Phenotypes and Lung Microbiota Signatures of Immunocompromised Patients with Pneumonia-Related Acute Respiratory Distress Syndrome

Abstract

Objective

We aim to identify the clinical phenotypes of immunocompromised patients with pneumonia-related ARDS, to investigate the lung microbiota signatures and the outcomes of different phenotypes, and finally, to develop a machine learning classifier for a specified phenotype.

Methods

This prospective study included immunocompromised patients with pneumonia-related ARDS. We identified phenotypes using hierarchical clustering to analyze clinical variables and serum cytokine levels. We then compared outcomes and lung microbiota signatures between phenotypes. Based on lung microbiota markers, we developed a random forest classifier for a specified phenotype with worse outcomes.

Results

This study included 92 patients, who were divided into three phenotypes, namely “type α” (N = 33), “type β” (N = 12), and “type γ” (N = 47). Compared to type α or type β, patients with type γ had no obvious inflammatory presentation and had significantly lower IL-6 levels and more severe oxygenation failure. Type γ was also related to higher 30-day mortality and lower ventilator free days. The microbiota signatures of type γ were characterized by lower alpha diversity and distinct compositions than those of other patients. We developed a lung microbiota-derived random forest model to differentiate patients with type γ from other phenotypes.

Conclusion

Immunocompromised patients with pneumonia-related ARDS can be clustered into three clinical phenotypes, namely type α, type β, and type γ. Phenotypes were distinguished from each other with different outcomes and lung microbiota signatures. Type γ, which was characterized by insufficient inflammation response and worse outcomes, can be detected with a random forest model based on lung microbiota markers.

Keywords:

• immunocompromised host
• respiratory failure
• microbiota

Data Sharing Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Ethics Approval and Consent to Participate

All participants of this study have signed the informed consent sheet and consented to participate. If the patient lacks capacity to give consent, eg, 1. dementia, 2. delirium 3. shock, stroke, hypoglycemia or sedatives induced unconsciousness. Once the patients regained consciousness, they will be asked to provide their own informed consent to participate in this study.

Consent for Publication

All authors have read this manuscript and consented to publication.

Disclosure

The authors report no conflicts of interest in this work.

Additional information

Funding

This project was supported by Peking University International Hospital Research Funds (No. YN2021QN02), The National Natural Science Foundation of China (Grant No. 82202326), Clinical Medicine Plus X – Young Scholars Project, Peking University, The Fundamental Research Funds for the Central Universities (PKU2022LCXQ031), Wu Jieping Medical Foundation Runze Fund for Critical Care Medicine (NO320·6750·2022-2-34) and Peking University People’s Hospital Scientific Research Development Funds(No. RDJP2022-54).