In patients with acute respiratory distress syndrome, the angiotensin-converting enzyme insertion/deletion polymorphism but not the angiotensinogen (-6)A/G promoter polymorphism is an independent risk factor with a pronounced effect on 30-day survival.
Positive findings indicate the implication of genetic polymorphisms of proinflammatory cytokines in premature birth; angiotensin converting enzyme in perinatal adaptation and angiotensin type 1 receptor in the closure of ductus arteriosus; surfactant proteins A and B in respiratory distress syndrome; interleukin (IL)-6 in sepsis, and IL-4-receptor alpha chain and IL-18 in NEC.
The circulating ACE<sup>+</sup> EMPs and ACE<sup>+</sup> EMP/EMP ratio on admission were significantly increased in septic patients who developed ARDS compared with septic patients who did not (p<0.001).Therefore, circulating ACE<sup>+</sup> EMPs may be a prognostic marker for the development of ARDS in the septic patients.
Increased A(1-9)/A(1-10) ratio suggests that angiotensin converting enzyme II (ACE2) activity is higher in patients who survived their ARDS insult while an increase in A(1-7)/A(1-10) ratio suggests that ACE activity is also higher in survivors.
Angiotensin converting enzyme (ACE1) insertion/deletion (I/D) polymorphism was previously reported to show association with the adult respiratory distress syndrome, which is also thought to play a key role in damaging the lung tissues in SARS cases.
Moreover, there is also no evidence that ACE I/D polymorphism is associated with the progression to ARDS or the requirement of intensive care in the SARS patients.
In a prospective study, adults (Germans of Caucasian ethnicity) with ARDS (n = 84) were recruited from the current authors' intensive care unit and genotyped for the ACE I/D and the AGT (-6)A/G polymorphisms, as were 200 healthy Caucasian controls.
After adjustment for those variables, the presence of the allele D of the ACE gene (odds ratio, 4.75; 95% confidence interval, 1.02-22.20; P = 0.048) was significantly associated with the diagnosis of ARDS.
The cumulative effect of the risk alleles in the genes comprising two sets of genes partners (xenobiotics detoxification: CYP1A1, AhR and RAS family: ACE, AGT, AGTR1) is associated with the development of both NP and ARDS.
For instance, in the acute respiratory distress syndrome (ARDS), ACE, AngII, and AT1R promote the disease pathogenesis, whereas ACE2 and the AT2R protect from ARDS.
This review highlights the deleterious action of ACE/Ang-II/AT1R axis and the beneficial role of ACE2/Ang-(1-7)/MasR axis, as well as AT2R, in VILI and ARDS, and also discusses the possibility of targeting RAS components with pharmacological interventions to improve outcomes in ARDS.
Increased A(1-9)/A(1-10) ratio suggests that angiotensin converting enzyme II (ACE2) activity is higher in patients who survived their ARDS insult while an increase in A(1-7)/A(1-10) ratio suggests that ACE activity is also higher in survivors.
Downregulation of ACE2 is always associated with the ALI or ARDS induced by avian influenza virus, severe acute respiratory syndrome-coronavirus, respiratory syncytial virus and sepsis.
Adenovirus 14p1 (Ad14p1) is an emergent variant of Ad serotype 14 (Ad14) that has caused increased severity of respiratory illnesses during globally distributed outbreaks, including cases of acute respiratory distress syndrome and death.
Multivariable analysis revealed that respiratory distress syndrome was associated with maternal single nucleotide polymorphisms in CYP3A5 (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.16-2.30) and the glucocorticoid resistance (OR, 0.28; 95% CI, 0.08-0.95) and fetal single nucleotide polymorphisms in ADCY9 (OR, 0.17; 95% CI, 0.03-0.80) and CYP3A7*1E (rs28451617; OR, 23.68; 95% CI, 1.33-420.6).