Chronic Obstructive Pulmonary Disease (COPD)

Overview

Definition

Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by airflow limitation resulting from airway disease and/or parenchymal destruction.

Types

The subtypes may have differing presentations and response to therapy. Patients may have any combination of both.

• Chronic bronchitis: 
  • Clinically defined
  • Productive cough > 3 months per year for at least 2 consecutive years 
  • Must be in the absence of other causes of chronic cough
• Emphysema: 
  • Pathologically or radiologically defined 
  • Destruction and permanent dilation of alveolar sacs

Epidemiology

• Worldwide: 
  • Prevalence: 11.7% (expected to rise)
  • Annual deaths: 3 million 
  • 4th leading cause of death (soon to be 3rd)
• In the United States:
  • Prevalence: 16 million people
  • Annual deaths: > 140,000
  • 3rd leading cause of death
• Age:
  • Prevalence peaks around 50–60 years of age 
  • Age of onset is lower for heavy smokers.
• Sex:
  • More prevalent in men
  • Rates in women are rising.
  • Mortality rate equal among men and women

Etiology

• Cigarette smoking (90% of cases)
• 2nd- hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand smoke
• Air pollution 
• Occupational exposure to toxins 
• Alpha-1 antitrypsin (AAT) deficiency Alpha-1 Antitrypsin (AAT) Deficiency Alpha-1 antitrypsin deficiency is a genetic disorder caused by inherited genetic mutations of the SERPINA1 gene, causing the defective production of the protease inhibitor alpha-1 antitrypsin (AAT). These mutations can lead to deficiency of the enzyme causing lung disease, production of an abnormal form of the enzyme leading to liver dysfunction, or both. Alpha-1 Antitrypsin (AAT) Deficiency

Risk factors

• Premature birth
• Low body weight
• Lower socioeconomic status
• Poor nutrition
• Childhood respiratory disorders
• Preexisting airway reactivity

Pathophysiology

Chronic bronchitis

Inhaled agents cause chronic inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation in the airways, which lead to progressive airway obstruction Airway obstruction Airway obstruction is a partial or complete blockage of the airways that impedes airflow. An airway obstruction can be classified as upper, central, or lower depending on location. Lower airway obstruction (LAO) is usually a manifestation of chronic disease, such as asthma or chronic obstructive pulmonary disease (COPD). Airway Obstruction through:

• Damage to endothelial cells → ↓ mucocilliary clearance
• Mucous gland hyperplasia → mucous hypersecretion and plugging
• Airway edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema and smooth muscle hyperplasia → luminal narrowing
• Peribronchial fibrosis → bronchial distortion

Emphysema

In normal lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs, there is a balance between:

• Proteases → break down elastin and connective tissue Connective tissue Connective tissues originate from embryonic mesenchyme and are present throughout the body except inside the brain and spinal cord. The main function of connective tissues is to provide structural support to organs. Connective tissues consist of cells and an extracellular matrix. Connective Tissue as part of normal tissue repair:
  • Neutrophil elastase
  • Matrix metalloproteinase (MMP)
  • Cathepsins
• Antiproteases → balance protease activity:
  • AAT
  • Secretory leukoprotease inhibitor derived from airway epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium
  • Elafin
  • MMP tissue inhibitor

In emphysema:

• Inflammatory response → activated neutrophils release proteases
• Protease activity exceeds antiprotease activity → tissue destruction
• Alveolar destruction leads to:
  • Enlarged alveoli
  • ↓ Elastic recoil
  • ↑ Compliance
• Consequences:
  • Airway closure during expiration → obstruction
  • Air trapping → lung hyperinflation

Morphologic patterns:

• Centriacinar emphysema (associated with cigarette smoking):
  • Destruction of the respiratory bronchioles and a central portion of the acini
  • More severe in the apical lung fields
• Panacinar emphysema (associated with AAT deficiency):
  • Destruction of all parts of the acinus
  • More severe in the basal lung fields

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Effects of the pulmonary vasculature

• Tissue destruction → ↓ ability to oxygenate blood
• Hypoxemia → vasoconstriction in small pulmonary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries → ↑ vascular resistance
• Chronic hypoxemia → vascular remodeling → irreversible pulmonary hypertension Pulmonary Hypertension Pulmonary hypertension (PH) or pulmonary arterial hypertension (PAH) is characterized by elevated pulmonary arterial pressure, which can lead to chronic progressive right heart failure. Pulmonary hypertension is grouped into 5 categories based on etiology, which include primary PAH, and PH due to cardiac disease, lung or hypoxic disease, chronic thromboembolic disease, and multifactorial or unclear etiologies. Pulmonary Hypertension

Clinical Presentation

Symptoms

Patients suffer from chronic, progressive symptoms with acute exacerbations.

General:

• Progressive dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea (particularly with exertion)
• Chronic cough
• Sputum production
• Chest tightness
• Weight gain or loss
• Fatigue

Acute exacerbation:

• Worsening dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
• Increased cough 
• Purulent sputum production
• Wheezing
• Fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever may or may not be present.

Physical examination

When examining a patient with possible COPD, look for the following findings:

Vitals:

• Tachypnea
• Hypoxia

General:

• Muscle wasting
• Barrel chest: increased anteroposterior chest wall Chest wall The chest wall consists of skin, fat, muscles, bones, and cartilage. The bony structure of the chest wall is composed of the ribs, sternum, and thoracic vertebrae. The chest wall serves as armor for the vital intrathoracic organs and provides the stability necessary for the movement of the shoulders and arms. Chest Wall diameter from hyperinflation

Pulmonary:

• Visual:
  • Respiratory distress (acute exacerbations)
  • Accessory muscle use
  • Pursed lip breathing
• Auscultation:
  • Prolonged expiration
  • Wheezing
  • Diminished breath sounds
• Palpation and percussion:
  • Hyperresonance on percussion
  • Reduced chest wall Chest wall The chest wall consists of skin, fat, muscles, bones, and cartilage. The bony structure of the chest wall is composed of the ribs, sternum, and thoracic vertebrae. The chest wall serves as armor for the vital intrathoracic organs and provides the stability necessary for the movement of the shoulders and arms. Chest Wall expansion

Extremities:

• Digital clubbing
• Cyanosis

Findings suggestive of cor pulmonale Cor Pulmonale Cor pulmonale is right ventricular (RV) dysfunction caused by lung disease that results in pulmonary artery hypertension. The most common cause of cor pulmonale is chronic obstructive pulmonary disease. Dyspnea is the usual presenting symptom. Cor Pulmonale:

• Jugular venous distension
• Peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema

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Clinical phenotypes

Signs and symptoms are associated more frequently with either chronic bronchitis or emphysema. However, patients often present with a mixture of features.

Chronic bronchitis (“blue bloater”):

• Patients are generally overweight.
• Frequent, productive cough
• Peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
• Cyanosis

Emphysema (“pink puffer”):

• Patients are generally thin.
• Barrel chest
• Infrequent cough
• Pursed lip breathing
• Accessory muscle use
• Tripod positioning
• Hyperresonant chest

Differential Diagnosis

• Asthma: a chronic, inflammatory condition characterized by reversible airflow obstruction in the lower airways. Patients present with intermittent or persistent wheezing Wheezing Wheezing is an abnormal breath sound characterized by a whistling noise that can be relatively high-pitched and shrill (more common) or coarse. Wheezing is produced by the movement of air through narrowed or compressed small (intrathoracic) airways. Wheezing, cough, and dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. Diagnosis is usually confirmed with a pulmonary function test showing a reversible, obstructive pattern. Management varies based on severity and includes bronchodilators and inhaled corticosteroids for inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation control.
• Bronchiectasis Bronchiectasis Bronchiectasis is a chronic disease of the airways that results from permanent bronchial distortion. This results from a continuous cycle of inflammation, bronchial damage and dilation, impaired clearance of secretions, and recurrent infections. Bronchiectasis: a chronic condition with bronchial dilation and destruction as a result of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and infection. Symptoms include dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, chronic cough, and purulent sputum. The diagnosis is made with imaging (X-ray and CT). Management includes bronchodilators and antibiotics for acute exacerbations.
• Bronchiolitis obliterans Bronchiolitis obliterans Bronchiolitis obliterans is an obstructive lung disease triggered by a bronchiolar injury, which leads to inflammatory fibrosis and narrowing of the distal bronchioles. The triggering bronchiolar injury is often due to inhalation of a noxious substance, infection, or drug toxicity. Bronchiolitis Obliterans: a chronic, obstructive disease of the small airways usually caused by repeated cycles of inflammation Inflammation Inflammation is a complex set of responses to infection and injury involving leukocytes as the principal cellular mediators in the body's defense against pathogenic organisms. Inflammation is also seen as a response to tissue injury in the process of wound healing. The 5 cardinal signs of inflammation are pain, heat, redness, swelling, and loss of function. Inflammation and scarring. Patients present with cough and persistent, progressive dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea. Pulmonary function tests are used for diagnosis. Management includes steroids and bronchodilators.
• Heart failure: an inability to produce normal cardiac output to meet metabolic needs. Patients present with dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, hypoxia, and peripheral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. BNP will be elevated and pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema may be seen on X-ray. Echocardiography confirms the diagnosis. Management relies on diuresis and medical optimization of cardiac function with beta blockers and ACE inhibitors.
• Cystic fibrosis Cystic fibrosis Cystic fibrosis is an autosomal recessive disorder caused by mutations in the gene CFTR. The mutations lead to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Common presentations include chronic respiratory infections, failure to thrive, and pancreatic insufficiency. Cystic Fibrosis: an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritancedisorder leading to dysfunction of chloride channels, which results in hyperviscous mucus and the accumulation of secretions. Patients often have chronic respiratory infections, failure to thrive Failure to Thrive Failure to thrive (FTT), or faltering growth, describes suboptimal weight gain and growth in children. The majority of cases are due to inadequate caloric intake; however, genetic, infectious, and oncological etiologies are also common. Failure to Thrive, and pancreatic insufficiency. The gold standard for diagnosis is the sweat chloride test, which can be complemented by genetic testing. Management includes cystic fibrosis transmembrane conductance regulator (CFTR) modulator therapy and system-specific strategies for supportive care. 
• Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism: obstruction of the pulmonary arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries most often due to thrombus migration from the deep venous system. Signs and symptoms include pleuritic chest pain Chest Pain Chest pain is one of the most common and challenging complaints that may present in an inpatient and outpatient setting. The differential diagnosis of chest pain is large and includes cardiac, gastrointestinal, pulmonary, musculoskeletal, and psychiatric etiologies. Chest Pain, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, tachypnea, and tachycardia. Severe cases can result in hemodynamic instability or cardiopulmonary arrest. Chest CTA is the primary method of diagnosis. Management includes oxygenation, anticoagulation, and thrombolytic therapy for unstable patients.