Table 9Description of studies in the diagnostic test accuracy review: Methacholine vs. ECT

Author YearStudy design; Order of tests
Study days; Challenges per day [N];
Time between challenges
Concomitant treatment for asthma
REFERENCE STANDARD (ECT)
Type; Duration (min)
Load; Environmental conditions
Follow-up time points
Author definition of EIB
INDEX TEST (MCH challenge)
Type; Description
Follow-up time points
Author definition of EIB
Anderson23 2009Cross sectional (prospective); ECT first
5 visits; 1;
ECT - MCH: 1–2 d; ECT - Mannitol: 1–2 d; MCH - Mannitol: 1 d
NR
Treadmill; 6
80–90% max H;
medical grade dry air from Douglas bag; 20–25oC
Pre-ECT, 5, 10, 15, 30 min post ECT
≥10% fall FEV1
5 breath dosimeter method; increasing concentrations from 0.0312–16 mg/ml;
measured within 3 min after each concentration
NR
PC20 MCH ≤ 16 mg/ml
Avital24 1989Cross sectional (prospective); NR
2; 1;
2 within a 2 mo period
NR
Treadmill; 6
6 km/hr at 10% slope
RH and temp NR
NR
≥10% fall FEV1
Steady state tidal breathing technique; concentrations and time NR
NR
PC20MCH <8 mg/ml
Avital25 2000Cross sectional (prospective); MCH first Varied; 3;
85% within 7 d; 15% within 30 d
Withheld: Bronchodilators ≥12 hr; SCG ≥20 hr; ICS continued unchanged
Treadmill; 6 (5 km/h, 10% slope)
NR
RH 48–56%; 22–26oC
Pre-ECT, 1, 3, 5, 10, 15 min post ECT
≥8% fall FEV1
2 min tidal breathing method; increasing concentrations from 0.03–32 mg/ml
measurements at 30, 90, 180 sec after each inhalation
NR
PC20 MCH <8 mg/ml
Chatham26 1982Case-control (prospective); MCH first 2; all within 48 hr;
24 hr
Withheld: bronchodilators, methylxanthines, antihistamines x 72 hr
Treadmill; 6
90 max HR
RH 40.1±13.3%; 22.3±1oC
Pre-ECT, 5, 15, 30, 60 min post ECT
≥20% fall FEV1
5 breath dosimeter method; increasing concentrations from 0.156–25 mg/ml in 7 increments
NR
PC20MCH
Clough27 1991Cross sectional (prospective); Randomized order: half MCH first, half ECT first
2; 1;
24 hr
Withheld: beta2-agonists x 6 hr; all other med. x 24 hr
Treadmill; 6
4.8 km/hr, 15% slope; 90% max HR
RH NR; air conditioned room
Pre-ECT, 3, 5, 10 min post ECT
≥15% fall FEV1
2 min tidal breathing method; doubling concentrations from 0.025–6.4 μmol
NR
PC20 MCH <6.4 μmol
Eggleston28 1979Cross sectional (prospective); ECT first
NR; NR;
<3 mo
Withheld: SABA x 8 hr; LABA x 12 hr; SCG x 2 wk
Treadmill; 5
90% max HR
RH and temp NR
Pre-ECT, 1, 5, 10, 15, 20 min post ECT
≥18% fall FEV1
5 breath dosimeter method; concentrations NR;
1.5 and 3 min after each
NR
PC20 MCH
Foresi29 1986Cross sectional (prospective); MCH first
3; 1;
48 hr
19 on no drugs or SABA as necessary; 2 on SABA (200 mcg 4 /d);

3 on IB 80 mcg + SABA 200 mcg 4 /d
Withheld: all x 12 hr
Bicycle ergometer; 6
Resistance of 2.0 – 3.5 watts/kg; workload=90% max HR
RH ≤50%; 22oC
Pre-ECT, immediately after, 5 min intervals x 30 min post ECT
>20% fall FEV1
2 min tidal breathing method; doubling concentrations from 0.03 – 65 mg/ml; before, 0.5, 1.5, 3 min after each inhalation
PC20 MCH
Henriksen30 2002Cross sectional (prospective); ECT first
2; 1;
2–7 d after d 1
NR
Treadmill; 6 to 8
5.5% incline; load increased during 1st 2 min by increasing speed to HR of 180 bpm; load further increased to 90% max HR of 220 bpm minus age during last 4 min
RH mean 34%, range 33–35%; mean 22oC, range 20–24oC
Pre-ECT immediately after, 3, 6, 10, 15 min post ECT
≥10% fall FEV1
2 min tidal breathing method; cumulative dose of 2 mg MCH in 5 increments
NR
PC20. MCH
Kiviloog31 1973Coss sectional (prospective); MCH first
1; 2 (MCH in am; ECT in pm); at least 4 hr
Withheld: steroids x 8 hr; bronchodilators, coffee, tea, antihistamines, anticholinergics x 24 hr
Bicycle ergometer; load increased every 6 min by 49 (males) or 33 watts (females) to exhaustion (80–102%); RH mean 41, range 15–66%; mean 19oC, range 18–25.5oC, no fan used
2, 6, 10, 15, 30 min post-exercise
≥15% fall in PEF for ECT within 10 min of termination
Concentrations of 0.025 (x5 inhalations), 0.25 (x5), 0.25 (x15), 2.5 (x5); inhale deeply for 2 sec at each breath
NR
Decrease in PEF by ≥ 15% below baseline within 3 min of termination of inhalation; MCH negative response decrease at 2.5% concentration
Koh32 1996Coss sectional (prospective); ECT first
2 consecutive d; 1;
17 hr (d1=MCH test at 4 pm; d2=ECT at 9 am)
Withheld: no meds or caffine on test day; ICS x 24 hr; cromolyn sodium x 7d
Treadmill; 6
80–90% max HR (slope/speed adjusted)
RH NR; no variations in environmental temp, air conditioned,
3–10 min apart until 60 min post-ECT
≥20% fall FEV1
5 breath dosimeter method; increasing concentrations from 0.075–150 mg/ml in 12 increments; measured 60–90 sec after inhalation
NR
PC20 MCH
Lin33 1991Case-control (prospective); ECT first
2; 1, then 4;
MCH then ECT 1–3 wk later
NR
Treadmill; 6
3 mph at 10% incline, adjusted until HR reached 90% predicted age max for 4 min
RH and temp NR
Pre-ECT, 5, 10, 15, 20, 25, 30 min post ECT
≥20% fall FEV1
5 breath dosimeter method; increasing concentrations from 0.1–25.0 in 7 increments
NR
PC20.MCH
Pedersen34 2008Cross sectional (prospective); NR
4 visits; NR;
at least 24 hr apart
NA
Treadmill; 5±1.1
Ran until exhausted at constant speed with gradiant increasing 2% every 2 min
RH and temp NR
Pre-ECT, 1, 3, 5, 10, 15, 20 min post ECT
≥10% fall FEV1
5 breath dosimeter method; concentrations NR; measured after each inhalation
NR
PC20. MCH ≤2μmol (~4 mg/ml)
Sekerel35 1997Cross sectional (prospective); randomized order of tests
3; 1;
within 1 wk at same time of d
Withheld: oral med x 24 hr; inhaled med x 12 hr
Bicycle ergometer; 6
90% max HR
RH and temp NR
1, 5, 10, 15, 20 min post ECT
≥20% fall FEV1
2 min tidal breathing method; increasing concentrations starting at 0.03 mg/ml; measured at 0.5 and 1.5 min after each inhalation
NR
PC20.MCH
Souza36 2005Cross sectional (prospective); randomized order of tests
3; 1 (all 8–10 am); min 24 h to 10 d
Withheld: coffee, tea, drinks with caffine x 2 hr; SABA x 12 h; antihistamines x 48 hr (short-acting) x 5 d (long-acting)
Bicycle ergometer; 6 (nose clips)
80–90% max HR after 1–2 min warmup (target 178±7 bpm)
compressed air RH ~50%; 21.1±1oC
3, 6, 10, 15, 20, 30 min post ECT
≥10% fall FEV1
5 breath dosimeter method; increasing concentrations from 0.25–25 mg/ml in 6 increments
NR
PC20 MCH ≥6.6μmol
Verges37 2005Case-control (prospective); MCH
first
1; 6;
mean interval of 6.2±1.5 hr (range=4–10 hr) between MCH and ECT
Withheld: SABA x 48 hr; ICS x 3 wk
Bicycle ergometer; 12 at >60% max HR, voluntary ventilation (35 x FEV1)
RH dry medical air; NR
Pre-ECT, 1, 3, 5, 7, 10, 15 min post ECT
≥10% fall FEV1
5 breath dosimeter method; increasing concentrations from 0.0156–4 mg in 6 increments; measured 2 min after each inhalation
NR
PC20 MCH <4 mg

bpm = beats per minute; C = Celsius; d = day(s); ECT = exercise challenge test; EIB/EIA = exercise-induced bronchoconstriction/asthma; hr = hour(s); HR = heart rate; km/hr = kilometers per hour; ICS = inhaled corticosteroids; m = meters; μmol = micromole; max = maximum; mcg = microgram; MCH = methacholine; med = medication(s); mg/ml = milligram per milliliter; min = minute(s); mo = month(s); mph = miles per hour; NR = not reported; PC20 = provocative concentration causing a 20% fall in FEV1; PEF = peak expiratory flow; PSI = pounds per square inch; RH = relative humidity; rpm = revolutions per minute; SABA = short-acting beta-agonist; SCG = sodium cromoglycate; SD = standard deviation; sec = seconds; temp = temperature; wk = week(s)

From: 3, Results

Cover of Exercise-Induced Bronchoconstriction and Asthma
Exercise-Induced Bronchoconstriction and Asthma.
Evidence Reports/Technology Assessments, No. 189.
Dryden DM, Spooner CH, Stickland MK, et al.

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