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Published on: November 7, 2020
Multi-omic characterization of pediatric ARDS via nasal brushings
James G Williams1, Rashika Joshi1, David Haslam2,3
1Critical Care Medicine, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, MLC 7006, Cincinnati, OH, 45229, USA.
Insights
Nasal gene expression patterns in pediatric acute respiratory distress syndrome (PARDS) can identify disease subtypes. These findings suggest nasal transcriptomics may help predict PARDS duration and guide treatment.
Area of Science:
- Pediatric critical care medicine
- Genomics and transcriptomics
- Pulmonary medicine
Background:
- Nasal brushing transcriptomics is used to identify disease subtypes in chronic pulmonary diseases.
- Its utility in pediatric acute respiratory distress syndrome (PARDS) remains unexplored.
Purpose of the Study:
- To determine if nasal transcriptomics and methylomics can identify clinically meaningful PARDS subgroups.
- To assess if these subgroups reflect underlying pathobiological processes.
Main Methods:
- Nasal brushings and serum samples were collected from control and PARDS subjects over 14 days.
- Nasal transcriptomic and methylomic patterns were analyzed.
- PARDS duration was the primary endpoint.
Main Results:
- Two nasal methylation patterns were identified, with one subgroup showing hypomethylation of inflammatory genes and enrichment for immunocompromised individuals.
- Four transcriptomic patterns were identified, reflecting temporal stages of injury, repair, and regeneration.
- Nasal transcriptomics was more predictive of prolonged PARDS than 17 serum biomarkers, with specific transcriptomic patterns associated with longer disease duration.
Conclusions:
- Nasal transcriptome patterns in PARDS may indicate distal lung injury, repair, and regeneration processes.
- A combined nasal PCR and serum biomarker assay could enhance predictive and diagnostic capabilities for PARDS.
Rationale:
While nasal brushing transcriptomics can identify disease subtypes in chronic pulmonary diseases, it is unknown whether this is true in pediatric acute respiratory distress syndrome (PARDS).
Objectives:
Determine whether nasal transcriptomics and methylomics can identify clinically meaningful PARDS subgroups that reflect important pathobiological processes.
Methods:
Nasal brushings and serum were collected on days 1, 3, 7, and 14 from control and PARDS subjects from two centers. PARDS duration was the primary endpoint.
Measurements And Main Results:
Twenty-four control and 39 PARDS subjects were enrolled. Two nasal methylation patterns were identified. Compared to Methyl Subgroup 1, Subgroup 2 had hypomethylation of inflammatory genes and was enriched for immunocompromised subjects. Four transcriptomic patterns were identified with temporal patterns indicating injury, repair, and regeneration. Over time, both inflammatory (Subgroup B) and cell injury (Subgroup D) patterns transitioned to repair (Subgroup A) and eventually homeostasis (Subgroup C). When control specimens were included, they were largely Subgroup C. In comparison with 17 serum biomarkers, the nasal transcriptome was more predictive of prolonged PARDS. Subjects with initial Transcriptomic Subgroup B or D assignment had median PARDS duration of 8 days compared to 2 in A or C (p = 0.02). For predicting PARDS duration ≥ 3 days, nasal transcriptomics was more sensitive and serum biomarkers more specific.
Conclusions:
PARDS nasal transcriptome may reflect distal lung injury, repair, and regeneration. A combined nasal PCR and serum biomarker assay could be useful for predictive and diagnostic enrichment. Trial registration Clinicaltrials.gov NCT03539783 May 29, 2018.
