Methacholine versus Mannitol Challenge in the Evaluation of Asthma Clinical applications of methacholine and mannitol challenges

Transcription

1 Methacholine versus Mannitol Challenge in the Evaluation of Asthma Clinical applications of methacholine and mannitol challenges AAAAI San Antonio Tx February 2013 Catherine Lemière MD, MSc Hôpital du sacré-cœur de Montréal Université de Montréal

2 Conflict of Interest Dr Lemière is a member of the advisory committees of : AstraZeneca Merck Dr Lemière is a member of the asthma committee of the Canadian Thoracic Society

3 Clinical applications Influence of asthma medications on methacholine and mannitol challenges Titration of ICS Assessment of asthma-related disability

4 Influence of anti-asthma medications on mannitol and methacholine challenges

5 Medications affecting methacholine challenge Medica'on Short ac)ng beta agonists 8h Ipratropium 24h Long ac)ng beta2 agonists Tiotropium Theophylline Minimum 'me Interval from last dose to study 48h Cromolyn sodium 8h Nedocromil 48h Hydroxazine, ce)rizine 1 week(?) Intermediate ac)ng: 24h, long ac)ng: 48h 3 days Leukotriene modifiers 24h The authors do not recommend routinely withholding oral or inhaled corticosteroids, but their antiinflammatory effect may decrease bronchial responsiveness (53, 54). Inhaled corticosteroids may need to be withheld depending on the question being asked. ATS, 1999

6 Mannitol responsiveness is modified by the same drugs that inhibit exercise -induced asthma Beta 2 agonists Leukotriene antagonists Inhaled corticosteroids Sodium cromoglycate Nedocromil sodium

7 Asthma and ICS Phase III trial results Results: Sensitivity to inhaled steroid in treated asthmatics 56% of asthmatics (204/363) using ICS were positive to mannitol when the last dose was the day before Mannitol Positive* Mannitol Negative Not on ICS N= 87 Using ICS N=204 Not on ICS N=37 Using ICS N=159 Clinical diagnosis of asthma N=487 Asthmatic with active airway inflammation that will respond to ICS Maintain or increase ICS dosage Consider alternative diagnosis Well controlled asthmatic. Consider reducing dosage of ICS * PD15 = 15% fall in FEV1 to a dose 635 mg

8 Does measurement of AHR with mannitol or methcholine help titrating ICS dose?

9 Am J Respir Crit Care Med 2001; 163: Aim: To determine the predictive factors for failed reduction of ICS in 50 subjects with well controlled asthma 50 subjects well controlled asthma, median does of ICS: 1000 mcg BDP. ICS halved every 8 weeks. Histamine, mannitol challenge, spirometry, exhaled NO and, induced sputum at baseline. Monthly visits to establish asthma stability, perform mannitol challenge, spirometry, eno, sputum Study end points: asthma exacerbation; no ICS treatment for two months 39 subjects with asthma exacerbation

10 100% The odds ratio was 4.38 ( ) p<0.05 to predict failure at or before the 2 nd ICS reduction 50% p=0.039 ICS (µg) months Leuppi J et al 2001, AJRCCM 163:406 12

11

12 ICS dose titration Comparison of ICS titration against mannitol AHR or a reference strategy based on symptoms and lung function. Initial ICS tapering to identify the minimal ICS dose then randomization into ICS titration according to mannitol or symptoms

13 ICS increased every 2 months if: Control group Fall in PEF 20% from baseline Deterioration in FEV1 20% from baseline Increase in use of reliever medication Increase in symptoms score >0.5 from baseline Mannitol group ICS increased until PD mg.

14 No difference in mannitol group over standard practice for the time to first exacerbation

15 27% less mild asthma exacerbation with the mannitol strategy compared to the control group. No difference in severe asthma exacerbations. Higher doses of ICS in the mannitol group Lipworth, Chest 2012

16 ICS )tra)on (Con t) 1. No requirement of ICS 2. Low dose ICS (400mcg budesonide) 3. Intermediate dose of ICS (800mcg) 4. High dose ICS 1600 mcg + short course of prednisone Sont et al, AmJ Respir Crit care Med 1999

17 ICS dose titration with methacholine vs standard strategy, less mild asthma exacerbations, higher dose of ICS Sont et al, AmJ Respir Crit care Med 1999

18 Assessment of impairment related to asthma

19 Assessment of asthma-related impairement in subjects with occupational asthma 30 workers diagnosed with occupational asthma by specific inhalation challenges six years ago. Assessment of AHR by both methacholine and mannitol challenge Lemiere et al JACI 2011

20 Mannitol was more closely associated with asthma severity in terms of respiratory function and airway inflammation than methacholine challenge

21 In subjects in whom asthma-related disability needs to be assessed, mannitol may provide a bettter estimation than methacholine challenge.

22 Conclusions Anti asthmatic medication affects results of both methacholine and mannitol challenges. The AHR to mannitol is predictive of the occurrence of asthma exacerbations when ICS dose is further reduced. AHR to both methacholine and mannitol may be helpful for titrating the dose of ICS. Mannitol seems more associated with the activity of asthma than methacholine.