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. Author manuscript; available in PMC: 2013 Aug 1.
Published in final edited form as: Pharmacol Ther. 2012 May 22;135(2):176–181. doi: 10.1016/j.pharmthera.2012.05.005

Table 3.

Severe Asthma Clinical Studies Examined

Author Design Key Inclusion Key Exclusion N Demographics Major Findings
(Holgate, et al., 2006) R, DB, PC, 32-week
steroid stable phase,
16-week steroid
reduction phase

  1. ≥ 1000 μg fluticasone ± LABA

  2. + skin test

  3. IgE 30-700 IU/mL

  1. Other asthma meds

  2. History (hx) of anaphylaxis

  3. Hx of infection within 4 weeks

 246

  1. FEV1% predicted 62.9-66%

  2. Mean BD reversibility 18.6-20.6%

  1. Significant reduction in fluticasone dose active vs. placebo, p = 0.003

  2. Significant percentage of patients with 50% reduction in fluticasone dose, p=0.001

  3. Insignificant change in FEV1
Djukanovic, et al., 2004 R, DB, PC, 16
weeks, airway
hyperresponsiveness
Sputum induction,
bronchoscopy

  1. Steroid naïve

  2. IgE 30-700 IU/mL

  3. Sputum eosinophilia of ≥2%

  4. PC20 methacholine < 8 mg/mL

 45

  1. FEV1% predicted 84%-86%

  2. Geometric Mean MCh PC20 mg/mL Active 1.01 Placebo 0.54

  1. Significant reduction in sputum eosinophilia active vs. placebo, p<0.05

  2. Insignificant change in AHR active vs. placebo, p=0.14
Prieto, et al., 2006 R, DB, PC, 12-week
treatment, AMP
challenge at weeks 4
and 12

  1. Mild-moderate asthma on low-med ICS treatment

  2. FEV1 % predicted ≥ 80%

  3. IgE 30-700 IU/mL

  4. + AMP

  5. + MCh challenge studies

  1. Smoking hx

  2. Hx of infection within 4 weeks

 34

  1. FEV1 % predicted 100-101.4

  2. Geometric Mean PC20 for MCh 1.27-2.13

  3. PC20 for AMP 14.32-31.20

  1. Changes in AMP doubling concentrations were significantly different at 4 weeks (p=0.02) but not 12 weeks (p=0.24) between active and placebo

  2. Insignificant difference in change in MCh doubling concentrations at 4 or 12 weeks between active and placebo

  3. Insignificant increase in FEV1
Howarth, et al., 2005 Open label,
uncontrolled, 12-
week treatment,
ACQ, PEFR, FEV1,
MCh challenge,
sputum induction,
biopsy

  1. Severe asthma, treatment with high dose ICS + prednisone

  2. Hx of bronchodilator reversibility

  1. Smoking hx

  2. Hx of TB

  3. Hx of autoimmune diseases

 17

  1. Severe asthma

  2. FEV1 % predicted 68.3

  3. Treatment with high dose ICS, prednisone, LABA, LTRA, theophylline

  1. Significant reduction in ACQ from 3.71 to 1.57, p< 0.001

  2. Significant increase in trough FEV1, p=0.01

  3. Significant increase in doubling concentration MCh, p=0.033
Author Design Key Inclusion Key Exclusion N Demographics Significant Findings
Erin, et al., 2006 R, DB, PC, 6 weeks,
PEFR, eNO, FEV1,
sputum induction

  1. FEV1 % predicted between 40%-90%

  2. Bronchodilator reversibility

  3. Treatment with ICS

 1. Treatment
 with other
 asthma
 medications
 except
 short-acting
 bronchodilat
 ors		 38

  1. FEV1 % predicted 66.4%-69.9%

  2. Bronchodilator reversibility 23%-26%

  3. ICS dose ~ 600-750 μg/day

  1. Insignificant change in AM/PM PEFR, p=0.09 and 0.14, respectively

  2. Significant worsening in diurnal variation in PEFR, active vs. placebo, p=0.02

  3. Insignificant change in FEV1 from baseline in active group, p=0.88

  4. Insignificant change in eNO

  5. Insignificant change in sputum cell counts
Wenzel, et al., 2009 R, DB, PC, dose-
ranging, 52-week
study, trough FEV1,
number of severe
exacerbations

  1. Severe asthma

  2. Treatment with high dose ICS + LABA

  3. ≥ 2 exacerbations in past year

  4. Bronchodilator reversibility within 5 years or AHR or ≥ 30% diurnal PEFR variability

 1. Smoking hx 309

  1. FEV1% predicted 58.9%-60.9%

  2. Bronchodilator reversibility 15.6%-17.8%

  3. ACQ 2.9-3.1

  1. Insignificant change in postbronchodilator FEV1 % predicted, p values range from 0.357 to 0.945

  2. Insignificant change in exacerbations, p values range from 0.256 to 0.779
Castro, et al., 2010 R, DB, sham-
controlled, 3
treatments 3 weeks
apart; treatment with
radiofrequency
ablation of airway
smooth muscle

  1. Treatment with high dose ICS + LABA

  2. Other asthma medications allowed

  3. AQLQ score ≥6.25

  4. FEV1 % pred >60%

  5. PC20 to methacholine < 8 mg/mL

  1. Smoking hx

  2. ≥3 lower respiratory infections

  3. ≥4 pulses of oral steroids

  4. ≥3 hospitalizati ons for asthma in past year

 297

  1. FEV1% pred 77.8%-79.7%

  2. PC20 mg/mL Geometric mean 0.27-0.31

 1. Insignificant difference
 between treatment and sham
 in change from baseline in
 integrated AQLQ measured at
 6, 9 and 12 months where
 treatment baseline went from
 5.71 to 5.80 at 12 months and
 sham baseline went from 5.49
 to 5.56 at 12 months

Abbreviations Used in Table 3

ACQ: Asthma Control Questionnaire, a validated instrument to assess asthma stability, developed by E.F. Juniper (Juniper, et al., 2006)

AHR: Airway hyperresponsiveness, also known as bronchial hyperresponsiveness or BHR

AMP: Adenosine monophosphate, an agent used to provoke airway constriction/inflammation

AQLQ: Asthma Quality of Life Questionnaire, a validated instrument to assess changes in quality of life, developed by E.F. Juniper (Juniper, et al., 2006)

BD: Bronchodilator

DB: Double blind

eNO: Exhaled nitric oxide, a biomarker of airway inflammation

Hx: History

ICS: Inhaled corticosteroid

LABA: Long-acting β-agonist

LTRA: Leukotriene receptor antagonist

MCh: Methacholine challenge, a measure of BHR

PC: Placebo-controlled

PEFR: Peak expiratory flow rate, the greatest velocity of air flow achieved during a maximal expiratory effort

R: Randomized

TB: Tuberculosis