Dr Conroy Wong. Professor Richard Beasley. Dr Sarah Mooney. Professor Innes Asher

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1 Professor Richard Beasley University of Otago Director Medical Research Institute of New Zealand Wellington Dr Sarah Mooney Physiotherapy Advanced Clinician Counties Manukau Health NZ Respiratory and Sleep Institute AKL Dr Conroy Wong Respiratory Physician Clinical Head of Respiratory Medicine Middlemore Hospita Auckland Professor Innes Asher Professor and Chair of Paediatrics School of Medicine University of Auckland Auckland 8:30-10:30 WS #4: Respiratory Medicine 101 Forum 11:00-13:00 WS #11: Respiratory Medicine 101 Forum (Repeated)

2 Bronchiectasis update on current management Conroy Wong Respiratory Physician Middlemore Hospital and University of Auckland Auckland

3 Disclosures None

4 Bronchiectasis Etiology Burden of disease in NZ Investigation Treatment

5 Bronchiectasis infection and inflammation Bronchos windpipe Ektasis - stretching N Engl J Med 2002

6 Bronchiectasis is a heterogeneous condition 56 studies 8216 pts Idiopathic 44.8% Post-infective 29.9% Immunodeficiency 5.0% COPD 3.9% Connective tissue dis. 3.8% ABPA 2.6% Ciliary dysfunction 2.5% Asthma 1.4% Inflammatory Bowel dis. 0.8% Others 5.3% Gao et al. Respirology 2016

7 49% of exacerbations are linked to viral infection Exacerbation 49% Coronavirus 39.2% Rhinovirus 24.6% Influenza 24.6% RSV 10.8% Stable 19% Gao et al. Chest 2015

8 Hospitalisations Pacific and Maori populations are disproportionately affected Hospital admissions Mean annual rate 25.7 per 100,000 Bimodal distribution children and elderly 9.1 fold higher for Pacific peoples, 4.9 fold higher for Maori Cost 2012/13 = $5.34 million Bibby et al. NZMJ 2015

9 Socioeconomic deprivation is a strong risk factor for the diagnosis of bronchiectasis Asthma and Respiratory Foundation report

10 Mortality in NZ is associated with ethnicity and socioeconomic deprivation Mortality rates 8.3 fold higher in Pacific peoples 4.7 fold higher in Maori Higher mortality if living in highly deprived areas Te Ao et al. World Bx meeting 2016

11 Factors associated with increased mortality Odds Ratio FEV1 <50% 5.19 Age >70y 4.98 Pseudomonas yes 2.37 Extent of disease >2 lobes 1.87 Dyspnoea mmrc Martinez-Garcia et al. Eur Respir J 2014

12 Pseudomonas aeruginosa colonisation increases morbidity and mortality FRIENDS cohort (Chalmers et al. ERS 2017) 8 European countries patients 5 year follow-up Radiological severity Dyspnea Quality of life Exacerbations (severe and moderate) Hospital admissions Mortality (HR 2.2) Confirm results of meta-analysis (3683 pts) (Finch et al. Ann ATS 2015)

13 What tests should you do for a new patient? High resolution CT scan is the gold standard for diagnosis Recommended Minimum Bundle (ERS guideline. ERJ 2017) 1) Differential blood count 2) Serum immunoglobulins (total IgG, IgA and IgM) 3) Testing for allergic bronchopulmonary aspergillosis (ABPA) Aspergillus specific IgE and IgG, Total IgE Also Sputum culture (routine and mycobacterial) Pulmonary function tests Additional tests depending on specific clinical features

14 Current treatments for bronchiectasis in adults Main pillars of treatment Broad spectrum antibiotics for exacerbations Sputum clearance and physiotherapy Prevention of infections Influenza vaccination Pneumococcal vaccination Pulmonary rehabilitation 2017 ERS guidelines (strong recommendation)

15 Limited evidence base for treatments in bronchiectasis Prolonged antibiotics Pulmonary rehabilitation Nebulised antibiotics Physiotherapy Inhaled and oral steroids Long-acting bronchodilators Mannitol Hypertonic saline Influenza vaccine Pneumococcal vaccine Nebulised DNase Macrolides beneficial Beneficial Limited evidence Insufficient evidence Insufficient evidence Insufficient evidence Increased mucus clearance Insufficient evidence No trials No trials Harmful

16 How should we treat exacerbations? Consensus definition of exacerbation (Hill et al. Eur Respir J 2017) Deterioration in 3 or more key symptoms for at least 48 hours Cough Sputum volume and/or consistency Sputum purulence Breathlessness and/or exercise tolerance Fatigue and/or malaise Haemoptysis Antibiotics ERS guideline recommends 14 days of treatment (Eur Respir J 2017) Antibiotics include amoxycillin-clavulanic acid, roxithromycin, doxycycline, clindamycin.

17 Additional points from Auckland Regional HealthPathways guideline for bronchiectasis Previous sputum bacteriology results should be used in guiding antibiotic choice. Obtain sputum for culture if possible prior to commencement of oral antibiotics. If no clinical improvement, modify the antibiotic once the pathogen is isolated and susceptibilities are available. If patient remains unwell, consider admission for intravenous antibiotics. Oral steroids are not recommended unless there is coexisting eosinophilic airway disease (e.g. asthma) Pseudomonas aeruginosa may be present as a colonising organism and does not necessarily need treatment if the patient is clinically stable. However, specific treatment should be considered if there are clinical features of acute infection.

18 ROBUST Study (RCT) limited benefit of LAMA Reduction Of exacerbations in Bronchiectasis USing Tiotropium 2.50 Exacerbation rates (per year) FEV Exacerbation rate 1.66 Baseline 6 months Tiotropium Placebo Tiotropium Placebo Rate ratio 0.96 p = 0.77 FEV 1 difference (Tiotropium placebo) 58 mls p = Wong et al. ERS 2017

19 Macrolides are effective in preventing exacerbations (azithromycin, erythromycin) Significant reduction in exacerbation frequency 43-62% reduction in rate Modest effects on lung function FEV1 20 ml (0.01) Improvement in quality of life SGRQ 5.4 u (p=0.02) Concerns about antimicrobial resistance Metaanalysis - Wu et al. Respirology 2014

20 Influenza and pneumococcal vaccination are recommended Annual influenza vaccine Efficacy in community ~ 60% Efficacy in hospitalised patients ~40% (SHIVERS study; Turner et al. Vaccine 2014) Pneumococcal vaccination NZ Immunisation Handbook 2017 Not funded for bronchiectasis 45% efficacy for vaccinetype pneumonia 75% efficacy for invasive disease Bonten et al. NEJM 2015 Naïve: 13-valent conjugate vaccine, then 23 valent vaccine at least 8 weeks later Previous 23-valent vaccine: give 13-valent vaccine 1 year later

21 Targeting treatable traits Chalmers et al. Lancet Resp Med 2018

22 Summary - Bronchiectasis Bronchiectasis is a heterogeneous condition Increasing burden of disease in NZ and worldwide Particularly for Pacific and Maori populations Treatment options are still limited but research activity increasing Antibiotics Physiotherapy and pulmonary rehabilitation Vaccination Macrolides