Respiratory Diseases: COPD, Asthma, and Influenza

• COPD, asthma, influenza, and bronchiectasis are common respiratory diseases with overlapping symptoms but distinct underlying mechanisms and management strategies. Symptom management, treatment options, and preventative measures vary for each condition.
• Understanding the risk factors, diagnostic approaches, and pharmacological treatments is essential for effective patient care

COPD (Chronic Obstructive Pulmonary Disease)

• COPD is a progressive lung disease characterized by airflow limitation that is not fully reversible, including emphysema and chronic bronchitis.
• The primary cause is long-term exposure to airborne irritants, most commonly from cigarette smoke, but other risk factors include air pollution, occupational dusts, and genetic factors.
• Pathophysiology involves inflammation and damage to the airways and alveoli, leading to airflow obstruction, air trapping, and impaired gas exchange.
• Diagnosis is based on pulmonary function tests (spirometry), particularly the FEV1/FVC ratio (forced expiratory volume in 1 second/forced vital capacity); a ratio less than 0.70 confirms airflow limitation.
• Symptoms include chronic cough, excessive mucus production, shortness of breath (dyspnea), and wheezing.
• Management includes smoking cessation, bronchodilators (beta-agonists, anticholinergics), inhaled corticosteroids (in some cases), pulmonary rehabilitation, and oxygen therapy (if hypoxemic).
• Pharmacological management focuses on symptom relief and reducing exacerbations but does not cure the disease.
• Preventative measures include smoking cessation and avoiding exposure to lung irritants; vaccination against influenza and pneumococcal pneumonia is also recommended.
• Subtypes include emphysema and chronic bronchitis.
• Emphysema involves destruction of the alveoli, leading to decreased gas exchange.
• Chronic bronchitis involves inflammation and excessive mucus production in the bronchioles.

Pathophysiology

• Primarily caused by chronic inflammation in the airways and lung parenchyma, leading to structural changes
• Key structural changes:
  • Alveolar destruction (emphysema)
  • Airway thickening
  • Increased mucus production
• Imbalance between proteases and antiproteases contributes to alveolar destruction
• Oxidative stress from cigarette smoke and inflammation damages lung tissue

Pathophysiology of COPD

• The primary cause is chronic inflammation due to inhaled irritants, most commonly tobacco smoke.
• Inflammation leads to structural changes in the lungs, including alveolar destruction and airway remodeling.
• Increased mucus production, ciliary dysfunction, and bronchoconstriction contribute to airflow limitation.
• Oxidative stress and protease-antiprotease imbalance play key roles in the disease process.

Risk Factors

• Smoking is the leading risk factor
• Occupational exposure to dusts, chemicals, and fumes
• Alpha-1 antitrypsin deficiency (genetic predisposition)
• Air pollution
• History of respiratory infections

Risk Factors for COPD

• Cigarette smoking is the leading risk factor.
• Other risk factors include occupational exposure to dusts, chemicals, and fumes, air pollution, and genetic factors like alpha-1 antitrypsin deficiency.

Diagnostics

• Spirometry is essential
• FEV1/FVC ratio < 0.70 confirms airflow limitation
• Assess disease severity using GOLD (Global Initiative for Chronic Obstructive Lung Disease) criteria
• Chest X-ray to exclude other lung diseases
• Assess exacerbation history and symptom severity

Diagnosis of COPD

• Diagnosis is based on clinical symptoms, physical examination, and pulmonary function tests.
• Spirometry is essential for diagnosis; a post-bronchodilator FEV1/FVC ratio of less than 0.70 confirms airflow limitation.
• Assessment of symptoms uses tools like the COPD Assessment Test (CAT) or the Modified Medical Research Council (mMRC) dyspnea scale.
• Chest X-rays or CT scans may be used to exclude other conditions and assess the severity of emphysema.

Pharmacological Management

• Bronchodilators:
  • Beta-2 agonists (short-acting and long-acting) relax airway smooth muscle
  • Anticholinergics (short-acting and long-acting) block muscarinic receptors, reducing bronchoconstriction
• Inhaled corticosteroids (ICS):
  • Reduce airway inflammation, typically used in combination with LABAs (long-acting beta-2 agonists) in severe COPD
• Phosphodiesterase-4 (PDE4) inhibitors:
  • Reduce inflammation and are used in severe COPD with frequent exacerbations
• Combination inhalers:
  • Combine multiple medications (e.g., LABA/ICS, LAMA/LABA) improve adherence and outcomes

Pharmacological Management of COPD

• Beta-2 agonists (e.g., albuterol, salmeterol) relax airway smooth muscle.
• Anticholinergics (e.g., ipratropium, tiotropium) block muscarinic receptors, reducing bronchoconstriction.
• Inhaled corticosteroids (e.g., fluticasone, budesonide) reduce airway inflammation and are often combined with long-acting beta-2 agonists (LABAs).
• Phosphodiesterase-4 (PDE4) inhibitors (e.g., roflumilast) reduce inflammation and are used in severe COPD with chronic bronchitis.
• Mucolytics (e.g., N-acetylcysteine) may help to reduce mucus viscosity in some patients.

Asthma

• Asthma is a chronic inflammatory disease of the airways characterized by reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation
• Common triggers include allergens, irritants, exercise, and respiratory infections.
• Pathophysiology involves inflammation of the airways, bronchoconstriction, and increased mucus production, leading to airflow obstruction.
• Diagnosis is based on a combination of clinical history, physical examination, and pulmonary function tests (spirometry with bronchodilator reversibility).
• Symptoms include wheezing, shortness of breath, chest tightness, and cough, which are often episodic and worse at night or early morning.
• Management includes avoidance of triggers, inhaled corticosteroids (to reduce inflammation), bronchodilators (beta-agonists for quick relief, long-acting beta-agonists for maintenance), leukotriene modifiers, and immunotherapy (for allergic asthma).
• Asthma action plans help patients monitor and manage their symptoms, including when to adjust medications or seek medical care.
• Preventative measures include avoiding triggers, using inhaled corticosteroids as prescribed, and having a written asthma action plan.
• Asthma involves a complex interplay of genetic and environmental factors.
• Asthma is characterized by reversible airflow limitation
• Airflow limitation is associated with airway hyperresponsiveness

Pathophysiology

• Airway inflammation is driven by Th2 lymphocytes, eosinophils, and mast cells
• Inflammatory mediators:
  • Leukotrienes
  • Histamine
  • Cytokines
• Airway hyperresponsiveness to various stimuli, such as allergens, irritants, and exercise
• Bronchoconstriction, airway edema, and mucus plugging lead to airflow obstruction

Pathophysiology of Asthma

• Allergic asthma is triggered by allergens, leading to IgE-mediated activation of mast cells and release of inflammatory mediators.
• Non-allergic asthma can be triggered by respiratory infections, exercise, cold air, or irritants.
• Airway inflammation leads to bronchoconstriction, mucus production, and airway remodeling.

Risk Factors

• Genetic predisposition (family history of asthma or atopy)
• Environmental factors:
  • Allergens (house dust mites, pollen, pet dander)
  • Irritants (tobacco smoke, air pollution)
  • Respiratory infections (especially in childhood)
• Obesity

Risk Factors for Asthma

• Genetic predisposition with a family history of asthma or allergies.
• Environmental factors include exposure to allergens (e.g., pollen, dust mites, pet dander), respiratory infections in early childhood, air pollution, and occupational exposures.

Diagnostics

• Detailed medical history and physical examination
• Spirometry:
  • Demonstrates reversible airflow obstruction (increase in FEV1 > 12% after bronchodilator)
• Bronchial provocation testing:
  • Methacholine challenge identifies airway hyperresponsiveness
• Allergy testing to identify triggers

Diagnosis of Asthma

• Diagnosis is based on clinical history, physical examination, and pulmonary function tests.
• Spirometry is used to assess airflow obstruction; improvement in FEV1 by ≥12% and ≥200 mL after bronchodilator administration indicates asthma.
• Bronchial provocation testing (e.g., methacholine challenge) may be used to assess airway hyperresponsiveness.
• Allergy testing helps identify triggers.

Pharmacological Management

• Quick-relief medications:
  • Short-acting beta-2 agonists (SABAs) provide rapid bronchodilation for acute symptoms
• Long-term control medications:
  • Inhaled corticosteroids (ICS) reduce airway inflammation
  • Long-acting beta-2 agonists (LABAs) provide sustained bronchodilation, always used in combination with ICS
  • Leukotriene modifiers block leukotriene receptors, reducing inflammation and bronchoconstriction
  • Mast cell stabilizers prevent mast cell degranulation, reducing inflammation
  • Theophylline is a bronchodilator used as an add-on therapy

Pharmacological Management of Asthma

• Short-acting Beta-2 agonists (SABAs) like albuterol provide rapid bronchodilation.
• Anticholinergics like Ipratropium can be considered in some cases.
• Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy, reducing airway inflammation.
• Long-acting beta-2 agonists (LABAs) provide sustained bronchodilation but should always be used in combination with ICS.
• Leukotriene modifiers (e.g., montelukast) block the effects of leukotrienes, reducing inflammation and bronchoconstriction.
• Mast cell stabilizers (e.g., cromolyn) prevent mast cell degranulation.
• Theophylline is a bronchodilator used less commonly due to side effects.
• Anti-IgE antibodies (e.g., omalizumab) are used for severe allergic asthma.
• Anti-IL-5 antibodies (e.g., mepolizumab, reslizumab) are used for eosinophilic asthma.
• Anti-IL-4 receptor alpha antibodies (e.g., dupilumab) are used for moderate-to-severe asthma with type 2 inflammation.

Influenza

• Influenza (flu) is a contagious respiratory illness caused by influenza viruses.
• The virus spreads through droplets made when people with flu cough, sneeze, or talk.
• Symptoms include fever, cough, sore throat, muscle aches, headache, fatigue, and sometimes vomiting and diarrhea (more common in children).
• Diagnosis is typically based on clinical symptoms, but rapid influenza diagnostic tests (RIDTs) can confirm the diagnosis.
• Management includes rest, fluids, and over-the-counter medications for symptom relief; antiviral medications (e.g., oseltamivir, zanamivir) can be used to reduce the severity and duration of illness, especially if started early (within 48 hours of symptom onset).
• Preventative measures include annual vaccination, frequent handwashing, avoiding close contact with sick people, and covering coughs and sneezes.
• There are three main types of influenza viruses: A, B, and C, with types A and B causing seasonal epidemics.
• Influenza A viruses are further classified into subtypes based on two surface proteins: hemagglutinin (H) and neuraminidase (N).

Pathophysiology

• Viral infection of the respiratory tract
• Inflammation and cell damage in the nasal mucosa, throat, and lungs
• Virus spreads through respiratory droplets
• Incubation period is typically 1-4 days

Pathophysiology of Influenza

• Influenza viruses enter the respiratory tract via droplets or aerosols.
• The virus infects and replicates in epithelial cells of the respiratory tract, causing cell damage and inflammation.
• Viral shedding occurs for several days, allowing the virus to spread to others.
• The immune response to influenza can cause systemic symptoms such as fever, muscle aches, and fatigue.

Risk Factors

• Age (young children and older adults)
• Chronic medical conditions (heart disease, lung disease, diabetes)
• Immunocompromised individuals
• Pregnancy
• Close contact with infected individuals

Risk Factors for Influenza

• Age: young children and older adults are at higher risk.
• Chronic medical conditions (e.g., asthma, COPD, diabetes, heart disease).
• Immunocompromised individuals.
• Pregnancy.

Diagnostics

• Clinical presentation:
  • Fever
  • Cough
  • Sore throat
  • Muscle aches
  • Fatigue
• Rapid influenza diagnostic tests (RIDTs) detect viral antigens in nasal or throat swabs
• Reverse transcription polymerase chain reaction (RT-PCR) is more sensitive and specific

Diagnosis of Influenza

• Diagnosis is typically based on clinical symptoms during influenza season.
• Rapid influenza diagnostic tests (RIDTs) can detect viral antigens in respiratory specimens (nasal swabs or washes).
• Reverse transcription polymerase chain reaction (RT-PCR) is more sensitive and specific than RIDTs and can identify the influenza virus type and subtype.

Pharmacological Management

• Antiviral medications (e.g., oseltamivir, zanamivir)
  • Reduce the duration and severity of symptoms if started within 48 hours of symptom onset
• Supportive care:
  • Rest
  • Hydration
  • Analgesics (acetaminophen, ibuprofen)
• Prevention:
  • Annual influenza vaccination

Pharmacological Management of Influenza

• Neuraminidase inhibitors (e.g., oseltamivir, zanamivir) reduce viral shedding and can shorten the duration of illness if started within 48 hours of symptom onset.
• Baloxavir marboxil is a single-dose antiviral that inhibits viral replication.
• Analgesics (e.g., acetaminophen, ibuprofen) help relieve fever and pain.
• Decongestants relieve nasal congestion.
• Annual influenza vaccination is the most effective way to prevent influenza infection.
• Inactivated influenza vaccines (IIVs) and recombinant influenza vaccines (RIVs) are available for different age groups.
• Live attenuated influenza vaccine (LAIV) is available as a nasal spray for certain individuals.

Bronchiectasis

• Bronchiectasis is a chronic respiratory disease characterized by irreversible dilatation of the bronchi

Pathophysiology

• Chronic inflammation and infection weaken bronchial walls, leading to structural damage
• Impaired mucociliary clearance results in mucus accumulation and recurrent infections
• Cycle of inflammation, infection, and structural damage perpetuates the disease

Risk Factors

• Cystic fibrosis (CF)
• Primary ciliary dyskinesia (PCD)
• Immunodeficiency
• Previous severe respiratory infections (e.g., pneumonia, pertussis)
• Allergic bronchopulmonary aspergillosis (ABPA)
• Alpha-1 antitrypsin deficiency

Diagnostics

• High-resolution computed tomography (HRCT) scan is the gold standard:
  • Demonstrates bronchial dilatation, bronchial wall thickening, and mucus plugging
• Sputum culture:
  • Identifies colonizing bacteria
• Sweat test or genetic testing to rule out cystic fibrosis
• Immunoglobulin levels to assess for immunodeficiency
• Ciliary function testing to rule out primary ciliary dyskinesia

Pharmacological Management

• Airway clearance techniques:
  • Chest physiotherapy
  • High-frequency chest wall oscillation (HFCWO)
  • Positive expiratory pressure (PEP) devices
• Bronchodilators:
  • Beta-2 agonists to improve airway clearance
• Mucolytics:
  • Help to thin mucus and improve clearance
• Antibiotics:
  • Treat acute exacerbations based on sputum culture results
  • Chronic suppressive antibiotics in severe cases
• Anti-inflammatory agents:
  • Inhaled corticosteroids or macrolides may reduce airway inflammation

Symptom Management (General)

• For all three conditions, symptom management involves a combination of medication, lifestyle modifications, and self-management strategies.
• Shortness of breath can be managed with medications (bronchodilators), breathing techniques (pursed-lip breathing), and activity pacing.
• Cough can be managed with cough suppressants (use with caution), expectorants, and by addressing the underlying cause.
• Exacerbations (acute worsening of symptoms) require prompt medical attention and may involve increased doses of medication, oral corticosteroids, or antibiotics.

Treatment Options (Pharmacology)

• Bronchodilators (beta-agonists, anticholinergics) relax the muscles around the airways, opening them up and making it easier to breathe; they are used in both COPD and asthma.
• Inhaled corticosteroids reduce inflammation in the airways and are a mainstay of asthma treatment; they are also used in some COPD patients with frequent exacerbations.
• Combination inhalers contain both a bronchodilator and an inhaled corticosteroid, providing both short-term and long-term relief.
• Oral corticosteroids are used for acute exacerbations of COPD and asthma to reduce inflammation.
• Antibiotics are used to treat bacterial infections that can complicate COPD and influenza.
• Oxygen therapy is used in COPD patients with chronic hypoxemia (low blood oxygen levels).
• Antiviral medications (e.g., oseltamivir, zanamivir) are used to treat influenza, especially in high-risk individuals.

Preventative Measures (General)

• Vaccination is a key preventative measure for both influenza and pneumococcal pneumonia (a common complication of COPD).
• Smoking cessation is the most important preventative measure for COPD.
• Avoiding exposure to air pollution, allergens, and other respiratory irritants can help prevent exacerbations of COPD and asthma.
• Regular exercise and a healthy diet can improve overall health and lung function.
• Pulmonary rehabilitation programs can help COPD patients improve their exercise tolerance and quality of life.
• Proper hand hygiene and respiratory etiquette (covering coughs and sneezes) can help prevent the spread of respiratory infections.

Key Differences

• COPD is characterized by irreversible airflow limitation due to lung damage, primarily caused by smoking.
• Asthma involves reversible airflow obstruction and airway hyperresponsiveness due to chronic inflammation.
• Influenza is an acute viral infection of the respiratory tract.
• COPD management focuses on symptom relief and preventing exacerbations with bronchodilators and anti-inflammatory medications.
• Asthma management aims to control airway inflammation and prevent symptoms with inhaled corticosteroids and bronchodilators.
• Influenza management includes antiviral medications and symptomatic treatment, with vaccination for prevention.