Table 1.

Included studies on the effect of tachykinin receptors antagonism on asthma

Study/reference	Design and participants	Intervention	Outcomes	Results
Shelfhout et al., 2009 [11]	• Single-center, RCT, double-blind, crossover • 12 non-smoking subjects males	• 2 or 8 mg of MEN 48968 (dual NK-1/NK-2 receptor antagonist) single inhaled dose	• Airway responsiveness to NK antagonist	• Decreased airway responsiveness
Boot et al., 2007 [13]	• Single-center, RCT, double-blind, crossover • 19 non-smoking subjects (15 females);mean age 30 yr	• 4.8 mg of AVE 5883 (dual NK-1/NK-2 receptor antagonist) single inhaled dose	• Airway responsiveness to NK antagonist • Lung function • Airway inflammation	• Decreased airway responsiveness • Inhibition of bronchoconstriction
Schelfhout et al., 2006 [16]	• Multi- center, RCT, double-blind, crossover • 15 subjects (7 females); mean age 30 yr	• 200 mg CS-003 (triple NK-1/NK-2/NK-3 receptor antagonist) single oral dose.	• Airway responsiveness to NK antagonist • Lung function	• Decreased airway responsiveness
Joos et al., 2004 [15]	• Multi- center, RCT, double-blind, crossover • 18 males; mean age 28 yr	• 100 mg DNK 333 (dual NK-1/NK-2 receptor antagonist) single orally dose.	• Airway responsiveness to NK antagonist • Lung function	• Decreased airway responsiveness
Kraan et al., 2001 [10]	• Single-center, RCT, double-blind, crossover • 12 atopic non-smoking males; mean age 30 yr	• 100 mg (4 × 25 mg) SR 48968C (NK-2 receptor antagonist) orally once-daily during 9 days.	• Airway responsiveness to NK antagonist • Lung function	• No effect
Schoor et al.,1998 [12]	• Single-center, RCT, double-blind, crossover • 12 non-smoking males; mean age 29 yr.	• 100 mg SR 48968 (NK-2 receptor antagonist) orally single dose	• Airway responsiveness to NK antagonist	• Decreased airway responsiveness
Joos et al., 1996 [14]	• Single-center, RCT, double-blind, crossover • 10 atopic non-smoking subjects (2 females); mean age 27 yr	• 4 mg FK224 (dual NK-1/NK-2 receptor antagonist) inhaled once-daily for 2 days.	• Airway responsiveness to NK antagonist • Lung function	• No effect
Summary	• 98 young adults (24 females, 74 males)	• Seven different antagonists acting on NK-1R, NK-2, NK-3 in mono, dual or triple combinations.	• Airway responsiveness to NK antagonist, lung function and airway inflammation.	• Five studies showed positive effects on airway responsiveness and/or lung function and two studies failed to demonstrate effects on asthma outcomes.