COPD Presentation (2025) - Disease Pathophysiology & Treatment - PDF

COPD  Objectives 1.Discuss the epidemiology of COPD. 2.Identify risk factors for the development and progression of COPD. 3.Describe the natural course of COPD. 4.Propose goals for chronic COPD management. 5.Apply tobacco cessation strategies to a patient scenario. 6.Recommend vaccines for a p...

COPD  Objectives 1.Discuss the epidemiology of COPD. 2.Identify risk factors for the development and progression of COPD. 3.Describe the natural course of COPD. 4.Propose goals for chronic COPD management. 5.Apply tobacco cessation strategies to a patient scenario. 6.Recommend vaccines for a patient with COPD. 7.Discuss the role of supplemental oxygen therapy in COPD management. 8.Apply the stepwise approach to COPD management to a patient scenario. 9.Describe the role of anti-inflammatory therapies in COPD management. 10.Compare and contrast the impact of chronic COPD management strategies on exacerbation rates. 11.Propose counseling points and monitoring parameters of chronic pharmacotherapy in a patient with COPD. 12.Discuss the approach to managing an acute exacerbation of COPD. Introduction Chronic obstructive pulmonary disease (COPD) is a common lung disease characterized by airflow limitation that is not fully reversible, in contrast to the reversibility of airflow limitation in asthma. COPD is both chronic and progressive and is associated with an abnormal inflammatory response of the lungs to noxious particles or gases. The two principal conditions are chronic bronchitis and emphysema, which are referred to as phenotypes. Guidelines: Global Initiative for Chronic Obstructive Lung Disease (GOLD) Introduction Chronic bronchitis Chronic or recurrent excessive mucus secretion into the bronchial tree with cough that is present on most days for at least 3 months of the year for at least two consecutive years in a patient in whom other causes of chronic cough have been excluded Emphysema Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls, without obvious fibrosis Epidemiology COPD affects 16 – 28 million Americans Leading cause???? Hint in picture over there  Etiology Cigarette smoking is the most common risk factor and accounts for 85% to 90% of cases of COPD in the United States 50% of all smokers develop COPD Environmental factors, such as tobacco smoke, occupational dust, and chemicals are modifiable factors that, if avoided, may reduce the risk of disease development Specific genes, such as matrix metalloproteinase 12 (MMP12), α1-antitrypsin, and other genetic markers have been implicated with decline of lung function and potential risk of developing COPD α1-antitrypsin (AAT) has been definitively shown to correlate with development of emphysema and pulmonary dysfunction Primary role of AAT, a plasma protein synthesized in hepatocytes, is to protect cells, especially those in the lung, from destruction by elastase released by neutrophils Accounts for < 1% of all COPD cases Pathophysiology Chronic obstructive pulmonary disease is characterized by chronic inflammatory changes that lead to destructive tissue changes and development of chronic airflow limitation The inflammation seen in COPD is often referred to as neutrophilic in nature, but macrophages and CD8+ lymphocytes also play major roles Increased oxidative stress and imbalance between destructive and protective defense systems in the lungs (proteases and antiproteases) Pathophysiology Mucus secretion is increased, and ciliary motility is impaired Thickening of smooth muscle and connective tissue in the airways Chronic inflammation results in a repeated injury and repair process that leads to scarring and fibrosis Reversible or irreversible? Pathophysiology As disease progresses, abnormalities in gas exchange lead to hypoxemia and/or hypercapnia Hypoxemia is attributed to hypoventilation (V) of lung tissue relative to perfusion (Q) of the area. This low (V/Q) ratio will progress over a period of several years, resulting in a consistent decline in the partial pressure of arterial oxygen (PaO2). ↓ PaO2 = 45-60 mm Hg (6.0-8.0 kPa) ↑ PaCO2 = 50-60 mm Hg (6.7-8.0 kPa) For testing purposes in this class, do not memorize kPa values Pathophysiology As the disease progresses…. pH balance will be maintained by kidneys Patients at risk for respiratory acidosis Development of pulmonary hypertension Right ventricle hypertrophy  right-sided heart failure Thoracic hyperinflation Dyspnea Increase in functional residual capacity (FRC); FRC = Expiratory reserve volume + residual volume Systemic effects include cardiovascular events associated with ischemia, cachexia (ie, weight loss & muscle wasting), osteoporosis, and anemia Clinical Presentation Clinical Presentation Diagnosis of COPD should be considered for any patient, age 40 years or older, with persistent or progressive dyspnea, with chronic cough productive of sputum, and who exhibits an unusual or abnormal decline in activity, especially in the presence of exposure to environmental tobacco smoke Spirometry combined with physical examination improves the diagnostic accuracy of COPD Reduction in FEV1/FVC ratio to less than 70% (0.70) FVC (forced vital capacity) is the total volume of air exhaled after maximal inhalation and FEV1 (forced expiratory volume in one second) is the total volume of air exhaled in one second Postbronchodilator spirometry results should be used in assessing lung function in patients with COPD Usual doses are 400 mcg of β-agonist, 160 mcg of anticholinergic, or the two combined FEV1 should be measured 10-15 minutes after a short-acting β-agonist or 30-45 minutes after a short- acting anticholinergic or combination Clinical Presentation Symptom assessment should be measured at baseline and then during routine visits using CAT or mMRC Patients with at least two exacerbations in the last 12 months, or one exacerbation requiring hospitalization, are considered high risk for future exacerbations (category E) Based on prognostic indices, mortality for patients with COPD increases with worsening airflow limitation (lower FEV1 percent of predicted), greater age, lower body mass index, higher dyspnea score (mMRC), shorter 6-minute walk distance, continued smoking, frequent and severe exacerbations, and presence of selected comorbidities This is to score the severity  Teaching Slide Set **Patients will also need a SABA for emergencies** © 2024, 2025 Global Initiative for Chronic Obstructive Lung Disease Treatment Goals of therapy Prevent progression Relieve symptoms Improve exercise tolerance Improve overall health status Prevent & treat exacerbations Prevent & treat complications Reduce morbidity and mortality Four major components of management: assess and monitor the condition, avoid or reduce exposure to risk factors, manage stable disease, and treat exacerbations Most treatments for COPD have not been shown to improve survival or to slow the progressive decline in lung function Many therapies do improve pulmonary function and quality of life as well as reduce the risk of COPD exacerbations and duration of hospitalization Treatment Smoking cessation Only intervention proven to affect long-term decline in FEV 1 and slow the progression of COPD Evidence from long-term cessation trials show that tobacco cessation, either sustained or intermittent, is of benefit at any point In general, available pharmacotherapies will double the effectiveness of a cessation effort Treatment Avoid bupropion for patients with PMH of seizures or eating disorders NRT contraindicated with recent (w/in 2 weeks) stroke or MI Varenicline relieves physical withdrawal symptoms and reduces the rewarding properties of nicotine MOA - partial agonist on nicotinic receptors Other options: tricyclic antidepressants, behavioral therapy and hypnosis E-cigarettes not recommended due to missing long-term safety data (UK is exception) Treatment Pulmonary rehabilitation Exercise three to seven times per week can produce long-term improvement in activities of daily living, quality of life, exercise tolerance, and dyspnea for patients with moderate-to-severe COPD Oxygen Therapy should be instituted if either of the following two conditions is observed and documented twice in a 3-week period: A resting PaO2 of less than 55 mm Hg (7.3 kPa) or SaO2 (arterial oxygen saturation) less than 88% (0.88) with or without hypercapnia (elevated carbon dioxide) A resting PaO2 between 55 and 60 mm Hg (7.3 and 8.0 kPa) or SaO2 less than 88% (0.88)with evidence of right-sided heart failure, polycythemia (elevated hematocrit or hemoglobin), or pulmonary hypertension 1 to 2 L/min, providing 24% to 28% (0.24 to 0.28) fraction of inspired oxygen (FiO 2) with a goal to raise PaO2 above 60 mm Hg (8.0 kPa) Treatment VACCINES Influenza Tdap RSV COVID-19 Pneumonia Treatment Adult pneumonia vaccines (2025) 19-49 years old w/ COPD; other indications have same recommendations (eg, smoking or heart failure) One dose: Prevnar-15, Prevnar-20, or Capvaxive (PCV21) IF Prevnar-15 is used then administer one dose of Pneumovax-23 one year later IF they had a previous Prevnar-13 vaccine then administer one shot of Prevnar-20 or Capvaxive one year later IF they had a previous Pneumovax-23 vaccine then administer one shot of Prevnar-15, Prevnar-20, or Capvaxive one year later IF they had a previous Prevnar-13 and Pneumovax-23 vaccine then administer one Prevnar-20 or Capsvaxive five years later Adults 50 years and older One dose: Prevnar-15, Prevnar-20, or Capvaxive (PCV21) IF Prevnar-15 is used then administer one dose of Pneumovax-23 one year later IF they had a previous Prevnar-13 vaccine then administer one shot of Prevnar-20 or Capvaxive one year later IF they had a previous Pneumovax-23 vaccine then administer one shot of Prevnar-15, Prevnar-20, or Capvaxive one year later IF they had a previous Prevnar-13 and Pneumovax-23 vaccine (BUT Pneumovax-23 was not administered by age 65) then administer one Prevnar-20 or Capsvaxive five years later Use shared clinical decision-making if Pneumovax-23 was administered on or after age 65 to determine if patient needs one Prevnar-20 or Capsvaxive five years later Treatment Bronchodilators Short-acting beta agonist (SABA) Albuterol (Ventolin, ProAir, Proventil) Metered-dose inhaler (MDI) or nebulizer solution Racemic mixture of (R)-albuterol, which is responsible for the bronchodilator effect, and (S)-albuterol, which has no therapeutic effect Levalbuterol (Xopenex) MDI or nebulizer solution Single-isomer formulation of (R)-albuterol No evidence to suggest better clinical efficacy or safety compared to albuterol Adverse effects Skeletal muscle tremors can occur initially but generally subside as tolerance develops Palpitations and “jitteryness” have been reported after use May cause sinus tachycardia and rhythm disturbances in predisposed patients Treatment Bronchodilators Short-acting anticholinergics (also known as antimuscarinics) MOA: M1 – 3 acetylcholine antagonist Ipratropium (Atrovent) MDI or nebulized solution Slower onset of symptom relief ( 5 minutes for albuterol vs. 20 minutes for ipratropium) Less risk of causing skeletal muscle tremor and tachycardia Adverse effects Dry mouth, nausea, and an occasional metallic taste May precipitate narrow-angle glaucoma symptoms Treatment Long-acting bronchodilators Long-acting inhaled bronchodilator therapy is more convenient for patients with persistent symptoms and has shown superior outcomes in improving lung function, relieving symptoms, and importantly reductions in exacerbation frequency and improved quality of life Not recommended for acute relief LABA monotherapy for COPD is not associated with increased mortality and is recommended as part of international guidelines 2023 guideline update recommends combination therapy (LAMA + LABA) for group B+E Salmeterol and formoterol have more outcome evidence to support use Improves lung function, symptoms, exacerbation frequency, and associated hospitalizations Tiotropium has more outcome evidence to support use Improvements in lung function and symptoms, as well as reduced exacerbation rates and hospitalization  Treatment Long-acting bronchodilators – Long-acting β2-agonists (LABAs) Salmeterol (Serevent Diskus) Dry powder inhaler (DPI) BID dosing 20 minute onset of action Most LABAs have a five minute onset of action Formoterol (Perfomist) Nebulized solution BID dosing Arformoterol (Brovana) Nebulized solution BID dosing Indacaterol (Arcapta) DPI Qday dosing Olodaterol (Striverdi) Soft mist inhaler (SMI) Qday dosing Treatment Long-acting bronchodilators – Long acting muscarine antagonists (LAMAs) Tiotropium (Spiriva Respimat or Spiriva Handihaler) SMI & DPI Qday Dosing 80 minute onset of action Most LAMAs have a 15 minute onset of action Aclidinium (Tudorza Pressair) DPI BID dosing Glycopyrrolate (Lonhala Magnair or Seebri Neohaler) Nebulized solution or DPI BID dosing Umeclidinium (Incruse Ellipta) DPI Qday dosing Revefenacin (Yupelri) Nebulized solution Qday dosing Treatment Corticosteroids Chronic therapy with oral steroids should be avoided in COPD patients Long-term adverse effects associated with systemic corticosteroid therapy include osteoporosis, muscular atrophy, thinning of the skin, development of cataracts, and adrenal suppression and insufficiency May use inhalation therapy with LAMA/LABA for chronic stable COPD in patients at high risk of exacerbation (category E) and short-term systemic use for acute exacerbations Decrease in exacerbation frequency and improvements in lung function and health status ICS monotherapy for patients with COPD is not recommended Use lowest effective dose to reduce the risk of fractures Recommend adequate intake of calcium and vitamin D and consider periodic bone mineral density testing for patients at risk of osteopenia Adverse risks Pneumonia and mycobacterial pulmonary infections Risk factors for developing pneumonia include age >55 years, body mass index (BMI) less than 25 kg/m 2 , current smoker, history of exacerbation or pneumonia (last 12 months), or severe airflow limitation Hoarseness, sore throat, oral candidiasis, and skin bruising Wash mouth after use Treatment Combination dual and triple therapy Significant improvement in lung function, symptoms, and quality-of-life measures compared with LABA or LAMA monotherapy Decrease frequency of moderate-to-severe exacerbations compared to either LAMA or LABA monotherapy ICS/LABA not recommended Triple therapy with ICS/LABA/LAMA may be considered instead of LAMA/LABA for patients with blood eosinophil ≥ 300 cells/μL (0.3 x 109/L) or ≥ 100 cells/uL and ≥ two moderate exacerbations or one exacerbation requiring hospitalization in the last year (high risk) Triple therapy with LAMA/LABA/ICS provides additional benefit in reducing frequency of moderate-to-severe exacerbations in patients with COPD Given the risk of adverse effects with ICS, clinicians may consider by-passing triple inhalation therapy (LAMA/LABA/ICS) for those patients with persistent exacerbations and lower blood eosinophil count ( = 300 cells / mcl and concurrent use of LAMA/LABA/ICD Dose: 300 mg injection every other week Warnings: eosinophilia, anaphylaxis, helminth infections, and live vaccines Adverse reactions: injection site reactions, increased risk of infections (eg, herpes and UTIs), and arthralgias Treatment Methylxanthines Theophylline (PO) and aminophylline (IV) MOA: (a) inhibition of phosphodiesterase, thereby increasing cAMP levels, (b) inhibition of calcium ion influx into smooth muscle, (c) prostaglandin antagonism, (d) stimulation of endogenous catecholamines, (e) adenosine receptor antagonism, and (f) inhibition of release of mediators from mast cells and leukocytes May offer improvements in lung function and gas exchange Reduces dyspnea Increases exercise tolerance Improves respiratory drive Dosing Initiated at 200 mg twice daily and titrated upward every 3 to 5 days to the target dose Target = troughs = 15 mcg/mL Monitoring Once or twice a year or When new medications are added that affect theophylline's metabolism During exacerbations Suspected toxicities Treatment Methylxanthines Theophylline (PO) and aminophylline (IV) Adverse effects Dyspepsia, nausea, vomiting, diarrhea, headache, dizziness, and tachycardia Toxicities (> 20 mcg/mL)  arrhythmias and seizures Narrow therapeutic index Drug interactions Decrease clearance of theophylline Cimetidine, clarithromycin, erythromycin, ciprofloxacin, levofloxacin Increase clearance of theophylline Smoking, phenytoin, phenobarbital, rifampin Treatment Phosphodiesterase 4 (PDE4) inhibitor Roflumilast (Daliresp) MOA: relaxation of airway smooth muscle cells and decreased activity of inflammatory cells and mediators such as TNF-α and IL-8 Recommended for patients with recurrent exacerbations despite treatment with triple inhalation therapy (LAMA/LABA/ICS) May also be considered as escalation therapy for patients with recurrent exacerbations on dual long-acting bronchodilators (LAMA/LABA) who are not candidates for ICS such as those with low blood eosinophil count (