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Obesity & Asthma Journal
 

Obesity & Asthma Journal

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    Obesity & Asthma Journal Obesity & Asthma Journal Presentation Transcript

    • 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
    • BACKGROUND
      • 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
    • OBJECTIVES
      • 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.
    • Keywords:
      • Asthma
      • Obesity
      • Phenotype
      • Asthma control
      • BMI
      • Methacholine
      • FRC
      • RV
      • FEV
      • TLC
      • ERV
      • Sputum induction
      • Inflammatory markers
    • METHODOLOGY
      • 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 )
    • Exclusion!
      • No informed consent
      • Pregnant
      • Comorbid illness
      • Double blind
      • Measurements
      • 1 st visit – ht., wt., hip circumference, spirometry w/ bronchodilator response, sputum induction, venous blood samples
      • PE
      • 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
    • Skin-prick Test:
      • 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.
      • Statistical Methods
      • 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.
    • Table 1 – Demographic & Medical Characteristics 0.78 ± 0.06 0.78 ± 0.07 σ waist-hip ratio 77.7 ± 8.9 79.0 ± 7.2 σ waist circ. 17 (77.3) 22 (100) Subj. w/ atopy 22.8 ± 2.4 23.3 ±1.8 BMI 11 (50) 7 (31.2) Ex. smokers 1 (4.5) 0 Subj. w/ GERD 0 0 Subj. w/ DM 2 2 (9) 0 Subj. w/ HPN 17.5 ± 12.1 18.6 ± 13.8 Asthma duration, yr 22 (100) 15 (68) Female gender 43.7 ± 13.3 32.5 ± 10.0 Age SABAs + ICS (n=22) SABAs (n=22) VARIABLES NON-OBESE
    • 15 (68.2) 21 (95.5) Subj. w/ atopy 107.3 ± 12.4 109.5 ± 16.2 σ waist circ. 0.88 ± 0.09 0.88 ± 0.09 σ waist-hip ratio 37.0 ± 5.8 37.2 ± 5.7 BMI 8 (36.4) 6 (27.3) Ex. smokers 3 (13.6) 2 (9) Subj. w/ GERD 2 (9) 1 (4.5) Subj. w/ DM 2 4 (18) 2 (9) Subj. w/ HPN 24.7 ± 13.6 16.7 ± 8.7 Asthma duration, yr 22 (100) 15 (68) Female gender 44.1 ± 13.5 36.5 ± 13.0 Age SABAs + ICS (n=22) SABAs (n=22) VARIABLES OBESE
      • Table 1
      • n = 44 (SABAs)
      • n =44 (ICS)
      • σ dose of ICS in obese= 827±282
      • σ dose of ICS in non-obese = 814±282
    • Total ACQ Scores
      • Significantly higher for the obese subjects than non-obese (p=0.005).
      • Obese subjects significantly more activity limitation (p=0.003) and
      • wheezing (p=0.005).
      • No significant different:
      • - No.of awakenings/night (p=0.15)
      • - ƒ of presence of symptoms on waking (p=0.10).
      • - amt. of SABA use (p=0.11)
      • ACQ total score was positively correlated w/ BMI (p=0.01, r=0.27)
      • - waist circumference (p=0.03, r=0.24)
      • - not to waist-to-hip ratio
      • Table 2
    • Table 2 – Spirometry, Lung Volumes, & Methacholine Test Results 106 ± 20 108 ± 25 σ IC % predicted 117 ± 33 108 ± 44 σ ERV % predicted 1.03 (0.66-1.61) 1.32 (0.79-2.20) PC 20 mg/mL 5.7 ± 4.6 6.5 ± 7.0 σ change % predicted reversibble FEV1 119 ± 28 125 ± 33 σ RV % predicted 115 ± 15 113 ± 18 σ TLC % predicted 56 ± 24 73 ± 23 σ FEF 25-75% % predicted 88 ± 11 92 ± 10 σ FEV/FVC 101 ± 15 111 ± 15 σ FVC % predicted 90 ± 17 98 ± 13 σ FEV1 % predicted SABAs + ICS (n=22) SABAs (n=22) VARIABLES NON-OBESE
    • 0.96 (0.55-1.68) 1.36 (0.77-1.61) PC 20 mg/mL 6.3 ± 5.6 4.9 ± 5.2 σ change % predicted reversibble FEV1 127 ± 24 124 ± 24 σ IC % predicted 67 ± 61 78 ± 36 σ ERV % predicted 117 ± 25 90 ± 23 σ RV % predicted 109 ± 12 104 ± 13 σ TLC % predicted 50 ± 22 79 ± 25 σ FEF 25-75% % predicted 90 ± 12 94 ± 7 σ FEV/FVC 92 ± 13 111 ± 18 σ FVC % predicted 81 ± 16 100 ± 18 σ FEV1 % predicted SABAs + ICS (n=22) SABAs (n=22) VARIABLES OBESE
    • Methacholine Challenge:
      • 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.
    • Table 3: Differential Cell Count in Induced Sputum 1.9 (2.1) 10.5 (17.1) Metachromatic cells 40.9 (17.1) 31.6 (21.8) Neutrophils 1.5 (1.3) 1.3 (0.9) Lymphocystes 40.6 (19.4) 54.5 (30.1) Macrophages 15.2 (19.6) 2.6 (3.7) Eosinophils SABAs + ICS SABAs VARIABLES NON-OBESE
    • 3.2 (4.1) 3.6 (3) Metachromatic cells 41.5 (26.7) 48.6 (21.3) Neutrophils 1.5 (1.0) 1.3 (1.2) Lymphocystes 48.7 (23.9) 42.1 (19.8) Macrophages 5.1 (8.8) 4.6 (12.9) Eosinophils SABAs + ICS SABAs VARIABLES OBESE
    • 2.4 ± 3.4 mg/L 4.3 ± 3.2 mg/L σ serum CRP (p=0.001) 3.1 ± 0.6 g/L 3.7 ± 0.7 g/L Serum level of Fibrinogen (p=0.0002) 219 ± 245 IU/mL 216 ± 367 IU/mL Serum IgE (p=0.96) NON-OBESE OBESE
      • 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.
    • DISCUSSION
      • 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.
      CONCLUSION
    • RECOMMENDATIONS
      • 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.
    • thank you!