An Update in COPD John Hurst PhD FRCP

Transcription

1 An Update in COPD John Hurst PhD FRCP Reader in Respiratory Medicine / Honorary Consultant University College London / Royal Free London NHS Foundation Trust j.hurst@ucl.ac.uk

2 What s new in COPD papers affecting clinical practice 1. Trajectories of disease progression 2. Phenotyping COPD 3. The Airway Microbiome 4. Co-Morbidity in COPD 5. Models of Care

3 What s new in COPD affecting clinical practice 1. Trajectories of disease progression 2. Phenotyping COPD 3. The Airway Microbiome 4. Co-Morbidity in COPD 5. Models of Care

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5 Emphysema Chronic Bronchitis COPD

6 Emphysema Chronic Bronchitis PATHOLOGICAL diagnosis COPD

7 Emphysema Chronic Bronchitis PATHOLOGICAL diagnosis CLINICAL diagnosis COPD

8 Emphysema Chronic Bronchitis COPD PHYSIOLOGICAL DIAGNOSIS: Post-BD FEV 1 /FVC <0.7

9 Emphysema Chronic Bronchitis COPD PHYSIOLOGICAL DIAGNOSIS: Post-BD FEV 1 /FVC <0.7

10 COPD Definition COPD, a common preventable and treatable disease, is characterised by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients. WHO/GOLD 2013 (

11 COPD Definition COPD, a common preventable and treatable disease, is characterised by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Exacerbations and comorbidities contribute to the overall severity in individual patients.

12 COPD: natural history Fletcher C and Peto R. BMJ 1977;6077:

13 COPD: natural history [with written patient permission] Fletcher C and Peto R. BMJ 1977;6077: STABLE EXACERBATION

14 The mean decline in FEV 1 was 24 ml per year in trajectory 1 (Panel A), 2 ml per year in trajectory 2 (Panel B), 53 ml per year in trajectory 3 (Panel C), and 27 ml per year in trajectory 4 (Panel D). The decline in FEV 1 in trajectory 3 was considered to be rapid. Accelerated decline in FEV 1 is not an obligate feature of COPD.

15 Disease Activity and Severity EARLY vs. LATE MILD vs. SEVERE SEVERITY Distance Travelled ACTIVITY Speed A B

16 Disease Activity and Severity SEVERITY Distance Travelled Cross-Sectional FEV 1 CT ACTIVITY Speed Longitudinal FEV 1 decline rate CT changes Inflammation?

17 Clinical Message COPD is diverse. Current assessments of disease severity do not address the more important question of disease activity Rate of lung function decline Exacerbations

18 What s new in COPD affecting clinical practice 1. Trajectories of disease progression 2. Phenotyping COPD 3. The Airway Microbiome 4. Co-Morbidity in COPD 5. Models of Care

19 Emphysema Chronic Bronchitis COPD PHYSIOLOGICAL DIAGNOSIS: Post-BD FEV 1 /FVC <0.7

20 Complexity in COPD

21 Phenotypes in COPD Chronic Bronchitis (Symptom based) FEV 1 (Physiological) Inflammation (Biomarker) Co-Morbidities [with written patient permission] Exacerbations (Clinical) Alpha-1 (Genetic) Emphysema (Radiological, incl. ILD) Needs to be STABLE and MEASURABLE. Phenotypes may overlap.

22 15 units, p<0.001 Seemungal TAR et al. AJRCCM 1998 Soler-Cataluna JJ et al. Thorax vs. 40ml/yr, p<0.05 Frequent Exacerbation Costs Donaldson GC et al. Thorax vs. 40 ml/year, p<0.05

23 High Risk Patients

24 ECLIPSE Methodology YEAR PRIOR YEAR 1 YEAR 2 YEAR 3 Number of courses of antibiotics/steroids / hospitalisations for exacerbation in prior year asked and recorded Recruitment Baseline Assessment Number of courses of antibiotics/steroids / hospitalisations for exacerbation in year one COUNTED Number of courses of antibiotics/steroids / hospitalisations for exacerbation in year two COUNTED Number of courses of antibiotics/steroids / hospitalisations for exacerbation in year three COUNTED ANALYSIS 1 How do baseline variables relate to observed exacerbations in year 1? ANALYSIS 2 How stable is exacerbation frequency over 3 observed years, and in relation to patient self report?

25 Exacerbations and COPD Severity

26 Multivariate Analysis Hurst JR et al. NEJM 2010;363:

27 Multivariate Analysis Suggests groups of patients or phenotypes who are inherently susceptible versus resistant to exacerbations (or at least reporting exacerbations) IS THIS STABLE OVER TIME? Hurst JR et al. NEJM 2010;363:

28 Exacerbation Phenotypes in COPD Hurst JR et al. NEJM 2010;363:

29 Identifying the Frequent Exacerbator How many courses of antibiotics and/or steroids did you need for you chest over the last year? [with written patient permission] Better targeting (personalised / stratified medicine).

30 GOLD 2011 Staging Revision: Exacerbations 4 3 C D 2 A: Low Risk, Fewer Symptoms B: Low Risk, More Symptoms C: High Risk, Fewer Symptoms D: High Risk, More Symptoms RISK GOLD Stage 2 A B 1 RISK Exacerbations 1 0 mmrc 0-1 mmrc 2 CAT<10 CAT 10 SYMPTOMS

31 Clinical Message COPD is diverse. Therapy should be directed against the phenotype(s) present, at baseline and exacerbation Targeting the frequent exacerbator

32 What s new in COPD papers affecting clinical practice 1. Trajectories of disease progression 2. Phenotyping COPD 3. The Airway Microbiome 4. Co-Morbidity in COPD 5. Models of Care

33 This talk, circa 2006 The healthy human airway is sterile, with several innate immune mechanisms acting in coordination to maintain this sterility. Smoking appears to disrupt these innate immune mechanisms, and as a consequence, microbial pathogens are able to persist in the lower airway in COPD AJRCCM 2006 free from bacteria or other living microorganisms; totally clean

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35 We identified 5,054 16S rrna bacterial sequences from 43 subjects. The bronchial tree was not sterile, and contained a mean of 2,000 bacterial genomes per cm 2 surface sampled. Pathogenic Proteobacteria, particularly Haemophilus spp., were much more frequent in bronchi of adult asthmatics or patients with COPD than controls. Conversely, Bacteroidetes, particularly Prevotella spp., were more frequent in controls than adult or child asthmatics or COPD patients.

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37 Bacterial Colonisation

38 PPM Prevalence 25% 52% Monso E et al. AJRCCM 1995;152:

39 Exacerbation Ecology Volcano plots indicating taxa that are significantly increased (upper right quadrant) or decreased (upper left quadrant) in pair-wise comparisons. Dashed lines indicate significant FDR-adjusted p- values and changes in relative abundance of at least 2-fold. Taxa exhibiting significant changes are coloured by phylum-level classification. Note that in addition to highlighted taxa, many other microbiota members exhibit smaller scale changes in abundance, which cumulatively may contribute importantly to microbiome community function. Sethi S et al. J Clin Micro 2014: in press

40 Viral infection predisposes to secondary bacterial infection AJRCCM 2013;188:

41 MACROLIDES HR for exacerbation per patient-year in the azithromycin group =0.73 (95% CI, 0.63 to 0.84; p<0.001). Increased macrolide resistance, and hearing impairment

42 Clinical Message The presence of an organism in sputum doesn t necessarily mean that the organism is causing a problem The field is moving quickly; we just don t know what to do with the data yet

43 What s new in COPD papers affecting clinical practice 1. Trajectories of disease progression 2. Phenotyping COPD 3. The Airway Microbiome 4. Co-Morbidity in COPD 5. Models of Care

44 Case Study A 75 year old female is hospitalised following a deterioration of her COPD symptoms, consistent with an exacerbation. [with written patient permission] She had previously been prescribed combination ICS- LABA and LAMA. She was known to have cardiovascular disease (previous MI) and diabetes mellitus.

45 Questions 1. Does the presence of IHD and diabetes affect the outcome of the exacerbation? 2. What are the implications of COPD for the therapy of IHD and diabetes? 3. Are these co-morbidities more likely because of the underlying COPD, or her COPD therapy? 4. Is this really an exacerbation, or an undetected co-morbidity?

46 The COPD Co-Morbidome Divo M et al. AJRCCM 2012;186:pp

47 Mortality in COPD

48 COPD and Cardiovascular Disease Cumulative incidence of first MI Cumulative incidence of first CVA

49 The Absence of Evidence Study A able to use medication correctly Serious, uncontrolled disease (including serious psychological disorders) likely to interfere with the study and/or likely to cause death within the 3-year study duration Study B Able to inhale study drug Significant diseases other than COPD which, in the opinion of the investigator, may either put the patient at risk because of participation in the study or a disease which may influence the results of the study or the patient s ability to participate in the study. A recent history (i.e., six months or less) of myocardial infarction. Any unstable or life threatening cardiac arrhythmia or cardiac arrhythmia... Hospitalization for heart failure (NYHA Class III or IV) within the past year. Patients with known moderate to severe renal impairment.

50 Clinical Message Many patients with COPD have many other diagnoses ( co / multi-morbidities ) Some of these are more prevalent in COPD through shared risk factors, therapy, or systemic consequences These may impact the course of COPD, or complicate COPD therapy, and COPD can impact the natural history of the co-morbidity However co-morbidity arises, outcomes will be better with a take a personalised, holistic approach to COPD management

51 What s new in COPD papers affecting clinical practice 1. Trajectories of disease progression 2. Phenotyping COPD 3. The Airway Microbiome 4. Co-Morbidity in COPD 5. Models of Care

52 Sources

53 Methodology Regular national COPD Audits: 2003, 2008, 2014 Organisational Secondary Care Primary Care PR All first-episode admitted exacerbations February April 2015 COPD Admissions risen 13% since 2008

54 Dataset patient exacerbations 100% of Trusts in E+W took part 183 English units in 142 Trusts Median (IQR) 61 (38-86) per unit Median (IQR) percentage of audit cases to total eligible (coded!) cases 67% (48%-91%)

55 Socio-Demographics First COPD audit in which females make up the majority (51%) of cases. Admitted patients were notably deprived in respect of income, employment, health deprivation/disability and education/skills/training. There is a clear association between age and area of residence with deprivation; younger COPD patients in England and more likely to live in the more deprived areas. National RFH Female 51% 50% Mean Age (y) Living in Most Deprived Quintile 34% 22%

56 Outcomes Mortality has fallen from 7.5-8% in 2003 and 2008 Mortality doesn t vary by day of admission, except highest deaths on a Tuesday for patients admitted on a Monday (and case-mix the same) Mortality 6.8% vs. 3.6% with consolidation LOS has fallen from days

57 7/7 working?

58 Specialist Advice Takes longer to see a specialist (if at all) for those in at the weekend, and on a Monday Recording of key information better if see a specialist Recommendation: All patients whose primary diagnosis is COPD exacerbation should receive a specialist respiratory opinion within 24 hours of admission. Patients with COPD exacerbation who need to remain in hospital should be managed on a respiratory ward.

59 Camden Model Integrated COPD Care Community Respiratory Service Close working links with both Acute Trusts Regular MDT and joint clinics Shared governance Primary Care education and support Case finding Close links with others teams

60 London Respiratory Value Pyramid

61 Clinical Message How can you achieve cost-effective care of patients with COPD in your services?

62 Questions Fixed airflow obstruction ( COPD ) may arise as an adult consequence of premature lung disease 1 YES 2 NO 3 Unsure

63 Questions It is possible to identify specific groups of COPD patients who respond better to specific therapies (stratified medicine) 1 YES 2 NO 3 Unsure

64 Questions I would prescribe antibiotics to a patient with COPD who has Haemophilus influenzae identified on a routine sputum culture 1 YES 2 NO 3 Unsure

65 Questions Most patients with COPD will die with, not from their COPD 1 YES 2 NO 3 Unsure

66 Questions 7 days access to specialist care is likely to improve outcomes in COPD 1 YES 2 NO 3 Unsure

67 Summary Diversity of COPD Trajectories of decline, disease severity and activity Phenotype based care The Airway Microbiome The Importance of Co-Morbidity in COPD The challenges of unplanned care in COPD

68 Thank You Comments and Questions