Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 May 14;9(1):55.
doi: 10.1186/s13613-019-0529-4.

Age-dependent differences in pulmonary host responses in ARDS: a prospective observational cohort study

Laura R Schouten  1   2   3 , Anton H van Kaam  4 , Franziska Kohse  5   6 , Floor Veltkamp  1 , Lieuwe D Bos  2   3 , Friso M de Beer  2   3 , Roosmarijn T van Hooijdonk  2   3 , Janneke Horn  2   3 , Marleen Straat  2   3 , Esther Witteveen  2   3 , Gerie J Glas  2   3 , Luuk Wieske  2   3 , Lonneke A van Vught  7 , Maryse A Wiewel  7 , Sarah A Ingelse  1 , Bart Cortjens  1 , Job B van Woensel  1 , Albert P Bos  1 , Thomas Walther  5   6 , Marcus J Schultz  2   3   8 , Roelie M Wösten-van Asperen  9   10 ; MARS consortium
Collaborators, Affiliations

Age-dependent differences in pulmonary host responses in ARDS: a prospective observational cohort study

Laura R Schouten et al. Ann Intensive Care. .

Abstract

Background: Results from preclinical studies suggest that age-dependent differences in host defense and the pulmonary renin-angiotensin system (RAS) are responsible for observed differences in epidemiology of acute respiratory distress syndrome (ARDS) between children and adults. The present study compares biomarkers of host defense and RAS in bronchoalveolar lavage (BAL) fluid from neonates, children, adults, and older adults with ARDS.

Methods: In this prospective observational study, we enrolled mechanical ventilated ARDS patients categorized into four age groups: 20 neonates (< 28 days corrected postnatal age), 29 children (28 days-18 years), 26 adults (18-65 years), and 17 older adults (> 65 years of age). All patients underwent a nondirected BAL within 72 h after intubation. Activities of the two main enzymes of RAS, angiotensin converting enzyme (ACE) and ACE2, and levels of biomarkers of inflammation, endothelial activation, and epithelial damage were determined in BAL fluid.

Results: Levels of myeloperoxidase, interleukin (IL)-6, IL-10, and p-selectin were higher with increasing age, whereas intercellular adhesion molecule-1 was higher in neonates. No differences in activity of ACE and ACE2 were seen between the four age groups.

Conclusions: Age-dependent differences in the levels of biomarkers in lungs of ARDS patients are present. Especially, higher levels of markers involved in the neutrophil response were found with increasing age. In contrast to preclinical studies, age is not associated with changes in the pulmonary RAS.

Keywords: ARDS; Aging; Angiotensin converting enzyme; Biomarkers; Host response; Pathophysiology.

PubMed Disclaimer

Conflict of interest statement

Ethics approval and consent to participate

This study was approved by the Institutional Review Board, and written informed consent was provided by legal guardians of the patient prior to enrollment.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flowchart. * ARDS was defined by the Berlin definition; ** A sample was considered invalid if no proteins could be measured. ARDS = acute respiratory distress syndrome 1 premature neonate, 36 weeks at time of inclusion. The exclusion criteria were not exclusive. In case a patient fulfilled more than one exclusion criteria, only one was chosen to report. AB antibiotics, ARDS acute respiratory distress syndrome, BALF bronchoalveolar lavage fluid, No IC no informed consent, SIRS systemic inflammatory response syndrome
Fig. 2
Fig. 2
Markers of inflammation, endothelial activation and epithelial activation in bronchoalveolar lavage fluid of ARDS patients. a Myeloperoxidase (MPO), b interleukin (IL)-6, c p-selectin, d intercellular adhesion molecule (ICAM)-1 levels in bronchoalveolar lavage (BAL) fluid of ARDS patients stratified by four age groups. Horizontal bars represent the median. Group differences were tested with a Dunn’s test with Bonferroni correction for multiple comparisons. A p value less than 0.05 was considered statistical significant
Fig. 3
Fig. 3
ACE and ACE2 activity in bronchoalveolar lavage fluid of ARDS patients. a ACE and b ACE2 activity in bronchoalveolar lavage (BAL) fluid of ARDS patients stratified by four age groups. c ACE2/ACE ratio. Horizontal bars represent the median. Group differences were tested with a Dunn’s test with Bonferroni correction for multiple comparisons. A p value less than 0.05 was considered statistical significant. ACE angiotensin converting enzyme
See this image and copyright information in PMC

References

    1. Smith LS, Zimmerman JJ, Martin TR. Mechanisms of acute respiratory distress syndrome in children and adults: a review and suggestions for future research. Pediatr Crit Care Med. 2013;14:631–643. doi: 10.1097/PCC.0b013e318291753f. - DOI - PubMed
    1. Schouten LRA, Schultz MJ, van Kaam AH, Juffermans NP, Bos AP, Wösten-van Asperen RM. Association between maturation and aging and pulmonary responses in animal models of lung injury:a systematic review. Anesthesiology. 2015;123:389–408. doi: 10.1097/ALN.0000000000000687. - DOI - PubMed
    1. Xie X, Chen J, Wang X, Zhang F, Liu Y. Age- and gender-related difference of ACE2 expression in rat lung. Life Sci. 2006;78:2166–2171. doi: 10.1016/j.lfs.2005.09.038. - DOI - PMC - PubMed
    1. Kuba K, Imai Y, Rao S, Jiang C, Penninger JM. Lessons from SARS: control of acute lung failure by the SARS receptor ACE2. J Mol Med (Berl) 2006;84:814–820. doi: 10.1007/s00109-006-0094-9. - DOI - PMC - PubMed
    1. Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436:112–116. doi: 10.1038/nature03712. - DOI - PMC - PubMed