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Pharmacotherapy of Chronic Obstructive Pulmonary Disease

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Chronic Obstructive Pulmonary Disease

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Pharmacotherapy of Chronic Obstructive Pulmonary Disease

  1. 1. 1 Lesson 3 Chronic Obstructive Pulmonary Disease (COPD) By: Tsegaye Melaku [MSc, Clinical Pharmacist] Jimma University tsegayemlk@yahoo.com or tsegaye.melaku@ju.edu.et +251913765609August, 2018 Respiratory disorders Pharmacotherapy
  2. 2.  A58-year-old man with a history of hypertension and COPD presents to the ED with complaints of increasing SOB, cough, sputum production, and fever. He is treated with oxygen, bronchodilators, corticosteroids, and empiric antibiotic therapy and then admitted to the hospital where similar treatment is continued. – Goal of therapy? – Exacerbations of COPD, evidences? – Optimal pharmacotherapeutic regimen? – Non-pharmacologic Rx? – Monitor & evaluate? 2
  3. 3.  It is a common, preventable and treatable disease – Characterized by persistent respiratory symptoms and airflow limitation** – Airflow limitation is not fully reversible and is both chronic and progressive – Causes significant extra-pulmonary effects – **that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. 3
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  5. 5.  Currently the 4th leading cause of death in the world1  Projected to be the 3rd leading cause of death by 20202  >3 million people died of COPD in 2012 accounting for 6% of all deaths globally.  ~~24 million Americans  Globally, the its burden is projected to increase in coming decades – Continued exposure to COPD risk factors and aging of the population. 1. Lozano R, Naghavi M, Foreman K, et al. Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 2012; 380(9859): 2095-128. 2. Mathers CD, Loncar D. Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 2006; 3(11): e442. 5
  6. 6.  Prevalence of COPD – Estimated 384 million COPD cases in 2010. – Estimated global prevalence of 11.7% (95% CI 8.4%–15.0%). – Three million deaths annually. – With increasing prevalence of smoking in developing countries, and aging populations in high-income countries – By 2030 predicted 4.5 million COPD related deaths annually. 6
  7. 7.  Prevalence of COPD... – Systematic review and meta-analysis (Halbert et al, 2006) – Included studies carried out in 28 countries between 1990 and 2004 – Prevalence of COPD was higher in smokers and ex-smokers compared to non-smokers – Higher ≥ 40 year group compared to those < 40 – Higher in men than women. 7
  8. 8.  Economic burden of COPD – Associated with significant economic burden. – Exacerbations account for the greatest proportion of the total COPD burden. – European Union: – Direct costs of respiratory disease ~6% of the total healthcare budget – COPD accounting for 56% (38.6 billion Euros) of the cost of respiratory disease. – USA: – Direct costs of COPD are $32 billion – Indirect costs $20.4 billion. 8
  9. 9.  Global Burden of Disease (GBD) study – High disability-Adjusted Life Year (DALY) – It is an increasing contributor to disability & mortality around the world. – In 2013, COPD was 5th leading cause of DALYs lost. – In the US, COPD is the 2nd leading cause of reduced DALYs, trailing only ischemic heart disease 9
  10. 10.  Two types 10 COPD Chronic Bronchitis* Emphysema** – *Cough on most days for at least 3 months of the year for at least 2 consecutive years – *Associated with chronic or recurrent excessive mucus secretion into the bronchial tree – **Abnormal permanent enlargement of the airspaces distal to the terminal bronchioles accompanied by destruction of their walls
  11. 11. – Main risk factor: tobacco smoking – (85% to 90% of cases) – Only 15% to 20% of them develop COPD – 12X of non-smokers – Other: environmental exposures such as biomass fuel exposure and air pollution – Host factors: genetic abnormalities, abnormal lung dev’t & accelerated aging 11
  12. 12. FEV1 vs Age 12
  13. 13.  Genetic factors  Age & gender  Lung growth and development  Exposure to particles  Socioeconomic status  Asthma & airway hyper-reactivity  Chronic bronchitis  Infections 13
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  15. 15. – Chronic inflammatory changes destructive changes development of chronic airflow limitation – Inflammation involves – Airways – Pulmonary vasculature – Lung parenchyma 15
  16. 16.  The inflammation of COPD is often neutrophilic in nature. – But, macrophages and CD8+ lymphocytes have major roles – Others: TNF-α, IL-8, LT-B4  Stimulus for activation: exposure to noxious particles and gas  Others: oxidative stress, imbalance proteases and anti-proteases 16
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  19. 19. 19 Features of Inflammation in COPD Compared with Asthma
  20. 20.  Pathology – Chronic inflammation – Structural changes  Pathogenesis – Oxidative stress – Protease-antiprotease imbalance – Inflammatory cells – Inflammatory mediators – Peribronchiolar and interstitial fibrosis  Pathophysiology – Airflow limitation and gas trapping – Gas exchange abnormalities – Mucus hypersecretion – Pulmonary hypertension 20
  21. 21. 21 Etiology of airflow limitation in COPD
  22. 22.  S & Sxs: dyspnea, chronic cough or sputum production, and/or a hx of exposure to risk factors.  Spirometry: post-bronchodilator FEV1/FVC < 0.70 confirms the presence of persistent airflow limitation.  Concomitant chronic diseases  Clinical pictures, P/E, Necessary laboratory tests  Symptoms of COPD – Chronic and progressive dyspnea – Cough – Sputum production – Wheezing and chest tightness – Others – including fatigue, weight loss, anorexia, syncope, rib fractures, ankle swelling, depression, anxiety. 22
  23. 23. 23 Key indicators for considering for diagnosis of COPD
  24. 24.  Patient’s exposure to risk factors  Past medical history  Family Hx of COPD or other chronic respiratory disease.  Pattern of symptom development  Hx of exacerbations or previous hospitalizations for respiratory disorder  Presence of comorbidities  Impact of disease on patient’s life  Social and family support available to the patient.  Possibilities for reducing risk factors, especially smoking cessation. 24
  25. 25. Normal trace 25 Obstructive disease
  26. 26. Considerations in performing spirometry 26
  27. 27. Based on post-bronchodilator FEV1 Always FEV1/FVC < 70% 27
  28. 28. Role of spirometry 28
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  30. 30. 30 A patient with advanced hypoxic COPD with central cyanosis. Pitting ankle oedema is a feature of cor pulmonale Gross tar staining of the fingers due to chronic cigarette smoking. Tar staining and finger clubbing
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  32. 32.  COPD Assessment Test (CATTM )  Chronic Respiratory Questionnaire (CCQ® ) http://www.ccq.nl  Modified Medical Research Council (mMRC) questionnaire http://www.goldcopd.org  St George’s Respiratory Questionnaire (SGRQ)  Chronic Respiratory Questionnaire (CRQ) Modified MRC dyspnea scale http://catestonline.org 32
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  35. 35. Example  Consider two patients: – Both patients with FEV1 < 30% of predicted – Both with CAT scores of 18 – But, one with 0 exacerbations in the past year and the other with 3 exacerbations in the past year.  Both would have been labelled GOLD D in the prior classification scheme.  With the new proposed scheme, the subject with 3 exacerbations in the past year would be labelled GOLD grade 4, group D.  The other patient, who has had no exacerbations, would be classified as GOLD grade 4, group B. 35
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  37. 37. Goal of Rx 37
  38. 38.  Smoking Cessation: greatest role  Vaccination (Pneumococcal & influenzae, others)… PCV13 & PPSV23 – Recommended for all patients ≥ 65 years of age  Pulmonary rehabilitation  Long-term oxygen therapy  Long-term non-invasive ventilation...in severe chronic hypercapnia  Surgical or bronchoscopic interventional...Emphysema 38
  39. 39.  Education and self-management  Physical activity  Exercise training  End of life and palliative care  Nutritional support 39
  40. 40. Education and self-management  Healthcare professionals should be a major component of the “Chronic Care Model” within the context of the healthcare delivery system.  Aim : motivate, engage and coach the patients to positively adapt their health behavior(s) and develop skills to better manage their disease. 40
  41. 41. Oxygen therapy Long-term oxygen therapy is indicated for stable patients who have:  PaO2 ≤ 7.3 kPa (55 mmHg) or SaO2 at or below 88%, with or without hypercapnia confirmed twice over a three week period; or  PaO2 between 55 to 60 mmHg, or SaO2 of 88%, if there is evidence of pulmonary hypertension, peripheral edema suggesting CHF or polycythemia (hematocrit > 55%. 41
  42. 42. Prescription of supplemental oxygen to COPD patients 42
  43. 43. Interventional bronchoscopy and surgery  In emphysema and significant hyperinflation refractory to optimized medical care...lung volume reduction  In selected patients with a large bulla, surgical bullectomy may be considered.  In selected patients with very severe COPD and without relevant contraindications, lung transplantation may be considered. 43
  44. 44.  A proposed inititation, then subsequent escalation and/or de-escalation Disease-modifying benefit? – Only oxygen..!? 44
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  46. 46.  Relax bronchial smooth muscle,  Improve lung emptying,  Reduce thoracic hyperinflation at rest and during exercise,  Improve exercise tolerance 46 SABDs: relieve symptoms and increase exercise tolerance LABDs: relieve symptoms, reduce exacerbation frequency, and improve quality of life and health status Example: LABAs by 23% Tiotropium by 29% ICs by 22%, ICs + LABAs by 28% β2-agonists, Anticholinergics, Methylxanthines
  47. 47.  SABA – Albuterol 47  SAMA – Ipratropium  SABA + SAMA  LABA – Salmeterol – Formoterol – Arformoterol – Indacaterol – Olodaterol – Vilanterol  LAMA – Tiotropium bromide – Aclidinium – Umeclidinium
  48. 48.  Includes: theophylline, aminophylline  Considered for patients who are intolerant or unable to use an inhaled bronchodilator.  Have multiple mechanisms (bronchodilation and antiinflammatory)  Offer improvements in lung function, vital capacity, FEV1, and gas exchange 48
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  50. 50.  Chronic systemic corticosteroid therapy should be avoided, if possible  Anti-inflammatory mxms – Reduction in capillary permeability to decrease mucus, – Inhibition of release of proteolytic enzymes from leukocytes, – Inhibition of prostaglandins.  Appropriate situations to consider – Short-term systemic use for acute exacerbations – Inhalation therapy for chronic stable COPD in selected patients. 50
  51. 51. Side effects from corticosteroids – Osteoporosis – Muscular atrophy, – thinning of the skin, – Development of cataracts, – Adrenal suppression and insufficiency – Hoarseness, sore throat, oral candidiasis, and skin bruising 51
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  53. 53. New recommendation – Following the disappointing results of chronic ICS studies  progressive decline in lung function – LABA + ICS: associated with greater improvements in clinical outcomes [FEV1, health status, & frequency of exacerbations] – Example: • Salmeterol + fluticasone • Budesonide+ formoterol, • Mometasone + formoterol 53
  54. 54. Phosphodiesterase 4 (PDE4) – Responsible for degrading cAMP – Production of TNF-α and IL-8. – Example: roflumilast [500 mcg orally once a day] – Recommended in severe or very severe COPD (Group C, D) – Side effects: weight loss neuropsychiatric effects [ suicidal thoughts, insomnia, anxiety, and new or worsened depression] 54
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  57. 57. Group A – Should be offered bronchodilator Rx based on its effect on breathlessness. – This can be either a short- or a long- acting bronchodilator. – This should be continued if symptomatic benefit is documented. 57
  58. 58. Group B – Initial therapy: long acting bronchodilator. – LABD are superior to SABD taken as needed, are therefore recommended. – For patients with persistent breathlessness on monotherapy the use of two bronchodilators is recommended. 58
  59. 59. Group B (continued) – For patients with severe breathlessness initial therapy with two bronchodilators may be considered. – If the addition of a second bronchodilator does not improve symptoms, we suggest the treatment could be stepped down again to a single bronchodilator. – Group B patients are likely to have comorbidities that may add to their symptomatology and impact their prognosis, and these possibilities should be investigated. 59
  60. 60. Group C – Initial therapy: a single long acting bronchodilator. – Patients with persistent exacerbations LABA+ LAMA or LABA+ICS. – As ICS increases the risk for developing pneumonia in some patients, primary choice is LABA/LAMA. 60
  61. 61. Group D – Recommendations tarting therapy with a LABA/LAMA combination because: – If a single bronchodilator is chosen as initial treatment, a LAMA is preferred for exacerbation prevention based on comparison to LABAs – A LABA + LAMA combination was superior to a LABA + ICS combination in preventing exacerbations and other patient reported outcomes in Group D patients – Group D patients are at higher risk of developing pneumonia when receiving treatment with ICS. 61
  62. 62. Group D (continued) – In some patients initial therapy with LABA/ICS e.g. asthma-COPD overlap. – High blood eosinophil counts may be considered as a parameter to support the use of ICS – In patients who develop further exacerbations on LABA/LAMA therapy ....two alternative pathways: – Escalation to LABA/LAMA/ICS. – Switch to LABA/ICS. If LABA/ICS therapy does not positively impact exacerbations/symptoms, add LAMA. 62
  63. 63. Group D (continued) – If patients treated with LABA/LAMA/ICS still have exacerbations the following options may be considered: – Add roflumilast. – Add a macrolide. – Stopping ICS. 63
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  68. 68. Monitoring disease progression and development of complications and/or comorbidities Measurements. Decline in FEV1 can be tracked by spirometry performed at least once a year. Symptoms. At each visit, information on symptoms since the last visit should be collected, including cough and sputum, breathlessness, fatigue, activity limitation, and sleep disturbances. Exacerbations. The frequency, severity, type and likely causes of all exacerbations should be monitored. Imaging. If there is a clear worsening of symptoms, imaging may be indicated. Smoking status. At each visit, the current smoking status and smoke exposure should be determined followed by appropriate action. 68
  69. 69. Pharmacotherapy and other medical treatment  Monitoring should focus on: Dosages of prescribed medications. Adherence to the regimen. Inhaler technique. Effectiveness of the current regime. Side effects.  Treatment modifications should be recommended. 69
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  71. 71. Defn: an acute worsening of respiratory symptoms that result in additional therapy  It is change in the patient’s baseline symptoms – …..dyspnea, cough, or sputum production – Sufficient to warrant a change in management – Lung hyperinflation worsened   worsening dyspnea & poor gas exchange. – Profound hypoxemia & hypercapnia   respiratory acidosis and respiratory failure. 71
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  73. 73.  Defined: change in one or more of the following clinical findings: – Worsening symptoms of dyspnea, – Increase in sputum volume, or – Increase in sputum purulence. Cardinal symptoms 73
  74. 74. 74 Increased sputum volume and purulence.
  75. 75. 75 Mild/type1 • 1 cardinal sxs** • Rx with SABDs only Moderate/type 2Moderate/type 2 •2 cardinal sxs •Rx with SABDs + abx and/or oral corticosteroids Severe/type 3 • 3 cardinal sxs • Require Hospitalization/ ER; risk of respiratory failure **plus at least one of the following: URTI within 5 days, fever without other explanation, increased wheezing, increased cough, increase in respiratory or heart rate >20% above baseline
  76. 76.  Desired outcome – Prevention of hospitalization or reduction in hospital stay, – Prevention of acute respiratory failure and death, – Resolution of exacerbation sxs and a return to baseline clinical status and quality of life. 76
  77. 77.  Pharmacotherapy – Intensification of bronchodilator therapy – Short course of systemic corticosteroids. – Antimicrobial: in the presence of selected symptoms 77
  78. 78.  Controlled Oxygen Therapy: Titrate oxygen to desired oxygen saturation (>90%)  Noninvasive Mechanical Ventilation  Bronchodilators: Doses and frequency increased: SABDs preferred  Systemic corticosteroids: short course (7-14 days)  Antimicrobial Therapy: as Respiratory infections a cause for exacerbations – Most common cause: H.influenzae/para-influenzae, M. catarrhalis, S.pneumoniae, including MDR pathogens, enteric Gm(-), P.aeruginosa 78
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  81. 81.  Maintenance therapy with long-acting bronchodilators should be initiated as soon as possible before hospital discharge.  Systemic corticosteroids can improve lung function (FEV1), oxygenation and shorten recovery time and hospitalization duration. Duration of therapy should not be more than 5-7 days.  Antibiotics, when indicated, can shorten recovery time, reduce the risk of early relapse, treatment failure, and hospitalization duration. Duration of therapy should be 5-7 days ~~ 10 days  Methylxanthines are not recommended due to increased side effect profiles. 81
  82. 82.  COPD often coexists with other diseases (comorbidities) that may have a significant impact on disease course.  In general, the presence of comorbidities should not alter COPD treatment and comorbidities should be treated per usual standards regardless of the presence of COPD.  Lung cancer is frequently seen in patients with COPD and is a main cause of death.  Cardiovascular diseases are common and important comorbidities in COPD. 82
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  84. 84.  Osteoporosis and depression/anxiety are frequent, important comorbidities in COPD, are often under-diagnosed, and are associated with poor health status and prognosis.  Gastroesophageal reflux (GERD) is associated with an increased risk of exacerbations and poorer health status.  When COPD is part of a multimorbidity care plan, attention should be directed to ensure simplicity of treatment and to minimize polypharmacy. 84
  85. 85.  Some common comorbidities occurring in patients with COPD with stable disease include: – Heart failure, Ischemic heart disease (IHD) – Arrhythmias, Peripheral vascular disease – Hypertension – Osteoporosis – Anxiety and depression – COPD and lung cancer – Metabolic syndrome and diabetes – Gastroesophageal reflux (GERD) – Obstructive sleep apnea 85
  86. 86.  Those with partially reversible airflow obstruction, an atopic symptoms, and minimal smoking history 86
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  90. 90.  Not clear  Specific asthma or COPD component  Read the detail of ACOS 90
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