Comprehensive Guide to Asthma

Definition and Pathophysiology

Asthma is a chronic inflammatory disorder of the airways characterized by three distinct pathophysiologic responses: inflammation, bronchial hyperresponsiveness, and airway remodeling, producing variable and reversible airflow obstruction. 1, 2, 3

Core Pathophysiologic Mechanisms

Inflammation involves multiple cellular players including mast cells, eosinophils, T lymphocytes, macrophages, and epithelial cells that drive the inflammatory cascade 2
Airflow obstruction occurs through three mechanisms: bronchoconstriction, airway edema with mucus plugging, and airway remodeling 2
Bronchial hyperresponsiveness results in exaggerated airway narrowing in response to various stimuli 4

Genetic and Environmental Factors

Strong genetic component: 80% of children with two asthmatic parents develop asthma 1, 2
Gene-environment interactions are critical, with environmental exposures during immune development being essential 1
In utero exposures, particularly maternal smoking, increase childhood asthma risk in a dose-dependent pattern 1
Major environmental triggers: airborne allergens (especially house dust mite and Alternaria) and viral respiratory infections (RSV and rhinovirus) are the most important factors in development, persistence, and severity 4

Diagnosis

Asthma is a clinical diagnosis requiring episodic symptoms of airflow obstruction PLUS objective demonstration of reversible airway obstruction using spirometry. 1, 2, 3

Key Symptom Indicators

History must include episodic symptoms of:

Cough (particularly worse at night) 4
Recurrent wheeze 4
Recurrent difficulty breathing 4
Recurrent chest tightness 4

Symptoms occur or worsen with:

Exercise 4
Viral infections 4
Inhalant allergens (animals with fur/hair, house-dust mites, mold, pollen) 4
Irritants (tobacco/wood smoke, airborne chemicals) 4
Weather changes 4
Strong emotional expression (laughing or crying hard) 4
Stress 4
Menstrual cycles 4
Nocturnal awakening 4

Physical Examination Findings

Upper respiratory tract examination:

Increased nasal secretion 4
Mucosal swelling 4
Nasal polyps 4

Chest examination:

Wheezing during normal breathing or prolonged forced exhalation 4
Hyperexpansion of thorax 4
Use of accessory muscles 4
Hunched shoulders 4
Chest deformity 4

Skin examination:

Atopic dermatitis 4
Eczema 4

Important caveat: Physical examination may be completely normal between episodes due to disease variability, so absence of findings does not rule out asthma 4

Objective Confirmation with Spirometry

Spirometry is mandatory for:

Initial assessment 1, 3
Evaluation of treatment response 1, 3
Reassessment every 1-2 years 1, 3

Characteristic spirometry findings:

Decreased FEV1 2
Decreased PEF 2
Reduced FEV1/FVC ratio indicating airflow obstruction 2

Reversibility criteria (positive bronchodilator test):

FEV1 increase ≥12% AND ≥200 mL from baseline after short-acting β2-agonist 4
Alternative: FEV1 increase ≥15% AND ≥200 mL, or PEF increase ≥20% AND ≥60 L/min 2
Some studies suggest 10% of predicted FEV1 increase may better separate asthma from COPD 4

Five Methods to Confirm Variable Airflow Limitation

When spirometry is normal or patient is already on treatment: 2, 3

Positive bronchodilator responsiveness test
Excessive peak expiratory flow (PEF) variability
Improvement after inhaled corticosteroid (ICS) trial
Positive bronchial challenge test (methacholine or histamine)
Excessive variation between visits

For patients already on ICS-containing medications: Repeat objective lung function measures and trial a step-down of ICS treatment to unmask reversibility 2

Classification of Asthma

By Severity (Pre-Treatment)

Disease severity is determined by pulmonary function measurements, asthma symptoms, and need for rescue medication BEFORE starting treatment. 1

Intermittent asthma 5
Persistent asthma: mild, moderate, or severe 5
Important note: Classification becomes difficult once treatment begins, as control rather than severity guides ongoing management 1

By Clinical Phenotype

Type 2 (T2-high) Asthma (80-85% of cases):

Driven by eosinophils, mast cells, and Th2 cells 6
Cytokines: IL-4, IL-5, IL-13 6
Associated with IgE production 6
Often has personal or family history of atopic conditions (eczema, allergic rhinitis) 1
Symptoms worsen after exposure to pollens, dust, feathered/furry animals 1
Responds well to inhaled corticosteroids 6

Non-Type 2 (T2-low) Asthma (15-20% of cases):

Characterized by neutrophilic inflammation 6
Driven by Th1 and Th17 immune responses 6
More common in older adults, smokers, and severe disease 6

Cough Variant Asthma:

Nonproductive cough as predominant or sole symptom without wheeze 1, 5
Responds to standard asthma treatment 1
Does not respond to antibiotics, expectorants, mucolytics, antitussives, or beta₂-agonists alone 5

Occupational Asthma:

New-onset asthma caused by workplace exposures 1
IgE-mediated type develops after latency period with sensitization to high-molecular-weight agents 1
Often associated with rhinitis, conjunctivitis, atopy 1
Irritant-induced type may occur with or without latency, including reactive airways dysfunction syndrome from high-level exposures 1
Critical management: Removing exposure to causative agent leads to best outcomes, though complete recovery not guaranteed 1

Management Principles

Managing asthma long-term requires four components: assessment and monitoring, patient education, control of environmental factors and comorbid conditions, and medications using a stepwise approach. 1, 3

Treatment Goals

Goals of asthma control include: 3

Minimal chronic symptoms
Minimal exacerbations
Minimal need for relieving bronchodilators
No limitations on activities
Minimal adverse effects from medicine

Medication Framework

Two categories of medications:

Long-term control medications: 4

Prevent symptoms by reducing inflammation
Must be taken daily
Do NOT provide quick relief
Inhaled corticosteroids are the standard of care for persistent asthma 1, 3

Quick-relief medications (Short-Acting Beta-Agonists): 4

Relax airway muscles for prompt symptom relief
Do NOT provide long-term asthma control
Using SABA >2 days per week indicates need for starting or increasing long-term control medications 4

Stepwise Medication Approach

For patients not responding to inhaled corticosteroids alone:

Add combination therapy with long-acting beta-agonists 1, 3

Transitioning from oral to inhaled corticosteroids:

Requires careful monitoring 1, 3
Reduce prednisone by 2.5 mg weekly during inhaled corticosteroid therapy 1, 3

For severe or treatment-resistant T2-high asthma, biologic therapies targeting specific pathways: 6

Anti-IgE: omalizumab
Anti-IL-5: mepolizumab, benralizumab
Anti-IL-4/IL-13: dupilumab

For T2-low asthma:

Macrolide antibiotics like azithromycin are being explored 6

Montelukast (Leukotriene Receptor Antagonist)

Dosing for asthma: 7

Adults and adolescents ≥15 years: 10 mg tablet once daily in evening
Children 6-14 years: 5 mg chewable tablet once daily
Children 2-5 years: 4 mg chewable tablet or oral granules once daily

For exercise-induced bronchoconstriction: 7

Take at least 2 hours before exercise
Not more than once daily
10 mg for adults and adolescents ≥15 years

Clinical trial results in adults: 7

Reduced "as-needed" β-agonist use by 26.1% vs 4.6% for placebo
Reduced nocturnal awakenings by 34% vs 15% for placebo
Treatment effect achieved after first dose and maintained throughout 24-hour dosing interval

Important behavioral warnings: 7

Behavior and mood-related changes reported: agitation, aggressive behavior, hostility, bad/vivid dreams, depression, anxiety, hallucinations, irritability, restlessness, sleepwalking, suicidal thoughts and actions, tremor, trouble sleeping
Tell doctor immediately if these occur

Assessment and Monitoring

At Each Visit

Questions to assess control: 4

How many days in past week had chest tightness, cough, shortness of breath, wheezing?
How many nights in past week had these symptoms?
How many days has asthma restricted physical activity?
Any asthma attacks since last visit?
Any unscheduled visits to doctor or emergency department?
How well controlled is asthma in patient's opinion?
Average puffs per day of quick-relief medication?

Medication review:

What problems taking medicine or following asthma action plan? 4
Review and demonstrate proper inhaler technique 4

Spirometry Schedule

Mandatory spirometry: 1, 3

Initial assessment
Treatment response evaluation
At least every 1-2 years

Patient Education and Self-Management

Asthma self-management education must be integrated into all aspects of care, beginning at diagnosis and continuing through follow-up. 4

Basic Facts Patients Must Understand

Airway pathophysiology: 4

Contrast between airways of person with and without asthma
Role of inflammation
What happens during an asthma attack

Medication understanding: 4

Long-term control medications prevent symptoms by reducing inflammation, must be taken daily, do not give quick relief
Quick-relief medications (SABAs) relax airway muscles for prompt relief, do not provide long-term control
Using SABA >2 days/week indicates need for starting or increasing long-term control

Essential Patient Skills

Medication administration: 4

Correct inhaler technique (demonstrate and have patient return demonstration)
Proper use of valved holding chamber (VHC) or spacer
Proper use of nebulizer if prescribed

Environmental control: 4

Identify and avoid allergens
Avoid irritants and pollutants
Avoid tobacco smoke

Self-monitoring: 4

Assess level of asthma control
Monitor symptoms and peak flow if prescribed
Recognize early signs of worsening asthma

Written Asthma Action Plan

All patients must receive a written asthma action plan that includes: 4

Instructions for daily management (long-term control medication if appropriate, environmental control measures)
Actions to manage worsening asthma (what signs, symptoms, and PEF measurements indicate worsening; what medications to take in response)
What signs and symptoms indicate need for immediate medical care

Particularly recommended for: 4

Moderate or severe persistent asthma (step 4,5, or 6)
History of severe exacerbations
Poorly controlled asthma

Environmental Control and Comorbidities

Environmental control is critical, with maternal smoking being one of the most important modifiable factors. 3

Stress and psychological factors:

Can amplify airway inflammatory responses 1, 3
Address both psychological stressors and physical triggers for patients with stress-related exacerbations or depression 1, 3

Associated comorbidities requiring treatment: 8

Rhinitis
Sinusitis
Gastroesophageal reflux disease
Obstructive sleep apnea
Depression

Common Pitfalls to Avoid

Diagnostic pitfalls:

Never use labels like "wheezy bronchitis," "recurrent pneumonia," or "reactive airway disease" - these can miss the opportunity to diagnose and treat asthma appropriately 3
Do not rule out asthma based on normal physical examination between episodes 4
Patients' perceptions of airflow obstruction are highly variable - always use objective spirometry 4

Management pitfalls:

Do not rely on symptoms alone to assess control - use objective measures 4
Ensure proper inhaler technique at every visit - poor technique is a common cause of treatment failure 4
Do not assume good adherence - poor adherence to inhaled corticosteroids is a common reason for poor response 9
Identify and treat exacerbating factors including unrecognized allergens, occupational sensitizers, gastroesophageal reflux, upper airway disease 9

Flowchart: Diagnostic Algorithm

Patient presents with episodic respiratory symptoms
(cough, wheeze, dyspnea, chest tightness)
                    ↓
Detailed history: Symptoms worse at night? Triggered by
exercise, allergens, irritants, viral infections?
                    ↓
Physical examination: Wheezing? Signs of atopy?
(May be normal between episodes)
                    ↓
SPIROMETRY (mandatory for diagnosis)
                    ↓
        ┌───────────┴───────────┐
        ↓                       ↓
FEV1/FVC reduced?          FEV1/FVC normal?
        ↓                       ↓
Bronchodilator test:    Consider: PEF variability,
FEV1 ↑≥12% AND ≥200mL?  bronchial challenge test,
        ↓               ICS trial, or repeat testing
        ↓                       ↓
    ASTHMA CONFIRMED ←──────────┘
        ↓
Classify severity (pre-treatment)
Identify phenotype (allergic vs non-allergic)
        ↓
Initiate stepwise treatment
Provide written action plan
Schedule follow-up with spirometry

Flowchart: Management Algorithm

ASTHMA DIAGNOSIS CONFIRMED
            ↓
Assess severity and control
            ↓
    ┌───────┴───────┐
    ↓               ↓
INTERMITTENT    PERSISTENT
    ↓               ↓
SABA as needed  Start ICS
                    ↓
            Reassess in 2-4 weeks
                    ↓
        ┌───────────┴───────────┐
        ↓                       ↓
    CONTROLLED              NOT CONTROLLED
        ↓                       ↓
Continue current        Step up therapy:
treatment              Add LABA to ICS
Monitor q 1-6 months        ↓
Spirometry q 1-2 years  Reassess in 2-4 weeks
        ↓                       ↓
Provide written         Still not controlled?
action plan                 ↓
Reinforce education     Consider:
Review inhaler          - Adherence issues?
technique               - Correct inhaler technique?
                        - Environmental triggers?
                        - Comorbidities?
                            ↓
                        Refer to specialist
                        Consider biologics

Multiple Choice Questions (MCQs)

Question 1

A 28-year-old woman presents with episodic wheezing and nocturnal cough for 6 months. Spirometry shows FEV1/FVC of 0.68 (predicted 0.80). After SABA, FEV1 increases by 15% and 250 mL. What is the next best step?

A) Prescribe SABA as needed only
B) Start inhaled corticosteroid and provide written action plan
C) Order chest X-ray before treatment
D) Refer to pulmonologist immediately

Answer: B - Diagnosis of asthma is confirmed by episodic symptoms plus reversible airflow obstruction on spirometry (FEV1 increase ≥12% AND ≥200 mL). Inhaled corticosteroids are the standard of care for persistent asthma, and all patients should receive a written action plan. 4, 1, 3

Question 2

A 45-year-old man with asthma uses his albuterol inhaler 4 days per week for symptom relief. He is not on any controller medication. What does this indicate?

A) His asthma is well-controlled
B) He needs to increase albuterol frequency
C) He needs to start or increase long-term control medication
D) He should switch to a different SABA

Answer: C - Using SABA >2 days per week indicates the need for starting or increasing long-term control medications. This is a key indicator of inadequate asthma control. 4

Question 3

Which of the following is the MOST important objective test for confirming asthma diagnosis in a patient ≥5 years old?

A) Chest X-ray
B) Spirometry with bronchodilator response
C) Peak flow monitoring at home
D) Allergy skin testing

Answer: B - Spirometry demonstrating reversible airflow obstruction is essential for asthma diagnosis. It is mandatory for initial assessment in patients ≥5 years old. Patients' perceptions of airflow obstruction are highly variable, making objective testing critical. 4, 1, 3

Question 4

A 12-year-old boy with moderate persistent asthma on inhaled corticosteroids continues to have symptoms. What is the most appropriate next step?

A) Switch to oral corticosteroids
B) Add long-acting beta-agonist to ICS
C) Discontinue ICS and try montelukast
D) Increase SABA frequency

Answer: B - For patients not responding to inhaled corticosteroids alone, combination therapy with long-acting beta-agonists is recommended. This represents appropriate step-up therapy. 1, 3

Question 5

Which finding on physical examination would INCREASE the probability of asthma?

A) Normal lung sounds
B) Nasal polyps
C) Clear rhinorrhea
D) Normal chest wall

Answer: B - Nasal polyps are a specific finding that increases the probability of asthma. However, the absence of physical findings does not rule out asthma because the disease is variable and signs may be absent between episodes. 4

Question 6

A patient with newly diagnosed asthma asks about the underlying cause. Which environmental factor has the STRONGEST evidence for contributing to asthma development and persistence?

A) Air pollution
B) House dust mite allergen exposure
C) Dietary factors
D) Cold air exposure

Answer: B - Airborne allergens, particularly sensitization and exposure to house dust mite and Alternaria, are the most important environmental factors in the development, persistence, and possibly severity of asthma. 4

Question 7

What percentage of children with two asthmatic parents will develop asthma?

A) 20%
B) 40%
C) 60%
D) 80%

Answer: D - There is a strong genetic component to asthma, with 80% of children with two asthmatic parents developing asthma. 1, 2

Question 8

A 35-year-old woman with asthma is pregnant and smokes. What is the most important counseling point regarding her smoking?

A) Smoking only affects her own asthma, not the baby
B) In utero tobacco exposure increases risk of childhood wheezing in a dose-dependent pattern
C) She should switch to e-cigarettes
D) Smoking cessation is only important after delivery

Answer: B - In utero exposures, particularly maternal smoking, increase the risk of childhood asthma in a dose-dependent pattern. This is one of the most important modifiable environmental factors. 1, 3

Question 9

Which statement about asthma inflammation is MOST accurate?

A) Inflammation only occurs during acute exacerbations
B) Inflammation is a primary target of treatment
C) Inflammation resolves completely with current treatments
D) Inflammation is not related to symptoms

Answer: B - Knowledge of the importance of inflammation to the central features of asthma underscores inflammation as a primary target of treatment. Current therapeutic approaches are effective in controlling symptoms, reducing airflow limitation, and preventing exacerbations. 4

Question 10

A patient with occupational asthma asks about prognosis. What is the BEST management approach?

A) Continue working with increased medication
B) Remove exposure to the causative agent
C) Use N95 mask at work
D) Switch to oral corticosteroids

Answer: B - Removing exposure to the causative agent leads to the best health outcomes in occupational asthma, though complete recovery is not guaranteed even with avoidance. 1

Diagram: Asthma Pathophysiology

GENETIC SUSCEPTIBILITY (80% if both parents asthmatic)
            +
ENVIRONMENTAL TRIGGERS
(Allergens, Viral infections, Tobacco smoke)
            ↓
═══════════════════════════════════════════════
        AIRWAY INFLAMMATION
═══════════════════════════════════════════════
            ↓
    ┌───────┴───────┬───────────┐
    ↓               ↓           ↓
BRONCHOCONSTRICTION  AIRWAY    AIRWAY
(Smooth muscle      EDEMA &    REMODELING
contraction)        MUCUS      (Structural
                    PLUGGING   changes)
    ↓               ↓           ↓
    └───────┬───────┴───────────┘
            ↓
VARIABLE & REVERSIBLE AIRFLOW OBSTRUCTION
            ↓
    ┌───────┴───────┬───────────┬──────────┐
    ↓               ↓           ↓          ↓
WHEEZING        DYSPNEA    CHEST      COUGH
                           TIGHTNESS  (worse at night)

Diagram: Type 2 vs Non-Type 2 Asthma

        ASTHMA PHENOTYPES
                |
    ┌───────────┴───────────┐
    ↓                       ↓
TYPE 2 (T2-HIGH)      NON-TYPE 2 (T2-LOW)
80-85% of cases       15-20% of cases
    |                       |
    ↓                       ↓
IMMUNE CELLS:         IMMUNE CELLS:
- Eosinophils         - Neutrophils
- Mast cells          - Th1 cells
- Th2 cells           - Th17 cells
    |                       |
    ↓                       ↓
CYTOKINES:            PATIENT PROFILE:
- IL-4                - Older adults
- IL-5                - Smokers
- IL-13               - More severe disease
- IgE production          |
    |                     ↓
    ↓                 TREATMENT:
CLINICAL FEATURES:    - Macrolides
- Allergic history    - Novel therapies
- Atopy                 (under study)
- Responds to ICS
    |
    ↓
TREATMENT:
- Inhaled corticosteroids
- Biologics:
  * Anti-IgE (omalizumab)
  * Anti-IL-5 (mepolizumab, benralizumab)
  * Anti-IL-4/IL-13 (dupilumab)

Diagram: Stepwise Asthma Management

STEP 1: INTERMITTENT ASTHMA
├─ SABA as needed for symptoms
└─ No daily controller medication

        ↓ (If symptoms >2 days/week or nocturnal awakening)

STEP 2: MILD PERSISTENT
├─ Low-dose ICS (daily)
└─ SABA as needed

        ↓ (If not controlled after 2-4 weeks)

STEP 3: MODERATE PERSISTENT
├─ Low-dose ICS + LABA
│  OR Medium-dose ICS
└─ SABA as needed

        ↓ (If not controlled after 2-4 weeks)

STEP 4: MODERATE-SEVERE PERSISTENT
├─ Medium-dose ICS + LABA
└─ SABA as needed

        ↓ (If not controlled after 2-4 weeks)

STEP 5: SEVERE PERSISTENT
├─ High-dose ICS + LABA
├─ Consider adding:
│  - Leukotriene modifier (montelukast)
│  - Theophylline
└─ SABA as needed

        ↓ (If still not controlled)

STEP 6: SEVERE PERSISTENT
├─ High-dose ICS + LABA
├─ Oral corticosteroids
├─ Consider biologics:
│  - Anti-IgE (omalizumab)
│  - Anti-IL-5 (mepolizumab, benralizumab)
│  - Anti-IL-4/IL-13 (dupilumab)
└─ SABA as needed

═══════════════════════════════════════════
AT EVERY STEP:
- Written asthma action plan
- Patient education
- Environmental control
- Treat comorbidities
- Spirometry every 1-2 years
- Review inhaler technique
- Assess adherence
═══════════════════════════════════════════

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