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Chronic Obstructive Pulmonary Disease (COPD)

Chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases. Symptoms include 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 and chronic cough. Prolonged expiration Expiration Ventilation: Mechanics of Breathing, 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, and/or diminished breath sounds may be noted on physical exam. The diagnosis is confirmed with a pulmonary function test Pulmonary function test Pulmonary function tests are a group of diagnostic procedures yielding useful, quantifiable information about the rate of the flow of air through the individual's airways, lung capacity, and the efficiency of gas exchange in relation to time. The most commonly utilized tests include spirometry (before and after bronchodilator use), lung volumes, and quantitation of diffusing capacity for carbon monoxide (CO). The tests can be influenced by the individual's effort/fatigue, disease state, or anatomical malformation. Pulmonary Function Tests. Management includes smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation, pulmonary rehabilitation, and pharmacotherapy.

Last updated: Nov 28, 2023

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Overview

Definition

Chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis (COPD) is a lung disease characterized by airflow limitation resulting from airway Airway ABCDE Assessment disease and/or parenchymal destruction.

Types

The subtypes may have differing presentations and response to therapy. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship may have any combination of both.

  • Chronic bronchitis Chronic bronchitis A subcategory of chronic obstructive pulmonary disease. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis. Rhinovirus
    • 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 Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 11.7% (expected to rise)
    • Annual deaths: 3 million 
    • 4th leading cause of death (soon to be 3rd)
  • In the United States:
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency: 16 million people
    • Annual deaths: > 140,000
    • 3rd leading cause of death
  • Age:
    • Prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency peaks around 50–60 years of age 
    • Age of onset is lower for heavy smokers.
  • Sex Sex The totality of characteristics of reproductive structure, functions, phenotype, and genotype, differentiating the male from the female organism. Gender Dysphoria:
    • More prevalent in men
    • Rates in women are rising.
    • Mortality Mortality All deaths reported in a given population. Measures of Health Status rate equal among men and women

Etiology

  • Cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases (90% of cases)
  • 2nd-hand smoke
  • Air pollution Pollution The presence of contaminants or pollutant substances in the air (air pollutants) that interfere with human health or welfare, or produce other harmful environmental effects. The substances may include gases; particulate matter; or volatile organic chemicals. Asthma 
  • Occupational exposure to toxins 
  • Alpha-1 antitrypsin Alpha-1 antitrypsin Plasma glycoprotein member of the serpin superfamily which inhibits trypsin; neutrophil elastase; and other proteolytic enzymes. Alpha-1 Antitrypsin (AAT) Deficiency (AAT) deficiency

Risk factors

  • Premature Premature Childbirth before 37 weeks of pregnancy (259 days from the first day of the mother’s last menstrual period, or 245 days after fertilization). Necrotizing Enterocolitis birth
  • Low body weight
  • Lower socioeconomic status
  • Poor nutrition
  • Childhood respiratory disorders
  • Preexisting airway Airway ABCDE Assessment reactivity

Pathophysiology

Chronic bronchitis Chronic bronchitis A subcategory of chronic obstructive pulmonary disease. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis. Rhinovirus

Inhaled agents cause chronic inflammation Chronic Inflammation Inflammation in the airways, which lead to progressive airway Airway ABCDE Assessment obstruction through:

  • Damage to endothelial cells → ↓ mucocilliary clearance
  • Mucous gland hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation → mucous hypersecretion and plugging
  • Airway Airway ABCDE Assessment 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 Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation and hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation → luminal narrowing
  • Peribronchial fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans → bronchial distortion Distortion Defense Mechanisms
Chronic bronchitis pathophysiology

Chronic bronchitis pathophysiology:
Inflammation, smooth muscle hypertrophy, and excess mucus production lead to progressive airway obstruction.

Image by Lecturio.

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: Anatomy, there is a balance between:

  • Proteases Proteases Proteins and Peptides → 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: Histology as part of normal tissue repair tissue repair The process of generating a scar or less functional tissue with a different form and/or composition of the original tissue. Wound Healing:
    • Neutrophil elastase Elastase A protease of broad specificity, obtained from dried pancreas. Molecular weight is approximately 25, 000. The enzyme breaks down elastin, the specific protein of elastic fibers, and digests other proteins such as fibrin, hemoglobin, and albumin. Proteins and Peptides
    • Matrix metalloproteinase Matrix metalloproteinase A family of zinc-dependent metalloendopeptidases that is involved in the degradation of extracellular matrix components. Pulmonary Fibrosis (MMP)
    • Cathepsins
  • Antiproteases → balance protease Protease Enzyme of the human immunodeficiency virus that is required for post-translational cleavage of gag and gag-pol precursor polyproteins into functional products needed for viral assembly. HIV protease is an aspartic protease encoded by the amino terminus of the pol gene. HIV Infection and AIDS activity:
    • AAT
    • Secretory leukoprotease inhibitor derived from airway Airway ABCDE Assessment 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: Histology
    • Elafin
    • MMP tissue inhibitor

In emphysema:

Morphologic patterns:

  • Centriacinar emphysema (associated with cigarette smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases):
    • Destruction of the respiratory bronchioles Bronchioles The small airways branching off the tertiary bronchi. Terminal bronchioles lead into several orders of respiratory bronchioles which in turn lead into alveolar ducts and then into pulmonary alveoli. Bronchial Tree: Anatomy 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

Effects of the pulmonary vasculature

  • Tissue destruction → ↓ ability to oxygenate blood
  • Hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure 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: Histology → ↑ vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
  • Chronic hypoxemia Hypoxemia Neonatal Respiratory Distress Syndrome vascular remodeling Vascular remodeling The active alterations of vascular wall structures, often leading to elevated vascular resistance. It is associated with aging; atherosclerosis; diabetes mellitus; hypertension; pregnancy; pulmonary hypertension; and stroke, but is also a normal part of embryogenesis. Cor Pulmonale → 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 Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia

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 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
  • 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:

General:

Pulmonary:

  • Visual:
    • Respiratory distress (acute exacerbations)
    • Accessory muscle use
    • Pursed lip breathing
  • Auscultation:
    • Prolonged expiration Expiration Ventilation: Mechanics of Breathing
    • 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
    • Diminished breath sounds
  • Palpation Palpation Application of fingers with light pressure to the surface of the body to determine consistency of parts beneath in physical diagnosis; includes palpation for determining the outlines of organs. Dermatologic Examination and percussion Percussion Act of striking a part with short, sharp blows as an aid in diagnosing the condition beneath the sound obtained. Pulmonary Examination:
    • Hyperresonance on percussion Percussion Act of striking a part with short, sharp blows as an aid in diagnosing the condition beneath the sound obtained. Pulmonary Examination
    • 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: Anatomy expansion

Extremities:

  • Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination
  • Digital clubbing Clubbing Cardiovascular Examination
    • Not typical for COPD alone
    • Presence should raise suspicion for other comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus (e.g., lung cancer Lung cancer Lung cancer is the malignant transformation of lung tissue and the leading cause of cancer-related deaths. The majority of cases are associated with long-term smoking. The disease is generally classified histologically as either small cell lung cancer or non-small cell lung cancer. Symptoms include cough, dyspnea, weight loss, and chest discomfort. Lung Cancer, 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, interstitial lung disease)

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:

Clinical phenotypes

Signs and symptoms are associated more frequently with either chronic bronchitis Chronic bronchitis A subcategory of chronic obstructive pulmonary disease. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis. Rhinovirus or emphysema. However, patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often present with a mixture of features.

Chronic bronchitis Chronic bronchitis A subcategory of chronic obstructive pulmonary disease. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis. Rhinovirus (“ blue bloater Blue bloater A subcategory of chronic obstructive pulmonary disease. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis. Rhinovirus”):

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are generally overweight.
  • Frequent, productive cough
  • Peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema
  • Cyanosis Cyanosis A bluish or purplish discoloration of the skin and mucous membranes due to an increase in the amount of deoxygenated hemoglobin in the blood or a structural defect in the hemoglobin molecule. Pulmonary Examination

Emphysema (“pink puffer”):

  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship are generally thin.
  • Barrel chest
  • Infrequent cough
  • Pursed lip breathing
  • Accessory muscle use
  • Tripod positioning
  • Hyperresonant chest
Pursed__lip__breathing

Demonstrating pursed lip breathing, which is seen in emphysema

Image: “Pursed lip breathing” by O.Chaigasame. License: CC BY 4.0

Diagnosis

Pulmonary function tests

Pulmonary function tests are used to confirm COPD diagnosis. Testing is indicative of obstruction, which is largely irreversible.

Spirometry Spirometry Measurement of volume of air inhaled or exhaled by the lung. Pulmonary Function Tests:

  • ↓ Forced expiratory volume in 1 second (FEV1): maximum volume of air forcefully expired 1 second after maximal inspiration Inspiration Ventilation: Mechanics of Breathing
  • ↓ Forced vital capacity Vital capacity The volume of air that is exhaled by a maximal expiration following a maximal inspiration. Ventilation: Mechanics of Breathing (FVC): maximum volume of air forcefully expired after maximal inspiration Inspiration Ventilation: Mechanics of Breathing
  • Greater loss of FEV1 than FVC → ↓ FEV1/FVC ratio:
    • FEV1/FVC: < 70%
    • FEV1/FVC: < 50% indicates severe disease.
  • Residual volume Residual volume The volume of air remaining in the lungs at the end of a maximal expiration. Common abbreviation is rv. Ventilation: Mechanics of Breathing and total lung capacity Total lung capacity The volume of air contained in the lungs at the end of a maximal inspiration. It is the equivalent to each of the following sums: vital capacity plus residual volume; inspiratory capacity plus functional residual capacity; tidal volume plus inspiratory reserve volume plus functional residual capacity; or tidal volume plus inspiratory reserve volume plus expiratory reserve volume plus residual volume. Ventilation: Mechanics of Breathing (air trapping)
  • Emphysema:
    • ↓ Diffusing capacity for CO:
      • Also known as transfer factor
      • Due to loss of surface area for gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange
    • Rapid fall in expiratory flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure (dynamic airway Airway ABCDE Assessment collapse) → produces a concave pattern

Post-bronchodilator test: 

  • Used to assess the reversibility of the obstructive condition
  • Minimal reversibility in COPD

Staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis

In addition to COPD diagnosis, spirometry Spirometry Measurement of volume of air inhaled or exhaled by the lung. Pulmonary Function Tests results may be used in conjunction with symptoms to help stage severity. The Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria are as follows:

Table: The Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria
GOLD class Severity of COPD Symptoms Spirometry Spirometry Measurement of volume of air inhaled or exhaled by the lung. Pulmonary Function Tests results
GOLD I Mild None or mild
  • FEV1: ≥ 80%
  • FEV1/FVC: < 70%
GOLD II Moderate On exertion
  • FEV1: 50%–79%
  • FEV1/FVC: < 70%
GOLD III Severe On minimal exertion
  • FEV1: 30%–49%
  • FEV1/FVC: < 70%
GOLD IV Very severe At rest
  • FEV1: < 30%
  • FEV1/FVC: < 70%
FEV1: forced expiratory volume in 1 second
FVC: forced vital capacity

Supporting evaluation

Laboratory studies:

  • Arterial blood gas Arterial blood gas Respiratory Alkalosis (ABG):
  • BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation in 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
  • AAT testing: Consider if COPD symptoms are present (not in typical demographic):
    • Younger
    • Nonsmoker
    • Concomitant, unexplained liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy disease

Chest X-ray X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests:

  • Barrel-shaped chest 
  • Wide intercostal spaces Intercostal spaces Chest Wall: Anatomy
  • Horizontal ribs Ribs A set of twelve curved bones which connect to the vertebral column posteriorly, and terminate anteriorly as costal cartilage. Together, they form a protective cage around the internal thoracic organs. Chest Wall: Anatomy 
  • Flattened, low diaphragm Diaphragm The diaphragm is a large, dome-shaped muscle that separates the thoracic cavity from the abdominal cavity. The diaphragm consists of muscle fibers and a large central tendon, which is divided into right and left parts. As the primary muscle of inspiration, the diaphragm contributes 75% of the total inspiratory muscle force. Diaphragm: Anatomy 
  • Hyperlucency
  • Attenuated peripheral vascular markings (due to parenchymal destruction)

Management and Complications

Principles

  • Improve symptoms.
  • Decrease exacerbations.
  • Improve patient function.
  • Improve quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life.

General management

  • Smoking Smoking Willful or deliberate act of inhaling and exhaling smoke from burning substances or agents held by hand. Interstitial Lung Diseases cessation (critical in slowing lung function decline)
  • Vaccinations for:
    • Pneumococcal pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Influenza Influenza Influenza viruses are members of the Orthomyxoviridae family and the causative organisms of influenza, a highly contagious febrile respiratory disease. There are 3 primary influenza viruses (A, B, and C) and various subtypes, which are classified based on their virulent surface antigens, hemagglutinin (HA) and neuraminidase (NA). Influenza typically presents with a fever, myalgia, headache, and symptoms of an upper respiratory infection. Influenza Viruses/Influenza
  • Pulmonary rehabilitation:
    • Guided exercise and behavioral interventions
    • Goal is to improve functional capacity.
  • O2 therapy:
    • If O2 saturation is < 88% in a stable patient (PO₂ < 55 mm Hg)
    • If concurrent 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, right-sided heart failure Right-Sided Heart Failure Ebstein’s Anomaly, or polycythemia Polycythemia An increase in the total red cell mass of the blood. Renal Cell Carcinoma

Medical therapy

  • Bronchodilators Bronchodilators Asthma Drugs
    • Short acting (used as needed for rescue):
      • Beta-2 adrenergic agonists Adrenergic agonists Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs (e.g., albuterol Albuterol A short-acting beta-2 adrenergic agonist that is primarily used as a bronchodilator agent to treat asthma. Sympathomimetic Drugs)
      • Anticholinergics Anticholinergics Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs (e.g., ipratropium bromide Ipratropium Bromide Asthma Drugs)
    • Long acting:
      • Beta-2 adrenergic agonists Adrenergic agonists Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators (î±, β, or dopamine receptors) of the sympathetic autonomic nervous system. Sympathomimetic drugs are classified based on the type of receptors the drugs act on (some agents act on several receptors but 1 is predominate). Sympathomimetic Drugs (e.g., salmeterol Salmeterol Asthma Drugs, formoterol Formoterol Asthma Drugs, indacaterol)
      • Anticholinergics Anticholinergics Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs (e.g., tiotropium, aclidinium Aclidinium Anticholinergic Drugs, umeclidinium)
  • Phosphodiesterase-4 inhibitors Phosphodiesterase-4 Inhibitors Compounds that specifically inhibit phosphodiesterase 4. Phosphodiesterase Inhibitors
    • Option: roflumilast Roflumilast Phosphodiesterase Inhibitors
    • Reduces 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
    • Can increase FEV1 and reduce exacerbations
  • Inhaled corticosteroids Corticosteroids Chorioretinitis
    • Options: budesonide Budesonide A glucocorticoid used in the management of asthma, the treatment of various skin disorders, and allergic rhinitis. Asthma Drugs, fluticasone Fluticasone A steroid with glucocorticoid receptor activity that is used to manage the symptoms of asthma; allergic rhinitis, and atopic dermatitis. Glucocorticoids
    • Can produce both marginal improvements and adverse effects
  • Theophylline Theophylline A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3. Asthma Drugs (oral bronchodilator)
  • Mucolytics

Surgical intervention

Surgery is reserved for severe cases not controlled with medical therapy to improve quality Quality Activities and programs intended to assure or improve the quality of care in either a defined medical setting or a program. The concept includes the assessment or evaluation of the quality of care; identification of problems or shortcomings in the delivery of care; designing activities to overcome these deficiencies; and follow-up monitoring to ensure effectiveness of corrective steps. Quality Measurement and Improvement of life.

Management of acute exacerbations

  • Outpatient or inpatient therapy depending upon severity
  • Short-acting bronchodilators Bronchodilators Asthma Drugs:
  • Systemic steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors
  • Antibiotics are indicated for:
    • Purulent sputum
    • Evidence of pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia
    • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship requiring hospitalization Hospitalization The confinement of a patient in a hospital. Delirium
  • Controlled O2 therapy for acute respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure:

Complications

  • Respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure
  • Respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease ( pneumonia Pneumonia Pneumonia or pulmonary inflammation is an acute or chronic inflammation of lung tissue. Causes include infection with bacteria, viruses, or fungi. In more rare cases, pneumonia can also be caused through toxic triggers through inhalation of toxic substances, immunological processes, or in the course of radiotherapy. Pneumonia)
  • 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 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
  • Long-term complications of steroids Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors osteoporosis Osteoporosis Osteoporosis refers to a decrease in bone mass and density leading to an increased number of fractures. There are 2 forms of osteoporosis: primary, which is commonly postmenopausal or senile; and secondary, which is a manifestation of immobilization, underlying medical disorders, or long-term use of certain medications. Osteoporosis
  • Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery or cachexia
  • Bullae Bullae Erythema Multiforme rupture → secondary spontaneous pneumothorax Secondary Spontaneous Pneumothorax Pneumothorax
Chest/abdomen x-ray showing right pneumothorax chronic obstructive pulmonary disease (copd)

X-ray showing a right-sided pneumothorax in a patient with chronic obstructive pulmonary disease (COPD):
Pneumoperitoneum (arrow points to air under the diaphragm) is noted due to a diaphragmatic defect, which allows air from the pneumothorax to escape into the abdominal cavity.

Image:“Chest/abdomen X-ray showing right pneumothorax and also air under diaphragm suggesting perforated viscus.” by Fernanda Duarte et al. License: CC BY 4.0

Differential Diagnosis

  • Asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma: a chronic, inflammatory condition characterized by reversible airflow obstruction in the lower airways. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Pulmonary function test Pulmonary function tests are a group of diagnostic procedures yielding useful, quantifiable information about the rate of the flow of air through the individual’s airways, lung capacity, and the efficiency of gas exchange in relation to time. The most commonly utilized tests include spirometry (before and after bronchodilator use), lung volumes, and quantitation of diffusing capacity for carbon monoxide (CO). The tests can be influenced by the individual’s effort/fatigue, disease state, or anatomical malformation. Pulmonary Function Tests showing a reversible, obstructive pattern. Management varies based on severity and includes bronchodilators Bronchodilators Asthma Drugs and inhaled corticosteroids Corticosteroids Chorioretinitis 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 X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests and CT). Management includes bronchodilators Bronchodilators Asthma Drugs and antibiotics for acute exacerbations.
  • Bronchiolitis Bronchiolitis Inflammation of the bronchioles. Pediatric Chest Abnormalities 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 Scarring Inflammation. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Steroids A group of polycyclic compounds closely related biochemically to terpenes. They include cholesterol, numerous hormones, precursors of certain vitamins, bile acids, alcohols (sterols), and certain natural drugs and poisons. Steroids have a common nucleus, a fused, reduced 17-carbon atom ring system, cyclopentanoperhydrophenanthrene. Most steroids also have two methyl groups and an aliphatic side-chain attached to the nucleus. Benign Liver Tumors and bronchodilators Bronchodilators Asthma Drugs.
  • Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR): an inability to produce normal cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics to meet metabolic needs. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship 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 Hypoxia Sub-optimal oxygen levels in the ambient air of living organisms. Ischemic Cell Damage, and peripheral edema Peripheral edema Peripheral edema is the swelling of the lower extremities, namely, legs, feet, and ankles. Edema. BNP BNP A peptide that is secreted by the brain and the heart atria, stored mainly in cardiac ventricular myocardium. It can cause natriuresis; diuresis; vasodilation; and inhibits secretion of renin and aldosterone. It improves heart function. It contains 32 amino acids. Renal Sodium and Water Regulation 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 X-ray Penetrating electromagnetic radiation emitted when the inner orbital electrons of an atom are excited and release radiant energy. X-ray wavelengths range from 1 pm to 10 nm. Hard x-rays are the higher energy, shorter wavelength x-rays. Soft x-rays or grenz rays are less energetic and longer in wavelength. The short wavelength end of the x-ray spectrum overlaps the gamma rays wavelength range. The distinction between gamma rays and x-rays is based on their radiation source. Pulmonary Function Tests. Echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) confirms the diagnosis. Management relies on diuresis and medical optimization of cardiac function with beta blockers and ACE inhibitors ACE inhibitors Truncus Arteriosus.
  • Cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans: 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 Inheritance disorder leading to dysfunction of chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes channels Channels The Cell: Cell Membrane, which results in hyperviscous mucus and the accumulation of secretions. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship often have chronic respiratory infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease, 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 Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes test, which can be complemented by genetic testing Genetic Testing Detection of a mutation; genotype; karyotype; or specific alleles associated with genetic traits, heritable diseases, or predisposition to a disease, or that may lead to the disease in descendants. It includes prenatal genetic testing. Myotonic Dystrophies. Management includes cystic Cystic Fibrocystic Change fibrosis Fibrosis Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury. Bronchiolitis Obliterans 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: Histology most often due to thrombus migration from the deep venous system. Signs and symptoms include pleuritic chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, 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 Tachypnea Increased respiratory rate. Pulmonary Examination, and tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children. Severe cases can result in hemodynamic instability or cardiopulmonary arrest Cardiopulmonary arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest. Chest CTA CTA A non-invasive method that uses a ct scanner for capturing images of blood vessels and tissues. A contrast material is injected, which helps produce detailed images that aid in diagnosing vascular diseases. Pulmonary Function Tests is the primary method of diagnosis. Management includes oxygenation, anticoagulation Anticoagulation Pulmonary Hypertension Drugs, and thrombolytic therapy for unstable patients Unstable Patients Blunt Chest Trauma.

References

  1. Han, M.K., Dransfield, M.T., and Martinez, F.J. (2020). Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging. In Hollingsworth, H. (Ed.), UpToDate. Retrieved March 31, 2021, from https://www.uptodate.com/contents/chronic-obstructive-pulmonary-disease-definition-clinical-manifestations-diagnosis-and-staging
  2. Weiss, S.T. (2019). Chronic obstructive pulmonary disease: Risk factors and risk reduction. In Hollingsworth, H. (Ed.), UpToDate. Retrieved March 31, 2021, from https://www.uptodate.com/contents/chronic-obstructive-pulmonary-disease-risk-factors-and-risk-reduction
  3. Ferguson, G.T., and Make, B. (2019). Stable COPD: Initial pharmacologic management. In Hollingsworth, H. (Ed.), UpToDate. Retrieved March 31, 2021, from https://www.uptodate.com/contents/stable-copd-initial-pharmacologic-management
  4. Stoller, J.K. (2020). COPD exacerbations: Management. In Hollingsworth, H. (Ed.), UpToDate. Retrieved March 31, 2021, from https://www.uptodate.com/contents/copd-exacerbations-management
  5. Mosenifar, Z, Harrington, A., Nikhanj, N.S., and Kamangar, N. (2020). Chronic obstructive pulmonary disease (COPD). In Oppenheimer, J.J. (Ed.), Medscape. Retrieved March 31, 2021, from https://emedicine.medscape.com/article/297664-overview
  6. Agarwarl, A.K., Raja, A., and Brown, B.D. (2021). Chronic obstructive pulmonary disease. [online] StatPearls. Retrieved March 31, 2021, from https://www.ncbi.nlm.nih.gov/books/NBK559281/
  7. Wise, R.A. (2020). Chronic obstructive pulmonary disease (COPD). [online] MSD Manual Professional Version. Retrieved March 31, 2021, from https://www.msdmanuals.com/professional/pulmonary-disorders/chronic-obstructive-pulmonary-disease-and-related-disorders/chronic-obstructive-pulmonary-disease-copd
  8. Pauwels, R.A., Buist, A.S., Ma, P., Jenkins, C.R., Hurd, S.S. GOLD Scientific Committee. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: National Heart, Lung, and Blood Institute and World Health Organization Global Initiative for Chronic Obstructive Lung Disease (GOLD): executive summary. Respir Care. 2001;46(8):798-825.

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