Sex differences in the ventilatory responses to exercise in mild to moderate obesity.

NEW FINDINGS: What is the central question of the study? What are the sex differences in ventilatory responses during exercise in adults with obesity? What is the main finding and its importance? Tidal volume and expiratory flows are lower in females when compared with males at higher levels of ventilation despite small increases in end-expiratory lung volumes. Since dyspnoea on exertion is a frequent complaint, particularly in females with obesity, careful attention should be paid to unpleasant respiratory symptoms and mechanical ventilatory constraints while prescribing exercise. ABSTRACT: Obesity is associated with altered ventilatory responses, which may be exacerbated in females due to the functional consequences of sex-related morphological differences in the respiratory system. This study examined sex differences in ventilatory responses during exercise in adults with obesity. Healthy adults with obesity (n = 73; 48 females) underwent pulmonary function testing, underwater weighing, magnetic resonance imaging (MRI), a graded exercise test to exhaustion, and two constant work rate exercise tests; one at a fixed work rate (60 W for females and 105 W for males) and one at a relative intensity (50% of peak oxygen uptake, V ̇ O 2 peak ${\dot{V}}_{{{\rm{O}}}_{\rm{2}}{\rm{peak}}}$ ). Metabolic, respiratory and perceptual responses were assessed during exercise. Compared with males, females used a smaller proportion of their ventilatory capacity at peak exercise (69.13 ± 14.49 vs. 77.41 ± 17.06% maximum voluntary ventilation, P = 0.0374). Females also utilized a smaller proportion of their forced vital capacity (FVC) at peak exercise (tidal volume: 48.51 ± 9.29 vs. 54.12 ± 10.43%FVC, P = 0.0218). End-expiratory lung volumes were 2-4% higher in females compared with males during exercise (P < 0.05), while end-inspiratory lung volumes were similar. Since the males were initiating inspiration from a lower lung volume, they experienced greater expiratory flow limitation during exercise. Ratings of perceived breathlessness during exercise were similar between females and males at comparable levels of ventilation. In summary, sex differences in the manifestations of obesity-related mechanical ventilatory constraints were observed. Since dyspnoea on exertion is a common complaint in patients with obesity, particularly in females, exercise prescriptions should be tailored with the goal of minimizing unpleasant respiratory sensations.

Repeatability of dyspnea measurements during exercise in women with obesity.

While the 0-10 Borg scale to rate perceived breathlessness (RPB) is widely used to assess dyspnea on exertion, the repeatability of RPB in women with obesity is unknown. We examined the repeatability of RPB in women with obesity during submaximal constant-load cycling following at least 10 weeks of normal daily life. Seventeen women (37 ± 7 yr; 34.6 ± 4.5 kg/m2) who rated their breathlessness as 3 on the Borg scale (i.e., "moderate") during 60 W submaximal cycling repeated the same test following 19 ± 9 weeks of normal living. Mean body weight (93.8 ± 16.1 vs. 93.6 ± 116.8 kg, p = 0.94) and RPB (3.0 ± 0.0 vs. 3.1 ± 1.4, p = 0.80) did not differ between pre- and post-normal living periods. We demonstrate that subjective ratings of breathlessness are repeatable for the majority of subjects and can be used to accurately assess DOE during submaximal constant-load cycling in women with obesity.

Recruitment and Retention of Healthy Women with Obesity for a Psychophysiological Study before and After Weight Loss: Insights, Challenges, and Suggestions.

OBJECTIVE: The objective of this paper is to present data on participant recruitment, retention, and weight loss success during a psychophysiological study in women with obesity. METHODS: Volunteers were women with obesity, 20 - 45 yr, with a BMI between 30 - 45 kg/m2. The study was approximately 20 weeks in duration, including a 12-week weight loss program. RESULTS: Recruitment was not completed until 8 months past the original projected date of 12 months. The study was not completed until 11 months past the original projected completion date of 14 months. On average 4.4 ± 2.1 (mean ± SD) volunteers were consented per month (N = 99) and 2.5 ± 1.1 participants started the weight loss program per month. 24% of consented volunteers were lost due to exclusion criteria, withdrawals, and unresponsive behavior before starting the weight loss program. Attrition of participants who started the weight loss program was 45%. Only 11% of those who started the program were unable to lose weight (N = 6). CONCLUSION: Recruiting and/or weight loss success do not always present the most challenging aspects of completing a psychophysiological weight loss intervention. While participant attrition during a weight loss program can occur for a wide range of reasons supportive efforts in the early phases of the intervention may maximize retention.

Dyspnea during exercise and voluntary hyperpnea in women with obesity.

Temporal responses of ratings of perceived breathlessness (RBP) during constant-load and incremental exercise, and during voluntary hyperpnea (EVH) were examined in women with obesity. Following 6 min of constant-load (60W) cycling, 34 women rated RPB≥4 (+DOE) and 22 women rated RPB≤2 (-DOE). Both groups completed an incremental cycling test and an EVH test at 40 and 60L/min; RPB was assessed each minute of incremental cycling and at the end of each EVH trial. RPB increased with ventilation during constant-load (+DOE: R2=0.86; -DOE: R2=0.82) and incremental (+DOE: R2=0.91; -DOE: R2=0.92) exercise, but + DOE had a greater y-intercept than -DOE (60W: -0.16±1.53 vs. -0.73±0.55; incremental: -0.50±1.40 vs. -1.71±0.84). Despite matching ventilation, RPB was greater in + DOE at baseline (0.97±1.14 vs. 0.14±0.28), 40L/min (2.50±1.43 vs. 0.98±0.91), and 60L/min (3.94±2.19 vs. 2.07±1.32) during EVH. These findings show that despite linear associations between RPB and ventilation during exercise and voluntary hyperpnea, breathlessness perception at a given ventilatory demand is heightened in +DOE compared with -DOE.

Multidimensional aspects of dyspnea in obese patients referred for cardiopulmonary exercise testing.

We investigated the contributions of obesity on multidimensional aspects of dyspnea on exertion (DOE) in patients referred for clinical cardiopulmonary exercise testing (CPET). Ratings of perceived breathlessness (RPB, Borg scale 0-10) were collected in obese (BMI ≥ 30; n = 47) and nonobese (BMI ≤ 25; n = 27) patients during two (one lower: ∼30 W; and one higher: ∼50 W) 4-6 min constant load cycling bouts. Multidimensional dyspnea profiles (MDP) were collected in the final 26 obese and 14 nonobese patients of the sample. RPB was greater (p = 0.05) in obese (3.3 ± 2.2 vs 2.4 ± 1.4) at lower work rates, but similar at higher work rates (4.9 ± 2.2 vs 4.4 ± 1.8). MDP sensory score including unpleasantness was 4.3 ± 2.2 in obese vs 2.5 ± 1.9 in nonobese (p < 0.001). The affective score was 1.9 ± 2.2 vs 0.7 ± 0.7, respectively (p < 0.01). Breathing sensations including 'air hunger', 'effort', and 'breathing at lot' were greater (p < 0.05) in obese, making these patients more frustrated/angry (p < 0.05). Obesity should be considered as a potential independent influencing factor that provokes DOE and unpleasantness when assessing breathlessness during CPET.

Weight loss reduces dyspnea on exertion and unpleasantness of dyspnea in obese men.

We hypothesized that weight loss would ameliorate dyspnea on exertion (DOE) and feelings of unpleasantness related to the DOE in obese men. Eighteen men (34 ± 7yr, 35 ± 4 kg/m2 BMI, mean ± SD) participated in a 12-week weight loss program. Body composition, pulmonary function, cardiorespiratory measures, DOE, and unpleasantness (visual analog scale) were assessed before and after weight loss. Subjects were grouped by Ratings of Perceived Breathlessness (RPB, Borg 0-10 scale) during submaximal cycling: Ten men rated RPB ≥ 4 (+DOE), eight rated RPB ≤ 2 (-DOE). Subjects lost 10.3 ± 5.6 kg (9.2 ± 4.5%) of body weight (n = 18). RPB during submaximal cycling was significantly improved in both groups (+DOE: 4.1 ± 0.3-2.8 ± 1.1; -DOE: 1.3 ± 0.7 to 0.8 ± 0.6, p < 0.001). Several submaximal exercise variables (e.g., V˙O2, V˙E) were decreased similarly in both groups (p < 0.01). Unpleasantness associated with the DOE was reduced (p < 0.05). The improved RPB was not significantly correlated with changes in body weight or cardiopulmonary exercise responses (p > 0.05). Moderate weight loss appears to be an effective option to ameliorate DOE and unpleasantness related to DOE in obese men.

Dyspnea on exertion provokes unpleasantness and negative emotions in women with obesity.

PURPOSE: While dyspnea on exertion (DOE) is a common complaint in otherwise healthy obese women, less is known about feelings of unpleasantness and/or negative emotions provoked by DOE. We examined whether ratings of perceived breathlessness (RPB) during exercise were associated with ratings of unpleasantness and negative emotions (depression, anxiety, frustration, anger, and fear) in obese women. METHODS: Seventy-four women (34 ± 7 yrs, 36 ± 4 kg/m2, 46 ± 5% body fat) performed 6 min of constant-load cycling (60 W); RPB (0-10 scale), and unpleasantness and negative emotions (visual analog scales, 10 cm) were assessed at the end. RESULTS: RPB were significantly correlated with unpleasantness and negative emotions (p < 0.05). The strongest correlations were between RPB and unpleasantness (r = 0.61, p < 0.001), and RPB and anxiety (r = 0.50, p < 0.001). CONCLUSIONS: DOE can significantly provoke unpleasantness and negative emotions during exercise in obese women. This may affect their willingness to engage in regular physical activity.

Verification of Maximal Oxygen Uptake in Obese and Nonobese Children.

PURPOSE: The purpose of this study was to examine whether a supramaximal constant-load verification test at 105% of the highest work rate would yield a higher V˙O2max when compared with an incremental test in 10- to 12-yr-old nonobese and obese children. METHODS: Nine nonobese (body mass index percentile = 57.5 ± 23.2) and nine obese (body mass index percentile = 97.9 ± 1.4) children completed a two-test protocol that included an incremental test followed 15 min later by a supramaximal constant-load verification test. RESULTS: The V˙O2max achieved in verification testing (nonobese = 1.71 ± 0.31 L·min and obese = 1.94 ± 0.47 L·min) was significantly higher than that achieved during the incremental test (nonobese = 1.57 ± 0.27 L·min and obese = 1.84 ± 0.48 L·min; P < 0.001). There was no significant group (i.e., nonobese vs obese)-test (i.e., incremental vs verification) interaction, suggesting that there was no effect of obesity on the difference between verification and incremental V˙O2max (P = 0.747). CONCLUSION: A verification test yielded significantly higher values of V˙O2max when compared with the incremental test in obese children. Similar results were observed in nonobese children. Supramaximal constant-load verification is a time-efficient and well-tolerated method for identifying the highest V˙O2 in nonobese and obese children.

Short-term modulation of the ventilatory response to exercise is preserved in obstructive sleep apnea.

BACKGROUND: The ventilatory response to exercise can be transiently adjusted in response to environmentally (e.g., breathing apparatus) or physiologically altered conditions (e.g., respiratory disease), maintaining constant relative arterial PCO2 regulation from rest to exercise (Mitchell and Babb, 2006); this augmentation is called short-term modulation (STM) of the exercise ventilatory response. Obesity and/or obstructive sleep apnea could affect the exercise ventilatory response and the capacity for STM due to chronically increased mechanical and/or ventilatory loads on the respiratory system, and/or recurrent (chronic) intermittent hypoxia experienced during sleep. We hypothesized that: (1) the exercise ventilatory response is augmented in obese OSA patients compared with obese non-OSA adults, and (2) the capacity for STM with added dead space is diminished in obese OSA patients. METHODS: Nine obese adults with OSA (age: 39±6 yr, BMI: 40±5kg/m2, AHI: 25±24 events/h [range 6-73], mean±SD) and 8 obese adults without OSA (age: 38±10 yr, BMI: 37±6kg/m2, AHI: 1±2) completed three, 20-min bouts of constant-load submaximal cycling exercise (8min rest, 6min at 10 and 30W) with or without added external dead space (200 or 400mL; 20min rest between bouts). Steady-state measurements were made of ventilation (V˙E), oxygen consumption V˙O2), carbon dioxide production (V˙CO2), and end-tidal PCO2 (PETCO2). The exercise ventilatory response was defined as the slope of the V˙E-V˙CO2 relationship (ΔV˙E/ΔV˙CO2). RESULTS: In control (i.e. no added dead space), the exercise ventilatory response was not significantly different between non-OSA and OSA groups (ΔV˙E/ΔV˙CO2 slope: 30.5±4.2 vs 30.5±3.8, p>0.05); PETCO2 regulation from rest to exercise did not differ between groups (p>0.05). In trials with added external dead space, ΔV˙E/ΔV˙CO2 increased with increased dead space (p < 0.05) and the PETCO2 change from rest to exercise remained small (<2mmHg) in both groups, demonstrating STM. There were no significant differences between groups. CONCLUSIONS: Contrary to our hypotheses: (1) the exercise ventilatory response is not increased in obese OSA patients compared with obese non-OSA adults, and (2) the capacity for STM with added dead space is preserved in obese OSA and non-OSA adults.

Exertional dyspnoea in obesity.

The purpose of cardiopulmonary exercise testing (CPET) in the obese person, as in any cardiopulmonary exercise test, is to determine the patient's exercise tolerance, and to help identify and/or distinguish between the various physiological factors that could contribute to exercise intolerance. Unexplained dyspnoea on exertion is a common reason for CPET, but it is an extremely complex symptom to explain. Sometimes obesity is the simple answer by elimination of other possibilities. Thus, distinguishing among multiple clinical causes for exertional dyspnoea depends on the ability to eliminate possibilities while recognising response patterns that are unique to the obese patient. This includes the otherwise healthy obese patient, as well as the obese patient with potentially multiple cardiopulmonary limitations. Despite obvious limitations in lung function, metabolic disease and/or cardiovascular dysfunction, obesity may be the most likely reason for exertional dyspnoea. In this article, we will review the more common cardiopulmonary responses to exercise in the otherwise healthy obese adult with special emphasis on dyspnoea on exertion.

Aerobic exercise training without weight loss reduces dyspnea on exertion in obese women.

Dyspnea on exertion (DOE) is a common symptom in obesity. We investigated whether aerobic exercise training without weight loss could reduce DOE. Twenty-two otherwise healthy obese women participated in a 12-week supervised aerobic exercise training program, exercising 30 min/day at 70-80% heart rate reserve, 4 days/week. Subjects were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60 W cycling: +DOE (n=12, RPB≥4, 37±7 years, 34±4 kg/m(2)) and -DOE (n=10, RPB≤2, 32±6 years, 33±3 kg/m(2)). No significant differences between the groups in body composition, pulmonary function, or cardiorespiratory fitness were observed pre-training. Post-training,peak was improved significantly in both groups (+DOE: 12±7, -DOE: 14±8%). RPB was significantly decreased in the +DOE (4.7±1.0-2.5±1.0) and remained low in the -DOE group (1.2±0.6-1.3±1.0) (interaction p<0.001). The reduction in RPB was not significantly correlated with the improvement in cardiorespiratory fitness. Aerobic exercise training improved cardiorespiratory fitness and DOE and thus appears to be an effective treatment for DOE in obese women.

Weight loss reduces dyspnea on exertion in obese women.

During submaximal exercise, some otherwise healthy obese women experience breathlessness, or dyspnea on exertion (+DOE), while others have mild or no DOE (-DOE). We investigated whether weight loss could reduce DOE. Twenty nine obese women were grouped based on their Ratings of Perceived Breathlessness (RPB) during constant load 60 W cycling: +DOE (n = 14, RPB ≥ 4, 34 ± 8 years, and 36 ± 3 kg/m(2)) and -DOE ( n= 15, RPB ≤ 2, 32 ± 8 years, and 36 ± 4 kg/m(2)) and then completed a 12-week weight loss program. Both groups lost a moderate amount of weight (+DOE: 6.6 ± 2.4 kg, -DOE: 8.4 ± 3.5 kg, and p < 0.001). RPB decreased significantly in the +DOE group (from 4.7 ± 1.1 to 3.1 ± 1.6) and remained low in the -DOE (from 1.5 ± 0.7 to 1.6 ± 1.1) (interaction p < 0.002). Most physiological variables measured (i.e. body composition, fat distribution, pulmonary function, oxygen cost of breathing, and cardiorespiratory measures) improved with weight loss; however, the decrease in RPB was not correlated with any of these variables (p > 0.05). In conclusion, moderate weight loss was effective in reducing breathlessness on exertion in obese women who experienced DOE at baseline.

Respiratory symptom perception differs in obese women with strong or mild breathlessness during constant-load exercise.

BACKGROUND: During constant-load exercise, some otherwise healthy obese women report substantially more dyspnea on exertion (DOE) than do others. The objective of this study was to investigate whether qualitative differences exist between the sensations of dyspnea felt by these women. METHODS: Seventy-eight women were categorized based on their ratings of perceived breathlessness (RPBs) (Borg 0-10 scale) after 6 min of 60-W cycling. Thirty-four women rated RPB ≥ 4 (+DOE) (34 ± 7 years, 36 ± 5 kg/m² BMI), and 22 women rated RPB ≤ 2 (-DOE) (32 ± 7 years, 37 ± 4 kg/m² BMI). Twenty-two women rated RPB as 3 (RPB = 3) (34 ± 7 years, 34 ± 4 kg/m² BMI) and were grouped separately to allow for a better delineation of the +DOE and the -DOE groups. After the exercise test, subjects were asked to pick three of 15 statements that best described their respiratory sensations. RESULTS: The +DOE and the -DOE groups were characterized differentially (P < .05) by the respiratory clusters "Breathing more" (82% of -DOE vs 41% of +DOE), "Shallow" (36% vs 6%), and "Heavy" (14% vs 53%). All four descriptors in the cluster "Work/Effort" were chosen more frequently by women in the +DOE group than by women in the -DOE group. Although relative exercise intensity was higher in the +DOE women (75% ± 13% vs 67% ± 10% of oxygen uptake at peak exercise, 41 ± 10 L/min vs 31 ± 8 L/min as % maximal voluntary ventilation, 83% ± 7% vs 76% ± 7% of peak heart rate), none of these variables was significantly associated with RPB. CONCLUSIONS: Not only is the intensity of dyspnea significantly different between the +DOE and the -DOE groups, but so are the self-reported qualitative aspects of their dyspnea. Women in the +DOE group reported an increased sensation of the work of breathing relative to women in the -DOE group, which may be associated with the elevated RPB.

Corrected end-tidal P(CO(2)) accurately estimates Pa(CO(2)) at rest and during exercise in morbidly obese adults.

BACKGROUND: Obesity affects lung function and gas exchange and imposes mechanical ventilatory limitations during exercise that could disrupt the predictability of Pa(CO(2)) from end-tidal P(CO(2)) (P(ETCO(2))), an important clinical tool for assessing gas exchange efficiency during exercise testing. Pa(CO(2)) has been estimated during exercise with good accuracy in normal-weight individuals by using a correction equation developed by Jones and colleagues (P(JCO(2)) = 5.5 + 0.9 x P(ETCO(2)) ­ 2.1 x tidal volume). The purpose of this project was to determine the accuracy of Pa(CO(2)) estimations from P(ETCO(2)) and P(JCO(2)) values at rest and at submaximal and peak exercise in morbidly obese adults. METHODS: Pa(CO(2)) and P(ETCO(2)) values from 37 obese adults (22 women, 15 men; age, 39 ± 9 y; BMI, 49 ± 7; [mean ± SD]) were evaluated. Subjects underwent ramped cardiopulmonary exercise testing to volitional exhaustion. P(ETCO(2)) was determined from expired gases simultaneously with temperature-corrected arterial blood gases (radial arterial catheter) at rest, every minute during exercise, and at peak exercise. Data were analyzed using paired t tests. RESULTS: P(ETCO(2)) was not significantly different from Pa(CO(2)) at rest (P(ETCO(2)) = 37 ± 3 mm Hg vs Pa(CO(2)) = 38 ± 3 mm Hg, P = .14). However, during exercise, P(ETCO(2)) was significantly higher than Pa(CO(2)) (submaximal: 42 ± 4 vs 40 ± 3, P < .001; peak: 40 ± 4 vs 37 ± 4, P < .001, respectively). Jones' equation successfully corrected P(ETCO(2)), such that P(JCO(2)) was not significantly different from Pa(CO(2)) (submax: P(JCO(2)) = 40 ± 3, P = .650; peak: 37 ± 4, P = .065). CONCLUSION: P(JCO(2)) provides a better estimate of Pa(CO(2)) than P(ETCO(2)) during submaximal exercise and at peak exercise, whereas at rest both yield reasonable estimates in morbidly obese individuals. Clinicians and physiologists can obtain accurate estimations of Pa(CO(2)) in morbidly obese individuals by using P(JCO(2)).

Dyspnea on exertion in obese men.

Recently, we reported that dyspnea on exertion is strongly associated with an increased oxygen cost of breathing in otherwise healthy obese women; the mechanism of dyspnea on exertion in obese men is unknown. Obese men underwent measurements of body composition, fat distribution, pulmonary function, steady state and maximal graded cycle ergometry, and oxygen cost of breathing. Nine men (34 ± 8 years, 35 ± 4 BMI) with ratings of perceived breathlessness of ≤2 during cycling, and ten men (36 ± 9 years, 38 ± 5 BMI) with ratings of perceived breathlessness ≥4 were studied (ratings of perceived breathlessness: 1.8 ± 0.4 vs. 4.7 ± 0.8, respectively; p<0.0001). Groups had only minor differences in fat distribution, pulmonary function, and steady state exercise. There was no association between ratings of perceived breathlessness and oxygen cost of breathing; but ratings of perceived breathlessness was strongly correlated with ratings of perceived exertion (RPE, rho=0.87, p<0.0001). The differences in exercise intensity, ventilatory demand, cardiovascular conditioning and/or the quality of respiratory sensation did not appear to play a role in the development of dyspnea on exertion. The mechanism of dyspnea on exertion in obese men seems unrelated to the oxygen cost of breathing.

Tracheal occlusion conditioning in conscious rats modulates gene expression profile of medial thalamus.

The thalamus may be the critical brain area involved in sensory gating and the relay of respiratory mechanical information to the cerebral cortex for the conscious awareness of breathing. We hypothesized that respiratory mechanical stimuli in the form of tracheal occlusions would modulate the gene expression profile of the thalamus. Specifically, it was reasoned that conditioning to the respiratory loading would induce a state change in the medial thalamus consistent with a change in sensory gating and the activation of molecular pathways associated with learning and memory. In addition, respiratory loading is stressful and thus should elicit changes in gene expressions related to stress, anxiety, and depression. Rats were instrumented with inflatable tracheal cuffs. Following surgical recovery, they underwent 10 days (5 days/week) of transient tracheal occlusion conditioning. On day 10, the animals were sacrificed and the brains removed. The medial thalamus was dissected and microarray analysis of gene expression performed. Tracheal obstruction conditioning modulated a total of 661 genes (p < 0.05, log(2) fold change ≥0.58), 250 genes were down-regulated and 411 up-regulated. There was a significant down-regulation of GAD1, GAD2 and HTR1A, HTR2A genes. CCK, PRKCG, mGluR4, and KCJN9 genes were significantly up-regulated. Some of these genes have been associated with anxiety and depression, while others have been shown to play a role in switching between tonic and burst firing modes in the thalamus and thus may be involved in gating of the respiratory stimuli. Furthermore, gene ontology and pathway analysis showed a significant modulation of learning and memory pathways. These results support the hypothesis that the medial thalamus is involved in the respiratory sensory neural pathway due to the state change of its gene expression profile following repeated tracheal occlusions.

Tracheal occlusion modulates the gene expression profile of the medial thalamus in anesthetized rats.

Conscious awareness of breathing requires the activation of higher brain centers and is believed to be a neural gated process. The thalamus could be responsible for the gating of respiratory sensory information to the cortex. It was reasoned that if the thalamus is the neural gate, then tracheal obstructions will modulate the gene expression profile of the thalamus. Anesthetized rats were instrumented with an inflatable cuff sutured around the trachea. The cuff was inflated to obstruct 2-4 breaths, then deflated for a minimum of 15 breaths. Obstructions were repeated for 10 min followed by immediate dissection of the medial thalamus. Following the occlusion protocol, 588 genes were found to be altered (P < 0.05; log(2) fold change ≥ 0.4), with 327 genes downregulated and 261 genes upregulated. A significant upregulation of the serotonin HTR2A receptor and significant downregulation of the dopamine DRD1 receptor genes were found. A pathway analysis was performed that targeted serotonin and dopamine receptor pathways. The mitogen-activated protein kinase 1 (MAPK1) gene was significantly downregulated. MAPK1 is an inhibitory regulator of HTR2A and facilitatory regulator for DRD1. Downregulation of MAPK1 may be related to the significant upregulation of HTR2A and downregulation of DRD1, suggesting an interaction in the medial thalamus serotonin-dopamine pathway elicited by airway obstruction. These results demonstrate an immediate change in gene expression in thalamic arousal, fear, anxiety motivation-related serotonin and dopamine receptors in response to airway obstruction. The results support the hypothesis that the thalamus is a component in the respiratory mechanosensory neural pathway.