Clinical applications of methacholine and mannitol challenges

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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

Transcript of Clinical applications of methacholine and mannitol challenges

Page 1: Clinical applications of methacholine and mannitol challenges

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

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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

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Clinical applications

•  Influence of asthma medications on methacholine and mannitol challenges

•  Titration of ICS

•  Assessment of asthma-related disability

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Influence of anti-asthma medications on mannitol and

methacholine challenges

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Medications affecting methacholine challenge

Medica'on Minimum'meIntervalfromlastdosetostudy

Shortac)ngbetaagonists 8h

Ipratropium 24h

Longac)ngbeta2agonists 48h

Tiotropium 1week(?)

Theophylline Intermediateac)ng:24h,longac)ng:48h

Cromolynsodium 8h

Nedocromil 48h

Hydroxazine,ce)rizine 3days

Leukotrienemodifiers 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

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Mannitol responsiveness is modified by the same drugs that inhibit

exercise -induced asthma

•  Beta2 agonists •  Leukotriene antagonists •  Inhaled corticosteroids •  Sodium cromoglycate •  Nedocromil sodium

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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

Well controlled asthmatic. Consider reducing dosage of ICS

Consider alternative diagnosis

Maintain or increase ICS dosage

Asthmatic with active airway inflammation that will respond to ICS

Clinical diagnosis of asthma N=487

Using ICS N=159 Not on ICS

N=37 Using ICS N=204 Not on ICS

N= 87 Mannitol Negative Mannitol Positive*

* PD15 = 15% fall in FEV1 to a dose ≤ 635 mg

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Does measurement of AHR with mannitol or methcholine help

titrating ICS dose?

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Am J Respir Crit Care Med 2001; 163: 409-12

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

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42

p=0.039

months

100%

50%

6

ICS(µg) 520.2 322.2 168.8 0

LeuppiJetal2001,AJRCCM163:406‐12

The odds ratio was 4.38 (1.03 –18.56) p<0.05 to predict failure at or before the 2nd ICS reduction

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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

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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 PD10 ≥ 635 mg.

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

exacerbation

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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,Chest2012

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ICS)tra)on(Con’t)

1.  NorequirementofICS2.  Low‐doseICS(400mcgbudesonide)3.  IntermediatedoseofICS(800mcg)4.  HighdoseICS1600mcg+shortcourseofprednisone

Sontetal,AmJRespirCritcareMed1999

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ICS dose titration with methacholine vs standard strategy, less mild asthma exacerbations, higher dose of ICS

Sontetal,AmJRespirCritcareMed1999

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Assessmentofimpairmentrelatedtoasthma

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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

LemiereetalJACI2011

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

than methacholine challenge

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

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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.