Year: 2022
Type: preprint
Study design: Observational Study
Abstract: RationaleWhile nasal brushing transcriptomics can identify disease subtypes in chronic pulmonary diseases, it is unknown whether this is true in pediatric ARDS (PARDS).ObjectivesDetermine whether nasal transcriptomics and methylomics can identify clinically meaningful PARDS subgroups that reflect important pathobiological processes.MethodsNasal 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 ResultsTwenty-four control and 39 PARDS subjects were enrolled. Two nasal methylation patterns were identified. Methyl Subgroup 1 had hypomethylation of cell adhesion genes and had only PARDS subjects. Methyl Subgroup 2 contained PARDS and control subjects with hypomethylation of cell metabolism genes. Neither methylation pattern had longer PARDS duration. 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). Control specimens were largely Subgroup C. In comparison with 17 serum biomarkers, the nasal transcriptome was more predictive of prolonged PARDS. Initial Transcriptomic Subgroup B or D subjects 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. ConclusionsPARDS 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.RegistrationClinicaltrials.gov NCT#03539783 May 29, 2018
Source: Research Square
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W4293085830