TABLE 1

Recent studies investigating metabolic changes in acute respiratory distress syndrome (ARDS)

First author [ref.]Cohorts comparedSample typeMetabolic alterations in ARDSRelationship to mitochondrial dysfunction
Izquierdo-García [11]H1N1 influenza virus pneumonia ARDS (n=12) and non-ARDS (n=18)Serum↓ glucose, alanine, glutamine and fatty acids
↑ phenylalanine and methylguanidine
Decreased TCA cycle intermediates
Increased utilisation of aerobic metabolism
Rogers [17]ARDS (n=16) and non-ARDS (n=13) groups with hydrostatic pulmonary oedemaPulmonary oedema fluid“High metabolite” subset (n=6); distinction in 250 out of 749 identified metabolites
Pathway analysis:
↑ alanine, aspartate and glutamine metabolism
↑ arginine and proline metabolism
↑ lysine degradation
Suggested correlation of high metabolite group with “hyper-inflammatory” subphenotype
Bos [23]Sepsis ARDS: “reactive phenotype” (n=128), “uninflamed phenotype” (n=82)Whole-blood leukocyte gene expression“Reactive” phenotype:
↑ neutrophil activation;
↑ oxidative phosphorylation
“Uninflamed” phenotype:
enrichment of MAP2K4- and RAF1-dependent MAPK pathways
Heterogenic subphenotypes of ARDS, with incomparable pathophysiology
Gene expression in “reactive” phenotype indicative of comparatively greater mitochondrial dysfunction
Viswan [9, 24]mBALF: ARDS (n=159), non-ARDS (n=40)
Serum: ARDS (n=197), non-ARDS (n=68)
mBALF and serummBALF:
↑ lysine, arginine, tyrosine, threonine, leucine, isoleucine and valine
Serum:
↑ proline, glutamate, phenylalanine and valine
TCA cycle and nitrogenous network disruption
Izquierdo-García [25]S. pneumoniae-induced ARDS (n=13) and non-ARDS (n=17)
Influenza A pneumonia-induced ARDS (n=18) and non-ARDS (n=12)
Serum↓ glucose, alanine, methylhistidine, fatty acids, creatine, citrate, valine and creatinine
↑ acetone
Comparable impairments to metabolic pathways irrespective of infective source
Enhanced energy requirements suspected in S. pneumoniae-induced ARDS

TCA: tricarboxylic acid; MAPK: mitogen-activated protein kinase; RAF1: Raf-1 proto-oncogene, serine/threonine kinase; mBALF: mini bronchoalveolar lavage fluid; S. pneumoniae: Streptococcus pneumoniae.