonic acid (AA). - Cyclooxygenase (COX) is an enzyme in arachidonic acid metabolism. - Two types - COX 1 -- involved in synthesis of protective prostaglandins. - COX2 -- involved in synthesis of inflammatory mediators and bronchoconstriction. - Hypothesized that in ASA induced asthma COX1 is inhibited and shunts AA metabolism away from the production of prostaglandins and towards COX2 generation resulting in the production of inflammatory mediators and bronchoconstriction. - ***This is important when the symptom relief medications ASA, ibuprofen and ketorolac are introduced.*** **Key Differences:** - **Cause**: Extrinsic asthma is caused by an allergic reaction to external allergens, while intrinsic asthma is triggered by non-allergic factors. - [**Prevalence**: Extrinsic asthma is more common and often starts in childhood, whereas intrinsic asthma is less common and typically begins in adulthood](https://www.medicalnewstoday.com/articles/325536) ***Distinction between extrinsic and intrinsic is less useful in clinical setting because often asthma sufferers manifest overlapping characteristics of both extrinsic and intrinsic asthma.*** The Asthma Patient ================== - Patients are often younger. - Asthma is often diagnosed early in life. Patients will tell you they are having an asthma attack. - Patients often already know their PMHx. Important to do SAMPLE history. - Consider asking if signs & symptoms are similar to previous attacks. - Auscultate - Expose the chest looking for work of breathing, accessory muscle use. Clinical features of asthma --------------------------- - Asthmatics can exhibit wide range of symptoms from episodic wheezing and chest tightness to acute, immobilizing attacks. - Attacks differ from person to person. - May occur spontaneously or in response to a trigger. - Often worse at night due to late response to allergen exposure and circadian variations in bronchial reactivity. - During an attack, airways narrow from bronchospasm, edema, and mucous plugging. - Expiration becomes prolonged. - Forced expiratory volume and peak expiratory flow rate decrease. - **Prolonged attacks result in air trapping behind occluded and narrow airways causing hyperinflation and increased residual volume (RV)** - Accessory muscle use may be required to overcome tension in lungs. Requires energy. - Causes dyspnea and fatigue. - Hypoxemia and hyperinflation = increase in pulmonary artery pressure and increased right sided cardiac workload. - Mild attack may present with chest tightness, tachypnea with prolonged expiratory phase, mild wheezing, cough. - More severe attack involves accessory muscle use, distant breath sounds, fatigue, loud wheezing, fatigue, diaphoresis, fatigue, anxiety, fatigue, and apprehension. - Severe attack results in markedly decreased airflow resulting in inaudible breath sounds with diminished wheeze, ineffective cough. Often onset of respiratory failure. - May present in a tripod position. It has been thought that the tripod position optimizes the mechanics of respiration by taking advantage of the accessory muscles of the neck and upper chest to get more air into the [lungs](https://en.wikipedia.org/wiki/Lungs). With the position of the arms secure, contraction of the [pectoralis](https://en.wikipedia.org/wiki/Pectoralis_major_muscle) results in elevation of the anterior wall of the chest. Asthma and ETCO~2~ ------------------ - Asthma is a problem of ventilation more than oxygenation. - During an asthma attack accessory muscles are needed to push air out. This causes a prolonged expiratory phase and wheezing from turbulent airflow through constricted airways. - During severe asthma attacks, patients cannot fully exhale before taking their next breath in. - Carbon dioxide builds up in the lungs as air gets trapped in the alveoli. Unless corrected, patients eventually tire from increased work of breathing and lose the ability to compensate. - The waveform represents air movement throughout the respiratory cycle and is normally rectangular shaped. Bronchoconstriction causes air to be released unevenly from the alveoli, which makes the capnography waveform appear rounded, like a shark fin. - Assess capnography, work of breathing, lung sounds and pulse-oximetry to determine the severity of an asthma attack. - Capnography displays real-time feedback on respiratory rate and the amount of CO~2~ eliminated at the end of exhalation, which helps determine the severity of an asthma attack. - End-tidal CO~2~ is normally 35-45 mm Hg. - When an asthma attack begins, bronchoconstriction triggers an increased respiratory rate to compensate and an excess of CO2 to be eliminated. - End-tidal CO~2~ will start to go down (below 35 mmHg) - As the attack progresses, air becomes trapped in the lower airways and the alveoli hyperinflate. - Respiratory failure begins when patients are unable to effectively eliminate CO2, and air trapping worsens with each breath the patient takes in. - This causes ETCO2 to rise above normal and the shark-fin waveform to be more pronounced. - In severe asthma, ETCO~2~ falls due to increased respiratory rate. - If untreated, ETCO~2~ will rise to "normal" level. - Signals the beginning of respiratory failure from air trapping and fatigue. - In the end stage, ETCO~2~ will climb to large numbers signaling impending respiratory failure. (even over 100mmHg) - Ventilate and treat to achieve ETCO~2~ 50-60mmHg. - Respiratory acidosis will not be too dangerous. - Limit hyperinflation and air trapping. - Limit intrathoracic pressure (lower risk of tension pneumothorax) - Permissive hypercapnia Status Asthmaticus ------------------ - A severe asthma attack that does not respond to treatment with an adequate amount of commonly used bronchodilators (beta adrenergic stimulants) - Is progressive and life threatening. - Usually related to inflammation of airways and mucosal plugging of airways - Inflammation and mucosal plugging cause hyperreactivity of airways perpetuating bronchospasm. - Hypoxemia, acidosis result **Signs & Symptoms** - Exhaustion, decreasing alertness, obtunded, hypoxia, cyanosis, No breath sounds. - Airways become so constricted that no air movement is occurring. **Treatment** - Support ventilations but allow as much passive exhalation as possible. - Consider administration of epinephrine IM A technique of "lateral chest compression" is described in which one provider compresses the ribcage laterally to force exhalation of trapped air. There are no systematic studies evaluating the effectiveness of this technique; however, several case reports and a few series support its effectiveness. A few historic case reports describe successful manual decompression of hyperexpanded lungs in arrested patients via thoracotomy, usually with dismal outcomes. Chronic Asthma -------------- Management of Acute Asthma -------------------------- ### Beta 2 Agonists - Salbutamol - Salbutamol is a β~2~-adrenergic agonist and thus it stimulates β~2~ adrenergic receptors. - The binding of salbutamol to β~2~ receptors in the lungs results in relaxation of bronchial smooth muscles. - In addition to bronchodilation, salbutamol inhibits the release of bronchoconstricting agents from mast cells, inhibits microvascular leakage, and enhances mucociliary clearance. - Quick onset of action therefore the preferred rescue medication in incidence of asthma ### Corticosteroids -- Dexamethasone - Work by decreasing inflammation. - Dexamethasone is a potent glucocorticoid. - It works by increasing surfactant levels and improving pulmonary circulation. - ### Anticholinergics -- Ipratropium Bromide - Is an antagonist of the muscarinic acetylcholine receptor in the parasympathetic nervous system. - Inhibits bronchial secretions & constriction. - Slower onset of action with longer duration - Often given after salbutamol or used as a maintenance drug. ### Sympathomimetics - Epinephrine - A sympathomimetic capable of working on both alpha and beta receptors. - Powerful bronchodilator but also causes vasoconstriction, increased cardiac output. - Used in stats asthma when patient is no longer able to move air to support their own ventilations.