Criterions defined by patient

1. Criterions defined by patient Ataturk Chest Diseases and Thoracic Surgery Education and Research Hospital ANKARA Feza Uğurman M.D, Assoc. Prof. http://www.ataturksanatoryumu.gov.tr/

2. Guidance for Industry Patient-Reported Outcome (PRO) Measures Some Treatment Effects Are Known Only to the Patient. http://www.fda.gov/cder/guidance/index.htm Eur Respir J 2003; 21: Suppl. 41, 36s Proc Am Thorac Soc; 4. 2007:597–601

3. Jones PW. Proc Am Thorac Soc 2006;3:222

4. What is COPD exacerbation? Increasing symptoms Increased dyspnea Increased chest tightness Increased sputum volume Symptoms of a common cold Increased sputum purulence Increased cough Increased wheeze Anthonisen NR et al., Antibiotic therapy in exacerbations of chronic obstructive pulmonary disease. Ann Intern Med. 1987;106(2):196-204.

5. change in the patient’s symptoms defined by patient • Symptom-based definitions • Event-based exacerbations • Based on, • Hospital admission, • Need to take antibiotics • Need to take oral corticosteroids

6. An acute exacerbation is an event in the natural course of the disease characterized by a change in the patient’s baseline dyspnea, cough, and/or sputum that is beyond normal day-to-day variations, is acute in onset, may warrant a change in regular medication in a patient with underlying COPD. Symptom-based exacerbations Event-based exacerbations

7. Perception of symptoms Calverley et al, Eur Respir J 2005; 26: 406–413 • Is there correlation symptom or between based event exacerbation definition? 2.5 • Symptoms begin, • Become intense, • At the most severe symptoms there is need for additional therapy. 2 Shortness of breath 1.5 Cough 1 Chest tightness Night-time awakening 7 14 21 28 • Event based definition is useful method . • There is a complete correlation but only 44 percent of the patients Exacerbation -28 -21 -14 -7 A problem with filling diary cards?

8. Perception of symptoms Primary Care Resp J. 2006;15:346-53. 127 patients – One year follow-up Symptom-based exacerbations Event-based exacerbations Mean yearly rates: 2.3 (total 296) Mean yearly rates: 2.8 (total 351) 41% of exacerbations are symptom based 54% of exacerbations are event based Dyspnea is most important factor FEV1 ≥ %50 Exacerbation rate: 2.2 FEV1 ≥ %50 Exacerbation rate FEV1 < %50 Exacerbation rate : 3.2 FEV1 < %50 Exacerbation rate : 2.5 p:0.36 p:0.003 A problem with filling diary cards?

9. Comment • Event-based exacerbations are a valid way of identifying acute symptom change • But, there are limited agreement between symptom and event-based definitions.

10. Exacerbations of COPD • can cause ventilatory failure and premature death, • lead to deteriorating health-related quality of life, • can result in a more rapid decline of lung function, • pose a considerable economic burden, • are now recognised as important events in the natural course of COPD. Wilkinson, et al Am J Respir Crit Care Med 2004;69: 1298 Early diagnose and treatment of exacerbations may decrease hospitalization and time of recovery Effing et al. Cochrane Database Syst Rev. 2007;17 Respir Med. 2008 Jun;102 Suppl 1:S3-15. Bourbeau et al. Arch Intern Med 2003;163

11. 184 exacerbations/year - (mean: 2.7) • Of the 184 exacerbations, 93 were reported (51%) • There were no differences in major symptoms or physiological parameters between reported and unreported exacerbations. • Reported exacerbations were associated with increased cough but a lower incidence of wheeze. Am J Respir Crit Care Med 1998; 157

12. Am J Respir Crit Care Med 2000;161. 1608–1613, • The aim of the study: to detect underlying pathophysiological and symptomatic changes during the exacerbation. • Of the 504 exacerbations, 54% were reported. • Exacerbation onset, duration, and recovery time are similar in both reported and unreported groups Time of FVC recovery 6 days 3 days

13. Am J Respir Crit Care Med 177;396–401, 2008 • Multicenter trial. 486 exacerbations • Diary cart, quality of life assessment • 67 percent exacerbations is unreported • Elderly patients • Mild disease Unreported • Wheezing • Cold symptoms • Cough • Sputum colour Reported • More than one symptom

14. Am J Respir Crit Care Med 177;396–401, 2008 • Worse SGRQ scores in whom reported their exacerbations • Symptoms domain • Impact domain • Reported exacarbation rate higher in whom used more reliever medications

15. Conclusion • More than half of events are not reported by patients • Cough is a disabling symptom. • Sputum purulence is important for patients. • Multiple symptoms increase perception of exacerbations by patients. • Worsening of “health-related quality of the life questionnaire” scores and higher frequency of relievers usage may increase patient’s perception of exacerbation • Older patients and patients whose diseases less severe may not report their exacerbations.

16. Measurement of symptoms • Measurement of perception

17. Measurement of Dyspnea Widely used scales BORG scale MRC (Medical Research Council)dyspnea scale • Application of the both scale are easy and rapid • Consistent with changes in short and long time periods BaselineDyspnea Index(BDI)(detailed and time consuming) Transition Dyspnea Index(TDI)(routine clinical usage isn’t advised, It is more appropiate for clinical research)

18. Most widely used health related quality of life questionaires • General • Nottingham Health Profile • Medical Outcomes Study ( Short form 36 ) • Sickness Impact Profile (SIP) • Disease Specific • Chronic Respiratory Questionarrie (CRQ) • St. George’s Respiratory Questionnaire (SGRQ) • Pulmonary Functional Status and Dyspnea • Questionnaire (PFSDQ) • Seattle Obstructive Lung Disease Questionnaire • (SOQL) • Airways Questionnaire (AQ) • Shortness of Breath Questionnaire (SBQ)

19. Jones ,Thorax 2001;56:880–887

20. Quality of Life during exacerbations • Quality of Life scores become depraved. • SGRQ scores increase during the exacerbation • CRQ and MYMOP (Measure Your Medical Outcome Profile) scores go bad. • Nottingham Health Profile (NHP) scores deteriorate. • SF-36 scores decrease Spencer et al. Thorax 2003;58:589 Miravitlles et al. Thorax 2004; 59: 387 Aaron et al. Chest 2002; 121 Patterson et al. Qual Life Res 2000;9:521 Doll et al. Qual Life Res 2003;12: 17 Doll et al. Respir Med 2002; 96: 39-51 Lorenz et al. J Int Med Res 2001;29:74 Tsai et al. J Clin Epidemiol. 2008;61:489 Wang Q. Respirology. 2005;10:334 Ilior et al. nt J Clin Pract. 2008;62:585 Bourbeau et al. Eur Respir J. 2007;30:907 Lorenz et al. J Int Med Res 2001;29:74 Doll et al. Qual Life Res 2003;12: 17

21. Life Quality After Exacerbation • Quality of life scores return to basal values in mean three months. • This improvement is more rapid in first 2-4 weeks. • Improvementis more prominent in patients whose exacerbationisn’t repeated Andersson et al. Respir Med 2002; 96: 944 Spencer et al. Thorax 2003;58:589 Doll et al. Qual Life Res 2003;12: 17 Doll et al. Respir Med 2002; 96: 39-51 Tsai et al. J Clin Epidemiol. 2008;61:489 Andenaes et al. Qual Life Res. 2006;15:249 Ilior et al. Int J Clin Pract. 2008;62:585

22. Health related quality of life during Acute Exacerbation as a Predictor of Outcome • There is no relation with age, sex, FEV1, and FVC – but related with SGRQ scores • Admissions to hospital decrease with the improvement of SF-36 scores • Frequent exacerbation and severe dyspnea deteriorate quality of life scores • There is relation with the severity of exacerbations and quality of life questionnaire scores Osman et al. Thorax 1997;52:67–71 Grossman et al. Chest 1998;113:131 Miravitlles et al. Thorax 2004; 59: 387 Garcia-Aymerich et al Thorax 2003;58:100 Wang Q. Respirology. 2005;10:334 Lorenz et al. J Int Med Res 2001;29:74 Ilior et al. nt J Clin Pract. 2008;62:585 Respir Med. 2008 ;102 Suppl 1:S3-15.

23. Clinical Expectations from Health Related Quality of Life Questionnaires • Discriminative properties • Disease-specific measures should be able to identify small differences between levels of disease severity. • Evaluative properties • Disease-specific measures should be sensitive to clinically worthwhile changes with therapy or during an exacerbation. • Symptoms • Dyspnea • Fatigue and Muscle Wasting • Sleep Disorders • Emotional status • It should give the summary of whole effects of disease with objective criteria • Reliability • Validity • Responsiveness • Interpretability Minimal Clinically Important Difference (MCID)

24. Minimal Clinically Important Difference (MCID) The smallest difference in score of a domain of interest that patients perceive as beneficial and which would mandate, in the absence of troublesome side effects and excessive cost, a change in the patient’s management. Make B, COPD 2007;4:191-4 In evaluation of the benefits of treatment In evaluation of the disease progression MCID MCID Chronic Respiratory Disease Questionnaire (CRQ) 2 Borg scale 0.5 10-20 St. George Respiratory Questionnaire 4 VAS Clinical COPD Questionnaire (CCQ) 1 0.4 TDI Quality of Well-Being Scale 0.03 FEV1 100 ml

25. 20% 4 Calverley PM, COPD 2005;2:143-8

26. Conclusion • Criteria defined by patients are useful in follow-up COPD and treatment response. • Correlations between improvements in HR-QOL scores and measures of clinical outcome have been reported • Health related quality of life questionnaire is not useful yet in concept of “patient reported outcome” • Standardized, practical and easily performed measurement methods are needed.

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