Prognostication in COPD: science or fiction?

Dr Laura-Jane Smith ST5 Respiratory Medicine

Wellcome Trust Clinical Research FellowWhittington Respiratory Meeting June 2015

COPD and death

Prognostication

Future practice

COPD REFRESHER

Inhaled noxious particles

(eg cigarette smoke, solid fuel fire smoke)

Inflammation, white cell

recruitment

Bronchial wall thickening

and fibrosis

Mucous gland hyperplasia

Alveolar destruction (neutrophil proteases)

CHRONIC BRONCHITIS

SMALL AIRWAYS NARROWING AND

OBSTRUCTION

EMPHYSEMA, BULLAE LOSS OF ELASTIC RECOIL

DYNAMIC AIRWAYS COLLAPSE

COPD is a systemic dise

ase

Images from Eureka: Respiratory Medicine 2015. Smith, Quint, Brown

WHAT DO WE DIE OF?

Prevalence of COPD increasing

globally, and projected to be the 3rd leading

cause of mortality and 5th leading

cause of disability by 2020

Many people die with COPD, or

from a complication related to it

COPD may not be cited as the

primary cause of death on their

death certificate - under-reported as a cause of death

HOW DO COPD PATIENTS DIE?

Trajectories of death

Trajectories of death

COPDHeart failure

Dementia Frailty

Cancer

From Spathis and Booth 2008. End of life care in chronic obstructive pulmonary disease: in search of a good death. International Journal of COPD. 2008;3(1):11–39. Adapted from Murray et al.

Respiratory failure

Lung cancer

Myocardial infarction Other

12%61%

14% 13%

Functional impairmentSymptom burden (breathlessness, anorexia, pain, cough, insomnia, confusion,

fatigue, low mood, anxiety, panic) Social isolation

Impaired HRQoLTreatment preferences

Invasive interventions near the end of life Advance care planning

Access to specialist palliative care services

Habraken JM et al. 2009Edmonds P et al.. 2001;15(4):287–95Gore et al 2000

COPD Lung cancer

All of these factors suggest that a palliative care approach would be beneficial for patients with advanced COPD. National and International guidelines recommend such an approach.

WHO definition of Palliative CarePalliative care is an approach that improves the quality of life of patients and their families facing the problem associated with life-threatening illness, through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment of pain and other problems, physical, psychosocial and spiritual. Palliative care:• provides relief from pain and other distressing symptoms• affirms life and regards dying as a normal process• intends neither to hasten or postpone death• integrates the psychological and spiritual aspects of patient care• offers a support system to help patients live as actively as possible until death• offers a support system to help the family cope during the patients illness and in their own

bereavement• uses a team approach to address the needs of patients and their families, including

bereavement counselling, if indicated• will enhance quality of life, and may also positively influence the course of illness• is applicable early in the course of illness, in conjunction with other therapies that are

intended to prolong life, such as chemotherapy or radiation therapy, and includes those investigations needed to better understand and manage distressing clinical complications

Why don’t COPD patients access palliative care?

Enhance access to a palliative

care approach

Improve prognostication

Move to a needs-based approach

Identify transitions in the course of disease

as triggers

Enhance access to a palliative

care approach

Improve prognostication

Move to a needs-based approach

Identify transitions in the course of disease

as triggers

PROGNOSIS IN COPD

How good is human intuition?

Chow et al 2001, Christakis 2000, Wildman 2007

Can data help?

FEV1% Hypoxaemia Breathlessness Cor pulmonale

Exacerbation frequency Hospitalisation Exercise

tolerance Biomarkers

Low BMI Older age RVSP Low serum albumin

ICU admission Co-morbid CCF Functional status Use of NIV

Nishimura 2002

Soler-Cataluña 2005 Knaus 1991, Almagro 2002

Ai-Ping 2005

Pinto-Plata 2004 Coxson 2013

Connors 1996 Connors 1996, Almagro 2002

Connors 1996 Connors 1996

Connors 1996 Dallari 1994

Anthonisen 1989 NOTT 1980

Plant 1998

Incalzi 1999

Can more data help?

BODE

Celli BR, Cote CG, Marin JM, Casanova C, Montes de Oca M, Mendez RA, et al. The body-mass index, airflow obstruction, dyspnea, and exercise capacity index in chronic obstructive pulmonary disease. New England Journal of Medicine. 2004;350(10):1005–12.

BODE

For each one-point increment in the BODE score the hazard ratio for death from any cause was 1.34 (95%CI 1.26-1.42) and the hazard ratio for death from a respiratory cause was 1.62 (95%CI 1.48-1.77).

Kaplan-Meier Survival curves for the 4 quartiles of the BODE index and the 3 stages of severity of COPD based on FEV1% as defined by the ATS.Quartile 1 = 0-2Quartile 2 = 3-4Quartile 3 = 5-6Quartile 4 = 7-10

Stage 1 = FEV1 >50% predictedStage 2 = FEV1 36-50% predictedStage 3 = FEV1 <36% predicted

Puhan MA, Hansel NN, Sobradillo P, Enright P, Lange P, Hickson D, et al. Large-scale international validation of the ADO index in subjects with COPD: an individual subject data analysis of 10 cohorts. BMJ Open. 2012 Jan 1;2(6):e002152.

BODE v2

ADO

Making models count

Wyatt JC, Altman DG. Commentary: Prognostic models: clinically useful or quickly forgotten? BMJ. 1995 Dec 9;311(7019):1539–41.

Clinical credibility• Patient data required for model is easily and reliably accessible• Avoid arbitrary thresholds for continuous variables• Simple to calculate at point-of-care

Evidence of accuracy• At least as accurate as clinician prediction• Error rates tested in large data set not used to generate model

Evidence of generality• Model testing in other populations, in time and space• Each item of data clearly defined to ensure easy use in different settings/languages• Prospective validation in well-defined populations

Evidence of clinical effectiveness• Measure effects on practice and outcomes of using model• Similar to phase III study in drug trials

FEV1% Specific co-morbidities

Multi-morbidity Breathlessness

Functional status

Previous need for

NIV/ventilationHRQL QoL

Socioeconomic group

Healthcare utilisation

Weight loss/cachexia/B

MI <21Sarcopenia

Exercise capacity Social isolation Use of long

term steroids

Contact with comm resp/pall

care team

IMPLICATIONS FOR PRACTICE

COPD model of care

Does this capture what patients and physicians want?What needs to happen to achieve this?

YouGov poll 2014

http://compassionindying.org.uk/

QUESTIONS?

Conclusions

• Many patients with COPD have a high symptom burden and poor quality of life, yet fail to access a palliative care approach

• Patients, carers, physicians, and policy makers would welcome greater prognostic certainty

• Current prognostic markers and scores are limited in their ability to accurately predict prognosis in individual patients

• There are great opportunities to improve the lives of patients with COPD and their carers, which requires research and investment

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