Inflammatory biomarkers associated with infection-related type I acute respiratory failure

doi:10.5847/wjem.j.1920-8642.2026.049

Abstract

Abstract:

BACKGROUND: Acute respiratory failure (ARF) is a heterogeneous syndrome in which early differentiation between infection-related and non-infection-related etiologies remains challenging. This study aimed to characterize the inflammatory profile of type I ARF and identify candidate biomarkers associated with the infection-related type I ARF.

METHODS: In this prospective observational cohort study, 98 patients with type I ARF and 30 healthy controls were enrolled. The plasma levels of 92 inflammation-related proteins were measured using the Olink Inflammation Panels. Type I ARF-associated biomarkers were first identified by comparing type I ARF patients with healthy controls, followed by the identification of infection-related biomarkers within the type I ARF cohort. False discovery rate correction and random forest-based feature ranking were applied.

RESULTS: Compared with non-infection-related type I ARF (NonInf-ARF), infection-related type I ARF (Inf-ARF) was associated with a higher incidence of acute respiratory distress syndrome (ARDS) and greater use of advanced life-support therapies. A comparison with healthy controls identified 64 significantly dysregulated biomarkers, representing the inflammatory features of type I ARF. Twenty of the 64 type I ARF-associated biomarkers remained significantly different between the Inf-ARF and NonInf-ARF groups (q<0.05). Neurotrophin-3 (NT-3), interleukin-18 receptor 1 (IL-18R1), interleukin-18 (IL-18), and C-X-C motif chemokine ligand 10 (CXCL10) consistently ranked among the top features across the different analytical methods.

CONCLUSION: NT-3, IL-18R1, IL-18, and CXCL10 were identified as candidate biomarkers associated with the Inf-ARF, which may provide additional information for early etiologic stratification.

Key words: Acute respiratory failure, Type I, Inflammatory biomarkers, Subphenotype

Kairui Ren, Jiatong Xu, Ya Wang, Yan Li, Huadong Zhu. Inflammatory biomarkers associated with infection-related type I acute respiratory failure[J]. World Journal of Emergency Medicine, 2026, 17(3): 237-243.

Figures/Tables 5

Figure 1.

Table 1.

Figure 2.

Figure 3.

Figure 4.

References 25

1	Cannon J, Pamplin J, Zonies D, Mason P, Sine C, Cancio L, et al. Acute respiratory failure. Mil Med. 2018; 183(suppl_2):123-9.
2	Bellani G, Laffey JG, Pham T, Fan E, Brochard L, Esteban A, et al. Epidemiology, patterns of care, and mortality for patients with acute respiratory distress syndrome in intensive care units in 50 countries. JAMA. 2016; 315(8): 788.
3	Cicchinelli S, Pignataro G, Gemma S, Piccioni A, Picozzi D, Ojetti V, et al. PAMPs and DAMPs in sepsis: a review of their molecular features and potential clinical implications. Int J Mol Sci. 2024; 25(2): 962.
4	Samarelli AV, Tonelli R, Marchioni A, Bruzzi G, Gozzi F, Andrisani D, et al. Fibrotic idiopathic interstitial lung disease: the molecular and cellular key players. Int J Mol Sci. 2021; 22(16): 8952.
5	Mokart D, Lambert J, Schnell D, Fouché L, Rabbat A, Kouatchet A, et al. Delayed intensive care unit admission is associated with increased mortality in patients with cancer with acute respiratory failure. Leuk Lymphoma. 2013; 54(8): 1724-9.
6	Jurado-Palomo J, Martín-Conty JL, Polonio-López B, Picón CR, López-Izquierdo R, Vegas CDP, et al. Prehospital critical care drug-therapy and 30-day mortality in patients with acute respiratory disease. World J Emerg Med. 2025; 16(1):43-50.
7	Renard Triché L, Fosset M, Jabaudon M, Futier E, Lucas B, Latroche C, et al. Temporal stability of inflammatory subphenotypes of acute respiratory distress syndrome: 28-day insights from the ICAR trial. Anaesth Crit Care Pain Med. 2025; 44(5): 101559.
8	Das SK, Choupoo NS, Rochwerg B, Goswami D, Ray S, Gupta A, et al. The impact of inflammatory biomarker subphenotypes on acute respiratory distress syndrome prognosis: a systematic review and meta-analysis. Indian J Crit Care Med. 2025; 29(7): 597-603.
9	Sarma A, Christenson SA, Shoshana BZ, Oliveira AP, Neyton LPA, Mick E, et al. Acute respiratory distress syndrome molecular phenotypes have distinct lower respiratory tract transcriptomes. Am J Respir Crit Care Med. 2025; 211(12):2352-62.
10	Rifai M, Bergounioux J, Sleiman N, Ismail J, Zini J. Infectious acute respiratory failure in patients under 5 years of age: a retrospective cohort study. BMJ Paediatr Open. 2024; 8(1):e002614.
11	Aliberti S, Dela Cruz CS, Amati F, Sotgiu G, Restrepo MI. Community-acquired pneumonia. Lancet. 2021; 398(10303): 906-19.
12	Kim HS, Ha SO, Han SJ, Kim HS, Lee SH, Jung KS, et al. Extracorporeal membrane oxygenation support in trauma versus nontrauma patients with noninfectious acute respiratory failure. Artif Organs. 2017; 41(5): 431-9.
13	Brinker A, Cheng C, Chan V. Association of noninfectious pneumonia with ustekinumab use. JAMA Dermatol. 2019; 155(2): 221-4.
14	Elemam NM, Talaat IM, Maghazachi AA. CXCL 10 chemokine: a critical player in RNA and DNA viral infections. Viruses. 2022; 14(11): 2445.
15	Elemam NM, Khalil BA, Maghazachi AA. Chemokines and chemokine receptors. Encyclopedia of Infection and Immunity. Amsterdam: Elsevier; 2022: 193-205.
16	Lee EY, Lee ZH, Song YW. CXCL10 and autoimmune diseases. Autoimmun Rev. 2009; 8(5): 379-83.
17	Lockhart-Bouron M, Vanel N, Levy M, Briant AR, Javouhey E, Breinig S, et al. Severe acute respiratory syndrome coronavirus-2-related and imputable deaths in children: results from the French pediatric national registry. World J Pediatr. 2024; 20(6):611-20.
18	Samah B, Porcheray F, Dereuddre-Bosquet N, Gras G. Nerve growth factor stimulation promotes CXCL-12 attraction of monocytes but decreases human immunodeficiency virus replication in attracted population. J NeuroVirology. 2009; 15(1): 71-80.
19	Ricci A, Graziano P, Bronzetti E, Saltini C, Sciacchitano S, Cherubini E, et al. Increased pulmonary neurotrophin protein expression in idiopathic interstitial pneumonias. Sarcoidosis Vasc Diffuse Lung Dis. 2007; 24(1):13-23.
20	Ruiz-Mendoza S, Macedo-Ramos H, Santos FA, Quadros-de-Souza LC, Paiva MM, Pinto TCA, et al. Streptococcus pneumoniae infection regulates expression of neurotrophic factors in the olfactory bulb and cultured olfactory ensheathing cells. Neuroscience. 2016; 317: 149-61.
21	Deniz İlgün J, Çövüt Y, Tuna C, Erkekoğlu S, Hastürkoğlu S, Güler S. Acute phencyclidine inhalation injury in the emergency department: a rare cause of acute respiratory distress syndrome and alveolar haemorrhage. World J Emerg Med. 2025; 16(3):292-4.
22	Dinarello CA, Novick D, Kim S, Kaplanski G. Interleukin-18 and IL-18 binding protein. Front Immunol. 2013; 4: 289.
23	Jarnig G, Kerbl R, van Poppel MNM. Changes in children's cardiorespiratory fitness and body mass index over the course of the COVID-19 pandemic: a 34-month longitudinal study of 331 primary school children. World J Pediatr. 2024; 20(2):185-8.
24	Cabug AF, Crawford JC, McQuilten HA, Foo IJH, Allen LF, Gebregzabher D, et al. High expression of interleukin-18 receptor alpha correlates with severe respiratory viral disease and defines T cells with reduced cytotoxic signatures. Nat Commun. 2025; 16: 10344.
25	Floros J, Londono D, Gordon D, Silveyra P, Diangelo SL, Viscardi RM, et al. IL-18R1 and IL-18RAP SNPs may be associated with bronchopulmonary dysplasia in African-American infants. Pediatr Res. 2012; 71(1): 107-14.

Clinical outcomes	NonInf-ARF (n=25)	Inf-ARF (n=73)	P-value
Worst PaO₂/FiO₂ ratio, median (IQR)	210 (168.0, 237.5)	139 (114.4, 199.0)	0.002
ARDS, n (%)	8 (32.0)	62 (84.9)	<0.001
Invasive mechanical ventilation, n (%)	7 (28.0)	56 (76.7)	<0.001
In-hospital mortality, n (%)	6 (24.0)	23 (31.5)	0.478