[thread] You know what's frustrating? There ARE phenotypes of ARDS. They've been rigorously derived, independently validated, and interrogated for biological and clinical significance. Yet they've been abandoned in COVID, replaced with unsupported "L vs H" speculation.

1/n

Carolyn Calfee and her team have done extensive, meticulous work identifying subphenotypes of ARDS. They didn't base it on hunches. They systematically studied tons of patients, predictors, and outcomes, using unsupervised clustering.

2/n

https://www.ncbi.nlm.nih.gov/pubmed/?term=Calfee+CS%5BAuthor%5D+subphenotypes

These ARDS phenotypes are robust across multiple cohorts (5? I've lost track) and have been validated by another research group ( @Acute_Pulmo_Med).

3/n

https://www.ncbi.nlm.nih.gov/pubmed/24853585 
https://www.ncbi.nlm.nih.gov/pubmed/27513822 
https://www.ncbi.nlm.nih.gov/pubmed/28450529 

These phenotypes are temporally stable within individuals, even after 3 days of mechanical ventilation. They aren't just "early" and "late" manifestations of the same disease.

4/n

https://www.ncbi.nlm.nih.gov/pubmed/29477989 

And these phenotypes appear to differ in their response to therapy! Including PEEP, fluid management, and simvastatin. Again: this is informed by thoughtful interrogation of RCT data, not intuition.

5/n

https://www.ncbi.nlm.nih.gov/pubmed/24853585 
https://www.ncbi.nlm.nih.gov/pubmed/27513822 
https://www.ncbi.nlm.nih.gov/pubmed/30078618 

Despite all this, Calfee et al. are quite measured in their interpretations, and urge caution in clinical implementation. They believe in tailored ARDS care, but know it'll take responsible, prospective studies to get there.

6/n

https://www.ncbi.nlm.nih.gov/pubmed/24853585 
https://www.ncbi.nlm.nih.gov/pubmed/32204722 

Contrast that with the "L vs H" advocates, who are recommending immediate changes in ARDS management, based on published observations from 16 patients. Data that are neither internally consistent nor supportive of their claims.

7/n
https://twitter.com/robertpdickson/status/1253775450415017994
https://jamanetwork.com/journals/jama/fullarticle/2765302

Interesting note: of the four essays/editorials published to date advocating for "L vs H," there is not a single citation to any of this prior ARDS phenotyping work. Including publications in @JAMA_current, @ATSBlueEditor, @Crit_Care @yourICM

8/n

It's disheartening to see years of hard-won insights cast aside during an ARDS pandemic. In our clinical management, in our understanding of ARDS heterogeneity, and in our standards for evidence.

9/9