Adult obese patients from the Department of Nutrition of the University Hospital of Reims (France) were consecutively referred for a systematic respiratory evaluation without specific reason and considered for inclusion in this study. Inclusion criteria were a BMI ≥ 30 kg/m² and an age > 18 year-old. Exclusion criteria were a known coexisting pulmonary or neuromuscular disease or an inability to perform a 6MWT or pulmonary function testing. The study was approved by the Institutional Review Board (IRB) of the University Hospital of Reims, and patient consent was waived.

Fifty four consecutive patients with a BMI ≥ 30 kg/m² were considered for inclusion. Of these, 9 patients were excluded because of an inability to perform the 6MWT related to an osteoarticular disorder (n = 2) or because of a diagnosed respiratory disease (n = 7; 5 asthma, 1 hypersensitivity pneumonia and 1 right pleural effusion).

Results of 45 patients were considered in the final analysis. Demographic characteristics of the patients are presented in Table 2. Mean BMI was 43 ± 9 kg/m², with 55% of the patients presenting an extreme obesity (BMI ≥ 40 kg/m², grade 3). Regarding smoking status, 56% of patients were never smokers and 11% were current smokers. The main comorbidities were hypertension (53%), dyslipidemia (40%) and diabetes (36%). Severe obstructive sleep apnea syndrome was present in 16 patients (43%).

Data are expressed as mean ± SD or number (%).

Results of dyspnea assessment are presented in Table 3. Dyspnea symptom assessed by the mMRC scale was very frequent in obese subjects with 84% (n = 38) of patients with a mMRC scale ≥ 1 and 40% (n = 18) of patients with a mMRC scale ≥ 2 (29% mMRC = 2, 9% mMRC = 3 and 2% mMRC = 4).

Data are expressed as mean ± SD or number (%).

mMRC: modified Medical Research Council, 6MWT: six-minute walk test.

The mean distance covered in 6MWT was 420 ± 112 m. Sixteen percent of patients had a decrease > 4% of SpO2 during the 6MWT and one patient had a SpO2 < 90% at the end of the 6MWT (Table 4). The dyspnea sensation at rest was very slight (Borg = 1 ± 1.5) but severe after exertion (Borg = 5.4 ± 2.4). Fifty-three percent of patients exhibited a Borg scale ≥ 5 after the 6MWT which is considered as severe exertional dyspnea. No complication occurred during the 6MWT. Subjects with a mMRC score ≥ 2 had a higher Borg score after the 6MWT than subjects with a mMRC score < 2 (6.5 ± 1.5 vs 4.7 ± 2.5, p < 0.05).

Data are expressed as mean ± SD or number (%).

FEV₁: expiratory volume in one second, VC: vital capacity, FRC: functional residual capacity, ERV: expiratory reserve volume, TLC: total lung capacity, DLCO: carbon monoxide diffusing capacity of the lung, pred: predicted value, 6MWT: six-minute walk test.

Results of spirometry, plethysmography and arterial blood gases are shown in Table 4. Overall, the PFTs results remained in the normal range for most of the patients, except for ERV predicted values which were lower (ERV = 56 ± 34%). There were an obstructive ventilatory disorder defined by a FEV₁/VC < 0.7 in 5 patients (11%) with 5 patients (13%) exhibiting a mMRC ≥ 1, a restrictive ventilatory disorder defined by a TLC < 80% in 5 patients (13%) with 5 patients (16%) exhibiting a mMRC ≥ 1, and a decrease in alveolar diffusion defined by DLCO < 70% in 10 patients (26%) with 9 patients (28%) exhibiting a mMRC ≥ 1. Arterial blood gases at rest were in the normal range with no hypoxemia < 70 mmHg and no significant hypercapnia > 45 mmHg.

Fifteen percent (n = 7) of patients presented anemia. All patients had a hemoglobin level ≥ 11 g/dL. Mean NT pro-BNP was 117 ± 285 pg/mL. Four patients (10%) had a pro-BNP > 300 pg/mL.Forty-five percent of patients had a fasting glucose level > 7 mmol/L, 51% a Hba1c > 6%, 29% a triglyceride level ≥ 1.7 mmol/L, 35% a total cholesterol level > 5.2 mmol/L and 31% a CRP level > 10 mg/L.

The comparisons between the mMRC scale and demographic, lung functional and biological parameters are shown in Table 5. Subjects in the mMRC ≥ 1 group had a higher BMI (p = 0.01) (Figure 1A), lower ERV (p < 0.005) (Figure 1B), FEV₁ (p < 0.05), covered distance in 6MWT (p < 0.01) (Figure 1C) and Hb level (p < 0.05) than subjects in the mMRC = 0 group. Of note, there was no association between the mMRC scale and age, sex, smoking history, arterial blood gases, metabolic parameters and the apnea/hypopnea index.

Data are expressed as number (%) or mean ± SD; *p value < 0.05, **p value < 0.01.

FEV₁: expiratory volume in one second, pred: predicted value, VC: vital capacity, FRC: functional residual capacity, ERV: expiratory reserve volume, TLC: total lung capacity, DLCO: carbon monoxide diffusing capacity of the lung, NT pro-BNP: N-terminal pro brain natriuretic peptide, CRP: serum C reactive protein, HbA1c: glycated hemoglobin.

Normal biological parameters values were based on the normal values for our laboratory: fasting glucose: 3.3 to 6.1 mmol/L; HbA1c: 4 to 6%; total cholesterol: 3 to 5.2 mmol/L; triglycerides: 0.3 to 1.7 mmol/L; NT-pro BNP < 300 pg/mL; CRP < 10 mg/L. Anemia was defined as hemoglobin level < 13 g/dL in men and 12 g/dL in women.

The relationships between the Borg scale after 6MWT and demographic, lung functional and biological parameters were also analysed. The Borg score after 6MWT was correlated with a higher BMI (correlation coefficient = +0.44, p < 0.005) and a lower FEV₁ (correlation coefficient = -0.33, p < 0.05). No relationship was found between the Borg score after 6MWT and ERV or hemoglobin level. The Borg score after 6MWT was correlated with a higher fasting glucose (correlation coefficient = +0.46, p < 0.005) whereas this parameter was not associated with the mMRC scale (data not shown). We found no statistically different change in Borg scale ratings of dyspnea from rest to the end of the 6MWT between the two groups (p = 0.39).

In this study, 45 consecutive obese subjects were specifically assessed for dyspnea in daily living using the mMRC scale. Our study confirms the high prevalence of dyspnea in daily living in obese subjects 2 with 84% of patients exhibiting a mMRC scale ≥ 1 and 40% a mMRC scale ≥ 2. Interestingly, the presence of dyspnea in daily living (mMRC ≥ 1) was associated with a higher BMI and a lower ERV, FEV₁, distance covered in 6MWT and hemoglobin level. Furthermore, a mMRC score ≥ 2 in obese subjects was associated with a higher Borg score after the 6MWT (data not shown).

The assessment of dyspnea in clinical practice is difficult. Regarding the mMRC scale, two versions of this scale have been used, one with 5 grades 20 as used in this study and an other with 6 grades 25 leading to some confusion. Other scales have been also used to assess dyspnea 26 . Collet at al. 3 , Ofir et al. 11 and El-Gamal 27 et al provided some evidence to support the use of the BDI, Oxygen cost diaphragm (OCD) and Chronic Respiratory Disease Questionnaire (CRQ) to evaluate dyspnea in obesity. El-Gamal et al 27 demonstated the responsiveness of the CRQ in obesity as they did measurements before and after gastroplaty-induced weight loss within the same subjects. The Baseline Dyspnea Index (BDI) uses five grades (0 to 4) for 3 categories, functional impairment, magnitude of task and magnitude of effort with a total score from 0 to 12 28 . The University of California San Diego Shortness of Breath Questionnaire comprises 24 items assessing dyspnea over the previous week 29 . It must be pointed out that these scores are much more time consuming than the mMRC scale and are difficult to apply in clinical practice.

To our knowledge, the mMRC scale has not been investigated in the assessment of dyspnea in daily living in obese subjects without a coexisting pulmonary disease. The mMRC scale is an unidimensional scale related to activities of daily living which is widely used and well correlated with quality of life in chronic respiratory diseases 20 such as chronic obstructive pulmonary disease (COPD) 21 or idiopathic pulmonary fibrosis 22 . The mMRC scale is easy-to-use and not time consuming, based on five statements describing almost the entire range of dyspnea in daily living. Our study provides evidence for the use of the mMRC scale in the assessment of dyspnea in daily living in obese subjects. Firstly, as expected, our results demonstrate an association between the mMRC scale and the BMI in the comparison between “dyspneic” and “non dyspneic” groups. Secondly, in our between-group comparisons, the mMRC scale was associated with pulmonary functional parameters (lower ERV, FEV₁ and distance walked in 6MWT) which might be involved in dyspnea in obesity. The reduction in ERV is the most frequent functional respiratory abnormality reported in obesity 6 7 8 . This decrease is correlated exponentially with BMI and is mainly due to the effect of the abdominal contents on diaphragm position 30 . While the FEV₁ might be slightly reduced in patients with severe obesity, the FEV₁/VC is preserved as seen in our study 31 . The determination of the walking distance and the Borg scale using the 6MWT is known to be a simple method to assess the limitations of exercise capacity in chronic respiratory diseases 23 . Two studies have shown a good reproducibility of this test 32 33 but did not investigate the relationships between the 6MWD and dyspnea in daily living. Our study confirms the feasibility of the 6MWD in clinical practice in obesity and demonstrates an association between covered distance in 6MWT and the presence or the absence of dyspnea in daily living assessed by the mMRC scale. It must be pointed out that the 6MWT is not a standardized exercise stimulus. Exercise testing using cycloergometer or the shuttle walking test could be of interest to determine the relationships between the mMRC scale and a standardize exercise stimulus. In our between-group comparisons, BMI and FEV₁ were associated with the mMRC scale and correlated with the Borg scale after 6MWT. Surprisingly, the ERV was associated with the mMRC scale but not with the Borg scale. Moreover, the fasting glucose was correlated with the Borg scale after 6MWT but not associated with the mMRC scale. Whether these differences are due to a differential involvement of these parameters in dyspnea in daily living and at exercise, or simply related to a low sample size remains to be evaluated.

As type 2 diabetes, insulin resistance, metabolic syndrome 17 18 19 , anemia and cardiac insufficiency have been shown to be associated with lung function and/or dyspnea, we also investigated the relationships between dyspnea in daily living and biological parameters. A mMRC scale ≥ 1 was associated with a lower hemoglobin level. However, all patients had a hemoglobin level > 11 g/dL and the clinical significance of the association between dyspnea in daily living and a mildly lower hemoglobin level has to be interpreted cautiously and remains to be evaluated. Of note, we did not find any associations between the mMRC scale and triglyceride, total cholesterol, fasting glucose, HbA1C, CRP or NT pro-BNP.

The strength of this study includes the assessment of the relationships between the mMRC scale and multidimensional parameters including exertional dyspnea assessed by the Borg score after 6MWT, PFTs and biological parameters. The limitations of this pilot study are as follows. Firstly, the number of patients included is relatively low. This study was monocentric and did not include control groups of overweight and normal weight subjects. Due to the limited number of patients, our study did not allow the analysis sex differences in the perception of dyspnea. Secondly, we did not investigate the relationships between the mMRC scale and other dyspnea scales like the BDI which has been evaluated in obese subjects and demonstrated some correlations with lung function 3 . Thirdly, it would have been interesting to assess the relationships between the mMRC scale and cardio-vascular, neuromuscular and psycho-emotional parameters which might be involved in dyspnea. Assessing the relationships between health related quality of life and dyspnea would also be useful. Finally, fat distribution (eg Waist circumferences or waist/hip ratios) has not been specifically assessed in our study but might be assessed at contributing factor to dyspnea. Despite these limitations, this pilot study suggests that the mMRC scale might be of value in the assessment of dyspnea in obesity and might be used as a dyspnea scale in further larger multicentric studies. It remains to be seen whether it is sensitive to changes with intervention.