Dr Richard LaingRespiratory Physician

St Georges Hospital

Christchurch

7:00 - 7:55 GSK Breakfast Session - Hot Topics in Airways Disease

Asthma/Severe Asthma and Bronchiectasis

Hot topics in Airways Disease:

Asthma/Severe Asthma and Bronchiectasis

Dr Richard LaingRespiratory Consultant

Canterbury District Health Board

Employee of Canterbury District Health Board

Member of the Thoracic Society of Australia and New Zealand

I have not received any payment from GSK to conduct this talk. I

am not GSK employee and do not hold shares in GSK. Any

opinion expressed during this presentation is my own opinion

and may not be that of GSK.

Conflict of Interest

Overview

Severe asthma or difficult to treat asthma

How to identify

When to refer

What we can do

Asthma and pregnancy

Bronchiectasis

what do I do in the absence of evidence?

OR

Asthma

Getting interesting!!!

New options are on the horizon

Growing toolbox

Global Initiative for Asthma. Pocket Guide for Asthma Management and Prevention; 2016. Available from: https://www.ginasthma.org/. ICS, inhaled corticosteroid;

LABA, long-acting β-agonist; LTRA, leukotriene receptor antagonists; OCS, oral corticosteroid; SABA, short-acting β2-agonist

As-needed short-acting beta2-agonist (SABA)As-needed SABA or low dose

ICS/formoterol**

Step 5

Refer for

add-on

treatment

e.g.

anti-lgE

Add low

dose OCS

Step 4

Med/hig

h

ICS/LAB

A

High dose

ICS+LTRA

(or +

theoph*)

Step 3

Low dose

ICS/LABA

Med/High dose

ICS Low dose

ICS+LTRA

(or + theoph*)

Step 2

Low dose ICS

Leukotriene receptor antagonists

(LTRA)

Low dose theophylline*

Step 1

Consider

low dose

ICS

PREFERRED CONTROLLER

CHOICE

Other controller

options

RELIEVER

Disease severity

GINA – Stepwise escalation of asthma therapy

Symptom Assessment

B agonist use

Exacerbation frequency

Questionnaires

ACQ – 5

ACQ

ACT

What are your options when uncontrolled on an ICS?

Asthma Symptoms not controlled on Inhaled Corticosteroid (ICS)

OR

Option 1.

ICS dose

Option 2 (preferred).

Add long acting beta2

agonist (LABA)

Global Initiative for Asthma. Pocket Guide for Asthma Management and Prevention; 2017. Available from: https://www.ginasthma.org/.

Cross-priming of ICS and LABA for a synergistic effect

Barnes PJ. Pharmaceuticals 2010, 3, 514-540; doi:10.3390/ph3030514

Adding LABA is better than increasing ICS1

*p<0.001 Months

Ch

an

ge i

n m

orn

ing

PE

F

(mea

n ±

sta

nd

ard

err

or

l/m

in)

Seretide 250/50 bd

60

50

40

30

20

10

0

0 1 2 3 4 5 6

Flixotide 250mcg bd

Flixotide 500mcg bd

* *

*

1. Ind et al Respir Med, 2003; 97 (5): 555-62 2. Masoli et al. Thorax 2004;59;16-20

Is it difficult to treat asthma or is it severe asthma?

Global Initiative for Asthma. Pocket Guide for Asthma Management and Prevention; 2016. Available from: https://www.ginasthma.org/.

ICS, inhaled corticosteroid; LABA, long-acting β-agonist; LTRA, leukotriene receptor antagonists; OCS, oral corticosteroid; SABA, short-acting β2-agonist

As-needed short-acting beta2-agonist (SABA)As-needed SABA or low dose

ICS/formoterol**

Step 5

Refer for

add-on

treatment

e.g.

anti-lgE

Add low

dose OCS

Step 4

Med/hig

h

ICS/LAB

A

High dose

ICS+LTRA

(or +

theoph*)

Step 3

Low dose

ICS/LABA

Med/High dose

ICS Low dose

ICS+LTRA

(or + theoph*)

Step 2

Low dose ICS

Leukotriene receptor antagonists

(LTRA)

Low dose theophylline*

Step 1

Consider

low dose

ICS

PREFERRED CONTROLLER

CHOICE

Other controller

options

RELIEVER

Disease severity

GINA – Stepwise escalation of asthma therapy

Tay et al MJA 2018

Difficult Asthma – Not Just Biology

GP assessment Adherence

Knowledge

Cost

Sustained therapy

Inhaler Technique

Spacer, ease of use, patient preference etc

Smoking cessation

Investigations

Spirometry

Serum IgE

Serum eosinophil count

What is abnormal?

Who to refer? Many definitions

Uncontrolled vs high intensity treatment to maintain control

Recognise at risk patients – who to refer?

Frequent exacerbations

2 or more courses OCS(/yr)

Severe exacerbation

Hospitalisation (ICU)

Long term OCS use

>50% previous year

Obesity + asthma

Abnormal spirometry

Diagnostic uncertainty

High B-agonist use despite reported ICS use

Prevalence – depends on definition

?400-500 patients in CDHB = 2-3/GP

Specialist Contribution Changing landscape

Severe asthma clinics

Systematic assessment

Multidisciplinary approach

SLT

Physiotherapy

ENT

Dieticians/Bariatric surgeons

Clinical psychology

Immunologist/Allergist

Targeted therapies

Therapeutic knowledge/adherence

Address comorbidities

Increasing range of pharmacotherapy available

Two way referral pathway

For both primary and secondary care

Adapted from http://ccn.health.nz/FocusAreas/ServiceLevelAlliances/Pharmacy/tabid/1347/ArticleID/1307/Funded-Inhalers-in-New-Zealand-2016.aspx

(accessed 20/03/2017) ICS = inhaled corticosteroid; LABA = long acting beta2 agonist; LAMA = long acting muscarinic antagonist

Omalizumab

Mepolizumab

Mr X 59yrs OP rv 2009

Asthma since early 20’s – on 5mg prednisone for many months

Atopy / Nasal polyps

6 yrs of worsening symptoms, more pronounced past 6/12

FEV1 – 19%! / IgE 2000+ / ANCA –ve / Eosins 1.3

No apparent salicylate intolerance (no aspirin challenge)

Significant improvement with sustained course steroids

2015 Rx 3/12 for ABPA – good response

2017 Frequent exacerbation -Further Rx ABPA

Requiring sustained low dose prednisone (5mg)

On tiotropium/montelukast

Allergist rv - silver birch immunotherapy

Eosin 0.8 / IgE 3028 / FeNO 84

2018 Jan commenced Mepolizumab

Improved lung function

ACQ5 – dropped from 15 1 ( >2 = uncontrolled asthma)

Summary

We need to get excited about treating asthma…….

Still a cause of significant morbidity and mortality

Stepwise escalation of therapy based off symptom control

Identify your difficult asthmatics and get busy!

Compliance

Comorbidities

Refer if struggling to gain control

Questions…..

Adapted from: http://www.aafa.org/page/asthma-during-pregnancy.aspx (sourced: Aug 2018)

Changes in asthma severity

Asthma and Pregnancy

What are the challenges?

Variable disease

Compliance with Rx

Morbidity associated with pregnancy in people with asthma

Impact on the child

Adherence

Woeful

Newcastle Study 3 cohort – 2004/2007/2013

Pregnant asthmatics on ICS 41%/29%/38%

40% non adherence

Perceived risk of drugs to foetus –major driver for reduced ICS use

Can impact on adherence through education

Antepartum - maximum increase achieved after 1 education

session around drug knowledge and inhaler technique

Post partum - sustained adherence only seen consistently in those

receiving the full 3 session education program

(Robijn et al J Asthma 2018)

Effect on the child

Congenital malformations

Low birth weight – 50% increase if mother had exacerbation during pregnancy Prematurity

Small for gestational age (Placental insufficiency)

(Wiles et al, Obstetric Medicine 2013)

Barker hypothesis – events in pregnancy leads to chronic disease for child later in life

Asthma pregnancy

Increased rates early childhood illness

Higher rates of bronchiolitis and subsequent childhood asthma

Titrating ICS using FeNO during pregnancy associated with reduced rates of bronchiolitis in year 1

(Mattes J Thorax 2014)

Getting pregnant

Woman with asthma take longer to get pregnant

Reduced IVF success

Very rare to have success in woman with asthma > 35 years old

General Management

Early review for pregnant woman with asthma

Anticipate poor adherence and educate appropriately

Treat comorbidities

Gastro-oesophogeal reflux disease

Sinusitis

Obesity (preemptive)

Key points

Asthma poses a significant issue for mum and child

Exacerbation prevention is key

Good management to achieve asthma control

improves outcomes

Education early in pregnancy is essential

Questions…..

Bronchiectasis

Clinical Assessment

Detection Common

Chronic sputum production

Recurrent LRTI Fatigue

Relapse post antibiotics

Haemoptysis

Chest pain

Investigation Spirometry

CXR – very insensitive

CT Chest

What do I do

History

Childhood events

Post menopausal

Risk factors

Level of morbidity

Investigation

Microbiology

Normal culture

AFB & culture

Immunoglobulins

ABPA Screen

IgE, serum eosinophils

Other – CF, Rh A, α-1 antitrypsin

Management of bronchiectasis Main aim is to minimise bacterial load

Physio/Exercise

Aggressively manage upper airway pathology

Surgery for CRS

Saline rinses

Mucolytic/Anti inflammatory

Nebulised hypertonic saline

PO macrolides – azithromycin

Nebulised antibiotics

Exacerbation therapy

Antibiotics = cornerstone

Targeted when able

Minimum 2/52

Recommend continue until reach baseline symptoms then consolidate for a further week(NB no evidence for this statement)

IV antibiotics via PICC line if patient does not settle

Summary

In Summary….

Stepwise approach to treating asthma

Difficult to treat asthma is not just about biology

Severe asthma has a new bag of tricks

Asthma poses a significant issue for mum and child

with exacerbation prevention key

Education early in pregnancy on the importance of

asthma control is essential to help improve

outcomes

Main aim in bronchiectasis is to minimise bacterial

load

Questions…..

Nucala® (mepolizumab 100mg) is a Prescription Medicine. Nucala is indicated as an add-on treatment for

severe refractory eosinophilic asthma in patients 12 years and over. Precautions: Should not be used to

treat acute asthma exacerbations. Asthma-related adverse events or exacerbations may occur during

treatment. Patients should seek medical advice if asthma remains uncontrolled or worsens after initiation.

Abrupt discontinuation of corticosteroids after initiations is not recommended. Acute and delayed systemic

reactions, including hypersensitivity reaction (urticaria, angioedema, rash, bronchospasm, hypotension)

have occurred following administration, some had a delayed onset (i.e. days). Pre-existing helminth

infections should be treated prior to Nucala therapy. Opportunistic infection from herpes zoster. Pregnancy:

Effect on human pregnancy is unknown. There is no data available for lactation and fertility in humans.

Paediatric use: Safety and efficacy in children under 12 years of age has not been established.

Interactions: No formal interaction studies have been performed with Nucala. Adverse reactions:

Headache, injection site reactions, back pain, fatigue, influenza, urinary tract infection, upper abdominal

pain, pruritus, eczema, muscle spasms, pharyngitis, lower respiratory tract infections, nasal congestion,

dyspnoea, skin rash, fever, dizziness, nausea, vomiting, infection with herpes zoster. This is not a full list,

please see full Data Sheet. Immunogenicity: Patients may develop antibodies to mepolizumab following

treatment. Neutralising antibodies were detected in one subject in clinical trials. Dosage and

Administration: Patients should have a blood eosinophil count of ≥150 cells/µl at initiation of treatment or

≥300 cells/µl in the prior 12 months. Adults and adolescents (12 years and older). Nucala should be

reconstituted by a healthcare professional (see full Data Sheet) and administered as a subcutaneous

injection (e.g. upper arm, thigh or abdomen) once every four weeks. Safety and efficacy not established in

adolescents weighing less than 45kg. Not recommended in children below 12 years. Before prescribing

Nucala, please review the Data Sheet at www.medsafe.govt.nz. Nucala is a registered trade mark of the

GlaxoSmithKline group of companies. Marketed by GlaxoSmithKline NZ Limited, Auckland. Adverse events

involving GlaxoSmithKline products should be reported to GSK Medical Information on 0800 808

500.

Flixotide® (fluticasone propionate inhaler; 50, 125 or 250mcg per actuation and Accuhaler® 50, 100 or

250mcg per actuation) is a Prescription Medicine. Flixotide is indicated for the prophylactic management

of mild, moderate and severe asthma. Flixotide Inhalers and Accuhalers are fully funded medicines,

normal pharmacy fees apply. Dosage: 16 years and older: 100mcg to 1000mcg twice daily. Children over

4 years: 50mcg to 200mcg twice daily. Children aged 1 to 4 years (for Flixotide Inhaler only): 100mcg

twice daily administered via a paediatric spacer device with a face mask. This medicine has risks and

benefits. Contraindications: Hypersensitivity to any ingredient in the preparation. Common Side

Effects: Candidiasis of the mouth and throat (thrush), hoarseness, cutaneous hypersensitivity reactions.

Paradoxical bronchospasm may occur. Warnings and Precautions: Not for use in acute attacks; a fast

and short-acting bronchodilator is required. Avoid concomitant use with ritonavir. Care when co-

administering CYP3A4 inhibitors (e.g. ketoconazole). Do not discontinue abruptly. Special care in patients

with active or quiescent pulmonary tuberculosis. Before prescribing Flixotide, please review the Data

Sheet at www.medsafe.govt.nz.

Flixotide is a registered trade mark of the GlaxoSmithKline group of companies. Marketed by

GlaxoSmithKline NZ Limited, Auckland. Adverse events involving GlaxoSmithKline products should

be reported to GSK Medical Information on 0800 808 500.

Seretide® (fluticasone propionate/salmeterol xinafoate inhaler 50/25 or 125/25mcg per actuation and

Accuhaler® 100/50, 250/50mcg per actuation) is a Prescription Medicine. Seretide is indicated for the

treatment of children (4 years and older) and adults with reversible obstructive airway disease (ROAD)

including asthma, and for the treatment of adults with chronic obstructive pulmonary disease (COPD).

Seretide is a fully funded medicine. Seretide 250/25mcg inhaler is a private purchase medicine; a

prescription charge will apply. Maximum Daily Dose: Metered Dose Inhaler (MDI) 2 puffs twice daily,

Accuhaler 1 inhalation twice daily. Maintenance Dose: Titrate to lowest effective dose 1-2 times daily. This

medicine has risks and benefits. Warnings and Precautions: Not for relief of acute symptoms. Do not

discontinue abruptly. Use care when co-administering strong CYP3A4 inhibitors (e.g. ketoconazole) or in

patients with pulmonary tuberculosis or thyrotoxicosis. Common Side Effects: Hoarseness/dysphonia,

throat irritation, headache, oral candidiasis and palpitations. Paradoxical bronchospasm may occur. Avoid

beta-blockers if possible. Before prescribing Seretide, please review the Data Sheet at

www.medsafe.govt.nz.

Seretide and Accuhaler are registered trade marks of the GlaxoSmithKline group of companies. Marketed

by GlaxoSmithKline NZ Limited, Auckland. Adverse events involving GlaxoSmithKline products should

be reported to GSK Medical Information on 0800 808 500.

TAPS DA1852JS/18AU/AST/0003/18