Outcomes of overweight and obese critically ill patients with severe acute respiratory infection

Abstract

Objectives

To assess the association of obesity with outcomes among patients with severe acute respiratory infection.

Methods

This is a retrospective cohort study of patients with severe acute respiratory infection admitted to the intensive care units in four referral hospitals in Saudi Arabia between September 2012 and June 2018. Patients were classified into two groups: overweight–obese patients (body mass index ≥25 kg/m²) and normal-weight patients (body mass index between 18.5 and 24.9 kg/m²). All underweight patients with a body mass index <18.5 kg/m² were excluded from the study.

Results

Of the 421 patients, 294 were in the overweight–obese group and 127 were in the normal-weight group. There was no difference in crude 90-day mortality between the two groups. However, multivariate regression analysis showed that overweight–obese patients had lower 90-day mortality than normal-weight patients (odds ratio, 0.71; 95% confidence interval, 0.60–0.85; P = 0.0002). Interestingly, increasing age was associated with a significant increase in mortality (odds ratio, 1.03; 95% confidence interval, 1.02–1.03; P < 0.0001). Moreover, the Sequential Organ Failure Assessment score was associated with a significant increase in mortality (odds ratio, 1.21; 95% confidence interval, 1.15–1.26; P < 0.0001).

Discussion

Our study showed lower mortality among overweight–obese patients, supporting the phenomenon of obesity paradox.

Conclusion

Overweight and obesity were common among patients with severe acute respiratory infection. Our study demonstrates that the obesity paradox exists among patients with severe acute respiratory infection.

Keywords

Severe acute respiratory infection acute respiratory distress syndrome obesity paradox 90-day mortality

Background

Obesity is a significant health issue worldwide and is associated with serious health risks.¹ Morbid obesity further increases the risk of obesity-related complications, such as coronary heart disease and end-stage renal disease.^2,3 In the United States, the prevalence of obesity was 42.4% in 2017–2018.⁴ Saudi Arabia is on the list of the most obese countries in the world,⁵ and the overall rate is projected to increase.⁶ Acute respiratory distress syndrome (ARDS) is commonly encountered in the critical care population and is associated with high mortality between 27% and 45%.⁷ To investigate the relationship between obesity and ARDS, two meta-analyses were conducted, which showed lower ARDS-associated mortality in obese patients, thus supporting the so-called obesity paradox.^8,9 In addition, a large cohort study revealed that a higher body mass index (BMI) is associated with improved survival following hospitalization for infections such as pneumonia, urinary tract infection, and sepsis.¹⁰ A post-hoc analysis of the OSCILLATE Trial investigated the relationship between BMI and mortality risk and found no difference in the adjusted hospital mortality across BMI strata in patients with moderate-to-severe ARDS.^9,11 Furthermore, a retrospective cohort study of the patients enrolled in the ARDS Network randomized controlled trials found that the short-term mortality in patients with ARDS is not affected by BMI or the presence of diabetes mellitus.¹²

Severe acute respiratory infection (SARI) is defined by the World Health Organization (WHO) as an acute respiratory illness that manifests within 10 days of onset with a history of fever (≥38°C), cough, and dyspnea, and the patient requires hospitalization.¹³ It is associated with a high percentage of intensive care unit (ICU) admissions and high mortality. The objective of our study was to assess the association of obesity with outcomes among patients with SARI.

Method

Study setting and design

This retrospective cohort study was conducted in the ICUs of four referral hospitals in Saudi Arabia between September 2012 and June 2018. The institutional review boards of the Ministry of National Guard Health Affairs, Riyadh, Saudi Arabia (IRB/2545/21) and all other participating hospitals approved the study. The study was conducted in accordance with the Helsinki Declaration 1975 as revised in 2024. All patient details were deidentified to ensure confidentiality and protect patient privacy. Because of the retrospective nature of the study, the need for informed consent was waived. The reporting of this study conforms to the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines.¹⁴

Study population

We included all adult patients (defined in the participating hospitals as aged >14 years) who were admitted to the ICU and fulfilled the diagnostic criteria for SARI. We excluded underweight patients with a BMI <18.5 kg/m².

Data collection

Data were extracted from the SARI database using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC) case report forms. In this study, we included patients’ demographic features, underlying comorbidities, physiological and laboratory parameters, radiographic findings, and severity of illness on ICU admission assessed by the Sequential Organ Failure Assessment (SOFA) score. We also described ICU management and oxygen rescue therapies, including neuromuscular blockade, high-frequency oscillation ventilation, extracorporeal membrane oxygenation (ECMO), nitric oxide, and prone positioning. The primary outcome was 90-day mortality; other outcomes included ICU and hospital mortality and ICU and hospital lengths of stay.

Statistical analysis

Patients were classified into two groups: overweight–obese group, which included patients with a BMI ≥25 kg/m², and normal-weight group, which included those with a BMI between 18.5 and 24.9 kg/m². We compared baseline characteristics, interventions during ICU stay, and outcomes between the two groups. All categorical variables were presented as numbers and percentages and were compared using chi-square or Fisher exact test. All continuous variables were described as medians and interquartile ranges and were compared using the Mann–Whitney U test. A P value of <0.05 was used to indicate statistical significance. Multivariate analyses were performed to examine whether obesity is an independent predictor of 90-day mortality in patients with SARI, adjusting for age; chronic cardiac disease; chronic neurological disease including hemiplegia, paraplegia, or dementia; chronic pulmonary disease including asthma; diabetes with chronic complication; and SOFA score. In addition, we assessed the association between the subgroups based on WHO classification (overweight: 25 to <30 kg/m²; obese: ≥30 kg/m²) and 90-day mortality, with normal weight as the reference to explore potential dose–response trends.

Results

Of the 421 patients with SARI who met the inclusion criteria, 294 were in the overweight–obese group and 127 were in the normal-weight group. Demographic and baseline characteristics of the overweight–obese and normal-weight groups are presented in Table 1. There was no statistically significant difference in the median age of the patients between the overweight–obese and normal-weight groups. Males constituted 51% of the overweight–obese group and 68% of the normal-weight group (P = 0.002). There were no statistical differences between the two groups in terms of chronic pulmonary disease, liver disease, chronic renal disease, rheumatologic disease, use of immunosuppressed therapy, and malignancy. However, chronic cardiac disease was more prevalent in the overweight–obese group (54.4%) than in the normal-weight group (54.4% vs. 38.6%, P = 0.003), and chronic neurological disease was less prevalent in the overweight–obese group than in the normal-weight group (7.8% vs. 21.3%, P < 0.0001). There was no significant difference between the two groups in terms of durations from the onset of the symptoms to the emergency room visit, ICU admission, and intubation. There were no differences between the two groups in the presenting symptoms and the median SOFA score on the first day of ICU admission. Table 2 presents the physiological parameters and laboratory findings for the two groups of patients on the first day of ICU admission. The partial pressure of carbon dioxide in arterial blood (PaCO₂) level was higher in the overweight–obese group than in the normal-weight group (43.9 vs. 41.1 mmHg, P = 0.02). The two groups did not differ in terms of leukocyte count, hematocrit level, platelet count, urea and creatinine levels, or bilirubin level. The overweight–obese group had higher median levels of hemoglobin (10.9 g/dL; quartile (Q)1, Q3: 9.1, 12.7 vs. 10.2 g/dL; Q1, Q3: 8.8, 11.7; P = 0.04) and higher glucose level (10.9 mmol/L; Q1, Q3: 7.40, 15.20 vs. 7.80 mmol/L; Q1, Q3: 6.00, 13.90; P = 0.005).

Table 1.

Baseline characteristics of severe acute respiratory infections in overweight–obese patients compared with normal-weight patients.

Variables	Overweight–obese patientsN = 294	Normal-weight patientsN = 127	P value
Demographics
Age (years), median (Q1, Q3)	70.0 (57.0, 79.0)	68.0 (50.0, 79.0)	0.29^a
BMI (kg/m²), median (Q1, Q3)	30.8 (27.8, 35.9)	22.5 (21.0, 23.5)	<0.0001^a
BMI > 30 (kg/m²), n (%)	160 (54.4)	0 (0.0)	<0.0001^b
Male sex, n (%)	150 (51.0)	86 (68.0)	0.002^b
Duration of illness
Duration from the onset of symptoms to the emergency room (days), median (Q1, Q3)	3.0 (2.0, 5.0)	4.0 (2.0, 6.0)	0.19^a
Duration from symptom onset to ICU admission (days), median (Q1, Q3)	4.0 (2.0, 7.0)	5.0 (3.0, 9.0)	0.18^a
Duration from symptom onset to intubation (days), median (Q1, Q3)	5.0 (3.0, 9.0)	6.0 (3.0, 12.0)	0.38^a
Comorbidities, n (%)
Chronic pulmonary disease (including asthma)	92 (31.3)	29 (22.8)	0.08^b
Chronic liver disease	16 (5.4)	13 (10.2)	0.07^b
Chronic renal disease	73 (24.8)	22 (17.3)	0.09^b
Chronic cardiac disease	160 (54.4)	49 (38.6)	0.003^b
Chronic neurological disease	23 (7.8)	27 (21.3)	<0.0001^b
Rheumatologic disease	8 (2.7)	3 (2.4)	>0.99^c
Any malignancy including leukemia, lymphoma, or solid tumors	25 (8.5)	12 (9.4)	0.75^b
Immunosuppressant use before admission	35 (11.9)	12 (9.4)	0.46^b

BMI: body mass index; ICU: intensive care unit; Q: quartile.

Mann–Whitney U test was used to calculate the P value.

Chi-squared test was used to calculate the P value.

Fisher exact test was used to calculate the P value.

Table 2.

Physiological parameters on day 1 of admission to the intensive care unit in overweight–obese versus normal-weight patients with severe acute respiratory infections.

Variables	Overweight–obese patientsN = 294	Normal-weight patientsN = 127	P value^a
Respiratory parameters on ICU day 1, median (Q1, Q3)
pH	7.4 (7.3, 7.4)	7.4 (7.3, 7.4)	0.05
PaCO₂ (mmHg)	43.9 (38.3, 55.9)	41.1 (35.70, 51.70)	0.02
FiO₂	0.5 (0.4, 0.7)	0.5 (0.3, 0.6)	0.12
PaO₂ (mmHg)	71.0 (56.2, 89.0)	73.0 (57.3, 105.3)	0.34
SaO₂ (%)	94.0 (89.9, 97.0)	94.0 (88.8, 97.0)	0.76
PaO₂/FiO₂ ratio	155.1 (96.0, 228.0)	178.6 (113.0, 252.0)	0.12
HCO₃	23.8 (20.0, 28.0)	23.4 (19.0, 26.9)	0.15
Base excess	−0.8 (−5.1, 3.7)	−1.0 (−5.5, 2.6)	0.53
Extrapulmonary parameters on ICU day 1, median (Q1, Q3)
Mean arterial pressure (mmHg)	67.0 (61.0, 79.0)	68.5 (61.2, 82.5)	0.43
Leukocytes (×10⁹/L)	11.2 (7.7, 15.2)	10.3 (7.3, 14.7)	0.27
Hemoglobin (g/dL)	10.9 (9.1, 12.7)	10.2 (8.8, 11.7)	0.04
Hematocrit	35.0 (30.0, 40.4)	33.0 (28.0, 38.4)	0.07
Platelets (×10⁹/L)	231.0 (163.0, 321.0)	220.0 (140.0, 327.5)	0.48
Glucose (mmol/L)	10.9 (7.4, 15.2)	7.8 (6.0, 13.9)	0.005
Blood urea nitrogen (mmol/L)	9.2 (5.9, 16.6)	9.3 (5.3, 16.7)	0.52
Creatinine (μmol/L)	106.0 (71.0, 189.0)	85.5 (62.5, 172.5)	0.09
Bilirubin (μmol/L)	11.1 (7.6, 19.7)	11.2 (6.9, 22.5)	0.71
SOFA score on ICU day 1, median (Q1, Q3)	7.0 (5.0, 10.0)	7.0 (5.0, 10.0)	0.54

Note: To convert to conventional units in mg/dL, divide by 88.4 for creatinine and 17.1 for bilirubin.

FiO₂: fraction of inspired oxygen; HCO₃: bicarbonate; ICU: intensive care unit; PaCO₂: partial pressure of carbon dioxide in arterial blood; Q: Quartile; SaO₂: oxygen saturation; SOFA: Sequential Organ Failure Assessment.

Mann–Whitney U test was used to calculate the P value.

Patients with SARI received different modalities of interventions and management, as shown in Table 3. Noninvasive positive pressure ventilation was used more frequently in the overweight–obese group than in the normal-weight group (47.3% vs. 30.7%, P = 0.002). There were also no significant differences between the two groups with regard to invasive mechanical ventilation and the duration of this support. In addition, other respiratory support measures and rescue therapies such as nitric oxide administration, prone position, ECMO, and tracheostomy rate showed no statistically significant difference between the two groups. Corticosteroid therapy was given more frequently to the obese–overweight group than to the normal-weight group (61.1% vs. 50.4%, P = 0.0329). Other medications, such as neuromuscular blockades, vasopressors, intravenous immunoglobulins, and oseltamivir, did not differ between the two groups. There was also no significant difference between the two groups with regard to other interventions, such as the initiation and duration of renal replacement therapy, blood transfusion, and tracheostomy.

Table 3.

Main interventions in overweight–obese compared with normal-weight patients with severe acute respiratory infection.

Variables	Overweight–obese patientsN = 294	Normal-weight patientsN = 127	P value
Interventions
Noninvasive positive pressure ventilation, n (%)	139 (47.3)	39 (30.7)	0.002^a
Duration, median (Q1, Q3)	2.0 (1.0, 4.0)	2.0 (1.0, 3.0)	0.89^b
Invasive ventilation, n (%)	195 (66.3)	91 (71.7)	0.28^a
Duration, median (Q1, Q3)	10.0 (5.0, 16.0)	8.5 (5.0, 15.0)	0.94^b
Neuromuscular blockade, n (%)	75 (25.5)	38 (29.9)	0.35^a
PEEP	8 (5, 10)	7 (5, 10)	0.05^b
Peak pressure (PEEP + driving pressure)	29 (25, 32)	27 (23, 31)	0.07^b
Tidal volume, median (Q1, Q3)	400 (350, 439)	380 (330, 429)	0.15^b
Plateau pressure, median (Q1, Q3)	24 (21, 28)	23 (21.5, 28)	0.66^b
ECMO, n (%)	3 (1.0)	1 (0.8)	>0.99^c
Nitric oxide, n (%)	9 (3.1)	4 (3.1)	>0.99^c
Prone positioning, n (%)	1 (0.3)	1 (0.8)	0.51^c
Duration, median (Q1, Q3)	–	2.0 (2.0, 2.0)
Any oxygen rescue therapy, n (%)	76 (25.9)	39 (30.7)	0.30^a
Vasopressors, n (%)	165 (56.1)	70 (55.1)	0.85^a
Duration, median (Q1, Q3)	6.0 (3.0, 11.0)	6.5 (3.0, 12.0)	0.69^b
Blood transfusion, n (%)	65 (22.1)	38 (29.9)	0.09^a
Therapy
Antibiotics, n (%)	286 (97.3)	123 (96.9)	0.76^c
Oseltamivir, n (%)	206 (70.1)	77 (60.6)	0.058^a
Corticosteroids, n (%)	181 (61.6)	64 (50.4)	0.03^a
Renal replacement therapy, n (%)	59 (20.1)	28 (22.0)	0.65^a
Duration, median (Q1, Q3)	7.0 (3.0, 15.0)	8.0 (3.0, 16.5)	0.82^b
Intravenous immunoglobulins, n (%)	5 (1.7)	5 (3.9)	0.18^c
Tracheostomy, n (%)	15 (5.1)	10 (7.9)	0.27^a

ECMO: extracorporeal membrane oxygenation; PEEP: positive end-expiratory pressure; Q: quartile.

Chi-squared test was used to calculate the P value.

Mann–Whitney U test was used to calculate the P value.

Fisher exact test was used to calculate the P value.

The outcomes of our patients are shown in Table 4. There was no significant difference in 28-day, 90-day, and hospital mortality between the two groups. The ICU mortality rate was lower in the overweight–obese group than in the normal-weight group (21.1% vs. 29.9%, P = 0.05). There was also no difference in ICU and hospital length of stay between the two groups.

Table 4.

Outcomes in overweight–obese patients with SARI compared with normal-weight patients with SARI.

Variables	Overweight–obese patientsN = 294	Normal-weight patientsN = 127	P value
Outcomes
ICU mortality, n (%)	62 (21.1)	38 (29.9)	0.05^a
Hospital mortality, n (%)	87 (29.6)	49 (38.6)	0.07^a
90-day mortality, n (%)	80 (27.2)	42 (33.1)	0.22^a
28-day mortality, n (%)	54 (18.4)	30 (23.6)	0.22^a
14-day mortality, n (%)	25 (8.5)	21 (16.5)	0.02^a
ICU length of stay (days), median (Q1, Q3)	11.0 (5.0, 21.0)	11.0 (5.0, 23.0)	0.94^b
Hospital length of stay (days), median (Q1, Q3)	22.0 (12.0, 39.0)	22.0 (11.0, 58.0)	0.38^b
Complications
Pneumothorax, n (%)	8 (2.7)	2 (1.6)	0.73^c
Pulmonary embolism, n (%)	4 (1.4)	2 (1.6)	>0.99^c

ICU: intensive care unit; Q: quartile; SARI: severe acute respiratory infection.

Chi-squared test was used to calculate the P value.

Mann–Whitney U test was used to calculate the P value.

Fisher exact test was used to calculate the P value.

We performed a multivariable regression analysis to examine the independent association of overweight–obesity with 90-day mortality (Table 5). Overweight–obese patients had lower mortality than normal-weight patients (odds ratio (OR), 0.71; 95% confidence interval (CI), 0.60–0.85; P = 0.0002), which was also confirmed by comparing the association between the overweight and obese subgroups separately against the normal-weight group. Interestingly, age was associated with a significant increase in mortality (for each year increase: OR, 1.03; 95% CI, 1.02–1.03; P < 0.0001). Moreover, the SOFA score was associated with a significant increase in mortality (for every one-unit increase: OR, 1.21; 95% CI, 1.15–1.26; P < 0.0001).

Table 5.

Multivariable model to examine whether obesity is an independent predictor of 90-day mortality.

Variables	OR	95% CI	P value
Overweight–obese patients compared with normal-weight patients (ref)	0.71	0.60, 0.85	0.0002
Overweight patients compared with normal-weight patients (ref)	0.87	0.84, 0.90	<0.0001
Obese patients compared with normal-weight patients (ref)	0.59	0.42, 0.83	0.002
Age (for 1-year increase)	1.03	1.02, 1.03	<0.0001
SOFA score (for every 1 unit increase)	1.21	1.15, 1.26	<0.0001
Chronic cardiac disease	0.89	0.67, 1.19	0.44
Diabetes with chronic complications	1.01	0.80, 1.28	0.93
Chronic neurological disease including hemiplegia or paraplegia or dementia	0.63	0.46, 0.87	0.006
Chronic pulmonary disease including asthma	0.72	0.54, 0.97	0.04

Note: SOFA score: Respiration score + Glasgow Coma Scale score + Bilirubin score + Platelet score + Creatinine score + Hypotension score.

CI: confidence interval; OR: odds ratio; Ref: reference; SOFA: Sequential Organ Failure Assessment.

Discussion

Studies on the association of obesity with the mortality of critically ill patients have shown inconsistent results. Some studies supported the obesity paradox,^8,9 whereas others suggested there were no differences^12,15 or indicated increased mortality among obese patients.^16,17 In our study focusing on SARI, we observed lower mortality among overweight–obese patients, suggesting the phenomenon of obesity paradox.

Ni et al.⁹ and Zhi et al.⁸ conducted two systematic reviews and meta-analyses that showed lower mortality in obese patients with ARDS. Zhang et al.¹⁷ conducted a retrospective cohort study to examine the association between obesity and short- and long-term mortality in patients who were admitted with ARDS using the Berlin definition and performed multivariable logistic regression and Cox regression analyses; they showed that obesity was associated with decreased risk of short- and long-term mortality in ARDS patients despite their illness severity. Our study, which accounts for patient comorbidities and severity of illness, supports the concept of the obesity paradox observed in previous studies.

We observed that obese patients received steroid therapy and noninvasive ventilation (NIV) more frequently than normal-weight patients. This may be related to more frequent hypercapnia, in which NIV plays an established role in mortality, as shown by decreasing mortality.¹⁸ This finding is consistent with those of a systematic review and meta-analysis that studied the association of all-cause mortality with overweight and obesity using standard BMI categories¹⁹ and another systematic review and meta-analysis that showed overweight or obese BMI was associated with lower adjusted mortality rates among adults who were admitted to the ICU with sepsis, severe sepsis, or septic shock.²⁰

The obesity paradox is attributed to some theories. One of them is that the increase in adipose tissue and fat-free mass can serve as metabolic reserves during the catabolic state of acute illness. Additionally, the increase in renin–angiotensin system activity in obese patients can elevate blood pressure. This can decrease the need for fluid resuscitation and vasopressor support, adversely worsening outcomes. Another theory is that obese patients have a chronic proinflammatory status that can minimize the aggressive second hit during critical illness. Moreover, the shifts from proinflammatory M1 to anti-inflammatory M2 macrophage phenotypes, combined with modifications in adipokine profiles, may promote increased resilience in critical illness.²¹ Another possibility that can lead to the obesity paradox is that obese patients attract more attention and early care and intervention from health care providers because of the provider’s perception of the obesity comorbidities and ominous clinical prognosis. Such obese patients with chronic respiratory morbidities may get early admission to ICU due to decompensation from mild illnesses. In contrast, a normal-weight patient with no pre-existing chronic lung disease usually requires a major critical illness to reach the point needed for ICU admission and care, which may result in late and advanced presentation.

The study’s strengths include using a standardized case report form and collecting detailed physiological parameters, therapeutic interventions, and outcomes. However, some limitations should be noted. It is a retrospective cohort study. We did not study the effect of the sedation protocols, fluid balance, and time and duration of antibiotics, which possibly affected the outcome. Similar to all nonrandomized observational studies, the possibility of unmeasured confounding, such as differences in pre-existing comorbidities, functional status, or treatment intensity, cannot be entirely ruled out.

In conclusion, overweight and obesity are common among patients with SARI. Our study demonstrates that the obesity paradox may exist among patients with SARI.

Supplemental Material

sj-pdf-1-imr-10.1177_03000605251370302 - Supplemental material for Outcomes of overweight and obese critically ill patients with severe acute respiratory infection

Supplemental material, sj-pdf-1-imr-10.1177_03000605251370302 for Outcomes of overweight and obese critically ill patients with severe acute respiratory infection by Abdurahman Najy Ayoup, Haytham Tlayjeh, Jesna Jose, Farhan Zayed Alenezi, Musharaf Sadat, Felwa Bin Humaid, Fahad Al-Hameed, Kasim Al Khatib, Shawgi Osman Mohammed Omer, Haifa AlHumedi, Samiyah Alrawy Alanazi, Nahlah Awadh Albaalharith and Yaseen M Arabi in Journal of International Medical Research

Footnotes

Acknowledgments

We thank the entire research team including Javed Memon from King Abdulaziz Hospital, AlAhsa, Saudi Arabia, in addition to the International Severe Acute Respiratory and Emerging Infection Consortium for their support in the database.

Author contributions

AA and YA: conception, design of the study, collection of data, interpretation of data, drafting the manuscript, and critical revision of the manuscript for important intellectual content.

HT, FA, MS, FH, FA, KK, SO, HH, SA, and NA: collection, interpretation of data and critical revision of the manuscript for important intellectual content.

JJ: design of the study, statistical analysis, and critical revision of the manuscript for important intellectual content.

All authors approved the final version of the manuscript.

Consent to participate

The IRB waived the need for informed consent because of the retrospective nature of the study.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available but will be made available from the corresponding author on reasonable request.

Declaration of conflicting interests

The authors declare no competing interests.

Ethics approval

The study was approved by the Ministry of National Guard Health Affairs Institutional Review Board (IRB) and by the IRBs of all participating sites.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

ORCID iD

Yaseen M Arabi

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