BRONCHIECTASIS - 2019STATE OF THE ARTLucy Morgan BMed PhD FRACP

1. To review the global epidemiology of bronchiectasis

2. To review the current evidence for treatments

3. To review the value of a treatable traits approach to

managing the individual patient with bronchiectasis

4. To explore the future for patients with bronchiectasis

1. To review the global epidemiology of bronchiectasis

2. To review the current evidence for treatments

3. To review the value of a treatable traits approach to

managing the individual patient with bronchiectasis

4. To explore the future for patients with bronchiectasis

STRU

CTU

RAL

DAM

AG

EAIRWAY DYSFUNCTION

INFLA

MM

ATIO

N

INFECTION

Vicious CycleChandrasekaran et al.

BMC Pulmonary Medicine (2018) 18:83

HISTORY

TUBERCULOSIS

2400BCEgyptian mummies reveal skeletal deformities typical of TB

TUBERCULOSIS

~2000BCFirst documenteddescriptions of TB (ancient Babylonian, Chinese and Indian texts)

PERTUSSIS

1819Rene Laennec used his invention (stethoscope) to describe a 3 year old who died after pertussis

Some causes have been known for centuries…

BRONCHIECTAIS

1880sWilliam Osler described clinical features of bronchiectasis and died of it

PRIMARY CILIARY DYSKINESIA

1904First description of PCD by A. K. Zivert; first report published on the subject in 1933 by Manes Kartagener

ABPA + CVID1950sInitial reports by Dr Hinson and Dr Janeway on allergic bronchopulmonary aspergillosis (ABPA) and CVID respectively

… some for decades…

THE FUTUREOF BE

… some for years…

CFTR1989Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene identified by geneticist Lap-Chee Tsui and colleagues

PCD GENES2010Identification of causative mutations in primary ciliary dyskinesia by GaëllePennarun and colleagues

|registries are the state of the art |

EMBARC

ABR

NZBR

NTM&BE Registry

IndianBE Registry

Chinese BE Registry

Registries - an international view

Chandrasekaran et al. BMC Pulmonary Medicine (2018) 18:83

Aetiology - an international view

James D. Chalmers et al. Breathe 2017;13:180-192

Research - an international view

0.5%

27%

28%

38%

6%

3

2

3

4

7

0

4

Patient registrations Sites per state

Australian Bronchiectasis Registry

1297+ Patients

23 Sites (New Zealand 7+ sites)

Never smokers: 66.4%Ever smokers: 12.9%Pack years >10: 8.5%Unknown: 20.7%Rhinosinusitis 21%Asthma 27%COPD 10%Cancer 8%

Aetiology

Gao et al. Respirology 2016

FACED

F FEV1A AgeC ColonisationE ExacerbationD Dyspnoea

|predictors of outcomes and response to treatment|

BSI – Bronchiectasis Severity IndexFEV1 % predicted

AgeColonisation with other microorganismsExacerbations in previous yearMRC Dyspnoea scoreHospital admission in previous yearPseudomonas aeruginosa colonizationRadiological severityBody mass index (BMI)

Severity Scores

BSI and outcomes

Chalmers JD et al. AJRCCM 2014;189(5):576-85.

Chalmers JD et al. AJRCCM 2014;189(5):576-85.

BSI and outcomes

Disease Severity - ABR

ABR: Australian Bronchiectasis Registry

Microbiology

Chalmers et al. Eur Respir J 2015; 45: 1446-1462

Stepwise Management Approach

Evidence-based approach

Copyright © BMJ Publishing Group Ltd & British Thoracic Society. All rights reserved.

Stepwise management

Adam T Hill et al. Thorax 2019;74:1-69

1. To review the global epidemiology of bronchiectasis

2. To review the current evidence for treatments

3. To review the value of a treatable traits approach to

managing the individual patient with bronchiectasis

4. To explore the future for patients with bronchiectasis

1. Macrolides for frequent exacerbations

2. Exercise and airway clearance

3. Vaccination Flu and pneumococcal disease

Treatment strategies

A significant reduction in the number of participants with exacerbations in the long-term macrolides group compared with control group.

Macrolides

Wu, Q. et al.Respirology 2014, 19: 321-329

RESPIRE- inhaled DPI Cipro FDA ✗• BPAExac ++

• Chosen trait was airway infection

• 4 trial arms- inconsistent results

AIRBX- aztreonam FDA ✗• 2 replicate trials

• Chosen trait airway infection

• Inconsistent results

Bronchitol- dry powder mannitol FDA ✗• RCT

• Chosen trait was retained secretions

• Failed to reduce exacerbations ( primary end point)

Recent trials

1. To review the global epidemiology of bronchiectasis

2. To review the current evidence for treatments

3. To review the value of a treatable traits approach to

managing the individual patient with bronchiectasis

4. To explore the future for patients with bronchiectasis

Asthma

7% General population

>25% Bronchiectasis

clinic

Difficult to treat asthma

40% radiological BX

20% clinically significant BX

8% Pulmonary trait

SAWD

Eur R ir J 1992 Gupta et al Chest 2009McDonald et al Respirology 2019

Overlap with Asthma

Severe COPD

Bx 60%

Bronchiectasis

Airflow obstruction

40%

Ni et al, Int J Chron Obstruct Pulmon Dis, 2015

Overlap with COPD

Am J Respir Crit Care Med, 2013https://www.atsjournals.org/doi/abs/10.1164/rccm.201208-1518OC

Overlap with COPD (cont’d)

Du Q. et al.PLOS ONE 2016, 11(3): e0150532

Overlap with COPD (cont’d)

Du Q. et al.PLOS ONE 2016, 11(3): e0150532

Overlap (COPD)

Du Q. et al.PLOS ONE 2016, 11(3): e0150532

Overlap (COPD)

Fig 2. Odd ratios for the association between comorbid bronchiectasis and risk for COPD exacerbations.

Du Q. et al.PLOS ONE 2016, 11(3): e0150532

Overlap (COPD)

Fig 3. Odd ratios for the association between comorbid bronchiectasis and risk for isolation of a potentially pathogenic microorganism.

Identificationof traits helps…

NTM

Connective Tissue

Disease

PostInfective

Immuno-deficiency

IBD

PCD

A1ATD

ABPA Cystic

INC

REA

SED

MORTALIT

Y

COPDEosino-philic

Neutro-philic

Frequent Exacerbation

P. aeruginosa

Obstruction

Sputumcolour

Severe Exacerbation

Functional impairment

Underlying Disorders

Idiopathic

UNKNOWN OUTCOMES

Linked to clinical outcomes

Exercise Intolerance

NTM

Connective Tissue

Disease

PostInfective

Immuno-deficiency

IBD

PCD

A1ATD

ABPA Cystic

INC

REA

SED

MORTALIT

Y

COPDEosino-philic

Neutro-philic

Frequent Exacerbation

P. aeruginosa

Obstruction

Sputumcolour

Severe Exacerbation

Functional impairment

Underlying Disorders

Idiopathic

UNKNOWN OUTCOMES

Linked to clinical outcomes

Exercise Intolerance

Frequent exacerbator phenotype

Eosinophilic Inflammation

NTM

Connective Tissue

Disease

PostInfective

Immuno-deficiency

IBD

PCD

A1ATD

ABPA Cystic

INC

REA

SED

MORTALIT

Y

COPDEosino-philic

Neutro-philic

Frequent Exacerbation

P. aeruginosa

Obstruction

Sputumcolour

Severe Exacerbation

Functional impairment

Underlying Disorders

Idiopathic

UNKNOWN OUTCOMES

Linked to clinical outcomes

Exercise Intolerance

Exercise Intolerance

NTM

Connective Tissue

Disease

PostInfective

Immuno-deficiency

IBD

PCD

A1ATD

ABPA Cystic

INC

REA

SED

MORTALIT

Y

COPDEosino-philic

Neutro-philic

Frequent Exacerbation

P. aeruginosa

Obstruction

Sputumcolour

Severe Exacerbation

Functional impairment

Underlying Disorders

Idiopathic

UNKNOWN OUTCOMES

Linked to clinical outcomes

Exercise Intolerance

Pathogenic Organisms

NTM

Connective Tissue

Disease

PostInfective

Immuno-deficiency

IBD

PCD

A1ATD

ABPA Cystic

INC

REA

SED

MORTALIT

Y

COPDEosino-philic

Neutro-philic

Frequent Exacerbation

P. aeruginosa

Obstruction

Sputumcolour

Severe Exacerbation

Functional impairment

Underlying Disorders

Idiopathic

UNKNOWN OUTCOMES

Linked to clinical outcomes

Exercise Intolerance

A) H influenzaeB) H1N1C) Pseudomonas spD) Staph Sp

Treatable traits

Treatable traits

Treatable traits Some important traits that could be treated:

• Airflow obstruction• Eosinophilia• Frequent exacerbators• CTD

P. aeruginosa infection is associated with worse clinical outcomes in bronchiectasis

Increased exacerbation frequency

Increased hospitalisation (OR 6.6)

Worse quality of life

Increased mortality (OR 2.9)

P. aeruginosa and mortality

Finch Ann Am Thorac Soc 2015

Treatable traits

Long-term macrolides for non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis

Respirology, Volume: 19, Issue: 3, Pages: 321-329, First published: 13 January 2014, DOI: (10.1111/resp.12233)

Long-term macrolides for non-cystic fibrosis bronchiectasis: A systematic review and meta-analysis

Respirology, Volume: 19, Issue: 3, Pages: 321-329, First published: 13 January 2014, DOI: (10.1111/resp.12233)

Visser et al 2018

Bronchiectasis is common and burdensome

There is a subgroup at highest risk for poor outcomesFrequent exacerbators

Best chance of improving outcomes for those at highest risk for poor outcomes

Identify treatable traits

Treat treatable traits

precision medicine

1. To review the global epidemiology of bronchiectasis

2. To review the current evidence for treatments

3. To review the value of a treatable traits approach to

managing the individual patient with bronchiectasis

4. To explore the future for patients with bronchiectasis

Where do we go from here?

A) H influenzae

B) H1N1

C) Pseudomonas sp

D) Staph Sp

A) H influenzae

B) H1N1

C) Pseudomonas sp

D) Staph Sp

A) airway clearance

B) ICS/LABA and airway clearance

C) long term macrolides and airway clearance

D) long term macrolides and mucolytics

A) airway clearance

B) ICS/LABA and airway clearance

C) long term macrolides and airway clearance

D) long term macrolides and mucolytics

Join colleagues from around the region to gain access to the CHEST learning and training experience at our regional congress. This unique program will go beyond the classroom-style setting to connect you to leading experts who will teach and develop you and your team.Learn More: athens.chestnet.org

ATHENS 2019GREECE | 27-29 JUNE

Visser S, Bye P, Morgan L. Med J Aust 2018