Clinical applications of methacholine and mannitol challenges
Transcript of 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
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
Clinical applications
• Influence of asthma medications on methacholine and mannitol challenges
• Titration of ICS
• Assessment of asthma-related disability
Influence of anti-asthma medications on mannitol and
methacholine challenges
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
Mannitol responsiveness is modified by the same drugs that inhibit
exercise -induced asthma
• Beta2 agonists • Leukotriene antagonists • Inhaled corticosteroids • Sodium cromoglycate • Nedocromil sodium
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
Does measurement of AHR with mannitol or methcholine help
titrating ICS dose?
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
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
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
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.
No difference in mannitol group over standard practice for the time to first
exacerbation
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
ICS)tra)on(Con’t)
1. NorequirementofICS2. Low‐doseICS(400mcgbudesonide)3. IntermediatedoseofICS(800mcg)4. HighdoseICS1600mcg+shortcourseofprednisone
Sontetal,AmJRespirCritcareMed1999
ICS dose titration with methacholine vs standard strategy, less mild asthma exacerbations, higher dose of ICS
Sontetal,AmJRespirCritcareMed1999
Assessmentofimpairmentrelatedtoasthma
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
Mannitol was more closely associated with asthma severity in terms of respiratory function and airway inflammation
than methacholine challenge
• In subjects in whom asthma-related disability needs to be assessed, mannitol may provide a bettter estimation than methacholine challenge.
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.