In the present single-center, cross-sectional study, the impact of obesity on pulmonary function was examined in Japanese adult patients with asthma. Notably, all of the patients followed by pulmonary physicians with the disease name of asthma covered by medical insurance in our institute from 2005 to 2019 were included, and 193 patients definitely diagnosed as having asthma by a pulmonary physician were analyzed; this approach likely led to decreased rates of misdiagnosis and selection bias. In addition, the data of pulmonary function testing for patients without asthma were used for the comparison, which facilitated the evaluation of the effect of obesity in patients with asthma along with those without asthma. The present results showed that pulmonary functions were lower in patients with asthma than in those without asthma. Furthermore, FEV1 and FVC was negatively correlated with BMI in patients with asthma even though the correlation coefficients were relatively low, and obese patients with asthma showed significantly lower pulmonary functions than non-obese patients with asthma. Importantly, those differences were not seen between obese patients without asthma and non-obese patients without asthma.
Pulmonary function testing is an important examination for patients with asthma 6 because decreased pulmonary function, including FEV1 and FVC, is associated with the severity of asthma. For example, decreased FEV1 is a major characteristic of severe asthma, along with increased symptoms and exacerbations 23, 24. Reduced FVC is also correlated with uncontrolled asthma defined by emergency department visits 25 and is significantly lower in asthma patients with severe airflow obstruction than in those with moderate airflow obstruction based on their baseline FEV1 26. These data and the present results show that decreased pulmonary function is an important parameter reflecting asthma severity.
There is increasing evidence that obesity is related to the severity of asthma. In Japan, To et al examined the impact of obesity defined by a BMI greater than 25 kg/m2 in 492 patients with severe asthma, and they found that obesity was associated with severe acute exacerbations in females 16. We also reported that the annual exacerbation rate was significantly higher in overweight patients than in non-overweight patients, although there was no significant difference in pulmonary function given the small sample size 17. In a cohort of 28,016 patients with asthma in the USA, seasonal exacerbations were significantly increased in overweight patients defined as those whose BMI was 25–29.9 kg/m2 and obese patients, defined as those whose BMI was greater than 30 kg/m2, than in those with normal BMIs 27. Importantly, in patients with asthma, exacerbations contribute to excess lung function decline 28, 29. Therefore, the present results indicating that obesity is related to lower pulmonary function in patients with asthma is consistent with those findings.
The present results showed that obese patients with asthma had significantly lower pulmonary functions than non-obese patients with asthma (Table 3). A population-based cohort study in the Netherlands of the epidemiology of obesity showed that in 472 patients with asthma, obesity (BMI > 30 kg/m2) was associated with lower FEV1 and FVC than non-obesity 30. Another longitudinal study also showed that obesity was significantly associated with decreased lung function (FVC), and the risk was higher in patients with asthma than in those without asthma,31 which supported the present results. As the mechanisms, decreased responses to corticosteroid therapy, which is one of the factors related to the severity of asthma with obesity 21, 32, might be involved. Indeed, the present study showed that obese patients with asthma were more often treated by high-dose ICS than non-obese asthma patients, even though their pulmonary functions were low (Table 5). In addition, the previous Japanese study mentioned above showed that obesity does not affect pulmonary functions when focusing on severe asthma patients treated by high-dose ICS compared to those without obesity, in contrast to the present study which included mild to severe patients with asthma. These data remind us of the possibility that obese patients with asthma might generally include more patients with resistance to corticosteroid therapy and, consequently, have reduced pulmonary function compared to non-obese patients with asthma.
Pulmonary function, especially FEV1, was significantly lower in obese patients with asthma than in non-obese patients with asthma, and those differences were not seen between obese patients without asthma and non-obese patients without asthma (Tables 3, 4). Furthermore, the obesity-induced decline of FEV1 was greater than that of FVC on correlation analysis and multivariate analysis (Fig. 3a, 3b, Table 4). As for the mechanisms, augmented airway and systemic inflammation induced by obesity should be considered 17, 19, 20, 33, but airway dysanapsis, a physiological incongruence between the growth of lung parenchyma and the caliber of the airway, might be involved in obese patients with asthma 34. Several studies reported that airway dysanapsis, explained by high FVC, normal FEV1, and low FEV1/FVC, was more frequently seen in overweight/obese asthmatic children than in those of normal weight 35, 36. Because obesity is associated with the incidence of asthma itself 37, the result that obesity decreased FEV1 featured by airway dysanapsis, considered a diagnostic factor of asthma, might be consistent.
Interestingly, the present results showed that FVC was also lower in obese patients with asthma than in non-obese patients with asthma, and these differences were not seen between obese patients without asthma and non-obese patients without asthma (Table 3). These results cannot be explained by the obesity-induced physical effects caused by mobility regulation of the diaphragm and thorax by increased fat37, 38. While we do not yet know the reason, obesity appears to have a specific impact on FVC along with FEV1 in patients with asthma, but not those without asthma. Sex differences are normally involved in the pathophysiology of asthma with obesity, and studies in Japan of asthma incidence and exacerbation related to obesity showed more impact in female than male patients 16, 39. In the present study, there were no sex differences in pulmonary function associated with obesity (Table S1, S2)
The present study has several limitations. First, the background characteristics were different between patients with asthma and those without asthma. This might have affected the impact of obesity on the results of pulmonary function testing in patients with and without asthma. We also exploratory performed propensity score matched (PSM) method to mitigate the risk of confounding due to differences between patients without and those with asthma and it was used to balance the groups with respect to known confounders including BMI, age, sex, and smoking history. The results of the PSM group comparison were also reproductively confirmed that pulmonary functions were lower in patients with asthma than those without asthma. And, FEV1 and FVC were significantly lower in obese patients with asthma than in non-obese patients with asthma. Those obesity-associated differences were not observed in patients without asthma (data not shown), which we believe reduced the biases, were confirmatory. Second, patients with chronic obstructive pulmonary disease may not have been completely excluded from the patients with asthma and patients without asthma, which would have affected the results of pulmonary function testing. Third, it is unclear that the observed obesity-induced decreased pulmonary function in asthma contributes to poor outcomes, especially mortality. This was not assessed, and recently, overweight was found to be associated with improvement of long-term survival in a Japanese cohort 40. Finally, the present study involved a small number of patients at a single hospital with limited ethnic diversity. To confirm the validity of the present results, multicenter, prospective studies designed with appropriate controls and larger numbers of patients should be performed.