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Original Research: Asthma |

Effects of Weight Loss on Airway Responsiveness in Obese Adults With AsthmaDoes Weight Loss Lead to Reversibility of Asthma?: Does Weight Loss Lead to Reversibility of Asthma? FREE TO VIEW

Smita Pakhale, MD; Justine Baron, PhD; Robert Dent, MD; Katherine Vandemheen, MSc; Shawn D. Aaron, MD
Author and Funding Information

From the Department of Medicine (Drs Pakhale, Dent, and Aaron), The Ottawa Hospital; University of Ottawa (Drs Pakhale, Baron, Dent, and Aaron); and Ottawa Hospital Research Institute (Drs Pakhale, Baron, Dent, and Aaron and Ms Vandemheen), Ottawa, ON, Canada.

CORRESPONDENCE TO: Smita Pakhale, MD, Department of Medicine, The Ottawa Hospital, 501 Smyth Rd, Ottawa, ON K1H 8L6, Canada; e-mail: spakhale@ohri.ca


FUNDING/SUPPORT: Funding for this study was provided by the Department of Medicine, The Ottawa Hospital, and the Ontario Thoracic Society.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;147(6):1582-1590. doi:10.1378/chest.14-3105
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Published online

BACKGROUND:  The growing epidemics of obesity and asthma are major public health concerns. Although asthma-obesity links are widely studied, the effects of weight loss on asthma severity measured by airway hyperresponsiveness (AHR) have received limited attention. The main study objective was to examine whether weight reduction reduces asthma severity in obese adults with asthma.

METHODS:  In a prospective, controlled, parallel-group study, we followed 22 obese participants with asthma aged 18 to 75 years with a BMI ≥ 32.5 kg/m2 and AHR (provocative concentration of methacholine causing a 20% fall in FEV1 [PC20] < 16 mg/mL). Sixteen participants followed a behavioral weight reduction program for 3 months, and six served as control subjects. The primary outcome was change in AHR over 3 months. Changes in lung function, asthma control, and quality of life were secondary outcomes.

RESULTS:  At study entry, participant mean ± SD age was 44 ± 9 years, 95% were women, and mean BMI was 45.7 ± 9.2 kg/m2. After 3 months, mean weight loss was 16.5 ± 9.9 kg in the intervention group, and the control group had a mean weight gain of 0.6 ± 2.6 kg. There were significant improvements in PC20 (P = .009), FEV1 (P = .009), FVC (P = .010), asthma control (P < .001), and asthma quality of life (P = .003) in the intervention group, but these parameters remained unchanged in the control group. Physical activity levels also increased significantly in the intervention group but not in the control group.

CONCLUSIONS:  Weight loss in obese adults with asthma can improve asthma severity, AHR, asthma control, lung function, and quality of life. These findings support the need to actively pursue healthy weight-loss measures in this population.

Figures in this Article

The growing obesity epidemic is a prominent public health issue worldwide.1 The prevalence of asthma increased to 7.9% in 2013, affecting > 2,400,000 Canadians.2 The simultaneously growing epidemics of asthma and obesity have led to a hypothesis of a causal link between the two.3,4 Research suggests that the incidence of asthma is 1.47 times greater in obese people than nonobese people5 and that a three-unit increase in BMI is associated with a 35% increase in the risk of asthma.4 Additionally, a one-unit increase in BMI has been associated with a 3.1% increase in airway hyperresponsiveness (AHR),6 the cardinal pathophysiologic feature of asthma.7 The direction of this causal link between obesity and asthma remains unclear.7 Research suggests that obesity affects lung function, resulting in respiratory symptoms similar to asthma and exaggerating the effects of preexisting asthma.7 Other research has shown asthma to be associated with decreased physical activity and that oral corticosteroid therapy prescribed for asthma is related to weight gain,8,9 suggesting that obesity may be a consequence of asthma.

Despite the asthma-obesity link, few studies have examined whether weight loss in obese people with asthma improves asthma outcomes. A 2008 review10 included four studies1114 focusing only on obese subjects with asthma and suggested that weight loss is associated with improvements in asthma control, asthma symptoms, medication use, asthma severity, dyspnea, FVC, and FEV1; three additional studies1517 identified in a subsequent review18 confirmed these findings. Three other studies15,1921 further confirmed some of these effects of weight loss in obese subjects with asthma. The methodologic quality of these studies was poor,18 and their sample sizes were small, but the consistency in the findings is promising. One major methodologic flaw in this area is that few studies11,14,16 rely on appropriate physiologic tests for asthma to determine study eligibility (ie, AHR, reversibility of airway obstruction). This is problematic because up to 30% of obese subjects who report a physician diagnosis of asthma have been found to have received a misdiagnosis.22 In addition, to our knowledge, only one study20 investigated the effects of weight loss on quality of life in obese subjects with asthma.

Importantly, the effect of weight loss on AHR has rarely been studied. To our knowledge, only two studies included AHR as the primary outcome.19,20 We designed the current study to examine the effects of weight loss on asthma severity as measured by AHR in obese subjects with appropriately diagnosed asthma.

Study Design

In this 3-month prospective, controlled, parallel-group study in obese participants with physiologically proven asthma, we compared intervention participants who followed a low-calorie diet for the first 3 months of a 12-month behavioral weight reduction program to control participants who engaged in no specific weight management strategy while waiting for bariatric surgery. The study was approved by the Ottawa Health Science Network Research Ethics Board (2009847-01H).

Setting

The Weight Management Clinic-Bariatric Centre of Excellence at the Ottawa Hospital offers a 12-month behavioral program in lifestyle modification and a bariatric surgical treatment program (laparoscopic Roux-en-Y gastroplasty). Waiting time for the surgical treatment program averages 12 months.

Participants

Patients aged 18 to 75 years with a BMI ≥ 32.5 kg/m2 and self-reported physician-diagnosed asthma were referred to The Weight Management Clinic-Bariatric Centre of Excellence at the Ottawa Hospital. We established a diagnosis of asthma by positive methacholine challenge test (MCT). A provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) < 16 mg/mL was used as the threshold to diagnose asthma. The exclusion criteria were contraindications for an MCT (FEV1 < 60%, pregnancy, or breastfeeding). Another eligibility criterion for control participants was to not intend to engage in any weight management strategy during the study period.

Recruitment

Patients of the bariatric center were presented with the option of pursuing a behavioral weight reduction program or undergoing bariatric surgery. Potential participants with a self-reported physician diagnosis of asthma were approached and informed about the study.

All interested and potentially eligible participants were invited to a baseline visit where they first completed a baseline questionnaire and then scheduled an MCT to objectively confirm the asthma diagnosis. All participants signed a consent form prior to completing study procedures. Participants with a positive MCT were prospectively followed and reassessed at 3 months. Those who had opted for the behavioral weight reduction program were enrolled as intervention participants, and those on the waiting list for bariatric surgery were enrolled as control participants.

Treatment Groups

We followed intervention participants during the first 3 months of the behavioral weight management program that comprised three daily liquid meal replacement supplements of 300 kcal each (OPTIFAST 900 [Nestlé] with 40% protein calories, 30% carbohydrate calories, and 30% fat calories) and weekly group sessions to discuss progress and listen to presentations by health professionals (eg, nutritionist, behavior therapist, exercise specialist) on weight management. Control participants were waiting for bariatric surgery during the study period and did not pursue a weight loss strategy.

Study Outcomes

The primary outcome was change in AHR to methacholine (PC20). Secondary outcomes were changes in lung function (FEV1, FVC, FEV1/FVC), asthma medication use, asthma control, and asthma quality of life.

Study Evaluation

Participant height, weight, and waist circumference were measured at baseline and 3 months prior to questionnaire completion. Their BMI (kg/m2) was calculated.

MCT and Lung Function

We performed a standardized MCT protocol endorsed by the American Thoracic Society.23 We administered increasing concentrations of inhaled methacholine (0.03, 0.06, 0.125, 0.25, 0.50, 1, 2, 4, 8, and 16 mg/mL) and performed spirometry after each inhalation using the 2-min tidal breathing method.23 The tests were stopped when the concentration of methacholine administered had induced a 20% fall in FEV1 from baseline or after a concentration of 16 mg/mL was administered. The tests were performed when participants were clinically stable. Short-acting bronchodilators were held for 8 h, and long-acting bronchodilators were held for 48 h before the MCT. If the MCT was negative (PC20 ≥ 16 mg/mL), the participant withheld asthma medications for 1 week, and the test was repeated. If results remained negative, the participant did not qualify for prospective follow-up. The MCT at 3 months was repeated in identical conditions as the baseline MCT with regard to asthma medications.

Asthma Control and Quality of Life

We used the seven-item Asthma Control Questionnaire (ACQ) with the standard 1-week recall, a reliable and validated survey24 that includes lung function in its overall rating. The overall ACQ score is the mean score of the seven items. Higher scores indicate more severely uncontrolled asthma.

We used the standardized 32-item Asthma Quality of Life Questionnaire (AQLQ)25 that includes four subscales (symptoms, activity limitation, emotional function, and environmental stimuli). The overall AQLQ score is the mean of all items, and the scores for individual domains are the means of domain-specific items. Higher scores indicate greater quality of life.

Asthma Medication Use

We asked participants to self-report use of asthma medications. The data were collected in the baseline and 3-month questionnaire assessments.

Physical Activity Levels

The focus of the weight-loss program was dietary, but the weekly group sessions included discussions on lifestyle modifications, including exercise. To monitor changes in exercise behaviors during the study, self-reported data on physical activity were captured in the baseline and 3-month questionnaires and translated into metabolic equivalent tasks (METs).

Statistical Analysis

We described baseline characteristics using measures of central tendency and dispersion and t, χ2, and Fisher exact tests to examine baseline differences between treatment groups. We also used these tests to compare participants followed prospectively to those excluded from the prospective follow-up after a negative MCT (e-Table 1). A PC20 ≥ 16 mg/mL was considered equal to 16 mg/mL for analysis purposes. PC20 was log-transformed because these data were not normally distributed. We used a one-factor repeated-measures analysis of variance to study 3-month changes in outcomes within treatment groups. We used a two-way repeated-measures analysis of variance to compare changes over time in treatment groups. Associations between absolute and percent changes in weight and in parameters significantly influenced by the intervention were examined using Pearson correlations. Statistical significance was set at P < .050.

Figure 1 presents the study flow. A total of 142 potentially eligible participants expressed interest in the study. Fifty-five (38.7%) refused to participate following contact with the research team, and 25 (17.6%) were excluded from the study. Sixty-two (43.7%) signed a consent form and completed a baseline questionnaire. Forty-four subsequently completed an MCT, 22 of whom had positive results that confirmed their asthma diagnosis and eligibility to be part of the prospective 3-month follow-up. Data collected on patients excluded from the study following a negative MCT (PC20 ≥ 16 mg/mL) showed that these patients were more physically active than those with a positive MCT (P = .012) (e-Table 1).

Figure Jump LinkFigure 1 –  Study flow diagram. MCT = methacholine challenge test; PC20 = provocative concentration of methacholine causing a 20% fall in FEV1.Grahic Jump Location

Table 1 describes the 22 participants followed for 3 months, 16 of whom (72.7%) were in the intervention group, and six of whom (27.3%) served as control subjects. The majority were women, well-educated, and never smokers. Their mean baseline BMI was 45.7 ± 9.2 kg/m2, which indicates severe obesity. Intervention group participants were significantly more physically active and had better asthma-specific quality of life than control participants on two AQLQ subscales (P < .001). One intervention participant withdrew because of lack of time. Table 2 shows the changes from baseline to 3 months in obesity parameters, AHR to methacholine, lung function, asthma control, and quality of life in both study groups.

Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of Intervention and Control Participants

Data are presented as mean ± SD or No. (%). Where percentages do not add up to 100 is a result of missing data on individual items; differences between groups on level of education, income, and smoking status were not tested given fewer than five participants in one or more categories. ACQ = Asthma Control Questionnaire; AQLQ = Asthma Quality of Life Questionnaire; ln = natural logarithm; MET = metabolic equivalent task; PC20 = provocative concentration of methacholine causing a 20% fall in FEV1.

a 

Significant differences between the intervention and control groups at P < .001.

Table Graphic Jump Location
TABLE 2 ]  Changes in Obesity Parameters, Airway Hyperresponsiveness to Methacholine (PC20), Lung Function, Asthma Control, and Quality of Life in the Intervention and Control Groups

Data are presented as mean ± SD. See Table 1 legend for expansion of abbreviations.

a 

One-factor repeated-measures analysis of variance.

Obesity Parameters

Changes in weight and BMI are shown in Figure 2. Intervention participants lost a mean ± SD of 16.5 ± 9.9 kg from baseline to 3 months (P < .001) compared with a mean weight gain of 0.6 ± 2.6 kg in the control group (P = .465), and the interaction between time and group was significant (P = .001). This was equivalent to a mean percent weight change of −14.2 ± 7.9% and 0.94 ± 2.40% for intervention and control participants, respectively. Improvements in BMI (P = .006) and waist circumference (P < .001) were significant in intervention participants. These parameters remained unchanged for the control group. The interaction between time and group was significant for BMI (P = .038) and waist circumference (P = .001).

AHR to Methacholine

PC20 improved from 5.02 mg/mL at baseline to 10.2 mg/mL at 3 months in the intervention group compared with an increase from 6.6 to 7.7 mg/mL in the control group. Analyses using natural logarithm PC20 showed that these improvements were marginally significant in the intervention group (P = .051) and nonsignificant in the control group. Figures 3 and 4 show the mean and individual natural logarithm PC20 values. The interaction between time and group was not significant (P = .458). At the 3-month follow-up, the baseline MCT had changed to negative (PC20 ≥ 16 mg/mL) for eight participants (50%) in the intervention group compared with two (33.3%) in the control group.

Figure Jump LinkFigure 3 –  Changes over time in PC20, FEV1, and FVC. ln = natural logarithm. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 4 –  Changes over time in individual PC20 values. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location
Lung Function

FEV1 and FVC improved by 5% in the intervention group compared with a decrease of 7% in the control group (Fig 3). These changes were only significant for the intervention group (P < .010). The interaction between time and group was significant for FEV1 (P = .021) and FVC (P = .028). The FEV1/FVC ratio remained stable during the study in all participants (P > .050), and there was no interaction between time and group (P = .971).

Use of Asthma Medication

One participant (6.3%) in the intervention group stopped taking asthma medication compared with none in the control group. The significance of this difference was not tested statistically given the low number of participants concerned.

Asthma Control and Asthma Quality of Life

The mean ACQ score in the intervention group improved from 1.4 ± 0.9 at baseline to 0.6 ± 0.6 at 3 months (P < .001), whereas these scores remained unchanged in the control group (1.6 ± 0.8 at baseline to 1.5 ± 1.0 at 3 months; P = .764). The interaction between group and time was significant (P = .008).

Asthma-specific quality of life significantly improved in the intervention group for overall mean scores (P = .003) and for three AQLQ subscales (P ≤ .002). Scores in the control group remained unchanged over time. The interaction between time and group was not significant (P = .277).

Physical Activity

Physical activity significantly increased in the intervention group from 15.5 ± 12.0 to 25.7 ± 17.9 METs (P = .047) and decreased in the control group from 4.6 ± 5.5 to 1.8 ± 2.9 METs (P = .146). The interaction between time and group was not significant (P = .335).

Associations Between Changes in Weight and Outcomes

Examination of correlations between absolute changes in weight (kg) and changes in outcomes significantly improved by the intervention yielded weak or moderate correlations (PC20, r = −0.29; FEV1%, r = 0.30; FVC%, r = 0.16; ACQ, r = −0.29; AQLQ-total, r = −0.12; AQLQ-limitations, r = 0.19; AQLQ-symptoms, r = 0.05; AQLQ-emotions, r = −0.12), none of which was significant. Results were similar when these associations were examined using absolute changes in BMI or waist circumference and when using percent rather than absolute weight change.

This study demonstrated that a behavioral weight reduction program is associated with significant improvements in PC20, FEV1, FVC, asthma control, and quality of life in obese people with physiologically proven asthma. There was no change in any of these asthma outcomes in control participants who followed no weight-loss strategy. The results support findings of previous research that relate weight loss to improved lung function, asthma control, and quality of life10,15,1821 and add to the current small body of evidence that has found effects of weight loss on AHR to be inconsistent.15,19,20

The magnitude of weight loss is one factor that could explain the inconsistency of the findings on the relationship between weight loss and AHR in obese adults with asthma. The present study and others showing weight loss to be associated with improvements in AHR involved mean reductions in BMI ≥ 8.5 units.19,20 More specifically, mean PC20 improved from 0.84 to 6.24 mg/mL following a mean BMI reduction of 16.8 units in a study by Boulet and colleagues,19 whereas a 13.9-unit decrease in BMI was associated with a doubling of mean baseline PC20 in Dixon et al.20 In comparison, another study involving a smaller weight reduction of 5.1 BMI units found this relationship to be nonsignificant.15 This suggests a dose-response relationship between weight loss and some asthma outcomes7,26 and that a minimum amount of weight loss is required for AHR to be significantly improved.

It is unclear why the correlations between changes in obesity parameters, such as weight, BMI, and waist circumference, and asthma outcomes were only found to be weak or moderate. These relationships are complex, and there are likely to be many confounding factors. Other factors such as physical activity levels may have contributed to the changes observed in asthma outcomes. The data on METs show an increase in physical activity levels in the intervention group in the current study. Physical training in obese and nonobese people has been associated with asthma outcomes such as AHR, FEV1, symptoms, and quality of life.27,28 It remains possible, therefore, that the effects observed in the present study on these outcomes resulted from exercise rather than from weight loss per se. Further research in this area would benefit from isolating the dietary and exercise components of a weight reduction program in the evaluation design. Finally, other factors that could have influenced the patient-reported outcomes in the intervention group are the social support experienced in the weekly group sessions, which may have resulted in a response shift in quality-of-life perception29 and the greater quality of life experienced by the intervention group at baseline.

A strength of the current study is that we confirmed the diagnosis of asthma based on AHR, which is the primary physiologic manifestation of asthma. Asthma misdiagnosis rates may be as high as 30%.22 The use of appropriate physiologic assessments to establish an asthma diagnosis is particularly important in obese people because of the asthma-obesity interaction.30 The present data show that 50% of 44 potential participants with a self-reported physician diagnosis of asthma had negative MCT results. The MCT is a highly sensitive test that is particularly useful in excluding the diagnosis of asthma31; therefore, its use in asthma-obesity research is important.

The current study has limitations. The sample size and imbalance between the two research groups limit the reliability and generalizability of the findings. Despite this, the consistency of the findings on the positive effects of weight loss on asthma outcomes in obese people is promising and supports the importance of actively treating comorbid obesity in people with asthma.32 The majority of studies published in this area have sample sizes with < 40 participants; thus, research with larger samples is urgently required. Given the number of participants interested in this study but subsequently found to be ineligible, a considerable pool of potential participants is likely to be needed for future studies to successfully achieve a large sample size. Including this consideration in a power analysis, using a multicenter design, and planning a lengthy recruitment period are recommended. The study relied on a self-reported measure of physical activity. Further research should aim to cross-validate these data with another objective measurement of physical activity. Further research specifically focusing on the effects of weight on asthma severity measured by AHR in obese people with appropriately diagnosed asthma is needed to improve our understanding of the links among asthma severity, obesity, and weight loss. Studies in obese people with asthma may also benefit from investigating the effects of weight loss on other markers of inflammation, such as sputum cell counts, and on serum markers.

This study suggests that weight loss in obese adults with asthma leads to significant improvements in asthma severity measured by AHR, resulting in normalization or improvements in AHR to methacholine (PC20), lung function, asthma control, and quality of life. These findings support the need to actively pursue healthy weight-loss measures in obese adults with asthma.

Author contributions: S. P. had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the analysis. S. P., R. D., K. V., and S. D. A. contributed to the study concept and design; S. P., J. B., R. D., and S. D. A. contributed to the data analysis and interpretation; and S. P., J. B., R. D., K. V., and S. D. A. contributed to the drafting, critical revision for important intellectual content, and final approval of the manuscript.

Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Role of the sponsors: The sponsors had no role in the design of the study, the collection and analysis of the data, or the preparation of the manuscript.

Other contributions: The authors thank Megan Beninger, BScN, and Avanti Garde, BSc, for data collection and data entry; the staff, especially Heather Doelle, MLT, BSc, CCRP, and Jeff Kilbreath, RN, BA, BScN, at The Weight Management Clinic-Bariatric Centre of Excellence at the Ottawa Hospital for recruitment efforts; Elizabeth Juniper, MCSP, MSc, for granting permission to use the AQLQ and ACQ in this research; the Pulmonary Function Lab staff at The Ottawa Hospital for accommodating the study participants; and the study participants for agreeing to take part in this study.

Additional information: The e-Table can be found in the Supplemental Materials section of the online article.

ACQ

Asthma Control Questionnaire

AHR

airway hyperresponsiveness

AQLQ

Asthma Quality of Life Questionnaire

MCT

methacholine challenge test

MET

metabolic equivalent task

PC20

provocative concentration of methacholine causing a 20% fall in FEV1

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Figures

Figure Jump LinkFigure 1 –  Study flow diagram. MCT = methacholine challenge test; PC20 = provocative concentration of methacholine causing a 20% fall in FEV1.Grahic Jump Location
Figure Jump LinkFigure 3 –  Changes over time in PC20, FEV1, and FVC. ln = natural logarithm. See Figure 1 legend for expansion of other abbreviation.Grahic Jump Location
Figure Jump LinkFigure 4 –  Changes over time in individual PC20 values. See Figure 1 legend for expansion of abbreviation.Grahic Jump Location

Tables

Table Graphic Jump Location
TABLE 1 ]  Baseline Characteristics of Intervention and Control Participants

Data are presented as mean ± SD or No. (%). Where percentages do not add up to 100 is a result of missing data on individual items; differences between groups on level of education, income, and smoking status were not tested given fewer than five participants in one or more categories. ACQ = Asthma Control Questionnaire; AQLQ = Asthma Quality of Life Questionnaire; ln = natural logarithm; MET = metabolic equivalent task; PC20 = provocative concentration of methacholine causing a 20% fall in FEV1.

a 

Significant differences between the intervention and control groups at P < .001.

Table Graphic Jump Location
TABLE 2 ]  Changes in Obesity Parameters, Airway Hyperresponsiveness to Methacholine (PC20), Lung Function, Asthma Control, and Quality of Life in the Intervention and Control Groups

Data are presented as mean ± SD. See Table 1 legend for expansion of abbreviations.

a 

One-factor repeated-measures analysis of variance.

References

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