Diagnosis and assessment of Chronic Obstructive Pulmonary Disease: COPD

Definition of COPD COPD is defined by GOLD (2014 update) as:* ‘a common preventable and treatable disease, 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’ Chronic airflow limitation in COPD is caused by a combination of: Small airways disease (bronchiolitis) Parenchymal destruction (emphysema) The relative contributions of each vary from person to person Major risk factors for developing COPD are: tobacco smoking exposure to occupational, outdoor and indoor air pollution (e.g. burning wood) Exacerbations and comorbidities contribute to overall severity in individual patients Reference GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Updated 2008. Available at http://www.goldcopd.com/ Many previous definitions of COPD have emphasized the terms 'chronic bronchitis' and 'emphysema', which are not included in the definition used in the GOLD 2014 report or earlier GOLD reports COPD = chronic obstructive pulmonary disease GOLD 2014 (http://www.goldcopd.org/)

Diagnosis of COPD Diagnosis of COPD should be considered in patients aged >40 with dyspnea, chronic cough or sputum production and/or a history of exposure to risk factors Spirometry is the gold standard for the diagnosis and assessment of COPD There is poor recognition of the essential role of spirometry in diagnosis of COPD and lack of adequate training in its use and interpretation Reference GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Updated 2008. Available at http://www.goldcopd.com/ COPD = chronic obstructive pulmonary disease GOLD 2014 (http://www.goldcopd.org/)

COPD is not usually diagnosed until it is clinically apparent and moderately advanced COPD is usually not diagnosed until it is clinically apparent and moderately advanced1 By the time COPD is diagnosed, often ≥50% of lung function has been lost and need for healthcare utilization is high2 Although airway obstruction may be very mild in early COPD, patients often have significant impairment of HRQoL and reduced ADL3 Many individuals consider breathlessness and low exercise tolerance as features of ageing Smoker’s cough may be regarded as normal Affected individuals often do not request medical attention ADL = activities of daily living; COPD = chronic obstructive pulmonary disease; HRQoL = health-related quality of life Celli BR et al. Eur Respir J 2004;23:932–46 Lundbäck et al. Eur Respir J 2003;21(Suppl. 40):3s–9s Decramer M et al. Respir Med. 2011;105:1576–87

COPD does not just affect elderly adults 50% of patients with COPD in the USA are <65 years old1 COPD prevalence is increasing in younger age groups, particularly in women2 N=573 References Confronting COPD in America: executive summary. Available from: http://ex.democracydata.com/CQRC/Advocacy/Confronting_COPD_In_America.pdf (last accessed 10 June 2013). Hernandez P et al. Respir Med 2009;103:1004–12. Figure adapted from Confronting COPD in America COPD, chronic obstructive pulmonary disease. 1. Confronting COPD in America; 2. Hernandez P. Respir Med 2009;103:1004–12 AARC 2003

Symptoms, a history of risk factors, and spirometry all contribute to the diagnosis of COPD Consider COPD if symptoms and/or a history of risk factors are present Confirm the diagnosis with spirometry (post-bronchodilator FEV1/FVC <0.70) Symptoms Dyspnea Chronic cough Chronic sputum Risk-factor history Tobacco smoke Home cooking/fuel smoke Occupational dusts/chemicals Reference GOLD 2014. Available from: http://www.goldcopd.org/. SPIROMETRY COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; GOLD = Global Initiative for Chronic Obstructive Lung Disease GOLD 2014 (http://www.goldcopd.org/)

Forced expiratory volume (L) Spirometry is the gold standard for the diagnosis and assessment of COPD Patients with COPD typically show a decrease in FVC and FEV1 FVC 5 4 3 2 1 FEV1 FVC Forced expiratory volume (L) FEV1 FVC FEV1/FVC Normal 4 L 5 L 80% COPD 1.8 L 3.2 L 56% 1 2 3 4 5 6 Spirometry is used to determine FVC and FEV1. In addition, it can be useful to calculate the ratio of these two measurements (FEV1/FVC). The ratio of FEV1/FVC is a measure of airflow limitation. A post-bronchodilator FEV1 <80% of the predicted value in combination with an FEV1/FVC <70% confirms the presence of airflow obstruction – either COPD or asthma. Where possible, values should be compared to age-related normal values to avoid over-diagnosis of COPD in the elderly. In order to minimize variability due to varying degrees of smooth muscle contraction, it is recommended that spirometry should be performed after an adequate dose of a short-acting bronchodilator (e.g. 400μg salbutamol). An improvement of FEV1 of >12% (either spontaneously or after inhalation of a bronchodilator and/or following a 2-week course of high dose oral steroids) indicates reversibility, and therefore suggests a diagnosis of asthma. Note that, if spirometry is unavailable, prolongation of the forced expiratory time beyond 6 seconds is a crude but useful guide to the presence of an FEV1/FVC ratio <50%. Reference GOLD. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Updated 2014. Available at http://www.goldcopd.com/ Time (seconds) The presence of a postbronchodilator FEV1/FVC <0.70 and FEV1 <80% predicted confirms the presence of airflow limitation that is not fully reversible COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; GOLD = Global Initiative for Chronic Obstructive Lung Disease GOLD 2014 (http://www.goldcopd.org/)

Obstructive lung disease has a characteristically different spirometry loop to ‘normal’ PEFR 10 8 FEF25 8 6 6 FEF50 4 FEF75 4 2 2 Volume (Litres) Flow (Litres/sec) Volume (Litres) Flow (Litres/sec) 1 2 3 4 5 6 –2 FEV0.5 FEV1 FEV3 FVC –2 –4 –4 –6 FIF75 –6 Reference http://www.morgansci.com/choose-your-pft-solution/what-is-a-pft-test/static-and-dynamic-spirometry.php. FIF25 –8 FIF50 –8 Normal The first landmark reached is the PEFR. The first blast of air exhaled from the patient reaches this flow rate almost immediately. The flow rate then quickly slows as more air is exhaled. This landmark is very important in judging if the patient is giving maximal effort, overall quality of the test, strength of expiratory muscles, and the condition of the large airways, such as the trachea and main bronchi. Emphysema Bronchitis This illustration shows the variety of flow volume loop shapes that often relate to particular disease. When looked at in relation to the lung volume further clinical information can be revealed. FEV = forced expiratory volume; FVC = forced vital capacity; FIF = forced inspiratory fraction; PEFR = peak expiratory flow rate http://www.morgansci.com/choose-your-pft-solution/what-is-a-pft-test/static-and-dynamic-spirometry.php

COPD and asthma are distinct conditions that can be differentiated from each other Onset Midlife Early in life (often childhood) Symptoms Slowly progressive Dyspnea during exercise Vary from day to day More common at night/early morning Airflow limitation Largely irreversible Largely reversible Main risk factors for development Tobacco smoke and airborne pollutants Exposure to allergens, infections, diet, tobacco smoke, socioeconomic status Additional features Allergy, rhinitis and eczema also present Family history of asthma Reference GOLD 2014. Available at http://www.goldcopd.com/. COPD = chronic obstructive pulmonary disease GOLD 2014 (http://www.goldcopd.org/)

High risk, Less symptoms GOLD 2014 COPD classification determines to which Group patients belong ‘Symptoms’ should be assessed first ‘Risk’ should be assessed second (choose the highest risk according to airflow limitation or exacerbation history) Patient will then be categorized as belonging to one of four Groups (A, B, C or D) 4 ≥2 or (C) (D) Risk GOLD classification of airflow limitation Risk Exacerbation history High risk, Less symptoms High risk, More symptoms, ≥1 leading to hospital admission 3 2 (A) (B) 1 (not leading to hospital admission) Low risk, Less symptoms Low risk, More symptoms Reference GOLD 2014. Available from: http://www.goldcopd.org/. 1 CAT <10 CAT ≥10 Symptoms mMRC 01 mMRC ≥2 Breathlessness CAT = COPD Assessment Test; COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity; GOLD = Global Initiative for Chronic Obstructive Lung Disease; HRQoL = health-related quality of life; mMRC = modified Medical Research Council GOLD 2014 (http://www.goldcopd.org/)

Despite objective measures and diagnosis guidelines, COPD is under-diagnosed globally BOLD study showed that fewer patients are diagnosed with COPD than actually have COPD 30 25 20 Percent 15 10 References Buist S et al. Lancet 2007;370:741–50. Personal communication with BOLD investigators. 5 South Africa China USA Turkey Austria Iceland Germany Poland Norway Canada Australia Philippines COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease Buist S et al. Lancet 2007;370:741–50

One third of patients have progressed to GOLD Stage III or IV by the time of diagnosis Study of patients with COPD in a US database during 1994–2006 31% of patients were in GOLD Stage III or IV (severe or very severe airflow limitation) at diagnosis COPD severity at initial spirometry-confirmed diagnosis COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease Mapel DW et al. Int Journal of COPD 2011;6:573–81

Conclusions Diagnosis of COPD requires assessment of symptoms, history of risk factors, and spirometry1 Assessment based on symptoms alone is insufficient for correct diagnosis of COPD2 Spirometry is the gold-standard for diagnosis of COPD1 Airflow limitation that is not fully reversible is confirmed by postbronchodilator FEV1/FVC <0.70 and FEV1 <80% predicted COPD and asthma have distinct characteristics1 Onset is typically in midlife in COPD and in early life in asthma1 Symptoms are slowly progressive in COPD and more variable in asthma1 Airflow is largely reversible in COPD and irreversible in asthma1 A clinically distinct population of patients have ‘COPD-asthma overlap’3 COPD is under-diagnosed4 By the time COPD is diagnosed, often ≥50% of lung function has been lost5 One third of patients have GOLD stage III or IV COPD by the time of diagnosis6 COPD = chronic obstructive pulmonary disease; FEV1 = forced expiratory volume in 1 s; FVC = forced vital capacity ; GOLD = Global Initiative for Chronic Obstructive Lung Disease 1. GOLD 2014 (http://www.goldcopd.org/); 2. Tálamo C, et al. Chest 2007;131:60–7; 3. Gibson PG & Simpson JL. Thorax;64:728–35; 4. Buist S et al. Lancet 2007;370:741–50; 5. Lundbäck et al. Eur Respir J 2003;21(Suppl. 40):3s–9s; 6. Mapel DW et al. Int Journal of COPD 2011;6:573–81