CMS250 - Wk 5, Asthma

• Asthma is a respiratory disorder.
• Janis Li, ND, teaches CMS250, and this presentation discusses asthma.
• It's important to recognize an asthma attack and understand asthma management.

Learning Outcomes for Asthma

• Define asthma according to sources like the National Asthma Education and Prevention Program and GINA.
• Diagnose asthma signs, symptoms, and clinical manifestations across age groups.
• Understand asthma's heterogeneity.
• Analyze pulmonary function tests, bronchoprovocation testing, spirometry, arterial blood gases, and chest radiography in diagnosing asthma.
• Consider medical history, physical exams, and exacerbating factors for diagnosing and managing asthma.
• Classify asthma severity and differentiate uncontrolled, severe, and refractory asthma.
• Identify triggers and exacerbating factors like allergens, viral infections, occupational exposure, drugs, and NSAID sensitivity
• Differentiate asthma from conditions like COPD, heart failure, and GERD.
• Evaluate investigations like lung function tests and blood tests for diagnosing asthma.
• Evaluate asthma education, control re-evaluation, inhaler adherence, and monitoring for disease management.
• Investigate asthma definition, characteristics, prevalence, epidemiology, prognosis, and progression.
• Identify risk factors for mortality and morbidity, including preventing asthma-related mortality and exacerbations.
• Understand the role of specialist care for acute exacerbations.
• Refer patients with persistent and severe symptoms despite optimal treatments for allergist evaluation.
• Critique the etiology, risk factors, triggers, comorbidities, and etiologic environmental factors of asthma.
• Evaluate the role of allergens, irritants, exercise, weather changes, stress, GERD, and medications as triggers for airway narrowing.
• Categorize asthma phenotypes and endotypes, the role of human and environmental microbiomes, and health disparities.
• Examine clinical heterogeneity and airway inflammation.
• Infer the association between asthma and other conditions like asthma-COPD overlap, exercise-induced symptoms, pregnancy, espiratory disease, and the impact of airway narrowing triggers.
• Investigate the definition, causes, and characteristics of occupational asthma, differentiating between sensitizer-induced and irritant-induced asthma.

Epidemiology

• Asthma prevalence is 8-10% in the USA and approximately 4.3% worldwide.
• It occurs more in children versus adults (8.4% and 7.7% respectively).
• Asthma in children is more common in males, with a 2:1 male-to-female ratio.
• Occurs more frequently in adult females.
• Morbidity and mortality rates are highest for urban minority groups, low-income populations, and children.
• Hospitalization rates are highest among Black persons and children.
• Death rates are highest among Black persons aged 15-24 years in the USA.
• The ethnicity with the greatest prevalence in the USA is the Puerto Rican population.

Definition

• According to the GINA Global Strategy for Asthma Management and Prevention Report, asthma is a heterogeneous disease characterized by chronic airway inflammation resulting in airflow limitation.
• According to the National Asthma Education and Prevention Program's Expert Panel Report, asthma is a chronic inflammatory disease of the airways with many cells and cellular elements playing a role.
• These cells and cellular elements include mast cells, eosinophils, neutrophils, T lymphocytes, macrophages, and epithelial cells.

Characteristics

• Variable airway obstruction or airflow limitation are key asthma characteristics.
• Airway hyperresponsiveness is another characteristic of asthma.
• Airway inflammation is a characteristic of asthma.

Timing

• Asthma has recurrent and intermittent patterns and is episodic in most patients.
• Most patients experience periods with no or only mild symptoms; some patients experience persistent or chronic symptoms.
• Symptoms are frequently worse at night or in the early morning.
• Exacerbations, known as "flares," are periods of increased disease activity identified by increased airflow obstruction, symptoms, and medication use.

Endogenous Risk Factors

• Endogenous risk factors include atopy.
• Airway hyperresponsiveness, ethnicity, gender, and genetic predisposition are endogenous risk factors.

Environmental Risk Factors

• Allergens, obesity, and occupational sensitizers are environmental risk factors.
• Parasitic and respiratory infections are environmental risk factors.
• Socioeconomic status and tobacco smoking are environmental risk factors.
• Premature birth, low birth weight, vitamin D deficiency, and low intake of omega-3 fatty acids are environmental risk factors.

Microbial influence

• An overview of potential microbial influences on asthma.
• Green-type denotes protective factors.
• Red-type denotes risk factors for asthma development.

Exacerbating Factors

• Respiratory infections, especially acute viral infections like rhinovirus, commonly trigger asthma exacerbations.
• Allergens include house dust mites, animal dander, cockroach, indoor fungi/mold, perennial allergens, and seasonal pollens.
• Weather changes like cold air and thunderstorms can trigger asthma exacerbations.
• Drugs, including ACE inhibitors, aspirin, beta-blockers, and NSAIDs, can exacerbate asthma.
• Other comorbidities like chronic rhinosinusitis, food allergy, GERD, obesity, and pregnancy can lead to asthma exacerbations.
• Psychological difficulties, socioeconomic issues, exercise, and hyperventilation can exacerbate asthma.
• Extreme emotional expression (laughing, hard crying, stress), irritants (household sprays, paint fumes, perfumes, organophosphates), sulfur dioxide, pollutant gases, and tobacco smoking can worsen asthma.
• Poor adherence to inhaler medications or incorrect inhaler technique can lead to the worsening of asthma.

Past classification based on atopy

• Atopic (extrinsic) asthma: Suspected role of allergens as etiologic factors.
• There is an exaggerated immune response, including immunoglobin E (IgE) activation and mast cell degradation.
• Patients present with other atopic diseases such as seasonal allergic rhinitis, allergic conjunctivitis, and atopic dermatitis.
• Nonatopic(intrinsic) asthma constitutes ~10% of asthmatics: onset may be later in disease, (adult-onset asthma), more severe and persistent symptoms, more sensitivity to aspirin, and commonly have nasal polyps

Clinical Phenotypes

• Phenotypes are distinct groups defined by clustering techniques.
• The four main phenotypes are early-onset mild allergic asthma, early-onset allergic moderate to severe remodeled asthma, late-onset nonallergic eosinophilic asthma, and late-onset noneosinophilic nonallergic asthma.
• There can be significant overlap between phenotypes.
• Other identified phenotypes include aspirin-exacerbated respiratory disease and exercise-induced asthma.

Clinical Endotypes

• Endotypes are groups defined by divergent molecular and immunologic mechanisms.
• Two main endotypes are T2-high and T2-low.
• T2-high asthma endotypes (aka type 2 asthma) show high levels of Th2 cytokines (IL-4, IL-5, IL-13) and include allergic and late-onset T2-high asthma.
• T2-high asthma endotypes (aka type 2 asthma) also includes aspirin/NSAID-induced respiratory disease and exercise-induced asthma.
• T2-low asthma endotypes (aka non-type 2 asthma) show low levels of Th2 cytokines (IL-4, IL-5, IL-13).
• T 2-low asthma endotypes (aka non-type 2 asthma) include very late-onset asthma, neutrophilic asthma, paucigranulocytic asthma, and obesity-associated asthma.

Type 2 Asthma

• T2-high asthma endotypes (aka type 2 asthma) include type 2 inflammation.
• T2-high asthma endotypes involve activation of T helper type 2 cells, eosinophils, and mast cells with production of cytokines like IL-4, IL-5, and IL-13.
• It usually begins in childhood linked with allergic diseases (e.g., eczema, allergic rhinitis, food allergy).
• Aeroallergen sensitization is frequently accompanied in type 2 asthma.
• Exposure to inhaled allergens causes symptoms immediately.
• Late asthmatic response includes symptoms that develop 4-6 hours after allergen exposure.
• It may develop as a sequelae of repeated viral infections in early life.

Non-type 2 Asthma

• T2-low asthma endotypes (aka non-type 2 asthma) do not include type 2 inflammation.
• Non-type 2 asthma encompasses heterogeneous mechanisms which implicate T helper type 1 or 17 cells and production of cytokines such as IL-6, IL-8, IL-1β, and interferon-y.
• They usually occur in adults.
• They may have more severe disease than type 2 asthma.

Exercise-Induced Asthma

• Exercise-induced asthma is a phenotype that falls into category of type 2 asthma.
• It includes worsening of asthma symptoms on or after physical exercise.
• Its trigger is thought to be hyperventilation and drying of the airway mucosa.
• Mast cell release and bronchospasm are a result of the trigger.

Aspirin-Exacerbated Respiratory Disease

• Aspirin-exacerbated respiratory disease (AERD) is a phenotype that makes up 5-10% of cases, which falls into category of type 2 asthma.
• It causes severe asthma exacerbations after ingesting cyclooxygenase-1 inhibitors (aspirin and NSAIDs).
• People with it can generally tolerate cyclooxygenase-2 inhibitors and acetaminophen.
• Its presentation is with eosinophilia, sinusitis, and nasal polyps.

Obesity-Related Asthma

• Obesity-related asthma falls into the category of non-type 2 asthma and often has its onset in childhood.
• This condition includes prominent respiratory symptoms, with the airway inflammation observed most often in obese people.
• Frequent asthma attacks can be connected with the condition.
• The possible links between obesity and asthma can be the mechanical consequences of obesity decreasing the amount of tidal volume, the shared environmental factors (pollution), pro-inflammatory cytokines from fat cells, and microbiome or food changes.

Occupational Asthma

• Occupational asthma makes up 5% of all asthma cases in adults.
• Specific worker exposure to a particular agent can trigger it.
• Sensitizer-induced asthma, a type of occupational asthma, results from a specific sensitizing agent through an identified immunologic mechanism.
• Irritant-induced asthma, a type of occupational asthma, is caused by exposure to irritant compounds.
• Work-exacerbated asthma, where nonspecific irritants trigger already present cases, must be in differential diagnosis.

Causes of Asthma

• Various agents and industries have been linked to sensitizing agent-induced asthma depending on the job.
• Acrylate, Anhydrides, Animal protein allergens, Cereals, Dyes and Enzymes are sensitizing agents.
• Formaldehyde, Gums, Isocyanates, Latex, Persulfate, Seafoods, and Wood dusts are sensitizing agents.
• Acids, alkaline dust, ammonia, bleach, and chlorine can cause irritant-induced asthma.
• Cleaning agents, diesel exhaust, endotoxins, formalin, mustard, oxide, and heated paints can cause irritant-induced asthma.

Signs and Symptoms

• Asthma signs and symptoms vary widely among patients in intensity and within individual cases.
• Wheezing, dyspnea, chest tightness, and cough are the general symptoms.
• Symptoms can occur spontaneously or be precipitated or exacerbated by triggers.
• Isolated cough with no other symptoms, chronic sputum production, chest pain, and shortness of breath with paresthesias decrease the likelihood of asthma.

Examining Asthma

• Prolonged expiration and wheezing during normal breathing suggest airflow obstruction.
• In mild asthma, the chest exam may be normal between exacerbations.
• Limited airflow during severe asthma exacerbations may only find reduced breath sounds.
• The absence of wheezing does not exclude the diagnosis of asthma.
• Tachycardia, tachypnea, accessory muscle use, and a hunched or tripod position are other potential signs.
• Signs for the examination in the case of allergic asthma include swelling of the nasal mucosa, an increase in nasal secretions, and a pale/blue hue to the nasal turbinates.
• Pulsus paradoxus is indicative of severe airway obstruction, with a decrease of > 10 mmHg in systolic blood pressure during inspiration.
• Stridor and intercostal retractions occur in infants and children.

Further Testing

• Pulmonary function testing (PFT), blood tests, skin prick testing, and chest radiography can be performed.
• Spirometry, bronchoprovocation challenge, body plethysmography, and expiratory flow are pulmonary function tests (PFT).
• Blood eosinophil count, Total serum immunoglobulin E (IgE), and blood tests of specific IgE to inhaled allergies are blood tests.
• Arterial blood gas (ABG) measurements are also blood tests.

Spirometry

• Spirometry helps determine the severity of airflow obstruction associated with asthma.
• Decreased forced expiratory volume in 1 second (FEV1) indicates potential asthma.
• A decreased FEV1/forced vital capacity (FVC) ratio, generally below 0.7, indicates potential asthma.
• Findings include reversibility, defined as at least a 200 mL increase in FEV1 and >12% improvement with bronchodilators.
• Spirometry helps determine the severity of exacerbation: mild, moderate and severe.

Bronchoprovocation Testing

• Bronchoprovocation testing is also called bronchial challenge testing (methacholine challenge test, if methacholine is used).
• Assesses bronchial hyperresponsiveness.
• Useful for diagnosing or excluding asthma in patients who have a suspicious history but normal spirometry findings.
• Provocation agents used may include Direct stimuli: histamine, methacholine or Indirect stimuli: adenosine monophosphate (AMP), mannitol, exercise, hypertonic saline, isocapnic hyperventilation
• A positive bronchoprovocation test has ≥20% decrease of FEV1 at ≤ 8 mg/mL provocative agent.
• A negative bronchoprovocation test has a 95% negative predictive value and excludes asthma diagnosis with great accuracy.

Body plethysmography

• Body plethysmography is usually performed by a lung specialist (pulmonologist)
• Patient seated in an airtight chamber and breathing normally in and out of a mouthpiece similar to spirometry testing
• Changes in Pressure determine a patient's residual volume by measuring airway resistance inside the chamber.
• May see an increase in residual volume and airway resistance in asthma

Explore key facts about asthma prevalence, characteristics, and symptom patterns. Learn about risk factors, diagnosis, and management strategies for asthma, including patient education and personalized action plans.