Bronchiectasis exacerbations; differences and management

Michael LoebingerRoyal BromptonImperial College

Plan

Bronchiectasis background and burden

Cases and practical management

Exacerbation and Management

Longer term Management

Bronchiectasis

What is the prevalence of bronchiectasis in the UK ? (x600 for number)

1) 1/100000

2) 10/100000

3) 100/100000

4) 500/100000

5) 1000/100000

6) nobody knows

7) I don’t know

0

4

13

75

12

7

1 2 3 45 6 7

What is the prevalence of bronchiectasis in the UK ?

1 1/100000

2 10/100000

3 100/100000

4 500/100000

5 1000/100000

6 nobody knows

7 I don’t know

Prevalence

52/100000 adults in US (Weycker clin pulm med 2005) Clinical Practice Research database 500/100000 (Quint ERJ 2015)

•Morbidity

321 clinic attendances from 100pts in 6/12 (Kelly et al E J Int

Med 2003)

greater inpatient stay and annual cost/pt than other chronic diseases (CCF, DM) (Weycker clin pulm med 2005)

Morbidity and mortality

•Mortality

UK 12 yr survival 68.3% (Loebinger et al ERJ 2009)

UK 4yr survival 89.8% (Chalmers et al ARJCCM 2014)

Spain 5 yr survival 81.2% (Martinez-Garcia et al ERJ 2014)

Turkey 4 yr survival 58% (Onen et al Respir med 2007)

•Increasing mortality (Roberts et al Respir Med 2010)

Morbidity and mortality

Pathophysiology

P o s t- in fe c tiv e

Id io p a th ic

C O P D

A sth m a

Im m u n o d e fic ie n c y

A B P A

R h e u m a to id a rth r it is

P C D

G O R D

IB D

A lp h a -1 -a n t it ry p s in d e f ic ie n c y

o th e rs

Aetiology

Exacerbation definition

A person with bronchiectasis with a deterioration in three or more of the

following key symptoms for at least 48 hours:

1) Cough

2) Sputum volume and / or consistency

3) Sputum purulence

4) Breathlessness and / or exercise tolerance

5) Fatigue and / or malaise

6) Haemoptysis

AND a clinician determines a change in bronchiectasis treatment is

required*

Pulmonary Exacerbation in Adults with Bronchiectasis: A Consensus

Definition from the First World Bronchiectasis Conference

14 days of antibiotics (conditional recommendation, very low quality

of evidence).

Microbiology and Treatment

• Treat underlying cause

• Physiotherapy

• Mucolytics/ HTS

Longer term management

• Treat underlying cause

• Physiotherapy

• Mucolytics/ HTS– Mannitol Ph3 (Bilton 2014 Thorax)

– HTS small studies varied results

(Kellett 2005 – 1 dose, 2011-3/12; Nicholson – 12/12 2012)

Management – airway clearance

• Treat underlying cause

• Physiotherapy

• Mucolytics/ HTS

• Antibiotics

– Long term

– Nebulised

– Oral

– Cyclical IVs

Management – long term antibiotics

Bacterial load (CFU/ml)

141 patients 08-09

≥ 1 exacerbation

500mg MWF 6/12 then 6/12 no treatment

83 patients 08-10

≥ 3 exacerbation

250mg od 12/12, 90/7 run out

117 patients 08-11

≥ 2 exacerbation

400mg bd erythromycin 11/12, 1/12 wash

out

• Colistin - ↓ exacerb in PP (Haworth et al ARJCCM 2014)

• AZLI – no change in QoLB(Barker et al Lancet Resp Med 2014)

• Gentamicin - ↓bacterial, exacerbations,↑QoL(Murray et al 2011 AJRCCM)

Management – long term inhaled

Oral CSx• No evidence

Inhaled CSx • 6RCTs Cochrane • Some ↓ sputum and i0 markers• No good evidence

Statins• ↓ LCQ

NSAIDs• Inhaled indomethacin 25pt • Some ↓ sputum and SOB• No good evidence

Development• CXCR2 antags / N0 elastase inhibs / PDE4 inhibs

Management – alternative anti-inflammatories

• Well as child

• Cough at sputum age 14

• Referred to local hospital at 17 – CT

• LLL and lingula lobectomy

Case 1 RL 20 female

• Well but relapse few months later

• 2/3 pot green sputm

• 4-5 infection/yr

• 2011 repeat CT scan

• Referred to RBH

• IgG <2, A<0.1, M<0.3g/L

• Normal B and T subsets almost absent memory B cells

• Diagnosed with CVID

• Started azithromycin

• IVIG (when trough 7.2 azithro discontinued)

• Case 1 underlying diagnosis

Case 1 RL 20 female

• Asthma as child

• Cough and sputum late 40s

• Bronchiectasis diagnosed 2009

• Idiopathic

• Pseudomonas

• Relatively stable 1-2 infection/yr

Case 2 VR 63 female

• Deterioration last couple of years

• More sputum

• More SOB

• More infections

• Limited effect of antibiotics

• Treated with steroids

• Case 2 additional diagnosis

Case 2 VR 63 female

• Well as child, young adult

• 8 yr history of productive cough

• 6 infections/yr

• Widespread bronchiectasis

• Host defence screen unremarkable

• Some reflux symptoms

• PPI

• Physio review,

Acapella, HTS, positive pressure

• Significant improvement

• 2 infections/yr

• Case 3 - optimisation

Case 3 EM 78 female

• Primary Ciliary Dyskinesia

• Deterioration age 40

• Multiple infections - Pseudomonas

• PSA eradication unsuccessful

• Colomycin nebulised

• Some stabilisation but increased infections

• Increased physiotherapy

• Addition of azithromycin

Case 4 JW 53 female

• More recently repeated need for antibiotics

• Needing several admissions for IV therapy per year

• Anxiety and Depression

• All management optimised

• Cyclical intravenous antibiotics

• Case 4 additional therapies

Case 4 JW 53 female

Adapted from Loebinger et al 2007

Management - practical

Summary

• Assessment

• Optimisation

• Further therapies

• M.loebinger@rbht.nhs.uk