Bronchial Provocation Results: What Does It Mean?

Transcription

1 Bronchial Provocation Results: What Does It Mean? Greg King 1 Department of Respiratory Medicine, Royal North Shore Hospital, St Leonards Woolcock Institute of Medical Research and Sydney Medical School, The University of Sydney, Glebe 2037 TSANZSRS April, 2016

2 Declaration COI Between Travel sponsorships:boehringer Ingelheim, Novartis Pfizer, AstraZeneca and GlaxoSmithKline Research and unrestricted grants, and consultancy fees AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Menarini, MundiPharma and Novartis. Consultancy services: related to asthma and COPD, advisory boards and delivering lectures at local, national and international meetings. Competitive grants: local philanthropic foundations, Sydney University, The National Health & Medical Research Council of Australia and The Australian Lung Foundation.

3 AHR: What Does It Mean (asthma)? Mechanisms Clinical associations A couple of cases

4 SHAPE OF HISTAMINE DOSE RESPONSE CURVE FEV1 (% FALL) MODERATE ASTHMA M = 100 α = β = 0.97 r = HISTAMINE DOSE (μmoles) MILD ASTHMA M = 43 α = β = 1.06 r = NORMAL M = 26 α = β = 1.69 r = Woolcock, Salome, Yan ARRD 1984

5 Mechanisms of AHR

6 Mechanisms of AHR Inflammation? Epithelial damage? Extra cellular matrix? Airway smooth muscle? Nerves? Surfactant? Parenchymal interdependence? Ventilation heterogeneity and airway closure?

7 Small Airways and AHR Downie et al. Thorax, 207; 62(8):684 9.

8 Predictors of Methacholine AHR >50yrs Is it geometry: narrower airways = greater AHR? Is it common pathways: pathophysiology = narrower airways & greater AHR? Harkaker et al. Chest, 2011; 136:

9 Mechanisms of AHR Non-specific abnormality Variety of causes Different associations in different clinical settings e.g. smoking, COPD e.g. age e.g. atopy

10 Dose Response Plateau Peter Macklem FEV1 (% FALL) Potential for unlimited narrowing to closure MODERATE ASTHMA HISTAMINE DOSE (μmoles) MILD ASTHMA NORMAL

11 Clinical Associations Persistence of childhood wheeze Airway remodelling Exacerbations/hospitalisation Lung growth & FEV1/FVC Failure of down-titration FEV1 decline

12 Use Of AHR For Diagnosis? Spirometry is uncommonly used, let alone challenge testing! What is AHR negative asthma like?

13 % of group Respiratory symptoms Wheeze Diagnosed asthma 20 0 Severe Moderate Mild Slight Normal Salome et al, Clin Allergy 1987;17:271

14 Normal Wheeze only AHR only Current asthma Diurnal Variability by Airflow Meter (%)

15 Treatment effects on methacholine DRC Placebo treatment Baseline Post 12/52 Rx fluticasone Overbeek et al EurRespirJ, 1996; 9:

16 Treatment effects on methacholine DRC H Reddel et al. Eur Resp J 2000; 16:26 35 B. Lundbäck. Respiratory Medicine 2009; 103:348 55

17 AHR Guiding Treatment? Presenting with first mild exacerbation Severe AHR, usual Rx Mild AHR, usual Rx Severe AHR, AHR Rx Sont et al, AJRCCM 1999; 159:

18 AHR Guiding Treatment? Sont et al, AJRCCM 1999; 159:

19 Forced ICS Withdrawal Exacerbation free Exacerbations risk: AHR to both mannitol and histamine at baseline Mannitol AHR during stepdown Leuppi et al. AJRCCM :406

20 Case 1: Mr DC 49 yrs old asthma for 20 years wheeze, breathlessness on moderate exercise chronic productive cough Co-morbidities nasal polyps hayfever hypertension Ex-smoker: 2 pack/years 20 years ago

21 Case 1: Mr DC budesonide/eformoterol 200/6 ii bd low pitched wheezes Chest X-ray: minor atelectatic band right base

22 Pred. LLN Pre Meas. % Pred Z-Score FEV1(L) FVC(L) FEV1/FVC(%) PEF(L/S) FEF25-75(L/S) FIVC(L) FEV1 FEV1 (% baseline) mannitol dose (mg)

23 Exercise Macrolide

24 Mr GW 63 yr male Wheeze, chest tightness, difficulty breathing for 2 years Triggers - viral infection but nil else Worse for several days - responsive to BDs and prednisone Near respiratory arrest under anaesthesia for hernia repair

25 Mr GW No FHx of asthma Normally fit and active Ex-smoker 30 yrs ago 10 pack/years 60g alcohol/day Marketing and advertising consultant

26 Mr GW Prednisone and SA bronchodilators intermittently Tiotropium - ceased when well Indacaterol symptomatic response takes when symptomatic

27 Mr GW Spirometry 2.71/3.38 FEV1 74% predicted FER No BD response Normal lung volumes & diffusion SPT: +ve ryegrass, HDM, cat CXR & CT - normal PD20 histamine 5.87 μmol

28 Mr GW Budesonide 400μg bd increase to 800μg bd if still symptomatic Action Plan House dust mite allergen avoidance Discussion: lifelong asthma Asthma education information

29 Mr GW 2 years Few symptoms Negative methacholine challenge test Exacerbation treated with prednisone not sure what s going on here Remain on BUD 200μg bd Encouraged action plan use (ICS)

30 Mr GW Started high dose combination ICS/LABA 3.14/4.00 (improved) Cough & mucous (bronchitis)

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32 Mr GW Admits to intermitted ICS/LABA use! Had stopped ICS and had URTI prior to anaesthetic!

33 Conclusions AHR likely has a variety of mechanistic causes Non-specific functional abnormality Well characterised clinical associations Negative and positive tests are useful Heterogeneous changes in AHR to inhaled corticosteroids have to be kept in mind