Curriculum Vitae. Head of Public Wing HCU - RSCM. Head of ICU Sari Asih Ciledug Hospital

Transcription

1 Curriculum Vitae Name : Dr. Ceva W. Pitoyo,SpPD,K-P,KIC,FINASIM POB / DOB : Jakarta, March 8th 1968 Education : o General Practitioner : FKUI 1993 o Internist : FKUI 2002 o Pulmonology Consultant : PAPDI-UI 2006 o Intensivist : PERDICI-UI 2008 Current Position : Head of Div of Respirology & Critical Illness - Dept. of Internal Medicine FKUI/RSCM Head of Public Wing HCU - RSCM Head of ICU Sari Asih Ciledug Hospital

2 GOLD 2017 : Refined Assessment Grid and Treatment Algorithm Ceva W Pitoyo

3 Definition of COPD GOLD 2008 n COPD is a preventable and treatable disease with some significant extra pulmonary effects that may contribute to the severity in individual patients. n Its pulmonary component is characterized by airflow limitation that is not fully reversible. n The airflow limitation is usually progressive and associated with an abnormal inflammatory response of the lung to noxious particles or gases.

4 Exacerbation history: most powerful single predictor of exacerbations (independent of GOLD Stage) Year 1 Year 2 Exacerbations in the following year Patients with no exacerbation Patients with 1 exacerbation Patients with 2 exacerbations Patient-based risk estimate Percent Year % 6% 2% 6% 3% 2% 2% 2% 1% 5% 3% 1% 3% 2% 2% Percent Percent % 2% 3% N=1679 patients who completed the 3-year study % 1% 1% 2% 2% 3% The percentages at right denote the proportions of all patients with no exacerbations, one exacerbation, or two or more exacerbations Percent % 4% 12% Hurst et al. N Engl J Med

5 Probability of survival Exacerbation Frequency and Severity Both Increase Mortality Risk Patients with no acute exacerbations p < p = p< Patients with 1 2 acute exacerbations requiring hospital management 0.2 Patients with 3 acute exacerbations Time (months) Soler-Cataluna JJ et al. Thorax 2005;60:

6 Subjects limited (%) COPD has a significant impact on patients Impact of COPD in Europe and North America in 2000 (n=3265) * <65 years 65 years *p< Sports and recreation Normal physical exertion Social Sleep Household chores Sex life Family Persons aged 45 years diagnosed as having emphysema, chronic bronchitis or COPD, or meeting symptomatic definition of chronic bronchitis. Rennard et al. Eur Respir J 2002

7 COPD Definition (GOLD 2011) Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease. It is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response of the airways and the lung to noxious particles or gases. Significant exacerbations, extrapulmonary effects and comorbidities contribute to the overall severity in individual patients. GOLD Strategy Document 2014 (

8 COPD Definition (GOLD 2011) Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease. It is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response of the airways and the lung to noxious particles or gases. Significant exacerbations, extrapulmonary effects and comorbidities contribute to the overall severity in individual patients. GOLD Strategy Document 2014 (

9 What We Learned From ECLIPSE Study FEV 1 decline is not invariably progressive over three years 8% of subjects had annual increase of >20mL/year 23% of subjects; stable (20mL/year decline to 20mL/year increase) 31% of subjects ; annual decline of >20mL to 40mL/year 38% of subjects; annual decline of >40mL/year these ECLIPSE findings challenge the concept of COPD as a relentlessly progressive loss of lung function N Engl J Med Sep 29;365(13):

10 COPD Definition (GOLD 2011) Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease. It is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response of the airways and the lung to noxious particles or gases. Significant exacerbations, extrapulmonary effects and comorbidities contribute to the overall severity in individual patients. GOLD Strategy Document 2014 (

11 COPD Definition (GOLD 2011) Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease. It is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response of the airways and the lung to noxious particles or gases. Significant exacerbations, extrapulmonary effects and comorbidities contribute to the overall severity in individual patients. GOLD Strategy Document 2014 (

12 Etiology Noxious agents : smoking and pollutants Host factors Pathobiology : Impaired lung growth Accelerated decline Lung injury Lung & systemic inflammation Pathology : Small airway disorders or abnormalities Emphysema Systemic effects

13 COPD Definition (GOLD 2017) Obstructive Pulmonary Disease (COPD) is a common preventable and treatable disease. It is characterized by persistent respiratory symptoms and airflow limitation that is due to airway and/or alveolar abnormalities usually caused by significant exposure to noxious particles or gases. Significant exacerbations, extrapulmonary effects and comorbidities contribute to the overall severity in individual patients. GOLD Strategy Document 2014 (

14 GOLD 2017: Current pathways to the diagnosis of COPD Symptoms to consider COPD Dyspnoea Chronic cough or Sputum production Symptoms Shortness of breath Chronic cough Sputum Risk factors Host factors Tobacco Occupation Indoor/outdoor pollution and/or history of exposure to risk factors Spirometry: Required to establish diagnosis Spirometry (post-bronchodilator) FEV 1 /FVC <0.7 confirms the presence of airway limitation

15 Classify using the greater risk Risk of future events based on spirometry GOLD III & IV Patient s own exacerbation risk 2 in last year GOLD I & II 1 in last year CAT score

16 Classifying of COPD in GOLD (C) (D) 2 Patient is now in one of four categories: A: Less symptoms, low risk 2 1 (A) mmrc 0-1 CAT 10 (B) mmrc 2 CAT 10 SYMPTOMS (mmrc or CAT score) 1 0 B: More symptoms, low risk C: Less symptoms, high risk D: More symptoms, high risk Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from

17 Chapter 2 GOLD 2017 (Diagnosis and initial assessment) Refined A, B, C, D assessment tool: overview Spirometrically confirmed diagnosis Assessment of airflow limitation Assessment of symptoms/risk of exacerbations Exacerbation history Postbronchodilator FEV 1 /FVC < 0.7 FEV 1 (% predicted) GOLD 1 80% GOLD GOLD GOLD 4 < 30 2 or 1 leading to hospital admission 0 or 1 (not leading to hospital admission) (C) (A) (D) (B) Symptoms CAT < 10 CAT > 10 mmrc 0 1 mmrc > 2

18 ABCD assessment 2017 has been refined: Spirometry Spirometrically confirmed diagnosis Assessment of airflow limitation Postbronchodilator FEV 1 /FVC < 0.7 FEV 1 (% predicted) GOLD 1 80% GOLD GOLD GOLD 4 < 30 Spirometry is still relevant for: Diagnosis Prognostication Treatment with nonpharmacological therapies Classification unchanged!

19 ABCD assessment 2017 has been refined: Groups Assessment of A, B, C, D and therapy recommendations are based exclusively on: Respiratory symptoms Exacerbation history Exacerbation history 2 or 1 leading to hospital admission Assessment of symptoms/risk of exacerbations (C) (D) 0 or 1 (not leading to hospital admission) (A) (B) CAT < 10 CAT > 10 Symptoms mmrc 0 1 mmrc > 2

20 Practical impact of the new ABCD assessment grid exemplified by GOLD group D patients Previous GOLD Assessment 0-1 exacerbation* in the past year Consider two patients both patients with FEV 1 < 30% of predicted, CAT scores > 10 2 exacerbations in the past year GOLD D GOLD D 2017 GOLD Assessment 0-1* exacerbation in the past year 2 exacerbations in the past year GOLD grade 4 Group B GOLD grade 4 Group D * Not leading to hospitalisation

21 Assessment of symptoms: mmrc Modified MRC dyspnoea scale 1 mmrc: GOLD A or C: 0-1 PLEASE TICK IN THE BOX THAT APPLIES TO YOU (ONE BOX ONLY) (GRADES 0-4) mmrc Grade 0 mmrc Grade 1 mmrc Grade 2 mmrc Grade 3 mmrc Grade 4 I only get breathless with strenuous exercise I get short of breath when hurrying on the level or walking up a slight hill I walk slower than people of the same age on the level because of breathlessness, or I have to stop for breath when walking on my own pace on the level I stop for breath after walking about 100 meters or after a few minutes on the level I am too breathless to leave the house or I am breathless when dressing or undressing Exacerbation history 2 or 1 leading to hospital admission 0 or 1 (not leading to hospital admission) GOLD B or D: 2 (C) (A) (D) (B) CAT < 10 CAT > 10 Symptoms mmrc 0 1 mmrc > 2 1. Fletcher CM BMJ 1960; 2:1662

22 Assessment of symptoms: COPD Assessment Test (CAT) For each item below, place a mark (x) in the box that best describes you currently - be sure to only select one response for each question EXAMPLE: I am very happy I am very sad SCORE I never cough I have no phlegm (mucus) in my chest at all My chest does not feel tight at all When I walk up a hill or one flight of stairs I am not breathless I am not limited doing any activities at home I am confident leaving my home despite my lung condition X My chest is completely full of phlegm (mucus) My chest feels very tight When I walk up a hill or one flight of stairs I am very breathless I am very limited doing activities at home I am not at all confident leaving my home because of my lung condition I don t sleep soundly because of my lung condition Exacerbation history 2 or 1 leading to hospital admission 0 or 1 (not leading to hospital admission) CAT: GOLD A or C: < 10 GOLD B or D: 10 (C) (D) (A) (B) I have lots of energy I have no energy at all Total Score CAT < 10 CAT > 10 Symptoms mmrc 0 1 mmrc > 2 CAT score ranges from 0 to 40 and correlates very closely with SGRQ

23 GOLD 2017 Chapter 4 (Management of stable COPD) Foundation of pharmacological treatment decision - Symptoms and future risk of exacerbations Reduction of symptoms and future risk of exacerbations are the primary treatment goals (have remained unchanged!) Management of stable COPD should be predominantly based on individualised assessment of symptoms and future risk of exacerbations Appropriate non-pharmacologic interventions should complement pharmacologic treatments

24 GOLD 2011 Pharmacologic Therapy on Stable COPD Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference Patient First choice Second choice Alternative choices D ICS + LABA or LAMA ICS and LAMA or ICS + LABA and LAMA or ICS+LABA and PDE4-inh. or LAMA and LABA or LAMA and PDE4-inh. Carbocysteine SABA and/or SAMA Theophylline C LAMA or ICS + LABA LAMA and LABA PDE4-inh. SABA and/or SAMA Theophylline B LAMA or LABA LAMA and LABA SABA and/or SAMA Theophylline A SAMA prn or SABA prn LAMA or LABA or Theophylline Global Strategy for the Diagnosis, Management, and Prevention of Chronic SABA Obstructive and SAMA Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease (GOLD) Available from

25 GOLD 2016 Pharmacologic Therapy on Stable COPD First Choice Alternative Choice GOLD Pocket Guide Updated 2016

26 Choosing Bronchodilator?

27 Probability of hospitalized COPD exacerbation (%) POET-COPD : Tiotropium Significantly Delayed Time to First Severe Exacerbation vs Salmeterol 20 Tiotropium Salmeterol No. of patients at risk: Time to event (days) Tiotropium Salmeterol % Risk difference Hazard ratio = 0.72* (95% CI, 0.61, 0.85) P<0.001 (log-rank test) *Cox regression adjusted for (pooled) centre and treatment. Vogelmeier C et al. N Engl J Med 2011;364:

28 Indacaterol vs. Tiotropium for Patients with Severe COPD (INVIGORATE) : Tiotropium Significantly Delayed Time to First Exacerbation Patients receiving indacaterol had a 29% higher rate of exacerbations versus patients receiving tiotropium Tiotropium statistically significant 20% reduce in the risk of the time to first COPD* exacerbation. Compared with patients given tiotropium, those given indacaterol needed rescue treatment less often and had fewer nighttime awakenings Time to first moderate or severe COPD exacerbation up to Month 12 (full analysis set) *COPD=chronic obstructive pulmonary disease. Decramer ML et al. Lancet Respir Med 2013;1:

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30 Change from baseline in rescue medication use (puffs per day) SPARK Study : Combination of LAMA + LABA reduces daily rescue medication use over 64 weeks compare to LAMA or LABA alone Open-label tiotropium 18 μg q.d. Glycopyrroniu m 50 μg q.d. QVA /50 μg q.d. QVA 149 : Indicaterol + Glycopyrronium =-0.76, p<0.001 Wedzicha, et al. SPARK study. Lancet Resp Med (3): =-0.81, p<0.001

31 THE EFFECT OF PDE4 IHN ON EXACERBATIONS WAS GREATEST IN PATIENTS WITH CHRONIC COUGH AND SPUTUM Rennard SI et al. Respiratory Research 2011;12:18.

32 C Pharmacologic treatment algorithms of stable COPD (GOLD 207) LAMA + LABA Further Exacerbation(s) LAMA LABA + ICS Consider rofumilast if FEV1 < 50% pred. and patient has Chronic bronchitis Further exacerbation(s) Further exacerbation(s) LAMA LAMA + LABA LAMA + LABA + ICS D Consider macrolide (in former smokers) LABA + ICS A Continue, stop or try alternative class of bronchodilators A bronchodilator evaluate effect LAMA + LABA Persistent symptoms A long acting bronchodiator (LABA or LAMA) B

33 What did NOT change in the GOLD strategy 2017? General aspects of new GOLD strategy 2017 Structure/flow Treatment goals for stable COPD Classification of degree of airflow obstruction (grades 1-4) Groups A, B, C, D are still existing, but... with modifications...

34 Executive summary of changes in GOLD 2017 at a glance Chapter 1: Definition and Overview Definition of COPD has been revised by emphasising persistent respiratory symptoms and airflow limitation Chapter 2: Diagnosis and initial assessment Refinement of ABCD assessment: focus on respiratory symptoms and exacerbations alone to assign ABCD groups Role of spirometry is now mainly focused on establishing the diagnosis. Spirometry is no longer recommended for pharmacological treatment decisions (but for non-pharmacological treatments) Chapter 3: Evidence supporting prevention and maintenance therapy Importance of assessment and regular evaluation of inhaler technique has been highlighted Updated evidence on non-pharmacologic management Chapter 4: Management of stable COPD An exacerbation is now defined as an acute worsening of respiratory symptoms resulting in additional therapy Symptoms and future risk of exacerbations serve as basis for treatment decisions Introduction of strategies for escalation and de-escalation of pharmacotherapy Chapter 5: Management of exacerbations Detailed hospital discharge and follow-up criteria are added, including integrated team care Chapter 6: COPD and comorbidities Management of comorbidities (cardiovascular diseases in particular) are discussed in more detail

35 General aspects of new GOLD strategy 2017 GOLD strategy 2017 implements (major) changes in the: Definition of COPD (Chapter 1) Assessment and assignment of GOLD group categories A, B, C, D (Chapter 2) - (re-)evaluation of the meaning of spirometry and airflow limitation for treatment decisions (Chapter 2) Significance of respiratory symptoms and future risk of exacerbations for treatment recommendations (Chapter 4) Recommendations of pharmacological therapy of stable COPD (Chapter 3,4) Importance of regular assessment, evaluation and training of inhaler technique for treatment success (Chapter 3)

36 Chapter 3 (Evidence supporting prevention and maintenance therapy) Addition of assessment and regular evaluation of inhaler technique The significance of the assessment and evaluation of inhaler technique has been considerably enhanced Inhaler technique needs to be assessed regularly to improve therapeutic outcomes Importance of education and training cannot be over-emphasised Choice of inhaler device has to be individualised and will depend most importantly on patient s ability and preference Instructions and demonstration of a proper inhalation technique are essential also a re-check at each visit to ensure a correct use of the inhaler Inhaler technique (and adherence) should be evaluated before a treatment is assessed as insufficient

37 GOLD strategy 2017 Further statements/preliminary recommendations Triple therapy (LAMA/LABA/ICS) At present evidence is lacking to draw conclusions on the benefit of triple therapy compared to LAMA/LABA In Group D patients with LAMA/LABA treatment who are still suffering from exacerbations an escalation to triple therapy can be considered If patients treated with LAMA/LABA/ICS still have exacerbations the addition of the following options may be considered: - roflumilast in patients with FEV 1 < 50% predicted and chronic bronchitis - a macrolide in selected patients (best existing evidence for azithromycin) But also stopping ICS in case of a lack of efficacy or increased risk of adverse effects (including pneumonia)

38 GOLD strategy 2017 Further statements/preliminary recommendations Withdrawal of ICS At present results from ICS withdrawal studies are assessed as inconsistent regarding consequences on lung function, symptoms and exacerbation rates Nevertheless in GOLD Group D patients the withdrawal of ICS is recommended in patients on triple therapy who do not clearly benefit from ICS High blood eosinophil counts may be of help to predict the effects of ICS on exacerbations

39 GOLD strategy 2017 Further statements/preliminary recommendations Blood eosinophilia Findings of post-hoc analyses of two clinical studies in COPD patients suggest blood eosinophil counts can serve as a - biomarker of exacerbation risk in patients with an exacerbation history 1 - predictor of the effects of ICS on exacerbation prevention 2 Other post-hoc analyses have shown an association between blood eosinophil counts and exacerbation prevention 3,4 Prospective trials are demanded - to validate the use of blood eosinophil counts to predict the ICS effect - to determine a cut-off threshold for eosinophil counts to predict future risk of exacerbations in COPD patients with an exacerbation history and for ICS response clarify cut-off values that can be used in clinical practice 1. Siddiqui SH et al Am J Respir Crit Care Med 2015;192: , 2. Pascoe S et al Lancet Respir Med ,, 3. Pavord ID et al Thorax 2016; 71; , 4. Watz H et al Lancet Respir Med 2016; 4:

40 GOLD strategy 2017 Further statements/preliminary recommendations ACO(S) Neither a chapter nor an appendix regarding ACO(S) is present in the current GOLD report 2017 In the context of Differential diagnoses there is a short note The diagnosis Asthma-COPD Overlap Syndrome (ACOS) or Asthma-COPD-Overlap (ACO) has been coined to acknowledge that this represents overlap of common disorders causing chronic airflow limitation rather than a distinct syndrome In patients with a history and/or findings suggestive of ACO(S), ICS/LABA treatment may be the first choice

41 Chapter 5 (Management of exacerbations) Extending guidance for hospital discharge Inclusion of hospital discharge criteria Full review of all clinical and laboratory data Check maintenance therapy and understanding Reassess inhaler technique Reassess need for long-term oxygen Document the capacity to do physical activities and activities of daily living Document symptoms: CAT or mmrcv Determine status of comorbidities Measure spirometry: FEV 1 * * weeks follow-up only

42 Chapter 5 (Management of exacerbations) Extending guidance for hospital discharge Recommendation for follow up 1-4 weeks of follow up weeks of follow up - Evaluate patients ability to cope in the usual environment - Review understanding treatment regimen - Reassessment of inhaler technique - Reassessment of long-term oxygen - Document the capacity to do physical activity and activities of daily living - Document symptoms: CAT or mmrc - Determine status of comorbidities - Measure spirometry: FEV 1 * * weeks follow-up only

43 Chapter 6 (COPD and comorbidities) Strategies for the management of comorbidities Strategies for the management of cardiovascular and other important comorbidities are presented in detail osteoporosis anxiety and depression lung cancer metabolic syndrome and diabetes gastroesophageal reflux (GERD) bronchiectasis obstructive sleep apnea COPD as a part of multimorbidity

44 Summary Overall key points of new GOLD strategy 2017 Management strategy for stable COPD should be predominantly based on the individualised assessment of: - symptoms - future risk of exacerbations The main treatment goals are reduction of symptoms and future risk of excerbations Management strategies are not limited to pharmacological treatments, and should be complemented by appropriate non-pharmacological interventions All individuals who smoke should be strongly encouraged and supported to quit

45 Summary What are the key changes in the GOLD strategy 2017? The ABCD assessment grid has been refined to utilize exclusively respiratory symptoms and exacerbation history to assign groups - This new approach matches to the COPD treatment objectives aimed at symptoms and exacerbations and acknowledges the limitations of FEV 1 in making treatment decisions for individualized patient care For each GOLD category more precise treatment recommendations are given, resulting in a shift towards a more personalized approach to treatment, with strategies for escalation and de-escalation of pharmacotherapy - BRONCHODILATOR (LAMA, LABA, LAMA/LABA) therapy is key for COPD treatment across the spectrum of patients with COPD in GOLD stage B-D - Physicians get clearer guidance on which subset of patients may benefit from the addition of ICS and when withdrawal can be considered

46 AlhamduliLllah and I thank you

47 Pharmacologic treatment in detail: GOLD Group A patients Continue, stop or try alternative class of bronchodilator Evaluate effect GOLD Group A As a preferred choice all group A patients should be offered a short- or a longacting bronchodilator (dependent on its effect on breathlessness). Continuation with treatment if symptomatic benefit is documented A bronchodilator (A) In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted

48 Pharmacologic treatment in detail: GOLD Group B patients Preferred treatment LAMA + LABA Persistent symptoms A long-acting bronchodilator (LABA or LAMA) (B) GOLD Group B Either LAMA or LABA - No evidence which is superior in this group of patients LAMA/LABA is recommended - if symptoms persist or - from the start in patients with severe breathlessness To step back down to 1 bronchodilator if 2 nd med does not improve symptoms In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted

49 Pharmacologic treatment in detail: GOLD Group C patients (C) LAMA + LABA Further exacerbation(s) LAMA LABA + ICS GOLD Group C Starting therapy with a LAMA In case of persistent exacerbations addition of a LABA LAMA/LABA as first choice (LABA/ICS could be an alternative but patients are on higher risk for developing pneumonia) Preferred treatment In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted

50 Pharmacologic treatment in detail: GOLD Group D patients Consider roflumilast if FEV 1 <50% pred. and patient has chronic bronchitis Further exacerbation(s) Further exacerbation(s) LAMA LAMA + LABA + ICS LAMA + LABA Consider macrolide (in former smokers) (D) Persistent symptoms/further exacerbation(s) LABA + ICS De-escalation from ICS containing to LAMA/LABA treatments if ICS shows lack of efficacy! GOLD Group D LAMA/LABA is recommended from the start - since a LAMA/LABA combination was superior to a LABA/ICS combination in preventing exacerbations and other patient reported outcomes in group D patients For patients with a history and/or findings of concurrent asthma or raised eosinophil count, LABA/ICS may be the first choice For patients who develop further exacerbations on LAMA/LABA two alternatives are suggested - escalation to triple therapy - switch to LABA/ICS (but no evidence) If triple therapy is inadequate for symptom control - add roflumilast (chronic bronchitis with low FEV1) - Add In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted

51 Treatment algorithm by GOLD groups: No role of ICS containing treatment in Groups A and B (C) LAMA + LABA LABA + ICS Consider roflumilast if FEV 1 <50% pred. and patient has chronic bronchitis Consider macrolide (in former smokers) Further exacerbation(s) LAMA Further exacerbation(s) Further exacerbation(s) LAMA + LABA + ICS (D) Persistent symptoms/further exacerbation(s) LAMA LAMA + LABA LABA + ICS GOLD Group A and B completely ICS-free Continue, stop or try alternative class of bronchodilator Evaluate effect A bronchodilator LAMA + LABA Persistent symptoms A long-acting bronchodilator (LABA or LAMA) (A) (B) In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted Preferred treatment

52 Treatment algorithm by GOLD groups: Limited role of ICS containing treatment No initiation with ICS containing treatment in GOLD Groups C and D* (C) LAMA + LABA Further exacerbation(s) LAMA in Groups C and D LABA + ICS Continue, stop or try alternative class of bronchodilator Consider roflumilast if FEV 1 <50% pred. and patient has chronic bronchitis Further exacerbation(s) Further exacerbation(s) LAMA LAMA + LABA + ICS LAMA + LABA LAMA + LABA Persistent symptoms Consider macrolide (in former smokers) (D) Persistent symptoms/further exacerbation(s) LABA + ICS Evaluate effect A bronchodilator A long-acting bronchodilator (LABA or LAMA) (A) (B) In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted *LABA/ICS may be the first choice in some patients. For example, those with a history and/or findings suggestive of asthma-copd overlap. Preferred treatment

53 Treatment algorithm by GOLD groups: LAMA/LABA plays a major role for (C) LAMA + LABA Further exacerbation(s) LAMA LABA + ICS GOLD B-D Consider Consider roflumilast if FEV 1 <50% pred. and patient has chronic bronchitis Further exacerbation(s) Further exacerbation(s) LAMA LAMA + LABA + ICS LAMA + LABA (D) macrolide (in former smokers) Persistent symptoms/further exacerbation(s) LABA + ICS LAMA/LABA plays an major role for GOLD B-D Continue, stop or try alternative class of bronchodilator Evaluate effect A bronchodilator LAMA + LABA Persistent symptoms A long-acting bronchodilator (LABA or LAMA) For GOLD B patients with severe breathlessness initial therapy with two bronchodilators may be considered (A) (B) In patients with a major discrepancy between the perceived level of symptoms and severity of airflow limitation, further evaluation is warranted Preferred treatment