OBESITY & ASTHMA A Specific Phenotype? Andrea Lessard, BSc; Helene Turcotte, MSc; Yum Cormier, MD; and Louis-Philippe Boulet, MD, FCCP Source: CHEST – Official Publication of the American College of Chest Physician Vol.134, No.2, p317-323, 2008
Obesity is associated with an increased prevalence of asthma, especially in women, and appears to be more severe in obese.
This study aimed to determine if obese subjects have a specific asthma phenotype
To examine obese & non-obese subjects with a confirmed diagnosis of asthma based on bronchodilator response or airway responsiveness measurements & compare the ff:
The level of asthma control.
Pulmonary function & airway responsiveness to methacholine.
Perception of asthma symptoms.
Airway & systemic inflammation.
Subjects & Design:
-> obese & non-obese subjects from Laval Hosp. outpatient clinics & advertisement .
-> diagnosed with asthma based on airway response to metacholine <16mg/ml.
-> obese (BMI≥30kg/m 2 )
-> non-obese (BMI<25kg/m 2 )
No informed consent
1 st visit – ht., wt., hip circumference, spirometry w/ bronchodilator response, sputum induction, venous blood samples
ACQ (Asthma Control Questionnaire)
- design to evaluate asthma control by asking the subjects to recall symptoms & β 2-agonist use in the last wk & their FEV1.
- 7-point scale
24 common aeroallergens
(+) atopy = wheal dm ≥3mm after 15min.
Bronchodilator measurements = 15 min. after the administration 200 μ g of inhaled salbutamol.
Induced-sputum Samples = analyzed for IgE, eosinophil, CRP & fibrinogen.
2 nd visit
- lung volumes using body plethysmography
- Methacholine inhalation testing w/ perception of respiratory symptoms.
Sample size – derived from a pilot project on a small group of obese vs non-obese subjects & on previous studies published.
The study was designed to have 80% power to detect a significant relationship between BMI and Asthma Control Score (ACQ) w/ a type I error of 5%.
Categorical variables were expressed using Fisher Exact test.
p value <0.05 using a two-tailed test was taken as significant for all statistical tests.
Data analysis was performed using statistical software ( SAS v9.1.3 and StatView v5.0.1; SAS Inst.;Cary, NC )
ANALYSIS OF RESULTS
Out of 96 subjects, 88 were eligible in the study.
3 obese and 3 non-obese subjects had PC 20 ≥ 16mg/mL were excluded.
1 participant was unable to to perform the methacholine challenge, and another failed to attend the 2 nd visit.
airway responsiveness to methacholine was higher in subject w/ ICS treatment.
No significant difference bet.the the airway responsiveness to obese & non-obese.
20% fall in FEV 1 in obese & non-obese subjects has the same amt. of wheezing (p=0.22), phlegm production (p=0.11), chest tightness (p=0.35), breathlessness (p=0.64), cough (p=0.21)
Despite similar expiratory flows, bronchodilator response, airways responsiveness to methacholine, and symptom perception scores, asthma control was poorer in obese subjects than in non-obese subjects (p=0.005).
Total Lung capacity (p=0.01), expiratory reserve volume (p<0.0001), functional residual capacity (p<0.0001), and residual volume (p=0.006) were lower in obese subjects than in non-obese subjects.
Induced-sputum eosinophil and neutrophil counts were similar in both groups, although there was an inverse correlation between sputum eosinophils and waist circumference and a trend for a similar relationship for BMI.
Blood serum C-reactive protein (p=0.009) and fibrinogen (p=0.0004) levels were higher in obese subjects than in non-obese subjects.
Airway hyperresponsiveness was comparable in both groups, but differences in airway & systemic inflammatory parameters, & changes in pulmonary function w/ obesity is suggestive of a particular asthma phenotype in obese subjects.
The blood level of CRP & waist circumference were correlated w/ lung vol.changes & w/ decrease induced-sputum eosinophil, which could indicate a possible impact of fat distribution & systemic inflammatory state in people who are obese on the dev’t & clinical presentation of asthma.
Based on the results, obese subjects have poorer asthma control than non-obese subject, Lavoie et al. found a significant association between BMI & a total ACQ score in 382 asthmatics.
Poor asthma control in obese individuals could also have been due to their having an altered perception of asthma symptoms. However in this study, they found no significant difference in asthma symptoms perception between in both groups w/ the same degree of bronchoconstriction.
A different phenotype of asthma, reduced response to treatment, or more severe asthma could explain the poorer asthma control in obese asthmatics.
Obesity & insulin resistance may be the the common pathways underlying lung function impairment & metabolic syndrome.
LIMITATION OF THE STUDY
Difficulty in determining how much of the observed abnormalities is related to the mechanical effect of obesity or to an altered immune response that could have influenced bronchoreactivity.
The type of systemic inflammatory markers are nonspecific.
More enrolled obese subjects are female.
Obese subjects have more comorbid illness.
Diferent smoking history of 2 groups.
Obese people with asthma had poorer asthma control than non-obese asthmatic despite similar symptoms perception.
Bronchial and systemic inflammatory characteristics and the specific pattern of pulmonary function changes suggest a different phenotype of asthma in these subjects.
Modulate a particular type of airway inflammation in various organs such as the airway in the subject w/ abdominal obesity.
Further studies w/ more specific markers of bronchial & systemic inflammation are needed to confirm these results.
The impact of weight distribution & body composition between women & men could have different effect to lung volumes & level of systemic inflammation, also hormonal effects could also influence these parameters.
The impact of comorbid illness to obese asthmatics needs further research.