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Original Research: ASTHMA |

Effect of Specific Allergen Inhalation on Serum Adiponectin in Human Asthma FREE TO VIEW

Akshay Sood, MD, MPH, FCCP; Clifford Qualls, PhD; JeanClare Seagrave, PhD; Christine Stidley, PhD; Tereassa Archibeque, RRT; Marianne Berwick, PhD; Mark Schuyler, MD, FCCP
Author and Funding Information

*From the Department of Medicine (Drs. Sood, Stidley, Berwick, and Schuyler, and Ms. Archibeque) and Clinical Translational Sciences Center (Dr. Qualls), University of New Mexico School of Medicine; and Experimental Toxicology Program (Dr. Seagrave), Lovelace Respiratory Research Institute, Albuquerque, NM.

Correspondence to: Akshay Sood, MD, MPH, FCCP, University of New Mexico School of Medicine, Department of Medicine, 1 University of New Mexico, MSC 10 5550, Albuquerque, NM 87131-0001; e-mail: asood@salud.unm.edu


This work was performed at the University of New Mexico, Albuquerque, NM.

This work was supported by University of New Mexico Clinical Translational Science Center grant No. NIH NCRR M01-RR-00997 and University of New Mexico Research Allocation Committee grant C-2290T.

The authors have no conflicts of interest to disclose.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).

For editorial comment see page 255


Chest. 2009;135(2):287-294. doi:10.1378/chest.08-1705
Text Size: A A A
Published online

Background:  Adiponectin is associated with asthma. The direction of this association is not known in humans. In mice, this association is bidirectional: allergen inhalation affects serum adiponectin, and exogenous adiponectin administration affects asthma. We sought to evaluate whether allergen inhalation affects serum adiponectin in human asthma.

Methods:  This study included eight sensitized subjects with mild asthma and six healthy control subjects. Asthmatic subjects were challenged with inhaled specific allergen (positive allergen skin test), methacholine, and irrelevant allergen (negative allergen skin test). Control subjects were challenged with irrelevant allergen. Sequential serum samples were obtained before and nine times after each challenge. Serum adiponectin- (primary outcome), leptin-, adiponectin-to-leptin ratio-, eotaxin-, and tumor necrosis factor-α–response curves, area under the curves, and baseline and peak concentrations were evaluated. Statistical analysis used repeated-measures analysis of variance and paired t tests.

Results:  There were no significant differences in outcome measures among the challenges in asthmatic subjects or when compared to control subjects. Type II error is an unlikely explanation for these findings because the study was adequately powered to detect changes in serum adiponectin, as reported in the literature. Further, pooled data showed that serum adiponectin diurnal variation curves were lower in asthmatic subjects than in control subjects.

Conclusions:  Serum adiponectin concentrations are lower in asthmatic subjects than in control subjects. Specific allergen inhalation in asthmatic subjects does not acutely affect serum adiponectin concentrations. The reverse association (ie, effect of adiponectin on asthma) needs further study. If future studies prove adiponectin to be a protective factor for asthma, modulating adiponectin may open a new approach toward managing asthma.

Figures in this Article

Adipokines, a diverse group of proteins secreted from adipose tissue, include various hormones, cytokines, chemokines, and acute-phase proteins. These may be antiinflammatory, such as adiponectin, or proinflammatory, such as leptin, eotaxin, and tumor necrosis factor (TNF)-α. Some investigators13 have hypothesized that adipokines may cause asthma. If this hypothesis is correct, modulating adipokines may open a new approach toward managing asthma.

Studies4,5 have confirmed that serum adiponectin is associated with asthma. Exogenous adiponectin administration in sensitized mice attenuates allergen-induced increase in airway hyperresponsiveness.5 In addition, serum adiponectin concentrations decrease following allergen challenge in sensitized mice.5 The adiponectin-asthma relationship is therefore bidirectional in mice, whereby allergen inhalation affects serum adiponectin and exogenous adiponectin administration affects asthma.

Our recent cross-sectional study4 shows that high serum adiponectin concentrations are associated with decreased risk for asthma in women. However, cross-sectional studies are unable to determine the direction of association and hence the need for longitudinal and interventional studies in this field. Therefore, we determined whether specific allergen inhalation affects serum adipokines in humans with asthma, similar to mice. The primary aim was to determine whether serum concentrations of adiponectin decrease following specific allergen inhalation in asthma. The secondary aim was to determine whether serum concentrations of leptin, eotaxin, and TNF-α increase, and whether the ratio of serum adiponectin-to-leptin decreases following specific allergen inhalation.

Study Design

This was an interventional study including eight sensitized subjects with asthma and six healthy control subjects. Asthma was defined by the presence of all of the following criteria: physician diagnosis of asthma, confirmed skin test “atopy,” presence of nonspecific airway hyperreactivity (provocative concentration of methacholine causing a 20% fall in FEV1 ≤ 16 mg/mL), and presence of specific airway reactivity (FEV1 decline ≥ 20%) to either inhaled Juniper-Mountain cedar or Bermuda grass allergen on screening evaluation. Control subjects were defined as those who met none of the first three criteria. All subjects with asthma had mild disease (intermittent or mild persistent in severity). This phenotype was chosen to minimize serious adverse reactions to allergen inhalation and to minimize the confounding effect of asthma medications. The study inclusion and exclusion criteria are outlined in the online supplement. The study protocol was approved by the local institutional review board. Informed consent was obtained from all study participants.

Exposures

All subjects underwent one to three inhalational challenges in random order on separate days (Table 1). All subjects inhaled incremental concentrations of an irrelevant allergen to which they were not sensitive (ie, associated with a negative skin-prick test result). Two additional inhalational challenges were similarly performed on all subjects with asthma, with a nonimmunologic stimulus (methacholine),6,7 and with specific allergen to which the subjects were sensitive (associated with a positive skin-prick test result).8 The specific allergens used were Bermuda grass (n = 3) and Juniper-Mountain Cedar (n = 5). Additional details of these procedures are in the online supplement.

Table Graphic Jump Location
Table 1 List of Inhalational Challenges Performed in Random Order
Outcome Measures

The primary outcome measure was the postchallenge change in concentration of serum adiponectin from baseline. Secondary outcome measures included similar changes in serum concentrations of leptin, adiponectin-to-leptin ratio, eotaxin, and TNF-α. Multiple venous blood samples were obtained in a fasting state at 15 min and just before the start of the challenge, just after the completion of the challenge (0 h), and at 1, 2, 3, 4, 5, 6, 9, and 23 h after the challenge. Baseline (or pretest) levels were derived from the mean of the first two levels obtained. Additional details are provided in the online data supplement.

Statistical Analysis

All outcome measures other than serum adiponectin-to-leptin ratio were logarithmically transformed due to their nonnormal distribution. Statistical analysis used repeated-measures analysis of variance (RM-ANOVA), with both the three challenges and time as repeated factors in subjects with asthma (SAS PROC-MIXED, SAS 9.1.3; SAS Institute; Cary, NC). Outcomes between subjects with asthma and control subjects were similarly compared using case status as the grouping factor and time as the repeated factor. If there were significant differences, post hoc testing with paired t tests was performed. Challenge response curves were plotted as geometric means for logarithmically transformed outcome measures, and as arithmetic means for serum adiponectin-to-leptin ratio. Additionally, area under the curves and baseline and peak concentrations of outcome measures were compared. The covariates studied included measures of obesity and insulin resistance that may affect serum adiponectin concentrations in humans.9,10 These covariates are further described in the online supplement. Statistical significance was accepted as p < 0.05.

Sample Size and Power Estimates

Based on a previous study11 and assuming a modest correlation of 0.7 between baseline and follow-up values, the SD of the difference was estimated at 4.4 μg/mL for serum adiponectin (Table E4 in online supplement). Therefore, our sample size of eight subjects with asthma was adequate to detect a difference of 5.1 μg/mL for serum adiponectin with α = 0.05 and β = 0.2. This study was therefore adequately powered because the published absolute difference in serum adiponectin in a human intervention study was 6.7 μg/mL.11 Further, the power estimate based on mice allergen challenge studies was also adequate.5 The actual power of the study was in fact greater than the above estimation because data were logarithmically transformed.

Fourteen subjects, 8 subjects with asthma and 6 control subjects, were studied, mostly premenopausal, overweight women (Table 2). Among all challenges, the decline in FEV1 following specific allergen inhalation was greatest in magnitude (28.8 ± 5.3%) and duration (Table 2; Table E3 in online supplement).

Table Graphic Jump Location
Table 2 Baseline Characteristics of Study Subjects*

*Data are presented as No. or mean ± SD. HOMA = homeostasis model assessment; N/A = not applicable.

†There was no significant difference between the two groups with respect to these variables (p > 0.05 for all analyses).

Following any inhalational challenge (in both asthma subjects and control subjects), there was an immediate rise in serum adiponectin concentration above baseline, lasting about an hour (Fig 1; Table E2 in online supplement). In addition, there was an immediate decline in serum leptin concentration below baseline, lasting several hours, returning to baseline by the next morning (Fig 2; Table E2 in online supplement). Despite these changes, there was no significant change in serum adiponectin-to-leptin ratio as compared to baseline (Fig 3). This lack of significant change was attributed to large SDs associated with this measure (Table E2 in online supplement). While serum eotaxin concentration (Fig 4) was unaffected by any inhalational challenge, a small transient decline in serum TNF-α concentration 2 to 3 h after the specific allergen and methacholine challenges in subjects with asthma was suggested (Fig 5).

Figure Jump LinkFigure 1 Serum adiponectin (geometric) mean response curves to inhalational challenge. Following any challenge, there was an immediate transient rise in serum adiponectin concentration. Comparison of the three response curves among the eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Logarithmically transformed data shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 2 Serum leptin (geometric) mean response curves to inhalational challenge. Following any challenge, there was an immediate transient decline in serum leptin concentration. Comparison of the three response curves among the eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in controls were compared. Logarithmically transformed data shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 3 Mean response curves of serum adiponectin to leptin ratio to inhalational challenge. Comparison of the three response curves among eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Raw data shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 4 Serum eotaxin (geometric) mean response curves to inhalational challenge. A main effect difference in eotaxin response curves was seen in the eight subjects with asthma using RM-ANOVA, between specific allergen challenge and methacholine and irrelevant allergen challenges. However, no significant differences at individual time points were seen between the various curves. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Logarithmically transformed data are shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 5 Serum TNF-α (geometric) mean response curves to inhalational challenge. Comparison of the three response curves among eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Logarithmically transformed data are shown in Table E2 in the online supplement.Grahic Jump Location
Repeated-Measures Analysis of Outcome Measures Among Subjects With Asthma

Comparison of the three challenges among subjects with asthma showed no significant differences with respect to the response curves, area under the curves, baseline and peak concentrations of serum adiponectin, leptin, adiponectin-to-leptin ratio, and TNF-α (Figs 13, 5; Table E1 in online supplement). A difference in the main effect of the eotaxin response curves between specific allergen and methacholine and irrelevant allergen challenges was noted. However, no significant difference at individual time points in (geometric) mean serum eotaxin level was seen among the various curves (all p > 0.30). Furthermore, there were no significant differences among the three challenges with respect to area under the curve and baseline and peak concentrations of serum eotaxin (Fig 4, Table E1 in online supplement).

Repeated-Measures Analysis of Outcome Measures Between Subjects With Asthma and Control Subjects

Comparison of the specific allergen challenge in subjects with asthma and irrelevant allergen challenge in control subjects again showed no significant differences with respect to the above outcome measures, except for a difference in main effects between the two eotaxin response curves (Figs 15; Table E1 in online supplement). Again, no significant differences in (geometric) mean serum eotaxin concentrations at individual time points, including the baseline, between the two curves were noted (all p > 0.18).

Further, when data from the three challenges in subjects with asthma were pooled, serum adiponectin curves during the 24-h period were significantly lower in subjects with asthma, compared to control subjects (p = 0.02). Adjustment for covariates, ie, obesity (body mass index, dual energy X-ray absorptiometry [DEXA]-assessed percentage of body fat, or percentage of truncal fat separately) and insulin resistance did not explain this observation, and in fact further strengthened the association of adiponectin diurnal variation curves with asthma status (p ≤ 0.01 for all analyses). Similar results were seen when serum adiponectin-to-leptin ratio was used instead of adiponectin.

This study of human subjects with mild asthma does not support the hypothesis established in mice that specific allergen inhalation affects serum adiponectin concentrations. We postulate the following explanations for this discrepancy. First, mice are not the same as humans, and mouse asthma is not the same as human asthma.12 Quite like the current study, the effects of adipokines (such as adipsin, resistin, and interleukin-6) on insulin resistance vary between humans and mice.13 Second, our results may be negative because of subject characteristics. Our subjects were predominantly overweight premenopausal and postmenopausal women and men with a mild asthma phenotype. The choice of subjects was partly based on safety of challenge testing. Further, the relevant animal studies were done on lean (BALB/cJ) mice of both sexes.5,14 Third, the severity of intervention in this study could not match that of the mice allergen challenge studies. Fourth, the results may be negative because of a small sample size (type II statistical error). Despite the small sample size, our power analysis was adequate to detect changes in serum adiponectin, as reported in the referenced human interventional study as well as in the mice allergen challenge experiments.5,11 A careful post hoc evaluation of the power analysis showed that our assumptions for SDs used to calculate effect size were in fact correct (Table E4 in online supplement). Furthermore, logarithmic transformation of data resulted in a greater effect size than was postulated in the prior power analysis.

Serum concentrations of adiponectin, an anti-inflammatory adipokine, are reduced among obese subjects.15,16 High serum adiponectin concentrations are associated with reduced risk of asthma in women after adjusting for obesity.4 In sensitized mice, exogenous adiponectin administration attenuates allergen-induced airway hyperresponsiveness.5 Further, adiponectin messenger RNA production in mice decreases following allergen challenge.5 The adiponectin-asthma relationship in mice is therefore bidirectional. However, the direction of the adiponectin-asthma association is not known in humans.

This study demonstrates transient changes in serum adiponectin and leptin concentrations (Fig 1, 2) following any inhalational challenge in both asthma and control subjects. There are two possible explanations for these findings. First, multiple spirometry maneuvers during the challenge test may itself affect the release of adipokines through a mechanism that is independent of the nature of the inhalant. Second and more likely, the change is due to the superimposed diurnal variations in serum adiponectin and leptin concentrations.17,18 The diurnal variation in serum adiponectin concentration is characterized by a nocturnal decline with a nadir in the early morning and a subsequent peak in the late morning. After peak levels are reached, there is minimum daytime variation.17 Since all challenges were performed between 7:00 am and 8:00 am in this study, the subsequent increase in adiponectin in Figure 1 may represent the described diurnal peak. Similarly, leptin shows diurnal variation with a peak between 10:00 pm and 3:00 am (median, 1:20 am) and a nadir between 8:00 am and 5:40 pm (median, 10:33 am) in one study,18 with an additional delay if subjects were fasting. The decline in serum leptin in Figure 2 may therefore also be explained by normal diurnal variation.18

Although we found a difference in main effects between the eotaxin response curves (Fig 4; Table E1 in online supplement), no significant differences at individual time points in (geometric) mean serum eotaxin concentration were seen among the various curves on post hoc analysis. We therefore postulate that the statistical difference between the eotaxin curves, as detected by the powerful RM-ANOVA analysis, does not have any clinical significance.

If specific allergen inhalation does not affect serum adiponectin concentrations in human asthma, how can we explain our previous cross-sectional observation4 that high concentrations of serum adiponectin are associated with decreased risk for asthma? One explanation is that this association is determined by the long-term effects of asthma on adipose tissue. If correct, the short-term experimental study conditions may not reflect the long-term effects of asthma on adipose tissue. However, we believe that the more plausible explanation is that serum adiponectin affects asthma status in humans (ie, a reverse direction of the adiponectin-asthma association than was hypothesized in this study). Thus, high serum concentration of adiponectin may be a protective factor for human asthma.4,19 However, this still remains to further investigated.

Additionally, we found that the diurnal variation curves of serum adiponectin concentrations in asthma subjects were lower than control subjects. This finding is consistent with the result of our previous large cross-sectional study4 in which serum adiponectin measure at a single time point was studied. Adiponectin inhibits mitogen-induced proliferation and migration of cultured murine vascular smooth-muscle cells,16,20 and may have similar effects on airway smooth muscle.5 Given that adiponectin receptors are expressed in human airway smooth cells,21 it is possible that continually decreased serum adiponectin may contribute toward increased airway smooth-muscle mass in asthma.1

The strengths of this study include careful characterization of subjects, multiple (within-group and between-group) comparison of specific allergen challenge, randomized and blinded administration of challenges, and extensive time-sensitive sampling of outcome measures in a fasting state. Further, this is the first human study translated from the novel theory formulated on mice experiments.5,14,22

Potential limitations include possibly lower level of severity of allergen intervention and truncated timing of the last serum sample drawn after challenge in this human study, as compared to the relevant mice study. Our abbreviated time strategy (23 h compared to 48 h in the mice study5) was influenced by the limits we could safely impose on fasting human volunteers to be interned in controlled conditions. It is also possible that airway adipokines may have been more relevant than serum adipokines in this study. However, the study objective was to replicate the mouse experiment that measured serum adipokines.5 Further, measurement of airway adipokines is technically difficult, and multiple measurements would not have been possible. Another potential weakness may be the inclusion of men and postmenopausal women in this study. However, post hoc analysis of the four premenopausal women in each group revealed similar results. It should be noted that this study was not designed to evaluate the interaction of sex, menopausal status, or obesity on adiponectin response to allergen challenge. The relevant animal study (that this human study was translated from) was done on lean mice of both sexes.5

To summarize, this study is the first to report lower diurnal variation curves of serum adiponectin in subjects with asthma as compared to healthy control subjects. Further, unlike mice, specific allergen inhalation in humans with mild asthma does not acutely affect serum adiponectin concentrations. We instead hypothesize the reverse association (ie, serum adiponectin may affect asthma status in humans).4 If future studies prove that serum adiponectin is a protective factor for human asthma, modulating adiponectin may open a unique and innovative approach toward managing asthma.

DEXA

dual energy X-ray absorptiometry

RM-ANOVA

repeated-measures analysis of variance

TNF

tumor necrosis factor

The investigators would like to thank Stephanie Shore, PhD, Senior Lecturer, Harvard School of Public Health; Ronald Schrader, PhD, Biostatistics and Informatics Core Laboratory, University of New Mexico Clinical Translational Science Center; and Julie Wilder, PhD, Lovelace Respiratory Research Institute, for their input into the study.

Shore SA. Obesity and asthma: lessons from animal models. J Appl Physiol. 2007;102:516-528. [PubMed] [CrossRef]
 
Beuther DA, Weiss ST, Sutherland ER. Obesity and asthma. Am J Respir Crit Care Med. 2006;174:112-119. [PubMed]
 
Shore SA. Obesity and asthma: implications for treatment. Curr Opin Pulm Med. 2007;13:56-62. [PubMed]
 
Sood A, Cui X, Qualls C, et al. Association between asthma and serum adiponectin concentration in women. Thorax. 2008;63:877-882. [PubMed]
 
Shore SA, Terry RD, Flynt L, et al. Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol. 2006;118:389-395. [PubMed]
 
Chai H, Farr RS, Froehlich LA, et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol. 1975;56:323-327. [PubMed]
 
Allen ND, Davis BE, Hurst TS, et al. Difference between dosimeter and tidal breathing methacholine challenge: contributions of dose and deep inspiration bronchoprotection. Chest. 2005;128:4018-4023. [PubMed]
 
Gerblich AA, Campbell AE, Schuyler MR. Changes in T-lymphocyte subpopulations after antigenic bronchial provocation in asthmatics. N Engl J Med. 1984;310:1349-1352. [PubMed]
 
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419. [PubMed]
 
Mather KJ, Hunt AE, Steinberg HO, et al. Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab. 2001;86:5457-5464. [PubMed]
 
Fallo F, Scarda A, Sonino N, et al. Effect of glucocorticoids on adiponectin: a study in healthy subjects and in Cushing's syndrome. Eur J Endocrinol. 2004;150:339-344. [PubMed]
 
Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004;172:2731-2738. [PubMed]
 
Arner P. Resistin: yet another adipokine tells us that men are not mice. Diabetologia. 2005;48:2203-2205. [PubMed]
 
Shore SA, Schwartzman IN, Mellema MS, et al. Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol. 2005;115:103-109. [PubMed]
 
Wulster-Radcliffe MC, Ajuwon KM, Wang J, et al. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun. 2004;316:924-929. [PubMed]
 
Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100:2473-2476. [PubMed]
 
Gavrila A, Peng CK, Chan JL, et al. Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab. 2003;88:2838-2843. [PubMed]
 
Saad MF, Riad-Gabriel MG, Khan A, et al. Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. J Clin Endocrinol Metab. 1998;83:453-459. [PubMed]
 
Sood A, Camargo CA Jr, Ford ES. Association between leptin and asthma in adults. Thorax. 2006;61:300-305. [PubMed]
 
Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002;106:2767-2770. [PubMed]
 
Shore SA, Johnston RA. Obesity and asthma. Pharmacol Ther. 2006;110:83-102. [PubMed]
 
Yeatts K, Sly P, Shore S, et al. A brief targeted review of susceptibility factors, environmental exposures, asthma incidence, and recommendations for future asthma incidence research. Environ Health Perspect. 2006;114:634-640. [PubMed]
 

Figures

Figure Jump LinkFigure 1 Serum adiponectin (geometric) mean response curves to inhalational challenge. Following any challenge, there was an immediate transient rise in serum adiponectin concentration. Comparison of the three response curves among the eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Logarithmically transformed data shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 2 Serum leptin (geometric) mean response curves to inhalational challenge. Following any challenge, there was an immediate transient decline in serum leptin concentration. Comparison of the three response curves among the eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in controls were compared. Logarithmically transformed data shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 3 Mean response curves of serum adiponectin to leptin ratio to inhalational challenge. Comparison of the three response curves among eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Raw data shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 4 Serum eotaxin (geometric) mean response curves to inhalational challenge. A main effect difference in eotaxin response curves was seen in the eight subjects with asthma using RM-ANOVA, between specific allergen challenge and methacholine and irrelevant allergen challenges. However, no significant differences at individual time points were seen between the various curves. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Logarithmically transformed data are shown in Table E2 in the online supplement.Grahic Jump Location
Figure Jump LinkFigure 5 Serum TNF-α (geometric) mean response curves to inhalational challenge. Comparison of the three response curves among eight subjects with asthma using RM-ANOVA showed no significant differences. Similar results were noted when specific allergen challenge in asthma and irrelevant allergen challenge in control subjects were compared. Logarithmically transformed data are shown in Table E2 in the online supplement.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1 List of Inhalational Challenges Performed in Random Order
Table Graphic Jump Location
Table 2 Baseline Characteristics of Study Subjects*

*Data are presented as No. or mean ± SD. HOMA = homeostasis model assessment; N/A = not applicable.

†There was no significant difference between the two groups with respect to these variables (p > 0.05 for all analyses).

References

Shore SA. Obesity and asthma: lessons from animal models. J Appl Physiol. 2007;102:516-528. [PubMed] [CrossRef]
 
Beuther DA, Weiss ST, Sutherland ER. Obesity and asthma. Am J Respir Crit Care Med. 2006;174:112-119. [PubMed]
 
Shore SA. Obesity and asthma: implications for treatment. Curr Opin Pulm Med. 2007;13:56-62. [PubMed]
 
Sood A, Cui X, Qualls C, et al. Association between asthma and serum adiponectin concentration in women. Thorax. 2008;63:877-882. [PubMed]
 
Shore SA, Terry RD, Flynt L, et al. Adiponectin attenuates allergen-induced airway inflammation and hyperresponsiveness in mice. J Allergy Clin Immunol. 2006;118:389-395. [PubMed]
 
Chai H, Farr RS, Froehlich LA, et al. Standardization of bronchial inhalation challenge procedures. J Allergy Clin Immunol. 1975;56:323-327. [PubMed]
 
Allen ND, Davis BE, Hurst TS, et al. Difference between dosimeter and tidal breathing methacholine challenge: contributions of dose and deep inspiration bronchoprotection. Chest. 2005;128:4018-4023. [PubMed]
 
Gerblich AA, Campbell AE, Schuyler MR. Changes in T-lymphocyte subpopulations after antigenic bronchial provocation in asthmatics. N Engl J Med. 1984;310:1349-1352. [PubMed]
 
Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28:412-419. [PubMed]
 
Mather KJ, Hunt AE, Steinberg HO, et al. Repeatability characteristics of simple indices of insulin resistance: implications for research applications. J Clin Endocrinol Metab. 2001;86:5457-5464. [PubMed]
 
Fallo F, Scarda A, Sonino N, et al. Effect of glucocorticoids on adiponectin: a study in healthy subjects and in Cushing's syndrome. Eur J Endocrinol. 2004;150:339-344. [PubMed]
 
Mestas J, Hughes CC. Of mice and not men: differences between mouse and human immunology. J Immunol. 2004;172:2731-2738. [PubMed]
 
Arner P. Resistin: yet another adipokine tells us that men are not mice. Diabetologia. 2005;48:2203-2205. [PubMed]
 
Shore SA, Schwartzman IN, Mellema MS, et al. Effect of leptin on allergic airway responses in mice. J Allergy Clin Immunol. 2005;115:103-109. [PubMed]
 
Wulster-Radcliffe MC, Ajuwon KM, Wang J, et al. Adiponectin differentially regulates cytokines in porcine macrophages. Biochem Biophys Res Commun. 2004;316:924-929. [PubMed]
 
Ouchi N, Kihara S, Arita Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation. 1999;100:2473-2476. [PubMed]
 
Gavrila A, Peng CK, Chan JL, et al. Diurnal and ultradian dynamics of serum adiponectin in healthy men: comparison with leptin, circulating soluble leptin receptor, and cortisol patterns. J Clin Endocrinol Metab. 2003;88:2838-2843. [PubMed]
 
Saad MF, Riad-Gabriel MG, Khan A, et al. Diurnal and ultradian rhythmicity of plasma leptin: effects of gender and adiposity. J Clin Endocrinol Metab. 1998;83:453-459. [PubMed]
 
Sood A, Camargo CA Jr, Ford ES. Association between leptin and asthma in adults. Thorax. 2006;61:300-305. [PubMed]
 
Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002;106:2767-2770. [PubMed]
 
Shore SA, Johnston RA. Obesity and asthma. Pharmacol Ther. 2006;110:83-102. [PubMed]
 
Yeatts K, Sly P, Shore S, et al. A brief targeted review of susceptibility factors, environmental exposures, asthma incidence, and recommendations for future asthma incidence research. Environ Health Perspect. 2006;114:634-640. [PubMed]
 
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