COPD Mohammad Ruhal Ain R Ph, PGDPRA, M Pharm (Clin. Pharm) Department of Clinical Pharmacy

Define !

Definition  COPD? •syndrome of chronic limitation in expiratory airflow encompassing emphysema or chronic bronchitis. Airflow obstruction may be accompanied by airway hyperresponsiveness and may be not be fully reversible.  Emphysema •abnormal permanent enlargement of the airspaces distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis Chronic Bronchitis? •consists of persistent cough plus sputum production for most days out of 3 months in at least 2 consecutive years

Inelastic collapsible bronchioles Emphysema Enlarged air sacs due to destruction of alveolar walls (bullae) Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis Destruction of the alveolar wall damages pulmonary capillaries by tearing, fibrosis, or thrombosis Inelastic collapsible bronchioles Abnormal permanent enlargement of the air spaces distal to the terminal bronchioles accompanied by destruction of their walls and without obvious fibrosis Walls of individual sacs torn (repair not possible)

Bronchiole Chronic Bronchitis Air passage narrowed by plugged and swollen mucous membrane Presence of chronic productive cough for 3 months in each of 2 successive years in a patient in whom other causes of chronic cough have been excluded Mucus and pus impede action of respiratory cilia

Inflammation: COPD vs Asthma Inflammation is an important component in the pathogenesis of asthma and COPD The inflammatory response in asthma and COPD is markedly different, although some cell types are present in both diseases The predominant inflammatory cells in asthma include Eosinophils Mast cells CD4+ T lymphocytes The predominant inflammatory cells in COPD include Neutrophils CD8+ T lymphocytes Macrophages The role of these cells in COPD is not fully understood

Asthma Sensitizing agent COPD Noxious agent Asthmatic airway inflammation CD4+ T-lymphocytes Eosinophils COPD airway inflammation CD8+ T-lymphocytes Macrophages Neutrophils Completely reversible Airflow limitation Completely irreversible

Differential Diagnosis: COPD and Asthma Onset in mid-life Symptoms slowly progressive Long smoking history Dyspnea during exercise Largely irreversible airflow limitation Onset early in life (often childhood) Symptoms vary from day to day Symptoms at night/early morning Allergy, rhinitis, and/or eczema also present Family history of asthma Largely reversible airflow limitation

COPD: Risk Factors Exposures Smoking (generally ≥90%) Passive smoking Ambient air pollution Occupational dust/chemicals Childhood infections (severe respiratory, viral) Socioeconomic status Host factors Alpha1-antitrypsin deficiency (<1%) Hyperresponsive airways Lung growth

indoor/outdoor pollution Diagnosis of COPD EXPOSURE TO RISK FACTORS SYMPTOMS shortness of breath tobacco chronic cough occupation sputum indoor/outdoor pollution è SPIROMETRY: Required to establish diagnosis

Spirometric Diagnosis of COPD COPD is confirmed by post– bronchodilator FEV1/FVC < 0.7 Post-bronchodilator FEV1/FVC measured 15 minutes after 400µg salbutamol or equivalent

GOLD Guidelines for COPD Stage 0: At Risk Diagnosis Chronic cough/sputum PFTs within normal limits No symptoms Treatment Avoid risk factors (smoking cessation)

GOLD Guidelines for COPD Stage I: Mild Diagnosis FEV1 >80% predicted FEV1/FVC <70% With/without symptoms Treatment Avoid risk factors Short-acting bronchodilator PRN

GOLD Guidelines for COPD Stage II: Moderate Diagnosis 50%  FEV1 <80% predicted FEV1/FVC <70% With/without symptoms Treatment Avoid risk factors Regular therapy with  1 bronchodilators Inhaled corticosteroids if significant symptoms and lung function response Rehabilitation

GOLD Guidelines for COPD Stage III:Severe Diagnosis 30%  FEV1 < 50% predicted FEV1/FVC < 70% With/without symptoms Treatment Avoid risk factors Regular therapy with  1 bronchodilators Rehabilitation Inhaled corticosteroids if significant symptoms and lung function response or if repeated exacerbations

GOLD Guidelines for COPD Stage IV: Very Severe Diagnosis FEV1 < 30% predicted FEV1/FVC < 70% Respiratory failure Right-side-of-the-heart failure Treatment Avoid risk factors Regular therapy with 1 bronchodilators Inhaled corticosteroids if significant symptoms and lung function response or repeated exacerbations Rehabilitation Treatment of complications Long-term O2 therapy for hypoxic respiratory failure Evaluate for surgical treatment

Case: S.H. is a 50-year-old male smoker with a recent diagnosis of COPD. Spirometry showed FEV1/FVC 60%; pre-bronchodilator FEV1 70% of predicted; and post bronchodilator FEV1 72% of predicted. The gold standard in diagnosing COPD patient is ? I.Spirometry II.Xray III.ABG

The diagnosis of COPD is based on Assessment-Dx The diagnosis of COPD is based on I. A history of exposure to risk factors II. The presence of airflow limitation that is not fully reversible, with or without the presence of symptoms. For the diagnosis and assessment of COPD, spirometry is the gold standard. FEV1/FVC less than 70% of predicted + a postbronchodilator FEV1 less than 80% = airflow limitation An FEV1/FVC ratio less than 70% is the hallmark of COPD Bronchodilator reversibility testing is generally performed only once, at the time of diagnosis, to rule out the diagnosis of asthma

Assessment S.H. is a 50-year-old male smoker with a recent diagnosis of COPD. Spirometry showed FEV1/FVC 60%; pre-bronchodilator FEV1 70% of predicted; and post bronchodilator FEV1 72% of predicted. The gold standard in diagnosing COPD patient is ? I.Spirometry II.Xray III.ABG When to use ABG? I.Patient with stable COPD II.Patient with FEV1 >70 % III.Patient with FEV1<50 % with and or clinical signs suggestive of respiratory failure or right heart failure.

Assessment S.H. is a 50-year-old male smoker with a recent diagnosis of COPD. Spirometry showed FEV1/FVC 60%; pre bronchodilator FEV1 70% of predicted; and post bronchodilator FEV1 72% of predicted. History of exposure to risk factors may play a role in S.H condition , what’s the most common risk factor I. tobacco smoke II. occupational dusts and chemicals, III. and smoke from home cooking and heating fuels Note: ALL of the above considered to be a risk factor

Plan Therapy Goals I.Relieve symptoms II.Improve exercise tolerance. III.Improve health status. I.Prevent and treat exacerbations. II.Prevent disease progression III.Prevent and treat complications. IV.Reduce mortality. V.Minimize adverse effects from treatment. Relieve symptoms Reduce risk

Case: S.H. is a 50-year-old male smoker with a recent diagnosis of COPD. Spirometry showed FEV1/FVC 60%; pre-bronchodilator FEV1 70% of predicted; and post bronchodilator FEV1 72% of predicted. Q. Which of the following is the severity classification (stage) of S.H.’s COPD A. Stage I: Mild. B. Stage II: Moderate. C. Stage III: Severe. D. Stage IV: Very severe.

FEV1/FVC always less than 70% in patient with COPD Patient has post bronchodilator FEV1 72% of predicted Global Initiative for Chronic Obstructive Lung Disease Workshop Executive Summary: Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. National Institutes of Health National Heart, Lung and Blood Institute, 2013update

Case: S.H. is a 50-year-old male smoker with a recent diagnosis of COPD. Spirometry showed FEV1/FVC 60%; pre-bronchodilator FEV1 70% of predicted; and post bronchodilator FEV1 72% of predicted. Q. Which of the following is the severity classification (stage) of S.H.’s COPD A. Stage I: Mild. B. Stage II: Moderate. C. Stage III: Severe. D. Stage IV: Very severe.

Plan Q.Which one of the following pharmacotherapy options is most appropriate for S.H. to be started on? A.Albuterol MDI 2 puffs every 4–6 hours as needed. B.Albuterol MDI 2 puffs every 4–6 hours as needed plus formoterol inhale 1 capsule 2 times/day. C.Albuterol MDI 2 puffs every 4–6 hours as needed plus salmeterol/fluticasone 50/500 1 puff 2 times/day. D.Albuterol MDI 2 puffs every 4–6 hours as needed plus salmeterol/fluticasone 50/500 1 puff 2 times/ day plus home oxygen.

Plan

Q: Which one of the following pharmacotherapy options is most appropriate for S.H. to be started on? A. Albuterol MDI 2 puffs every 4–6 hours as needed. B. Albuterol MDI 2 puffs every 4–6 hours as needed plus formoterol inhale 1 capsule 2 times/day. C. Albuterol MDI 2 puffs every 4–6 hours as needed plus salmeterol/fluticasone 50/500 1 puff 2 times/day. D. Albuterol MDI 2 puffs every 4–6 hours as needed plus salmeterol/fluticasone 50/500 1 puff 2 times/ day plus home oxygen.

Plan Complete the following sentence •…………. Is the most important component of COPD management? Q: Other pharmacologic treatments for COPD a. Smoking cessation b. Influenza vaccine annually c. Pneumococcal vaccine d. α1-Antitrypsin augmentation therapy in patient with Severe hereditary α1-antitrypsin deficiency and established emphysema D. All of the above MCQ

Plan Complete the following sentence •…………. Is the most important component of COPD management? (Smoke caesation) Q: Other pharmacologic treatments for COPD a. Smoking cessation b. Influenza vaccine annually c. Pneumococcal vaccine d. α1-Antitrypsin augmentation therapy in patient with Severe hereditary α1-antitrypsin deficiency and established emphysema D. All of the above MCQ

True or false? Q. Bronchodilator medications are central to the symptomatic management of COPD ? True False Q. The preferred route for bronchodilators in the management of COPD is by inhalation ? True False Q. Regular treatment with LABAs is more effective and convenient than with SABAs for treating COPD patient ? Q. Combining bronchodilators with different mechanisms and durations of action may improve efficacy with the same or fewer adverse effects compared with increasing the dose of a single bronchodilator? Q. All bronchodilators have been shown to improve exercise capacity, but they may not significantly improve FEV1 in patient with COPD? Q. LABAs improve health status and decrease COPD exacerbations.

True or false? Q. Bronchodilator medications are central to the symptomatic management of COPD ? True Q. The preferred route for bronchodilators in the management of COPD is by inhalation ? Q. Regular treatment with LABAs is more effective and convenient than with SABAs for treating COPD patient ? Q. Combining bronchodilators with different mechanisms and durations of action may improve efficacy with the same or fewer adverse effects compared with increasing the dose of a single bronchodilator? Q. All bronchodilators have been shown to improve exercise capacity, but they may not significantly improve FEV1 in patient with COPD? Q. LABAs improve health status and decrease COPD exacerbations.

MCQ Q. Treatment with a long-acting anticholinergic in patients with COPD I. Delays first exacerbation II. Reduces the overall number of COPD exacerbations III. Improves the effectiveness of pulmonary rehabilitation IV. All of the above .

MCQ Q. In COPD patients , ICS is appropriate for I. Patients with an FEV1 less than 50% (stages III and IV) of predicted and repeated exacerbations II.Patient with FEV1/FVC < 70% and 50% ≤ FEV1< 80% of predicted (stage II Moderate) III.Patient FEV1/FVC < 70% FEV1 ≥ 80% of predicted (Stage 1 mild)

MCQ Q. In COPD patients , ICS is appropriate for I. Patients with an FEV1 less than 50% (stages III and IV) of predicted and repeated exacerbations II.Patient with FEV1/FVC < 70% and 50% ≤ FEV1< 80% of predicted (stage II Moderate) III.Patient FEV1/FVC < 70% FEV1 ≥ 80% of predicted (Stage 1 mild)

Q. Regarding the use of ICS in COPD I. ICSs decrease the frequency of exacerbations II. ICSs alone do not modify the progressive decline in FEV III. ICSs alone do not decrease mortality. IV. ICSs Increased incidence of pneumonia V. All of the above

Q. Regarding the use of ICS in COPD I. ICSs decrease the frequency of exacerbations II. ICSs alone do not modify the progressive decline in FEV III. ICSs alone do not decrease mortality. IV. ICSs Increased incidence of pneumonia V. All of the above

True or false Q. In stable COPD patient , An ICS combined with a LABA is more effective than the individual components? True False Q. In stable COPD , An ICS-LABA combination reduces the rate of decline of FEV1 Q. In stable COPD , Chronic treatment with OCSs should be avoided because of an unfavorable benefit-risk ratio

True or false Q. In stable COPD patient , An ICS combined with a LABA is more effective than the individual components? True False Q. In stable COPD , An ICS-LABA combination reduces the rate of decline of FEV1 Q. In stable COPD , Chronic treatment with OCSs should be avoided because of an unfavorable benefit-risk ratio

Case: K.R. is a 60-year-old man with COPD who smokes ½ pack/day (cut down from 2 packs/day). He has had a gradual worsening in shortness of breath. Spirometry shows FEV1/FVC 55% and FEV1 63%. His current COPD medications are tiotropium (Spiriva) once daily and albuterol HFA as needed. Which one of the following is the most appropriate course of action? A. Add salmeterol 1 puff 2 times/day. B. Change tiotropium to salmeterol 1 puff 2 times/day. C. Add fluticasone 110 mcg 2 puffs 2 times/day. D. Discontinue tiotropium and start Advair 250/50.

Case: K.R. is a 60-year-old man with COPD who smokes ½ pack/day (cut down from 2 packs/day). He has had a gradual worsening in shortness of breath. Spirometry shows FEV1/FVC 55% and FEV1 63%. His current COPD medications are tiotropium (Spiriva) once daily and albuterol HFA as needed. Which one of the following is the most appropriate course of action? A. Add salmeterol 1 puff 2 times/day. B. Change tiotropium to salmeterol 1 puff 2 times/day. C. Add fluticasone 110 mcg 2 puffs 2 times/day. D. Discontinue tiotropium and start Advair 250/50.

Case: A 60-year-old man with mild chronic obstructive pulmonary disease (COPD) has been using albuterol HFA (ProAir) 2 puffs 4 times/day as needed. His symptoms have worsened during the past few months, and now, he has persistent symptoms and shortness of breath, even while walking around his house. His spirometry showed a forced expiratory volume in 1 second (FEV1) of 70% of predicted and an FEV1/forced vital capacity (FEV1/FVC) of 60% of predicted. Which one of the following Q. Which Medications is best to initiate A. Fluticasone (Flovent). B. Tiotropium (Spiriva). C. Montelukast (Singulair). D. Omalizumab (Xolair).

Case: A 60-year-old man with mild chronic obstructive pulmonary disease (COPD) has been using albuterol HFA (ProAir) 2 puffs 4 times/day as needed. His symptoms have worsened during the past few months, and now, he has persistent symptoms and shortness of breath, even while walking around his house. His spirometry showed a forced expiratory volume in 1 second (FEV1) of 70% of predicted and an FEV1/forced vital capacity (FEV1/FVC) of 60% of predicted. Which one of the following Q. Which Medications is best to initiate A. Fluticasone (Flovent). B. Tiotropium (Spiriva). C. Montelukast (Singulair). D. Omalizumab (Xolair).

Q. Side effects of anti cholinergic (eg ,Ipratropium bromide , tiotropium ) include the following except I.Dry mouth , headache , Blurred vision II.Flushed skin , Tachycardia III.Hypokalemia Q. Difference between ipratopium and tiotropium include the following I.Tiotropium half life is longer than ipratropium II.Ipratropium availbale as nebulization as well as inhlation III.Duration of Tiotropium is more than 24 hr while ipratropium is 8 hrs IV.All of the above

Q. Side effects of anti cholinergic (eg ,Ipratropium bromide , tiotropium ) include the following except I.Dry mouth , headache , Blurred vision II.Flushed skin , Tachycardia III.Hypokalemia Q. Difference between ipratopium and tiotropium include the following I. Tiotropium half life is longer than ipratropium II. Ipratropium availbale as nebulization as well as inhlation III. Duration of Tiotropium is more than 24 hr while ipratropium is 8 hrs IV. All of the above

Logbook Question •GG is a 52-year-old man who complains to his physician of increasing shortness of breath and when walking his dog. •He has been experiencing several months of persistent, very productive cough that is particularly bothersome when he wakes up in the morning. •His medical history generally is unremarkable, except for smoking 2 packs per day of cigarettes for the past 20 years. •On physical examination, he is noted to be a moderately obese male who is slightly cyan- otic. Coarse breath sounds are noted on auscultation. Spirometry results indicate a forced expiratory capacity at 1 second (FEV 1 ) that is 65% of predicted, which improves slightly after administration of an inhaled short-acting -agonist. An initial diagnosis of chronic obstructive pulmonary disease (COPD) is made.

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