The concept of control in chronic obstructive pulmonary disease: Development of the criteria and validation for use in clinical practice

Guidelines of treatment of chronic obstructive pulmonary disease (COPD) identify symptom reduction and prevention of exacerbations as the main goals of therapy. Initial pharmacological treatment must be guided by these parameters, and effectiveness must be assessed at each clinical visit. However, there is no clear guidance as to how this assessment must be performed. The concept of control has been well developed in asthma, but it has been elusive in COPD. Patients with COPD may not be completely free from symptoms or exacerbations even under optimized therapy; therefore, control in COPD does not mean cure or absence of symptoms, but rather reaching the best clinical status possible according to the level of disease severity. A control tool has been developed based on a cross sectional evaluation of the impact of the disease and a longitudinal evaluation of stability. Low impact is a disease status defined by at least 3 of the following: low levels of dyspnoea, absence of or white sputum, low use of rescue medication and self-declared walking time of more than 30 minutes a day, and stability is the absence of moderate or severe exacerbations in the previous 3 months. Control can also be defined by COPD Assessment Test (CAT) scores ≤ 10 units for patients with FEV1 ≥ 50% and 16 for patients with FEV1 < 50% and stability as a change in CAT ≤ 2 units. Control of COPD is then defined as a status of low impact and stability. The control tool has been validated prospectively in several studies and has demonstrated to be sensitive to clinical changes and to have a good predictive value for poor outcomes. Clinical criteria are more reliable than CAT scores for the evaluation of control. The control tool is a quick and inexpensive method to evaluate clinical status and future risk of exacerbations that can be used at all levels of healthcare. 

1. Koblizek V., Milenkovic B., Barczyk A. et al. Phenotypes of COPD patients with a smoking history in Central and Eastern Europe: the POPE study. Eur. Respir. J. 2017; 49 (5): 1601446. DOI: 10.1183/13993003.01446-2016.

2. Calle Rubio M., Rodríguez Hermosa J.L., Soler-Cataluña J.J. et al. Medical care according to risk level and adaptation to Spanish COPD guidelines (GesEPOC): the Epoconsul study. Arch. Bronconeumol. 2018; 54 (5): 270–279. DOI: 10.1016/j.arbres.2017.11.015 (in English, Spanish).

3. Erro Iribarren M., Alonso Pérez T., Soriano J.B., Ancochea Bermúdez J. Adjusting the level of intervention in patients with chronic obstructive pulmonary disease according to the risk stratification proposed by the Spanish COPD guidelines (GesEPOC) version 2017. Arch. Bronconeumol. 2020; 56 (3): 183–185 DOI: 10.1016/j.arbres.2019.09.016 (in English, Spanish).

4. Singh D., Agusti A., Anzueto A. et al. Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Lung Disease: the GOLD science committee report 2019. Eur. Respir. J. 2019; 53 (5): 1900164. DOI: 10.1183/13993003.00164-2019.

5. Miravitlles M., Soler-Cataluña J.J., Calle M. et al. Spanish guidelines for Management of сhronic obstructive lung disease (GesEPOC) 2017: Pharmacological treatment of stable phase. Arch. Bronconeumol. 2017; 53 (6): 324–335. DOI: 10.1016/j.arbres.2017.03.018 (in English, Spanish).

6. Aisanov Z., Avdeev S., Arkhipov V. et al. Russian guidelines for the management of COPD: Algorithm of pharmacologic treatment. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 183–187. DOI: 10.2147/COPD.S153770.

7. Thomas M., Kay S., Pike J. et al. Asthma Сontrol Test (ACT) as a predictor of GINA guideline-defined asthma control: analysis of a multinational cross-sectional survey. Prim. Care Resp. J. 2009; 18 (1): 41–49. DOI: 10.4104/pcrj.2009.00010.

8. Duarte Araújo A., Hespanhol V., Correia-de-Sousa J. Is COPD control a useful concept? Assessing treatment success by evaluating COPD-related health status. Arch. Bronconeumol. 2017; 53 (9): 530–531. DOI: 10.1016/j.arbres.2016.11.024 (in English, Spanish).

9. Guimarães M., Bugalho A., Oliveira A.S. et al. COPD control: Can a consensus be found? Rev. Port. Pneumol. 2016; 22 (3): 167–176. DOI: 10.1016/j.rppnen.2016.01.004.

10. Monteagudo M., Rodríguez-Blanco T., Llagostera M. et al. Factors associated with changes in quality of life of COPD patients: a prospective study in primary care. Respir. Med. 2013; 107 (10): 1589–1597. DOI: 10.1016/j.rmed.2013.05.009.

11. Carter R.I., Stockley R.A. Disease "activity", "severity" and "impact": interrelationships in COPD; is a measure of disease "activity" the Holy Grail for COPD, or a variable impossible to quantify? COPD. 2014; 11 (4): 363–367. DOI: 10.3109/15412555.2013.808616.

12. Agusti A., Calverley P.M., Celli B. et al. Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) investigators. Characterisation of COPD heterogeneity in the ECLIPSE cohort. Respir. Res. 2010; 11: 122.

13. Soler-Cataluña J.J., Alcázar B., Miravitlles M. Clinical control in COPD: A new therapeutic objective? Arch. Bronconeumol. 2020; 56 (2): 68–69. DOI: 10.1016/j.arbr.2019.06.011.

14. Soler-Cataluña J.J., Alcazar-Navarrete B., Miravitlles M. The concept of control in COPD: a new proposal for optimising therapy. Eur. Respir. J. 2014; 44 (4): 1072–1075. DOI: 10.1183/09031936.00064414.

15. Soler-Cataluña J.J., Alcazar-Navarrete B., Miravitlles M. The concept of control of COPD in clinical practice. Int. J. Chron. Obstruct. Pulmon. Dis. 2014; 9: 1397–1405. DOI: 10.2147/COPD.S71370.

16. Merriam-Webster Dictionary. Available at: https://www.merriam-webster.com/dictionary/control?src=search-dict-box [Accessed: April 17, 2020].

17. Miravitlles M., Ribera A. Understanding the impact of symptoms on the burden of COPD. Respir. Res. 2017; 18 (1): 67. DOI: 10.1186/s12931-017-0548-3.

18. García-Río F., Soriano J.B., Miravitlles M. et al. Frequency of multi-dimensional COPD indices and relation with disease activity markers. COPD. 2013; 10 (4): 436–443. DOI:10.3109/15412555.2012.761959.

19. Jones P.J., Miravitlles M., van der Molen T., Kulich K. Beyond FEV1 in COPD: a review of patient-reported outcomes and their measurement using a new generation of instruments. Int. J. Chron. Obstruct. Pulmon. Dis. 2012; 7: 697– 709. DOI: 10.2147/COPD.S32675.

20. Hanania N.A., O'Donnell D.E. Activity-related dyspnea in chronic obstructive pulmonary disease: physical and psychological consequences, unmet needs, and future directions. Int. J. Chron. Obstruct. Pulmon. Dis. 2019; 14: 1127–1138. DOI: 10.2147/COPD.S188141.

21. Nishimura K., Izumi T., Tsukino M., Oga T. Dyspnea is a better predictor of 5-year survival than airway obstruction in patients with COPD. Chest. 2002; 121 (5): 1434–1440. DOI: 10.1378/chest.121.5.1434.

22. Bestall J.C., Paul E.A., Garrod R. et al. Usefulness of the Medical Research Council (MRC) dyspnoea scale as a measure of disability in patients with chronic obstructive pulmonary disease. Thorax. 1999; 54 (7): 581–586. DOI: 10.1136/thx.54.7.581.

23. Miravitlles M. Cough and sputum production as risk factors for poor outcomes in patients with COPD. Respir. Med. 2011; 105 (8): 1118–1128. DOI: 10.1016/j.rmed.2011.02.003.

24. Miravitlles M., Marin A., Monsó E. et al. Colour of sputum is a marker of bacterial colonization in chronic obstructive pulmonary disease. Respir. Res. 2010; 11 (1): 58. DOI: 10.1186/1465-9921-11-58.

25. Jenkins C.R., Postma D.S., Anzueto A.R. et al. Reliever salbutamol use as a measure of exacerbation risk in chronic obstructive pulmonary disease. BMC Pulm. Med. 2015; 15: 97. DOI: 10.1186/s12890-015-0077-0.

26. Ramon M.A., Ter Riet G., Carsin A.E. et al. The dyspnoeainactivity vicious circle in COPD: development and external validation of a conceptual model. Eur. Respir. J. 2018; 52 (3): 1800079. DOI: 10.1183/13993003.00079-2018.

27. Ramon M.A., Esquinas C., Barrecheguren M. et al. Selfreported daily walking time in COPD: relationship with relevant clinical and funcional characteristics. Int. J. Chron. Obstruct. Pulmon. Dis. 2017; 12: 1173–1181. DOI: 10.2147/COPD.S128234.

28. Jones P.W., Harding G., Berry P. et al. Development and first validation of the COPD Assessment Test. Eur. Respir. J. 2009; 34 (3): 648–654. DOI: 10.1183/09031936.00102509.

29. Miravitlles M., Koblizek V., Esquinas C. et al. Determinants of CAT (COPD Assessment Test) scores in a population of patients with COPD in Central and Eastern Europe: The POPE study. Respir. Med. 2019; 150: 141–148. DOI: 10.1016/j.rmed.2019.03.007.

30. Nibber A., Chisholm A., Soler-Cataluña J.J. et al. Validat - ing the concept of COPD control: a real-world cohort study from the United Kingdom. COPD. 2017; 14 (5): 504–512. DOI: 10.1080/15412555.2017.1350154.

31. Wedzicha J.A., Decramer M., Ficker J.H. et al. Analysis of chronic obstructive pulmonary disease exacerbations with the dual bronchodilator QVA149 compared with glycopyrronium and tiotropium (SPARK): a randomised, doubleblind, parallel-group study. Lancet Respir. Med. 2013; 1 (3): 199–209. DOI: 10.1016/S2213-2600(13)70052-3.

32. Barrecheguren M., Kostikas K., Mezzi K. et al. COPD clinical control as a predictor of future exacerbations: concept validation in the SPARK study population. Thorax. 2020; 75 (4): 351–353. DOI: 10.1136/thoraxjnl-2018-212752.

33. Miravitlles M., Sliwinski P., Rhee C.K. et al. Evaluation criteria for clinical control in a prospective, international, multicenter study of patients with COPD. Respir. Med. 2018; 136: 8–14. DOI: 10.1016/j.rmed.2018.01.019.

34. Soler-Cataluña J.J., Marzo M., Catalán P. et al. Validation of clinical control in COPD as a new tool for optimizing treatment. Int. J. Chron. Obstruct. Pulmon. Dis. 2018; 13: 3719–3731. DOI: 10.2147/COPD.S178149.

35. Soler-Cataluña J.J., Alcazar B., Marzo M. et al. Evaluation of changes in control status in COPD: An opportunity for early intervention. Chest. 2020; 157 (5): 1138–1146. DOI: 10.1016/j.chest.2019.11.004.

36. Cabrera López C., Casanova Macario C., Marín Trigo J.M. et al. Prognostic validation using GesEPOC 2017 Severity Criteria. Arch. Bronconeumol. 2019; 55 (8): 409–413. DOI: 10.1016/j.arbres.2018.12.002 (in English, Spanish).

37. Miravitlles M., Sliwinski P., Rhee C.K. et al. Predictive value of control of COPD for risk of exacerbations: An international, prospective study. Respirology. 2020. Apr. 6. DOI: 10.1111/resp.13811. [Epub ahead of print].

38. Miravitlles M., Roche N., Cardoso J. et al. Chronic obstructive pulmonary disease guidelines in Europe: a look into the future. Respir. Res. 2018; 19: 11. DOI: 10.1186/s12931-018-0715-1.

39. Alcázar Navarrete B., Ancochea Bermúdez J., García-Río F. et al. Patients with chronic obstructive pulmonary disease exacerbations: Recommendations for diagnosis, treatment and care. Arch. Bronconeumol. 2019; 55 (9): 478–487. DOI: 10.1016/j.arbr.2019.02.011 (in English, Spanish).