dr paul dawkins - gp cme north/sat_plenary_1640_paul...dr paul dawkins respiratory physician...
TRANSCRIPT
Dr Paul DawkinsRespiratory Physician
Middlemore Hospital
1640 - 1700 Reducing the Incidence and Impact of Lung Disease
DR PAUL DAWKINS
Respiratory PhysicianMiddlemore Hospital Auckland
Reducing the Incidence and Impact of Respiratory Disease
Saturday 22 June 2019
Rapid tour of hot topics in key areas
bull Smoking cessationndash NRT and e-cigarettes
bull Asthma ndash Phenotypes treatable traits
bull COPDndash Role of inhaled steroids eosinophil directed therapy
bull Bronchiectasisndash Macrolides
bull Idiopathic pulmonary fibrosisndash New antifibrotics
bull Lung cancerndash Screening
E-cigarettes and NRT
A Randomized Trial of E-Cigarettes versus Nicotine-Replacement TherapyN Engl J Med 2019 380629-637
bull N=886 participants underwent randomization
bull 1-year abstinence rate
bull 180 in e-cigarette group
bull 99 in the NRT group
bull Relative risk 183 95 confidence interval [CI] 130 to 258 Plt0001)
bull Among participants with 1-year abstinence those in the e-cigarette group more likely than those in the NRT group to use their assigned product at 52 weeks (80 [63 of 79 participants] vs 9 [4 of 44 participants])
Caution with e-cigarettes
bull Nicotine addiction persists
bull Pro-inflammatory effect of vaping chemicals
bull Unregulated
bull Targeting of youngsters
bull Normalisation of smoking behaviour
bull Involvement of tobacco industry
Asthma phenotypes
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
DR PAUL DAWKINS
Respiratory PhysicianMiddlemore Hospital Auckland
Reducing the Incidence and Impact of Respiratory Disease
Saturday 22 June 2019
Rapid tour of hot topics in key areas
bull Smoking cessationndash NRT and e-cigarettes
bull Asthma ndash Phenotypes treatable traits
bull COPDndash Role of inhaled steroids eosinophil directed therapy
bull Bronchiectasisndash Macrolides
bull Idiopathic pulmonary fibrosisndash New antifibrotics
bull Lung cancerndash Screening
E-cigarettes and NRT
A Randomized Trial of E-Cigarettes versus Nicotine-Replacement TherapyN Engl J Med 2019 380629-637
bull N=886 participants underwent randomization
bull 1-year abstinence rate
bull 180 in e-cigarette group
bull 99 in the NRT group
bull Relative risk 183 95 confidence interval [CI] 130 to 258 Plt0001)
bull Among participants with 1-year abstinence those in the e-cigarette group more likely than those in the NRT group to use their assigned product at 52 weeks (80 [63 of 79 participants] vs 9 [4 of 44 participants])
Caution with e-cigarettes
bull Nicotine addiction persists
bull Pro-inflammatory effect of vaping chemicals
bull Unregulated
bull Targeting of youngsters
bull Normalisation of smoking behaviour
bull Involvement of tobacco industry
Asthma phenotypes
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Rapid tour of hot topics in key areas
bull Smoking cessationndash NRT and e-cigarettes
bull Asthma ndash Phenotypes treatable traits
bull COPDndash Role of inhaled steroids eosinophil directed therapy
bull Bronchiectasisndash Macrolides
bull Idiopathic pulmonary fibrosisndash New antifibrotics
bull Lung cancerndash Screening
E-cigarettes and NRT
A Randomized Trial of E-Cigarettes versus Nicotine-Replacement TherapyN Engl J Med 2019 380629-637
bull N=886 participants underwent randomization
bull 1-year abstinence rate
bull 180 in e-cigarette group
bull 99 in the NRT group
bull Relative risk 183 95 confidence interval [CI] 130 to 258 Plt0001)
bull Among participants with 1-year abstinence those in the e-cigarette group more likely than those in the NRT group to use their assigned product at 52 weeks (80 [63 of 79 participants] vs 9 [4 of 44 participants])
Caution with e-cigarettes
bull Nicotine addiction persists
bull Pro-inflammatory effect of vaping chemicals
bull Unregulated
bull Targeting of youngsters
bull Normalisation of smoking behaviour
bull Involvement of tobacco industry
Asthma phenotypes
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
E-cigarettes and NRT
A Randomized Trial of E-Cigarettes versus Nicotine-Replacement TherapyN Engl J Med 2019 380629-637
bull N=886 participants underwent randomization
bull 1-year abstinence rate
bull 180 in e-cigarette group
bull 99 in the NRT group
bull Relative risk 183 95 confidence interval [CI] 130 to 258 Plt0001)
bull Among participants with 1-year abstinence those in the e-cigarette group more likely than those in the NRT group to use their assigned product at 52 weeks (80 [63 of 79 participants] vs 9 [4 of 44 participants])
Caution with e-cigarettes
bull Nicotine addiction persists
bull Pro-inflammatory effect of vaping chemicals
bull Unregulated
bull Targeting of youngsters
bull Normalisation of smoking behaviour
bull Involvement of tobacco industry
Asthma phenotypes
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
A Randomized Trial of E-Cigarettes versus Nicotine-Replacement TherapyN Engl J Med 2019 380629-637
bull N=886 participants underwent randomization
bull 1-year abstinence rate
bull 180 in e-cigarette group
bull 99 in the NRT group
bull Relative risk 183 95 confidence interval [CI] 130 to 258 Plt0001)
bull Among participants with 1-year abstinence those in the e-cigarette group more likely than those in the NRT group to use their assigned product at 52 weeks (80 [63 of 79 participants] vs 9 [4 of 44 participants])
Caution with e-cigarettes
bull Nicotine addiction persists
bull Pro-inflammatory effect of vaping chemicals
bull Unregulated
bull Targeting of youngsters
bull Normalisation of smoking behaviour
bull Involvement of tobacco industry
Asthma phenotypes
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Caution with e-cigarettes
bull Nicotine addiction persists
bull Pro-inflammatory effect of vaping chemicals
bull Unregulated
bull Targeting of youngsters
bull Normalisation of smoking behaviour
bull Involvement of tobacco industry
Asthma phenotypes
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Asthma phenotypes
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Asthma cluster analysis
Am J Respir Crit Care Med 2008 Aug 1178(3)218-224Haldar P1 Pavord ID1 Shaw DE1 Berry MA1 Thomas M2Brightling CE1 Wardlaw AJ1 Green RH1
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
ldquoTreatable traitsrdquo
bull Precision medicine
bull Airways disease (abandoning terms COPD and asthma)
bull Pulmonary
bull Extrapulmonary
bull BehaviourallifestyleTreatable traits toward precision medicine of chronic airway diseases
Alvar Agusti Elisabeth Bel Mike Thomas Claus Vogelmeier Guy Brusselle Stephen Holgate Marc Humbert Paul Jones Peter G Gibson Joslashrgen Vestbo Richard Beasley Ian D Pavord
European Respiratory Journal 2016 47 410-419
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
COPD inhaled steroids
COPD inhaled steroids
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
ICS LABA
LABA
LAMA
LABA LAMA
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
WISDOM study
bull Triple therapy
ndash Tiotropium salmeterol fluticasone
ndash Withdrawal of fluticasone
bull No increase in moderate or severe exacerbations
bull But greater decline in FEV1 (43ml)
bull Interpretation
ICS good or bad
n-=2485
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
WISDOM study eosinophil counts
bull Exacerbation rate was higher in the ICS-withdrawal group versus the ICS-continuation group in patients with eosinophil counts of
ndash 2 or greater (rate ratio 1middot22 [95 CI 1middot02-1middot48])
ndash 4 or greater (1middot63 [1middot19-2middot24])
ndash 5 or greater (1middot82 [1middot20-2middot76])
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Targeted therapy with ICS using blood eosinophil counts
bull Cheap and easily
accessible biomarker
bull Higher levels
(gt2 ~gt02-03 x109L)
predict exacerbations
and response to inhaled steroids
bull Rationalendash Blood eosinophils correlate well with airway eosinophilia (sputum [90 PPV] biopsies)
ndash Inhaled steroids reduce eosinophilic airway inflammation (but not blood eosinophil counts)
Bruselle et al Lancet RM 2015
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Macrolides in bronchiectasis
Macrolides in bronchiectasis
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Recent randomised controlled trialsof prolonged macrolide Rx
bull EMBRACE ndash NZ - Azithromycinndash Wong et al Lancet 2012 380 660
bull BAT ndash Netherlands - Azithromycinndash Altenburg et al JAMA 20133091251
bull BLESS ndash Australia - Erythromycinndash Serisier et al JAMA 20133091260
bull BIS ndash Australia and NZ ndash Azithromycinndash Valery et al Lancet Resp Med 20138610
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
EMBRACE BAT
BLESS BIS
Time to first exacerbation
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Macrolides improve quality of life (SGRQ)
Total SGRQ
bull 54 u (p=002)
Wu et al Respirology 201419321
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Azithromycin adverse effects
bull Care with NTM
bull Tinnitus
bull Prolonged QT interval
bull Community antibiotic resistance
bull Liver function
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Antifibrotics in IPF
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Ascend study
bull NEJM 2014 3702093-2101
bull TGF-beta inhibitor
bull N=555 pirfenidone 2403mg (801mg TDS) or placebo per day 52 weeks
bull FVC 50-90 DLCO 30-90
bull Primary FVC fall gt10 or death
bull Secondary 6MWD PFS
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Inpulsis study
bull NEJM 2014 3702071-2082
bull Triple kinase inhibitor
(PAGF EGF VEGF)
bull N=1066 nintedanib 150mg bd placebo 32 52 weeks
bull FVC gt50 DLCO 30-79
bull Could be on up to 15mg prednisone
bull Primary annual rate of decline FVC
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Criteria for antifibrotics in NZ
bull Diagnosis of IPF
ndash New criteria will require regional MDM confirmation
ndash Needs UIP pattern on CT scan or lung biopsy
ndash No underlying cause found
bull VC 50-80 predicted (pirfenidone) and 50-90 predicted (nintedanib)
bull Has to be stopped if drop in VC by 10 in one year
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Lung cancer screening
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Problems with lung cancer screening
bull No easy to measure biomarker
bull No symptom-based approach (cw early detection)
bull Involves radiation
bull Involves expense (scanners radiographers radiologists infrastructure)
bull Access issues (geographic transport)
bull Equity issues (people who need it most least likely to use screening)
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Lung cancer screening papers
bull National Lung Cancer Screening Trial (USA) 2011 53454 enrolled RR reduction 200 from lung cancer and 67 all cause
ndash NEJM 365(5) 395-409
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
P=0004
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Screening programme relevant to NZ
bull Numbers captured versus cost effectiveness
bull Focus on highest risk populations for NZ (age smoking history Maori ethnicity other risk factors in model)
bull Mode of delivery (eg mobile scanners opportunistic versus formal invitation targeted engagement)
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population
Conclusions
bull E-cigarettes improve smoking cessation but at what cost
bull We need to think about asthma phenotypes (split rather than lump)
bull We should target inhaled steroids in COPD to those who will benefit (high eosinophils)
bull Macrolides beneficial in bronchiectasis but caution with side effects (refer to secondary care)
bull There are new antifibrotics for IPF that halt progression
bull There are mortality benefits of lung cancer screening but we need to adapt to NZ population