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Ayman Farghaly MD FCCP Military Medical Academy COPD Guideline Ayman Farghaly MD FCCP Military Medical Academy

© Global Initiative for Chronic Obstructive Lung Disease G O L D lobal Initiative for Chronic bstructive ung isease © Global Initiative for Chronic Obstructive Lung Disease

GOLD Objectives Increase awareness of COPD among health professionals, health authorities, and the general public Improve diagnosis, management and prevention Decrease morbidity and mortality Stimulate research

Definition and Overview Diagnosis and Assessment Therapeutic Options Global Strategy for Diagnosis, Management and Prevention of COPD, 2011: Chapters REVISED 2011 Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities

Definition and Overview Diagnosis and Assessment Therapeutic Options Global Strategy for Diagnosis, Management and Prevention of COPD, 2011: Chapters REVISED 2011 Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities

Global Strategy for Diagnosis, Management and Prevention of COPD Definition of COPD COPD, a common preventable and treatable disease, is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients.

Mechanisms Underlying Airflow Limitation in COPD Global Strategy for Diagnosis, Management and Prevention of COPD Mechanisms Underlying Airflow Limitation in COPD Small Airways Disease Airway inflammation Airway fibrosis, luminal plugs Increased airway resistance Parenchymal Destruction Loss of alveolar attachments Decrease of elastic recoil AIRFLOW LIMITATION

COPD is a leading cause of morbidity and mortality worldwide. Global Strategy for Diagnosis, Management and Prevention of COPD Burden of COPD COPD is a leading cause of morbidity and mortality worldwide. The burden of COPD is projected to increase in coming decades due to continued exposure to COPD risk factors and the aging of the world’s population. COPD is associated with significant economic burden.

Aging Populations Risk Factors for COPD Genes Infections Global Strategy for Diagnosis, Management and Prevention of COPD Risk Factors for COPD Genes Infections Socio-economic status Aging Populations

Definition and Overview Diagnosis and Assessment Therapeutic Options Global Strategy for Diagnosis, Management and Prevention of COPD, 2011: Chapters REVISED 2011 Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities

Global Strategy for Diagnosis, Management and Prevention of COPD Diagnosis and Assessment: Key Points A clinical diagnosis of COPD should be considered in any patient who has dyspnea, chronic cough or sputum production, and/or a history of exposure to risk factors for the disease. Spirometry is required to make the diagnosis; the presence of a post-bronchodilator FEV1/FVC < 0.70 confirms the presence of persistent airflow limitation and thus of COPD.

Global Strategy for Diagnosis, Management and Prevention of COPD Diagnosis and Assessment: Key Points The goals of COPD assessment are to determine the severity of the disease, including the severity of airflow limitation, the impact on the patient’s health status, and the risk of future events. Comorbidities occur frequently in COPD patients, and should be actively looked for and treated appropriately if present.

indoor/outdoor pollution Global Strategy for Diagnosis, Management and Prevention of COPD Diagnosis of COPD EXPOSURE TO RISK FACTORS SYMPTOMS shortness of breath tobacco chronic cough occupation sputum indoor/outdoor pollution SPIROMETRY: Required to establish diagnosis

Spirometry: Obstructive Disease Normal 5 4 3 Volume, liters FEV1 = 1.8L FVC = 3.2L FEV1/FVC = 0.56 2 Obstructive 1 1 2 3 4 5 6 Time, seconds

Chronic cough: May be intermittent and may be unproductive. Global Strategy for Diagnosis, Management and Prevention of COPD Symptoms of COPD The characteristic symptoms of COPD are chronic and progressive dyspnea, cough, and sputum production. Dyspnea: Progressive, persistent and characteristically worse with exercise. Chronic cough: May be intermittent and may be unproductive. Chronic sputum production: COPD patients commonly cough up sputum.

Use the COPD Assessment Test(CAT) or mMRC Breathlessness scale Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Assess comorbidities Use the COPD Assessment Test(CAT) or mMRC Breathlessness scale

Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of Symptoms COPD Assessment Test (CAT): An 8-item measure of health status impairment in COPD (http://catestonline.org). Breathlessness Measurement using the Modified British Medical Research Council (mMRC) Questionnaire: relates well to other measures of health status and predicts future mortality risk.

Global Strategy for Diagnosis, Management and Prevention of COPD Modified MRC (mMRC)Questionnaire

Assess degree of airflow limitation using spirometry Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Assess comorbidities Use spirometry for grading severity according to spirometry, using four grades split at 80%, 50% and 30% of predicted value

In patients with FEV1/FVC < 0.70: Global Strategy for Diagnosis, Management and Prevention of COPD Classification of Severity of Airflow Limitation in COPD* In patients with FEV1/FVC < 0.70: GOLD 1: Mild FEV1 > 80% predicted GOLD 2: Moderate 50% < FEV1 < 80% predicted GOLD 3: Severe 30% < FEV1 < 50% predicted GOLD 4: Very Severe FEV1 < 30% predicted *Based on Post-Bronchodilator FEV1

Assess degree of airflow limitation using spirometry Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of COPD Assess symptoms Assess degree of airflow limitation using spirometry Assess risk of exacerbations Assess comorbidities Use history of exacerbations and spirometry. Two exacerbations or more within the last year or an FEV1 < 50 % of predicted value are indicators of high risk

(C) (D) (B) (A) Risk Risk Symptoms Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD 4 (C) (D) > 2 3 (Exacerbation history) Risk (GOLD Classification of Airflow Limitation) Risk 2 (A) (B) 1 1 mMRC 0-1 CAT < 10 mMRC > 2 CAT > 10 Symptoms (mMRC or CAT score))

Use combined assessment Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD Use combined assessment Patient is now in one of four categories: A: Les symptoms, low risk B: More symtoms, low risk C: Less symptoms, high risk D: More Symtoms, high risk 4 (C) (D) > 2 3 (GOLD Classification of Airflow Limitation) Risk (Exacerbation history) Risk 2 1 (A) (B) 1 mMRC 0-1 CAT < 10 mMRC > 2 CAT > 10 Symptoms (mMRC or CAT score))

COPD patients are at increased risk for: Cardiovascular diseases Global Strategy for Diagnosis, Management and Prevention of COPD Assess COPD Comorbidities COPD patients are at increased risk for: Cardiovascular diseases Osteoporosis Respiratory infections Anxiety and Depression Diabetes Lung cancer These comorbid conditions may influence mortality and hospitalizations and should be looked for routinely, and treated appropriately.

COPD and Asthma ASTHMA COPD Onset early in life (often childhood) Global Strategy for Diagnosis, Management and Prevention of COPD Differential Diagnosis: COPD and Asthma COPD Onset in mid-life Symptoms slowly progressive Long smoking history ASTHMA Onset early in life (often childhood) Symptoms vary from day to day Symptoms worse at night/early morning Allergy, rhinitis, and/or eczema also present Family history of asthma

Global Strategy for Diagnosis, Management and Prevention of COPD Additional Investigations Chest X-ray: Seldom diagnostic but valuable to exclude alternative diagnoses and establish presence of significant comorbidities.  Lung Volumes and Diffusing Capacity: Help to characterize severity, but not essential to patient management.  Oximetry and Arterial Blood Gases: Pulse oximetry can be used to evaluate a patient’s oxygen saturation and need for supplemental oxygen therapy. Alpha-1 Antitrypsin Deficiency Screening: Perform when COPD develops in patients of Caucasian descent under 45 years or with a strong family history of COPD.  

Global Strategy for Diagnosis, Management and Prevention of COPD Additional Investigations Exercise Testing: Objectively measured exercise impairment, assessed by a reduction in self-paced walking distance (such as the 6 min walking test) or during incremental exercise testing in a laboratory, is a powerful indicator of health status impairment and predictor of prognosis. Composite Scores: Several variables (FEV1, exercise tolerance assessed by walking distance or peak oxygen consumption, weight loss and reduction in the arterial oxygen tension) identify patients at increased risk for mortality.

Definition and Overview Diagnosis and Assessment Therapeutic Options Global Strategy for Diagnosis, Management and Prevention of COPD, 2011: Chapters REVISED 2011 Definition and Overview Diagnosis and Assessment Therapeutic Options Manage Stable COPD Manage Exacerbations Manage Comorbidities

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Key Points Smoking cessation has the greatest capacity to influence the natural history of COPD. Health care providers should encourage all patients who smoke to quit. Pharmacotherapy and nicotine replacement reliably increase long-term smoking abstinence rates. All COPD patients benefit from regular physical activity and should repeatedly be encouraged to remain active.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Key Points Appropriate pharmacologic therapy can reduce COPD symptoms, reduce the frequency and severity of exacerbations, and improve health status and exercise tolerance. None of the existing medications for COPD has been shown conclusively to modify the long-term decline in lung function. Influenza and pneumococcal vaccination should be offered depending on local guidelines.

Brief Strategies to Help the Patient Willing to Quit Smoking ASK Systematically identify all tobacco users at every visit ADVISE Strongly urge all tobacco users to quit ASSESS Determine willingness to make a quit attempt ASSIST Aid the patient in quitting ARRANGE Schedule follow-up contact. Reduction of total personal exposure to tobacco smoke, occupational dusts and chemicals, and indoor and outdoor air pollutants are important goals to prevent the onset and progression of COPD. Smoking cessation is the single most effective - and cost effective - intervention to

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Risk Reduction Encourage comprehensive tobacco-control policies with clear, consistent, and repeated nonsmoking messages. Emphasize primary prevention, best achieved by elimination or reduction of exposures in the workplace. Secondary prevention, achieved through surveillance and early detection, is also important. Reduce or avoid indoor air pollution from biomass fuel, burned for cooking and heating in poorly ventilated dwellings. Advise patients to monitor public announcements of air quality and, depending on the severity of their disease, avoid vigorous exercise outdoors or stay indoors during pollution episodes.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: COPD Medications Beta2-agonists Short-acting beta2-agonists Long-acting beta2-agonists Anticholinergics Short-acting anticholinergics Long-acting anticholinergics Combination short-acting beta2-agonists + anticholinergic in one inhaler Methylxanthines Inhaled corticosteroids Combination long-acting beta2-agonists + corticosteroids in one inhaler Systemic corticosteroids Phosphodiesterase-4 inhibitors

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Bronchodilators Bronchodilator medications are central to the symptomatic management of COPD. Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms. The principal bronchodilator treatments are beta2- agonists, anticholinergics, theophylline or combination therapy. The choice of treatment depends on the availability of medications and each patient’s individual response in terms of symptom relief and side effects..

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Bronchodilators Long-acting inhaled bronchodilators are convenient and more effective for symptom relief than short-acting bronchodilators. Long-acting inhaled bronchodilators reduce exacerbations and related hospitalizations and improve symptoms and health status. Combining bronchodilators of different pharmacological classes may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Inhaled Corticosteroids Regular treatment with inhaled corticosteroids (ICS) improves symptoms, lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV1 < 60% predicted. Inhaled corticosteroid therapy is associated with an increased risk of pneumonia. Withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients.

Long-term Use of Inhaled Corticosteroids and the Risk of Pneumonia in Chronic Obstructive Pulmonary Disease Sonal Singh, MD, MPH; Aman V. Amin, MD; Yoon K. Loke, MD , Arch Intern Med. 2009 . Conclusion  Among patients with COPD, inhaled corticosteroid use for at least 24 weeks is associated with a significantly increased risk of serious pneumonia, without a significantly increased risk of death

Invasive Aspergillosis Intermediate Risk Prolonged corticosteroid therapy COPD Autologous HSCT Cirrhosis with duration of stay >7 days Solid-organ cancer HIV infection Lung transplantation Systemic disease requiring prolonged immunosuppression Meersseman W ,et al .Clin Infect Dis. 2007;45(2):205-216

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Combination Therapy An inhaled corticosteroid combined with a long- acting beta2-agonist is more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD. Addition of a long-acting beta2-agonist/inhaled glucorticosteroid combination to an anticholinergic (tiotropium) appears to provide additional benefits.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Systemic Corticosteroids Chronic treatment with systemic corticosteroids should be avoided because of an unfavorable benefit-to-risk ratio.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Phosphodiesterase-4 Inhibitors In patients with severe and very severe COPD (GOLD 3 and 4) and a history of exacerbations and chronic bronchitis, the phospodiesterase-4 inhibitor (PDE-4), roflumilast, reduces exacerbations treated with oral glucocorticosteroids.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Theophylline Theophylline is less effective and less well tolerated than inhaled long-acting bronchodilators and is not recommended if those drugs are available and affordable. There is evidence for a modest bronchodilator effect and some symptomatic benefit compared with placebo in stable COPD. Addition of theophylline to salmeterol produces a greater increase in FEV1 and breathlessness than salmeterol alone. Low dose theophylline reduces exacerbations but does not improve post-bronchodilator lung function.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Other Pharmacologic Treatments Influenza vaccines can reduce serious illness. Pneumococcal polysaccharide vaccine is recommended for COPD patients 65 years and older and for COPD patients younger than age 65 with an FEV1 < 40% predicted. The use of antibiotics, other than for treating infectious exacerbations of COPD and other bacterial infections, is currently not indicated.

Antitussives: Not recommended. Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Other Pharmacologic Treatments Alpha-1 antitrypsin augmentation therapy: not recommended for patients with COPD that is unrelated to the genetic deficiency. Mucolytics: Patients with viscous sputum may benefit from mucolytics; overall benefits are very small. Antitussives: Not recommended. Vasodilators: Nitric oxide is contraindicated in stable COPD. The use of endothelium-modulating agents for the treatment of pulmonary hypertension associated with COPD is not recommended.

Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Rehabilitation All COPD patients benefit from exercise training programs with improvements in exercise tolerance and symptoms of dyspnea and fatigue. Although an effective pulmonary rehabilitation program is 6 weeks, the longer the program continues, the more effective the results. If exercise training is maintained at home the patient's health status remains above pre- rehabilitation levels.

Ain Shams Univ. & Aeromedical Inst. Cardio-pulmonary Exercise Test in Assessment of COPD Patients Undergoing Rehabilitation Programme Ain Shams Univ. & Aeromedical Inst. 2001 Mohammed Ali , Mona Mansour , Tarek Safwat , Ayman Farghaly

(2) Group II Twenty-five patients (1) Group I Twenty five patients pulmonary rehabilitation and received anabolic steroid ( Nandrolone deconoate 50mg / three-weeks for twelve weeks) (2) Group II Twenty-five patients only pulmonary rehabilitation and no anabolic steroid. (3) Group III Twenty five patients considered as a control group,

Cardio-Pulmonary exercise test;-  a) It was done for all COPD patients included in this study before and after the exercise training program. b) There was no reported complications during and after testing. c) The cardiopulmonary exercise system supplied by computer with color monitor, gas analyzer, keyboard, colored printer connected with treadmill and E.C.G monitor. It uses Bruce protocol with incremental increase in the work load every three minutes.

Exercise Training Program After primary assessment measures, the selected COPD patients were enrolled into a program of exercise training that was planned according to exercise rehabilitation program done by Vogiatzis et al.,1999. Taking the following into consideration:- (1) Warm up and cool down (2) Aerobic exercise (endurance) i.e. Not allow patient to be exhausted. (3) Modality:- patients were submitted to lower limb exercise in the form of walking on flat, treadmill, cycling and upper limb exercise in the form of lifting objects, arm rotator and cycling. (4) Frequency:- three Times weekly.

Comparison between the three groups as regards, CPET Parameters (1) Time of test stage ( in minutes):     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 1.37 ± 0.53 3.816± 1.355 8.327 0.000 Group II 1.27 ± 0.4903 3.728 ± 1.9215 7.33 Group III 1.424 ± 0.6715 1.340 ± 0.660 0.725 0.476 ANOVA 0.470 24.816 0.627

Comparison between the three groups as regards, (2) Work Load (in watt):     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 61.84 ± 11.960 123.24 ± 26.912 12.585 0.000 Group II 60.80 ± 19.773 107.84 ± 41.372 6.48 Group III 59.0 ± 10.29 57.17 ± 12.66 1.52 0.142 ANOVA 0.043 34.411 0.958

Comparison between the three groups as regards, (3) Maximum Oxygen Consumption (ml/minute) (VO2 max.):     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 1609.16 ± 446.8 2552.68 ± 8.352 4.651 0.001 Group II 1688.72 ± 547.06 2192.52 ± 589.9 3.542 0.002 Group III 1615.35 ± 687.95 1595.80 ± 529.615 0.171 0.866 ANOVA 0.127 14.816 0.881 0.000

Comparison between the three groups as regards, (4) Maximum Oxygen Consumption Percent of Predicted (VO2 max.%):     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 65.76 ± 14.45 97.76 ± 33.05 4.351 0.000 Group II 66.80 ± 17.8699 88.44 ± 24.211 6.098 Group III 66.36 ± 24.871 65.64 ± 22.009 1.717 0.099 ANOVA 2.827 8.246 0.66 0.001

Comparison between the three groups as regards, (5) Normalized VO2 (VO2 per Kg body weight):     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 20.716 ± 5.517 30.592 ± 10.396 3.573 0.002 Group II 20.952 ± 5.9967 24.828 ± 8.9158 2.654 0.014 Group III 23.028 ± 9.329 19.624 ± 7.2048 1.717 0.099 ANOVA 0.791 9.426 0.457 0.000

Comparison between the three groups as regards, (6) Oxygen Pulse at maximum exercise (VO2 /HR) in ml/beat:     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 14.24 ± 3.929 20.64 ± 9.699 2.784 0.01 Group II 17.60 ± 8.426 20.28 ± 10.998 1.033 0.312 Group III 18.36 ± 9.429 17.24 ± 4.40 1.63 0.11 ANOVA 2.056 2.917 0.135 0.061

Comparison between the three groups as regards, (9) Maximum Minute Ventilation (VE max in liters/min):     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 57.32 ± 20.68 68.54 ± 21.25 2.844 0.009 Group II 54.996 ± 17.6 71.09 ± 20.42 4.629 0.000 Group III 41.52 ± 23.21 44.54 ± 17.62 1.87 0.08 ANOVA 4.277 18.552 0.18

Comparison between the three groups as regards, [2] FVC% (% of predicted):-     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 54.52 ± 10.128 58.52 ± 9.2427 2.316 0.029 Group II 57.8 ± 11.310 58.84 ± 9.800 0.869 0.393 Group III 53.81 ± 8.88 54.67 ± 8.7996 0.841 0.352 ANOVA 1.736 1.379 0.184 0.259

Comparison between the three groups as regards, [3] FEV1 (in Liters):-     Before program Mean ± SD After program Mean ± SD Paired t-test P-value Group I 1.407 ± 0.346 1.623 ± 0.347 4.32 0.01 Group II 1.4404 ± 0.327 1.580 ± 0.3351 3.962 0.04 Group III 1.364 ± 0.3837 1.42 ± 0.391 1.998 0.067 ANOVA 0.295 2.205 0.746 0.118

Conclusion Pulmonary rehabilitation is a multidisciplinary program that attempts to return the patient to the highest possible functional capacity. • Evidence supports the use of lower extremity exercise training as it improves exercise tolerance. • Upper extremity strength and endurance training is recommended. • Pulmonary rehabilitation improves dyspnoea, improves quality-of-life scores, and reduces the number of hospitalizations and days in the hospital; the effects on survival are not definite.

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