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Airway response to emotional stimuli in asthma: The role of the cholinergic
Thomas Ritz, Antje Kullowatz, Michael D. Goldman, Hans-Jürgen Smith, Frank Kanniess, Bernhard Dahme, and Helgo Magnussen Pictures were selected from the International Affective Picture System (9). They included pleasant affective states with reference numbers 8490, 7325, 8540, 2091, 2000, 2080, 8600, 1710, 8420, 2340, 1750, 2070, 2352, 2020, 8497, 8496, 8461, 8280; for unpleasant affective states reference numbers were 3071, 3400; 3051, 3064, 9570, 3060, 3102, 3170, 3110, 3010, 3150, 3550, 3061, 9253, 9433, 3030, 3140, 3080; and for neutral affective states reference numbers were: 2200, 7170, 2210, 7500, 7130, 2850, 7010, 7550, 7050, 7030, 2190, 7620, 2230, 6000, 7700, 7190, 2890, 7100. Effect of emotion induction on the airways and its modulation by ipratropium bromide Online Table 1 provides means and 95%CIs for resistance change by group, condition, Online Table 2 shows percent changes in Rrs (%ΔRrs) at 5 and 20 Hz during unpleasant stimulation under placebo or cholinergic blockade conditions for both groups. Effect of the specific emotion induction method on resistance. Film stimuli in general lead to stronger increases in Rrs at 5 and 20 Hz, with method effects being F(1,77)=12.72 and 17.87, p=.001 and .006, η 2 respectively. Rrs20 in particular, in asthma patients, increased during both stimulation methods, while controls only showed substantial increases to films, with significant interaction effects of Group by Method, F(1,77)=2.99 and 6.30, p=.088 and 0.14, Evidence for central vs. peripheral effects on the airways: Effects of emotion induction No effects were found for Xrs5. Additional effects were observed for Xrs20 and AX, but none of them reflected the specific increases in Rrs observed for asthma patients and their attenuation during iprtropium. Xrs20 decreased particularly during unpleasant films and pictures as well as neutral films compared to other stimuli, as reflected in a Method by Emotion interaction, F(2,154)= 3.68, p=.029, ε=.96, η 2 specific to groups or condition were observed. AX showed effects of emotion, F(2,136)=5.51, p=.012, ε=.72, η 2 Method by Emotion, F(2,136)=3.58, p=.043, ε=.77, η 2 unpleasant compared to neutral and pleasant stimuli that were more pronounced for films. In addition, AX increased for unpleasant stimuli more substantially during placebo conditions, Condition by Emotion effect with F(2,136)=3.34, p=.039, ε=.99, η 2 Fres was not significantly affected by the emotion induction procedure. Effects on emotion and physical symptoms Both ratings of pleasantness and arousal showed a clear distinction between emotional states, with F(2,142)=125.6 and 82.5, ps<.001, ε=.79 and .93, η 2 .541, respectively, for the emotion effect. In addition, interactions of Method by Emotion, F(2,142)=17.95 and 14.01, ps<.001, ε=.94 and .98, η 2 p =.202 and .167, for pleasantness and arousal, respectively were due to significantly greater unpleasantness for unpleasant pictures and greater pleasantness and arousal for pleasant films. Asthma patients reported significantly higher overall levels of chest tightness, F(1,76)=6.26, p=.013, η 2 p =.078, and a tendency toward increased breathlessness and dizziness, F(1,76)=3.01 and 3.30, p=.087 and .073, η 2 Overall dizziness was higher in ipratropium vs. placebo conditions, but only for asthma patients, as suggested by significant effects of Group by Condition, F(1,76)=6.18, Symptoms were generally higher for unpleasant stimuli than for others regardless of the condition, significant emotion effects were found for shortness of breath, chest tightness, dizziness, lightheaded, nausea, heart pounding and fatigued, F(2,152)=9.32, 7.81, 10.69, 9.70, 42.27, and 7.26, p=.001, .001, .001, .003, .001, .001, .001 ε=.85, .85, p =.124, .106, .138, .113, .348, .357 and .087, respectively. Correlations between emotions or symptoms and Rrs change were not significant, except for nausea levels, which showed consistently positive associations with Rrs5 and Rrs20 changes in asthma patients. This was observed for both ipratropium and placebo conditions during unpleasant pictures, median r(54)=.35 (range .29 to .39, ps=.037 - .003) and unpleasant films, median r(54)=.27 (range .22 to .34, ps=.140 - .013), as well as under ipratropium for Rrs20 during pleasant films (r(54)=.29, p=.034). Respiratory pattern. Only RR showed significant ANOVA effects of method with F(1,76)=34.21, p<.001, η 2 p =.310, emotion, F(2,152)=10.26, p<.001, ε=.95 ηp =.119, and Method by Emotion, F(2,152)=7.39, p=.003, ε=.97, η 2 mainly due to increased RR during presentation of pleasant (1.2 breaths/min, 95%CI:0.6- 1.8) and unpleasant (1.8, 95%CI:1.1-1.4) as compared to neutral stimuli (0.5, 95%CI: 0.1-0.8), while for pictures no substantial changes were observed. Only healthy controls showed weak correlations (Spearman’s Rho) between Rrs and RR changes, with negative associations at 5 and 20 Hz for neutral films and pleasant pictures (rs=-.38 to -.42, End-tidal PCO2. Larger increases in PCO2 were observed across groups for all picture stimuli (0.7 mmHg, 95% CI: 0.4-1.0) compared to films (0.2 mmHg, 95%CI: 0.0- 0.5), with F(1,46)=9.62, p=.003, η 2 p =.173, for the ANOVA method effect. Positive associations were found between PCO2 and changes in Rrs5 and/or Rrs20 for neutral stimuli in asthma patients during ipratropium with Rrs20 (r(34)=.32 and.27, p=.033 and .075, during neutral pictures and films, respectively) and in controls under placebo conditions during neutral pictures (r(34)=.57 and .47, p=.014 and .047, respectively). Overall, the changes in ventilation were small and did not match the pattern of Rrs Association of airway responses with demographics, asthma manifestation, and Xrs20 decreased for women but increased for men during unpleasant, neutral, and pleasant pictures in the placebo condition, t(52)=2.50, 2.18, and 2.38, p=.016, .034, and Association of airway responses with nonspecific hyperreactivity and airway Beyond the one significant association of Rrs5 and Rrs20 with PC20 during placebo conditions and neutral films, other coefficients were nonsignificant and mostly negative, mdn r(52)=.08 (range -.26 to .09, p=.059 to .886). For asthma patients, the median correlations of difference scores of Rrs5 and Rrs20 with FeNO across emotional stimuli were r(54)=.07 and .04 (ranges -.37 to .18 and -.21 to .17) under placebo and blockade conditions, respectively. Similarly, the median correlation for healthy participants were r(25)=-.21 and -.10 (ranges -.38 to .01 and -.33 to .30) under placebo and blockade conditions, respectively. Association of airway responses with self-reported triggers of asthma Associations of the ATI psychological trigger scale changes in Rrs5 and Rrs20 under ipratropium condition remained insignificant, r(51)=.01 and .06, respectively, as were associations during pleasant films under placebo condition, r(51)=.18 and .15, Other ATI trigger reports also predicted airway responses to emotional stimuli under placebo conditions, such as exercise triggers associated with both Rrs5 and Rrs20 changes during unpleasant films and pictures, r(51)= .30 to .51, p=.035 to .001, as well as the general allergen scale associated with Rrs5 and Rrs20 changes to unpleasant and neutral pictures, r(51)=.24 to. 37, p=.084 to .007. Online Table 1. Means and (95% CI) of Rrs changes during emotion induction under placebo or cholinergic blockade conditions for asthma patients (n=54) and controls (n=25) ____________________________________________________________________________________________________________________ _____________________________________________ ___________________________________________________ _____________________________________________________________________________________________________________________ Online Table 2. Percent change in Rrs (%ΔRrs) at 5 and 20 Hz during unpleasant stimulation under placebo or cholinergic blockade conditions for asthma patients and _________________________________________________________________________ ____________________ _____________________ ______________________________________________________________________________

Source: http://jap.physiology.org/content/suppl/2010/05/17/japplphysiol.00818.2009.DC1/datasupp.pdf