The 2017 GOLD «approach» Margherita

Transcription

1 Fabiano Di Marco

2 The 2017 GOLD «approach» Margherita

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4 The incidence of pneumonia was 3.2% in the indacaterol-glycopyrronium group and 4.8% in the salmeterol-fluticasone group (P=0.02).

5 Blood eosinophilia and response to ICS in COPD Pascoe S. et al,

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7 Why are illustrative cases important? In real-life settings, more than 80% of COPD subjects are currently treated by protocols based on results of RCTs for which they would not have been eligible. COPD = chronic obstructive pulmonary disease; FEV 1 = forced expiratory volume in 1 second; RCT = randomized controlled trial Scichilone N, et al. Respiration 2014;87:11 7

8 Giacomo 55-year-old male Giacomo Former smoker (quit aged 50, smoking history 35 pack years) Diagnosed with COPD 3 years ago Complaint of progressively worsening dyspnea (mmrc 3) No history of exacerbation in the previous year Past medical history uneventful, with the exception of COPD (maintenance treatment with ICS/LABA FDC as suggested by his GP) Physical examination unremarkable, aside from diminished breath sounds on both lungs GP = General Practitioner; ICS = inhaled corticosteroid; LABA = long-acting β 2 -agonist; mmrc = modified Medical Research Council Picture for illustrative purposes only.

9 Giacomo Spirometry Forced vital capacity Meas. Normal Pred % Pred z score Flow (L/s) FET = forced expiratory time; FVC = forced vital capacity; MEF = middle of expiratory flow; PEF = peak expiratory flow; pred = predicted; VEXT = extrapolated volume

10 How common is Giacomo? From 2016 to 2017 GOLD classification 60 70% CAT = COPD Assessment Test; ECOPD = exacerbations of COPD; GOLD = Global initiative for chronic Obstructive Lung Disease; mmrc = modified Medical Research Council; SGRQ = St George s Respiratory Questionnaire Agusti A, et al. Eur Respir J 2013;42:

11 Patients (%) 100% 80% 60% 40% 20% 0% How far is real life from COPD therapy guidelines? An Italian observational study Mild Moderate Severe Very severe Stage I Stage II Stage III Stage IV O Without exacerbation LAMA LABA ICS FDC LAMA + ICS LAMA + FDC LABA + ICS ICS + LABDs Other U C O U C O U C O U C (%) Severity of COPD determined by degree of airflow limitation (Stage I mild COPD (FEV 1 80% pred); Stage II moderate COPD (50% FEV 1 <80% pred); Stage III severe COPD (30% FEV 1 <50% pred); Stage IV very severe COPD (FEV 1 <30% pred. or FEV 1 <50% pred. with PaO2 <60 mmhg)) C = correct prescription; FDC = fixed dose combination; LAMA = long-acting antimuscarinic agents; O = over-prescription; U = under-prescription Corrado A, Rossi A. Respir Med 2012;106:989 97

12 Giacomo Do we need more information to decide the inhalation treatment for Giacomo? A. No more information needed B. CAT score C. Cardiopulmonary exercise testing D. Second-line pulmonary function tests and high-resolution computed tomography E. Blood eosinophils Giacomo FEV 1 % pred 48% mmrc 3 No exacerbations ICS/LABA treatment

13 Giacomo COPD Assessment Test (CAT) score Example: I am very happy I am very sad I never cough I cough all the time 2 I have no phlegm (mucus) in my chest at all My chest is completely full of phlegm (mucus) 2 My chest does not feel tight at all My chest feels very tight 3 When I walk up a hill or one flight of stairs I am not brethless I am not limited doing any activities at home I am confident leaving my home despite my lung condition I sleep soundly x x x x x xx x x When I walk up a hill or one flight of stairs I am very brethless 4 I am very limited doing activities at home 4 I am not at all confident leaving my home because of my lung condition 3 I don t sleep soundly because of my lung condition 3 I have lots of energy I have no of energy at all 4 SCORE COPD Assessment Test and the CAT logo are trademarks of the GlaxoSmithKline group of companies GlaxoSmithKline. All rights reserved. TOTAL SCORE 25

14 Characterisation of COPD heterogeneity in the ECLIPSE cohort Giacomo Augusti A, et al. Respir Res 2010;11:122

15 Giacomo Cardiopulmonary exercise testing SBP (mmhg): DBP (mmhg): bpm = beats per minute; BTPS = body temperature (37 C), ambient pressure and gas saturated with water vapor; DBP = diastolic blood pressure; SBP = systolic blood pressure

16 Giacomo Second-line pulmonary function tests Body plethysmography Meas. Normal Pred % Pred z score Flow (L/s) Lung volumes ERV = expiratory reserve volume; FRC = functional residual capacity; Gaw = airway conductance; Raw = airway resistance; RV = residual volume; TLC = total lung capacity

17 Giacomo Second-line pulmonary function tests DLCO DLCO DLCO corr ml/min/mmhg ml/min/mmhg Meas. Normal Pred %Pred Z score 19,16 16,53 30,42 23, ,16 16,53 30,42 23, Time of apnea (Jones and Meade) Residual volume Sampling volume DLCO/VA VA TLC (DLCO) Hb ml/min/mmhg/l L L g/dl 3,45 5,56 6,79 14,6 2,36 5,12 5,12 7,42 5,27 7, ,74 6,27 6, % Best VC Time (s) DLCO = diffusing capacity of the lung for carbon monoxide; Hb = haemoglobin VA, alveolar ventilation; VC = vital capacity

18 Giacomo High-resolution computed tomography

19 Suggested benefit risk ratio of ICS in COPD according to blood eosinophilia Giacomo s blood eosinophils: 0.7% 100/μL Brusselle G, et al. Lancet Respir Med 2015;3:416 7

20 Giacomo Do we need to modify the therapy? If yes, how? A. Continue ICS/LABA B. Withdraw ICS C. Switch to LABA/LAMA FDC D. Add a LAMA (triple therapy) Giacomo FEV 1 % pred 48% mmrc 3 No exacerbations ICS/LABA treatment Eosinophils 100/μL

21 The 2017 GOLD «approach» Giacomo, treated with ICS/LABA, does not exist! Group B LAMA + LABA Persistent symptoms A long-acting bronchodilator (LABA or LAMA) GOLD Available from:

22 Giacomo Summary Dyspnea is a complex symptom In the case of severe dyspnea in a Group B patient, the use of dual bronchodilation is suggested In the case of persistent dyspnea on LABA/LAMA: what next?

23 CASI CLINICI Pierachille Santus Università degli Studi di Milano UOC Pneumologia Ospedale L. Sacco ASST Fatebenefratelli Sacco, Milano

24 PROLOGO 1

25 PROLOGO 2

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27 Exacerbations/year I pazienti BPCO che riacutizzano frequentemente sono una quota importante, ma costituiscono una piccola percentuale nella popolazione totale dei soggetti BPCO Susceptibility to exacerbation in 1679 patients Year 1 Percentage % PROLOGO 3 Year 2 Year 3 Percentage Percentage Percentage Percentage % 11% Hurst et al. NEJM, 2010

28 Riacutizzazioni e conseguenze della BPCO Il tempo mediano trascorso dalla prima alla seconda riacutizzazione che ha portato al ricovero è stato di circa 5 anni ed è sceso a <4 mesi dalla nona alla decima Suissa et al. Thorax 2012

29 Exacerbations Frequency Exacerbations Severity

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31 Blood eosinophilia and COPD exacerbations Pascoe S. et al, Lancet RM 2015

32 Blood eosinophilia and response to ICS in COPD Pascoe S. et al, Lancet RM 2015

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35 DOVE SIAMO!? - MOLTE EVIDENZE CHE SOSTENGONO UNA MIGLIORE EFFICACIA DEL LABA/LAMA FDC vs LABA o LAMA NEL MIGLIORARE LA DISPNEA E LA QoL - DIVERSE EVIDENZE CHE SOSTENGONO UNA MIGLIORE EFFICACIA DEL LABA/LAMA FDC vs LABA o LAMA NEL PREVENIRE LE RIACUTIZZAZIONI (*) - IMPORTANTE EVIDENZA CHE SOSTIENE UNA MIGLIORE EFFICACIA DEL - LABA/LAMA FDC vs LABA/ICS NEL PREVENIRE LE RIACUTIZZAZIONI (*) - BUONA PROSPETTIVA A SOSTENGNO DI UNA MIGLIORE EFFICACIA DEL - LABA/LAMA FDC vs LAMA o LABA NEL RIDURRE/RALLENTARE IL DECLINO FUNZIONALE

36 CASO 1 - DONNA DI 53 ANNI, FUMATRICE (25 PACK YEARS) - APR: negativa - DISPNEA: mmrc 1-2 episodi di AECB/anno precedente - Eosinofili periferici 2.5% = 195 cell/microl

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39 TERAPIA? LABA/LAMA FDC

40 Margherita Margherita 74-year-old female Current smoker (few cigarettes per day, history 45 pack years) Past medical history: Mixed anxiety-depressive disorder COPD (mmrc 3; treated with ICS/LABA for many years) Chronic bronchitis with at least two exacerbations per year, treated by GP with antibiotics One year ago admitted to hospital with bilateral pneumonia; H. influenzae isolated from sputum Margherita comes to our outpatients clinic for a «second opinion», worried about long-term effect of inhaled steroids (mainly for osteoporosis). BID = twice daily Picture for illustrative purposes only

41 Margherita Chest X-ray

42 Margherita Spirometry Forced vital capacity Meas. Normal Pred %Pred z score Flow (L/s)

43 Margherita Margherita is warried about ICS and osteoporosis A. She s right B. She s wrong C. I don t know Margherita FEV 1 46% mmrc 3 History of COPD exacerbations, pneumonia, chronic bronchitis ICS/LABA treatment

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46 Margherita The level of dyspnea is out of proportion? A. No B. No she s a woman C. Yes, is out of proportion Margherita FEV 1 46% mmrc 3 History of COPD exacerbations, pneumonia, chronic bronchitis ICS/LABA treatment

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48 Margherita Inhalation treatment for Margherita A. Continue ICS/LABA B. Withdraw ICS (LABA alone) C. Switch to LABA/LAMA FDC D. Add a LAMA (triple therapy) Margherita FEV 1 46% mmrc 3 History of COPD exacerbations, pneumonia, chronic bronchitis ICS/LABA treatment

49 The 2017 GOLD approach Group D Consider roflumilast if FEV 1 <50% pred. and patient has chronic bronchitis Consider macrolide (in former smokers) Margherita Further exacerbation(s) Further exacerbation(s) LAMA + LABA + ICS Persistent symptoms/further exacerbations LAMA LAMA + LABA LABA + ICS GOLD Available from:

50 Therapeutic recommendations based on exacerbation phenotype Margherita s blood eosinophils: 250/μL (2.3%) Miravitlles M, et al. Respir Res 2016;17:112

51 CASO 2 - MASCHIO DI 80 ANNI, EX FUMATORE (45 PACK YEARS) - APR: Pregressa cardiopatia ischemica; Ipertensione - Terapia: Sartanico, furosemide 1 cp/die, CardioASA e Beta bloccante (Carvedilolo 12,5 mg/die). - DISPNEA: mmrc 2-1 episodio di AECB/anno precedente

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54 TERAPIA? LABA/LAMA FDC

55 CASO 4 - MASCHIO DI 89 ANNI, EX FUMATORE (50 PACK YEARS) - APR:???? - DISPNEA:??? -? episodi di AECB/anno precedente

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58 TERAPIA? LABA/LAMA FDC o LABA/ICS+LAMA

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