Ten Minute Tutorial Natural History of COPD Clinical course of COPD The characteristic symptoms of COPD are exertional breathlessness, chronic cough, regular sputum production, frequent winter bronchitis and wheeze.2 As the symptoms worsen, the patient’s quality of life (QoL) and functional health will also deteriorate. Patients may feel increasingly isolated as they may become unable to carry out everyday activities. This can result in patients suffering from anxiety and depression. Exacerbations (the acute onset of sustained worsening of symptoms requiring additional medical attention), become more likely as the disease progresses.3 Chronic cough and sputum production precede the development of airflow limitation by many years. This pattern offers a unique window of opportunity to identify smokers and others at risk of COPD, and intervene when the disease is not yet a major health problem. The progression of COPD has historically been assessed using changes in airflow obstruction, especially lung function (by measuring forced expiratory volume in one second - FEV1). Natural history of COPD: Fletcher & Peto Curve 1977 Concepts relating to the natural history of COPD arise most importantly from the classic study of Fletcher, Peto and colleagues, which remains the landmark reference for the natural history of COPD.4 They performed an eight-year prospective study of working men in London and developed the much reproduced diagram, frequently termed the “Fletcher-Peto curve” (Figure 1). This schematic diagram continues to form the basis for understanding the progression of this disorder. Figure 1 illustrates the relationship between long-term cigarette smoking, decline in lung function (FEV1) and life expectancy, and suggests slower decline in lung function during the earlier stages of the disease.4 However, not all patients will follow the same clinical course outlined in the Fletcher-Peto curve, and clinical factors other than airflow limitation that are relevant to COPD natural history (e.g. cough, dyspnoea and QoL measures), remain undefined within the curve. www.COPDexchange.co.uk FEV1 % value at age 25 years 100 Never smoked - non-susceptible 75 Smoker 50 Stopped at 45 Disability 25 0 Stopped at 65 Death 25 35 45 55 Age (years) 65 75 Figure 1. Effects of smoking and smoking cessation on decline in lung function (Fletcher-Peto curve) adapted with permission (Fletcher & Peto, 1977).4 Natural history of COPD: Current evidence Recent studies have suggested that FEV1 decline may in fact be greater in earlier rather than later stages of the disease.5–7 This is reflected in the recently published, modified curve (Figure 2),8 which includes data from the Framingham study (healthy non-smokers aged 13-80 years followed for 26 years with standardised spirometry)9 and various large trials where there was a faster decline in GOLD stage I-II than stage III-IV groups (susceptible smokers).5-7 The implication of this new data is that early detection is critical to preserve lung function by interventions such as smoking cessation. Earlier detection allows treatment of symptoms by pharmacological interventions and improvement of outcomes with pulmonary rehabilitation. 100 FEV1 % value at age 25 years The progressive nature of chronic obstructive pulmonary disease (COPD) is so fundamental that it is included in the definition adopted in the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines. According to GOLD, COPD is a disease state ‘characterised by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lungs to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients.’1 Never smoked 75 50 Disability Early smoking cessation Susceptible Smoker Late smoking cessation 25 0 Death 25 50 Age (years) 75 Figure 2. Modified Fletcher-Peto curve redrawn by Jones & Østrem to incorporate findings of recent advances in the natural history of COPD including FEV1 decline data from the UPLIFT study demonstrating greater annual rate of FEV1 decline during early stages of disease Adapted with permission of the editors, Primary Care Respiratory Journal8 Clinical implications of early lung decline in COPD Patients with early lung decline may be missed as most COPD patients remain undiagnosed or are diagnosed in a late stage of the disease, even though they are smokers or have a smoking history (Table 1).8 Under-diagnosis or misdiagnosis of COPD can mean that patients remain untreated, or that they receive inappropriate or suboptimal treatment, leading to poor outcomes.10,11 Table 1. Reasons for under-diagnosis/misdiagnosis and undertreatment of COPD and potential solutions. Adapted with permission from Jones & Ostrem 2011.8 Reasons Under-diagnosis Physician's lack of symptom awareness and risk factors for COPD Potential solutions Consider screening for COPD (spirometry) in patients at risk Perception that COPD is selfinflicted Increase education of physicians Under-use of spirometry as a diagnostic tool Increase availability and training in spirometry use Patients lack symptom awareness and knowledge of risk factors Consider asking questions about symptoms and general quality of life (QoL) Smokers' Encourage perception of documentation cough as ‘normal’ of smoking status and consider spirometry screening Misdiagnosis Inaccurate use of spirometry Increase staff training on spirometry use Confusion between COPD and asthma Consider differences in presentation and symptoms between COPD and asthma and perform spirometry Achieving earlier diagnosis in practice NICE suggests that in order to identify early disease, post-bronchodilator spirometry should be performed in anyone who is over 35, a current or ex-smoker, and has a chronic cough.2 The next step is to conduct a detailed assessment of symptoms through direct questioning and physical examination, with diagnosis being confirmed by spirometric measurements of airflow limitation (primarily FEV1 and forced vital capacity - FVC). Please see the ten minute tutorials (TMT): ‘Diagnosing COPD’ and ‘COPD or Something Else?’ for more information. www.COPDexchange.co.uk Traditionally, the severity of disease has been equated with the degree of airflow limitation (Table 2), but NICE recommends that no single measure can give an adequate assessment of the true severity of the disease in an individual patient and that there should be a more comprehensive assessment of severity using tools such as the BODE index (Body Mass Index, Obstruction [FEV1% predicted], Dyspnoea [MRC score], Exercise [as measured by six-minute walk test]) and the DOSE (Dyspnoea [MRC score], Obstruction [FEV1% predicted], Smoking status, Exacerbation frequency) score.2 Table 2. Severity of airflow obstruction Severity of airflow obstruction FEV1 (% predicted)* Mild ≥80%** Moderate 50% – 79% Severe 30% – 49% Very severe <30% (or <50% + respiratory failure) * Where FEV1/FVC <0.7 ** If FEV1 ≥80% predicted, then the patient must be symptomatic Copyright ©NCGC. Reproduced and adapted by permission. National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre. Available from: http://guidance.nice.org.uk//CG101/Guidance/pdf/English Last accessed September 2013. For those patients who are at risk and who have potentially early disease, the International Primary Care Respiratory Group (IPCRG) also recommends that anyone over 35 years old should be evaluated for their risk of developing or having COPD, by taking a history or using validated screening questionnaires such as the IPCRG COPD risk evaluation questionnaire. Those who screen positive should then be further assessed by:12,13 • P erforming ‘case-identification’ spirometry to exclude those with normal FEV1 and so identify those who require more complete investigation for COPD. Those testing positive should then undergo clinical review and diagnostic standard spirometry • Going directly to diagnostic spirometry. This should be done for patients who have symptoms and risk factors, or a positive screening questionnaire, or whose screening FEV1 is outside normal limits. Treatment Current NICE guidance recommends that COPD treatment should follow a stepwise approach depending on disease severity (Figure 3).2 However, active risk reduction (e.g. smoking cessation and influenza vaccination) should also be part of the overall treatment plan. In early stages of COPD, life style changes including smoking cessation and physical activity may affect outcome. Very often, patients do not get this information until their disease is advanced and the best opportunities to help are lost. Pulmonary rehabilitation is usually reserved for people with an MRC dyspnoea scale of three or above, or an MMRC dyspnoea scale of grade two or above, but may also be effective in people with a lower degree of impairment. Figure 3. NICE algorithm on use of inhaled therapies for COPD Related Ten Minute Tutorials A Basic Guide to Diagnosing COPD COPD or Something Else? Spirometry and Lung Function Early Diagnosis: Case Finding or Screening? Managing the COPD Patient What you need to know Symptoms of COPD, such as chronic cough and sputum production precede the development of airflow limitation by many years. Patients with early lung decline may remain undiagnosed (and therefore untreated) leading to poor outcomes. Abbreviations: SABA: Short-acting ß2 agonist SAMA: Short-acting muscarinic antagonist LABA: Long-acting ß2 agonist LAMA: Long-acting muscarinic antagonist *SABA (as required) may continue at all stages —————> Offer therapy (strong evidence) -------> Consider therapy (less strong evidence) Copyright ©NCGC. Reproduced and adapted by permission. National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre. Available from: http://guidance.nice.org.uk//CG101/Guidance/pdf/English Last accessed September 2013. As the disease progresses and lung function declines, regular (maintenance) treatment with one or more long-acting bronchodilators, such as a long-acting muscarinic antagonist (LAMA; also known as a longacting anticholinergic) or long-acting ß2-agonist (LABA), should be introduced. In addition, for those with FEV1 <50% predicted and exacerbations, inhaled steroids are indicated. Potential benefits of earlier treatment with long acting bronchodilators Bronchodilator therapy is a foundation treatment for symptomatic COPD, reducing breathlessness and improving quality of life, allowing some to maintain physical activity.1 Data from TORCH and UPLIFT studies suggest that long-acting bronchodilator therapy in GOLD stages II and III may reduce the decline in lung function.5,6 Recent data from the ECLIPSE study also suggests that there is a distinct COPD phenotype characterised by frequent exacerbations; patients with this phenotype may also benefit from earlier and aggressive therapy.14 Those patients with a history of frequent exacerbations tend to have faster lung function decline than patients with infrequent exacerbations.15 Results from studies suggest that exacerbations, where the patient was treated early, after the onset of symptoms, had a faster recovery time compared with exacerbations where there was a delay in treatment.15 Summary In conclusion, it is important for all healthcare professionals to identify early-stage COPD patients and to initiate smoking cessation before too much damage is done. Earlier identification allows people with symptoms and exacerbations to receive drug treatment to relieve their distress and make life style changes which can keep them healthier. www.COPDexchange.co.uk Early identification of COPD can result in better long term outcomes, as the decline in lung function is faster in early stages, thus late diagnosis means there is less to gain by smoking cessation. Case identification can be used to identify patients at risk and/or those with early disease. It is important to advocate lifestyle changes (such as smoking cessation and physical activity) in patients with early disease. Depending on assessment of symptoms and exacerbations, long-acting bronchodilator and inhaled steroids therapy should be used. Think about… • Are you aware of the implications of early decline in lung function? • How would you identify those patients at risk of early stage disease? • What lifestyle changes would you recommend? • Do you understand what bronchodilator therapies should be used and when (NICE algorithm)? References 1. Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management and Prevention of COPD (updated 2013). Available from: http://www.goldcopd.org Last accessed September 2013. 2. National Clinical Guideline Centre. (2010) Chronic obstructive pulmonary disease: management of chronic obstructive pulmonary disease in adults in primary and secondary care. London: National Clinical Guideline Centre. 3. Burge S, Wedzicha JA. COPD exacerbations: definitions and classifications. Eur Respir J Suppl 2003;41:46s–53s. 4. Fletcher C, Peto R. The natural history of chronic airflow obstruction. Br Med J 1977;1(6077):1645–8. 5. Decramer M, Celli B, Kesten S et al. Effect of tiotropium on outcomes in patients with moderate chronic obstructive pulmonary disease (UPLIFT): a prespecified subgroup analysis of a randomised controlled trial. Lancet 2009;374(9696):1171–8. 6. Jenkins CR, Jones PW, Calverley PM, et al. Efficacy of salmeterol/fluticasone propionate by GOLD stage of chronic obstructive pulmonary disease: analysis from the randomised, placebo-controlled TORCH study. Respir Res 2009;10:59. 7. Beaucage F, Frémault A, Janssens W et al. FEV1 decline in COPD patients according to severity stages. Am J Respir Crit Care Med 2008;177:A401. 8. Jones R, Ostrem A. Optimising pharmacological maintenance treatment for COPD in primary care. Prim Care Respir J 2011;20(1):33-45. DOI: http:// dx.doi.org/10.4104/pcrj.2010.00069. Last accessed September 2013. 9. Kohansal R, Martinez-Camblor P, Agusti A et al. The natural history of chronic airflow obstruction revisited: an analysis of the Framingham offspring cohort. Am J Respir Crit Care Med 2009;180(1):3–10. 10.Yawn B, Mannino D, Littlejohn T et al. Prevalence of COPD among symptomatic patients in a primary care setting. Curr Med Res Opin2009;25(11):2671–7. 11.Bednarek M, Maciejewski J, Wozniak M et al. Prevalence, severity and underdiagnosis of COPD in the primary care setting. Thorax 2008;63(5):402–7. 12.IPCRG Opinion Sheet No 5. Early diagnosis of COPD does help! Date: 17th November 2009. 13.Price D, Crockett A, Arne M et al. Spirometry in primary care caseidentification, diagnosis and management of COPD. Primary Care Respiratory Journal 2009 18 (3) 216–23. 14.Hurst JR, Vestbo J, Anzueto A et al. Susceptibility to exacerbation in chronic obstructive pulmonary disease. N Engl J Med. 2010 Sep 16;363(12):1128–38. 15.Wedzicha JA & Wilkinson T. Impact of chronic obstructive pulmonary disease exacerbations on patints and payers. Proc Am Thorac Soc 2006; 3: 218–21. The COPDexchange medical education initiative was developed and funded by Boehringer Ingelheim Ltd. COPDexchange is peer reviewed and the editorial panel retains final editorial control of the content. The opinions expressed in COPDexchange are not necessarily those of Boehringer Ingelheim Ltd. © 2013 Boehringer Ingelheim. All rights reserved. www.COPDexchange.co.uk UK/RESP-131120 Date of preparation: September 2013