Asthma, Obesity
Conditions
Keywords
Asthma, Obesity
Brief summary
The purpose of this study is to examine whether there are higher levels of cysteinyl leukotrienes in obese subjects than in non-obese subjects. Cysteinyl leukotrienes are pro-inflammatory substances that cause asthma by narrowing the airways of the lung. The investigators want to see if subjects with increased fat stores and therefore increased leptin, which is a fat-related protein that regulates leukotrienes, have increased levels of leukotrienes in the blood, lung and urine. The investigators would also like to determine the relationship between cysteinyl leukotrienes and exhaled nitric oxide levels in asthmatics with and without obesity. Nitric oxide is anti-inflammatory and suppresses leukotriene synthesis.
Detailed description
This is a cross-sectional observational study to characterize the association between obese asthmatics and the inflammatory mediators cysteinyl leukotrienes. Our hypothesis is that altered adipokine levels in obesity result in augmented cysteinyl leukotriene synthesis that play a significant role in the pathogenesis of asthma in these subjects.
Interventions
None listed
Sponsors
Merck Sharp & Dohme LLC
University of Michigan
Study design
Observational model
CASE_CONTROL
Time perspective
CROSS_SECTIONAL
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* 18-65 yr old adults with asthma, non-smoking for at least one year * Healthy non-smoking adults, aged 18-65 without asthma * Heavy subjects with BMI \> 30 kg/m2 * Subjects with normal weight (BMI between 20-25 kg/m2) * Subject not taking anti-leukotriene therapy (Singulair, Accolate, Zyflo)
Exclusion criteria
* No chronic oral steroid use * No recent history of infection * No recent history of flare of lung disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Plasma Leptin | Observational: one time point from a blood draw after more than 6 hours fasting | Measurement of plasma leptin in obese and non obese asthmatics and non-asthmatic subjects from a single blood draw. |
| Exhaled Nitric Oxide (FeNO) | Observational: Two exhalations within 1 minute | Exhaled breath nitic oxide ppb (averaged values from 2 exhalations per participant) |
| Urine Cysteinyl Leukotriene Per Creatinine | sample taken over 5 minutes or less | Urine inflammatory mediators measured from a single urine sample |
| Ratio U Cys-LT/FeNO | sample taken over 5 minutes or less | Responsiveness to leukotriene modifier medication by measuring the urine cysteinyl leukotriene/exhaled nitric oxide ratio |
Countries
United States
Participant flow
Recruitment details
OA Obese Asthma BMI \>30 NANO Non asthma non obese ANO Asthma non obese NAO Non asthma obese BMI \>30 Started July 2010 completed May 2013
Pre-assignment details
Pre-assignment weight determined and pulmonary function testing prior to enrollment in observational study One time point study when mediators were mesaured.
Participants by arm
| Arm | Count |
|---|---|
| Obese Asthma (OA) BMI \> 30 Obese
Asthma based on asthma questionnaire, peak flow meter, spirometry, history, physical examination and medication use. | 30 |
| Non Asthma Non-obese (NANO) BMI 20-25 Non obese | 30 |
| Asthma Non Obese (ANO) BMI 20-25 Non obese
Asthma based on asthma questionnaire, peak flow meter, spirometry, history, physical examination and medication use. | 29 |
| Non Asthma Obese (NAO) BMI \> 30 Obese | 28 |
| Total | 117 |
Baseline characteristics
| Characteristic | Obese Asthma (OA) | Non Asthma Non-obese (NANO) | Asthma Non Obese (ANO) | Non Asthma Obese (NAO) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 44.0 years STANDARD_DEVIATION 10.3 | 31.5 years STANDARD_DEVIATION 11.6 | 29.9 years STANDARD_DEVIATION 9.8 | 42.7 years STANDARD_DEVIATION 13.6 | 37.0 years STANDARD_DEVIATION 13.6 |
| BMI | 38.9 kg/m^2 STANDARD_DEVIATION 6.1 | 22.9 kg/m^2 STANDARD_DEVIATION 1.7 | 22.8 kg/m^2 STANDARD_DEVIATION 1.7 | 37.7 kg/m^2 STANDARD_DEVIATION 5.4 | 30.8 kg/m^2 STANDARD_DEVIATION 9.2 |
| Sex: Female, Male Female | 21 Participants | 15 Participants | 20 Participants | 21 Participants | 77 Participants |
| Sex: Female, Male Male | 9 Participants | 15 Participants | 9 Participants | 7 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 30 | 0 / 30 | 0 / 29 | 0 / 28 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 | 0 / 29 | 0 / 28 |
Outcome results
Primary
Exhaled Nitric Oxide (FeNO)
Exhaled breath nitic oxide ppb (averaged values from 2 exhalations per participant)
Time frame: Observational: Two exhalations within 1 minute
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obese Asthma (OA) | Exhaled Nitric Oxide (FeNO) | 17.8 parts per billion (ppb) | Standard Deviation 9.3 |
| Non Asthma Non-obese (NANO) | Exhaled Nitric Oxide (FeNO) | 20.7 parts per billion (ppb) | Standard Deviation 14 |
| Asthma Non Obese (ANO) | Exhaled Nitric Oxide (FeNO) | 29.5 parts per billion (ppb) | Standard Deviation 22.4 |
| Non Asthma Obese (NAO) | Exhaled Nitric Oxide (FeNO) | 19.9 parts per billion (ppb) | Standard Deviation 10.4 |
p-value: 0.002ANOVA
Primary
Plasma Leptin
Measurement of plasma leptin in obese and non obese asthmatics and non-asthmatic subjects from a single blood draw.
Time frame: Observational: one time point from a blood draw after more than 6 hours fasting
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obese Asthma (OA) | Plasma Leptin | 55.4 ng/ml | Standard Deviation 26.9 |
| Non Asthma Non-obese (NANO) | Plasma Leptin | 8.9 ng/ml | Standard Deviation 8.8 |
| Asthma Non Obese (ANO) | Plasma Leptin | 24.2 ng/ml | Standard Deviation 12.9 |
| Non Asthma Obese (NAO) | Plasma Leptin | 46.5 ng/ml | Standard Deviation 24.2 |
p-value: <0.0001ANOVA
Primary
Ratio U Cys-LT/FeNO
Responsiveness to leukotriene modifier medication by measuring the urine cysteinyl leukotriene/exhaled nitric oxide ratio
Time frame: sample taken over 5 minutes or less
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obese Asthma (OA) | Ratio U Cys-LT/FeNO | 0.5 ratio | Standard Deviation 0.4 |
| Non Asthma Non-obese (NANO) | Ratio U Cys-LT/FeNO | 0.42 ratio | Standard Deviation 0.3 |
| Asthma Non Obese (ANO) | Ratio U Cys-LT/FeNO | 0.3 ratio | Standard Deviation 0.21 |
| Non Asthma Obese (NAO) | Ratio U Cys-LT/FeNO | 0.44 ratio | Standard Deviation 0.21 |
p-value: 0.16ANOVA
Primary
Urine Cysteinyl Leukotriene Per Creatinine
Urine inflammatory mediators measured from a single urine sample
Time frame: sample taken over 5 minutes or less
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Obese Asthma (OA) | Urine Cysteinyl Leukotriene Per Creatinine | 7.21 pg/mg creatinine | Standard Deviation 3.2 |
| Non Asthma Non-obese (NANO) | Urine Cysteinyl Leukotriene Per Creatinine | 6.35 pg/mg creatinine | Standard Deviation 3.3 |
| Asthma Non Obese (ANO) | Urine Cysteinyl Leukotriene Per Creatinine | 6.31 pg/mg creatinine | Standard Deviation 2.65 |
| Non Asthma Obese (NAO) | Urine Cysteinyl Leukotriene Per Creatinine | 6.67 pg/mg creatinine | Standard Deviation 3.3 |
p-value: 0.725ANOVA