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Table 1 Studies to identify risk, understand pathophysiology, and provide insight into newer individualized therapies for severity of CAP-induced ARDS in children

From: Interpretation of gene associations with risk of acute respiratory distress syndrome: P values, Bayes factors, positive predictive values, and need for replication

Study (year) Patient group (n) Time frame (years) Gene variants examined OR (unadjusted) OR (adjusted) Comment
[4] (2008) African American (515) and Caucasian (232) March 2004 to August 2006; 2 centers IL-1ra: absent A1 allele MV 8.6% vs no-MV 2.6% (P = 0.003) OR 2.65, P = 0.046 To predict MV (n = 96). Not statistically significant if African Americans and Caucasians analyzed separately
ARDS 9.1% vs no-ARDS 2.9%, P = 0.023 OR 3.10, P = 0.052 To predict ARDS (n = 49)
[5] (2010) African American (443) Not stated 4 MYLK SNPs P = 0.39 to 1.0 - To predict MV (n = 41) and ARDS (n = 28)
Caucasian (253) Not stated 5 MYLK SNPs P = 0.26 to 1.0 - To predict MV (n = 33) and ARDS (n = 19)
[6] (2011) African American (395) March 2004 to August 2006; 2 centers 7 SP-B SNPs
rs1130866
rs3024793
P = 0.016
P = 0.030
OR 2.27, P = 0.040
OR 3.00, P = 0.012
To predict MV (n = 37)
Not statistically significant if adjust for bacterial culture positive
rs7316 P = 0.06 OR 2.95, P = 0.031 To predict ARDS (n = 26)
[3] (2012) African American (474) Not stated; 3 centers CFTR 2 low risk vs 1 or 2 high risk [(TG)≥12T≤5] alleles P = 0.0013 OR 3.19, P = 0.0007 To predict MV (n = 43)
P = 0.0061 OR 3.36, P = 0.0032 To predict ARDS (n = 29). Nasal swab was done in 113 and positive for a virus in 43 (38%)
Caucasian (304) Not stated; 3 centers As above P = 0.21 Not statistically significant To predict MV (n = 42)
P = 0.84 Not statistically significant To predict ARDS (n = 32). Nasal swab was done in 89 and positive for a virus in 22 (25%)
[7] (2014) African American (443) Not stated; 3 centers Caspase-12 long allele P = 0.83 and 0.48 - For MV (n = 41), ARDS (n = 28). Also reported for: mortality (n = 5), severe sepsis (n = 17), vasopressor use (n = 15), renal dysfunction (n = 11), hematologic dysfunction (n = 9)
[2] (2016) African American (474) Not stated; 3 centers Splicing factors of CFTR mRNA (7 genes, 66 SNPs) 19 SNPs in 6 genes with P < 0.20 3 SNPs in CELF-2 (OR 2.95, 4.28, and 2.66 with P = 0.032, 0.004, and 0.044).
2 SNPs in TIA-1 (OR 3.70, 5.42 with P = 0.005, 0.018)
ARDS (n = 29). Also (TG)≥12T≤5 allele (OR 3.01, P = 0.012) and age ≥11 years (OR 14.9, P < 0.0001)
Caucasian (304) Not stated; 3 centers 7 genes, 41 SNPs 8 SNPs in 4 genes with P < 0.20 1 (different) SNP in CELF-2 (OR 3.22, P = 0.014). No TIA-1 SNPs or (TG)≥12T≤5 alleles ARDS (n = 32). Also age ≥11 years (OR 9.20, P < 0.0001) and asthma (OR 0.20, P = 0.04)
  1. ARDS acute respiratory distress syndrome (including PaO2/FIO2 ≤ 300), CELF-2 elav-like family member 2, CFTR cystic fibrosis transmembrane conductance regulator, IL1-ra interleukin 1 receptor antagonist, MV invasive (endotracheal tube or tracheostomy) or noninvasive (nasal prongs or face mask)—oxygen delivered by low or high flow via nasal cannula was not considered MV [4], MYLK myosin light chain kinase, OR odds ratio, SNP single nucleotide polymorphism, SP-B surfactant protein B, TIA-1 T-cell intracellular antigen 1
  2. Quality control: 5–10% genotyped a second time; blinded analysis of genotype to clinical status (but also state; two individuals independently assessed the results from the analyses and assigned genotypes [4]). Comparisons are between 0 and 1 versus 2 copies; or sometimes 0 versus 1 or 2 copies