Introduction
Acute respiratory distress syndrome (ARDS) is an acute inflammatory lung injury that is accompanied by severe hypoxemia, increased lung weight, increased pulmonary vascular permeability, and loss of aerated lung tissue [
1,
2]. In the intensive care unit (ICU), ARDS is a leading cause of death and a major healthcare burden; for example, the Global Impact of Severe Acute Respiratory Failure (LUNG SAFE) research found that over 34% of patients died from the condition [
3]. Despite improvements in our knowledge of the processes underlying ARDS, the mortality rate improvement has been far from satisfactory [
4]. In order to help doctors make treatment decisions and identify individuals at high risk, it is necessary to find prognostic indicators of ARDS [
5].
Obesity is considered an epidemic and is brought on by people’s increasing desire for calorie-dense foods and sedentary lifestyles. The increased morbidity of conditions such as cancer, hypertension, diabetes, coronary heart disease, and others is a result of obesity and overweight [
6,
7]. Recent research, however, has uncovered a “obesity paradox” in which obesity may potentially act as a preventative measure for certain illnesses, such as chronic renal disease and heart failure [
8‐
10]. Numerous studies [
11‐
14] have looked at the connection between obesity and ARDS outcomes. According to a meta-analysis by Yue et al. [
15] that pooled data from five studies and 6268 individuals, being underweight was linked to greater mortality when compared to being at a normal weight, while reduced mortality was more likely to be caused by obesity and morbid obesity. These studies did not take into account a number of significant confounding variables, including alcohol use status, illness severity, and cardiovascular disease. However, the existence of the obesity paradox in relation to ARDS has remained debatable.
Therefore, using real-world data from the most recent Multiparameter Intelligent Monitoring in Intensive Care (MIMIC-III) database, we sought to evaluate the relationship between obesity and the chances of short- and long-term death in patients with ARDS.
Discussion
After controlling for confounding variables, we discovered that, compared to normal weight, obesity was independently related to risk of both short- and long-term death. Additionally, there was a U-shaped association between BMI and ARDS mortality. A BMI over 31.5 kg/m2 was associated with a slightly increased risk of death. Between ARDS patients who are underweight and those who are of normal weight, the risks of death were not significantly different.
The findings of epidemiological studies that showed how obesity affected the outcome of patients with ARDS have been debatable so far [
26‐
28]. Increasing BMI was initially associated with a decrease in mortality in patients with end-stage renal illness, according to Fleischmann et al. in 1999 [
29]. Additionally, this link was seen in CHF, CHD, COPD, and critical illness [
30‐
33]. The “obesity paradox” was the term given to the phenomenon. Jayanama et al. found that overweight (BMI 25.0–29.9 kg/m
2) was a protective factor for mortality in people with moderate/severe debilitation people, and grade 1 obesity (30.0–34.9 kg/m
2) was a protective factor for mortality in people with mild debilitation. By contrast, in the population without debilitation, class 2 or 3 obesity (≥ 35.0 kg/m2) may be associated with a higher risk of mortality [
34].
According to a previous meta-analysis [
26], individuals with obesity had greater ARDS morbidity than those who were of normal weight, and obesity was strongly linked to a lower ARDS fatality rate. Obese individuals are more likely to have comorbidities, including cardiovascular disease, respiratory conditions, and AKI; however, these studies did not account for these conditions. To support the conclusion, our research included detailed clinical, laboratory, and physiologic data. We made adjustments for a number of variables, including illness severity and cardiovascular risk, and we used curve fitting to fit the association between BMI and ARDS prognosis. The connection was seen to be U‑shaped. The two-stage study determined that 31.5 kg/m
2 was the cutoff BMI.
The following might be the reason for our finding. First, ARDS development is significantly influenced by inflammation. Blood proinflammatory cytokines are higher in obese patients [
35], which decreases antioxidant reserves, upregulates adhesion molecules on lung endothelium, and increases endothelium sensitivity to injury [
36]. Second, an imbalance in adipokine secretion and reaction might result from obesity [
35]. Adipokine imbalance, as shown by Shah et al. [
37,
38], affected the expression of endothelial junctional adherens and adhesion proteins, predisposed the lung to acute damage, and disrupted pulmonary vascular homeostasis in obese mice. Finally, compared to people who are lean, patients who are obese undergo a number of modifications in pulmonary mechanics. The total lung capacity, functional residual capacity, and vital capacity are a few of the things that are altered in obese people. These changes also lead to atelectasis, increased airway resistance and closure, and ventilation/perfusion mismatch. These results firmly establish a connection between obesity and an increased risk of ARDS.
We further discuss the protective effects of a BMI of < 31.5 kg/m
2 in patients with ARDS. Previous studies have found that a higher rate of body fat is associated with a higher degree of frailty after controlling for BMI [
30]. Body fat rate has a mediating effect in the association of BMI with frailty, and the association of BMI with frailty in the vast majority of patients can be explained by higher body fat. But an increase in BMI does not exclusively mean an increase in body fat content. Body weight consists of fat mass, muscle mass, bone mineral mass, and body moisture. The increase in BMI may also be caused by an increase in these body components [
39]. Studies have shown better quality of life in populations with high skeletal muscle mass and strength, with significant reductions in infection rates, hospital stay, immobilization, and mortality [
40]. It is therefore reasonable to speculate that the protective effect in patients with BMI < 31.5 kg/m
2 may be due to increased fat free mass.
There were several advantages in the present study. In order to ensure that the population included in the research was fairly representative and the findings were somewhat trustworthy, we first employed a database with a large multicenter sample for rigorous screening. Second, we employed a number of models to successively account for the impact of several known confounders on ARDS, including age, sex, comorbidities, heart rate, blood pressure, and other parameters. These models revealed a consistent correlation between BMI and sepsis survival. Finally, a two-segment linear regression model was used to examine the threshold effect of BMI on 30-day mortality in order to more thoroughly investigate the relationship between BMI and ADRS mortality than was done in earlier studies. The association between BMI and 30-day mortality was analyzed by smooth curve fitting (penalized spline method).
Nevertheless, there were limitations to be acknowledged. First, because this was a retrospective cohort research, it was unable to establish a link between BMI and death. Second, as with any cohort analysis, we attempted to control for potential risk factors including CVD, comorbidities, and others; nevertheless, residual confounders, such as proinflammatory variables, marital status, and other known or unknown confounders, cannot be fully ruled out. Third, only the first 24 h after admission were considered for BMI; the prognosis was not examined in connection to later BMI changes. Using only baseline evaluation raised the possibility of categorization bias.