SESSION TITLE: Late Breaking Diffuse Lung Disease PostersSESSION TYPE: Original Investigation PostersPRESENTED ON: 10/18/2022 01:30 pm - 02:30 pmPURPOSE: Sarcoidosis is a disease with a highly variable clinical presentation that includes disabling symptoms such as fatigue and cognition dysfunction that impair different facets of quality of life as a result to chronic inflammation. Because currently available treatments are not aimed at improving these patient-related outcomes (PROs), further study thereof may provide novel insight into the psycho-biologic mechanisms of these debilitating symptoms.METHODS: We leveraged our access to the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study, where sarcoidosis subjects (n=195) were administered PRO questionnaires including the Fatigue Assessment Scale (FAS), Cognitive Failure Questionnaire (CFQ), and Short Form Survey (SF-12) to assess physical (PCS) and mental (MCS) quality of life. Next, we quantified Th2 cytokines (IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13) which are associated with fatigue in the available plasma of 150 GRADS subjects and sought statistical correlations between symptoms and cytokines and meaningful differences in cytokine levels in subjects with low and high PRO scores.RESULTS:99% GRADS subjects met criteria for fatigue and 21% met extreme fatigue levels, with a median FAS score of 33.75 ± interquartile range (IQR) of 7.75. Median FAS Mental Scores were 16.75 ± 3.75 and FAS Physical Scores of 17 ± 4. 22.97% GRADS subjects displayed cognition failure, with a median CFQ score was 32.0 ± 21. 98% GRADS subjects exhibited impaired quality of life in the physical component scale and 59% in the mental component, with a median PCS-12 of 43.30 ± 6.23 and MCS-12 of 53.32 ± 1.83. There was no statistical correlation between FAS scores and cytokines. Moreover, there was no difference in cytokine levels between GRADS participants stratified with fatigue (FAS 22-35) versus extreme fatigue (FAS>35), or between mental versus physical fatigue. There was no statistical correlation between CFQ scores and cytokines, and no difference in cytokines between those with low (≤ 43) versus high (>44) scores. There was a significant correlation between IL-13 and PCS (Spearman r = 0.138, p=0.012) and IL-6 and MCS (Spearman r = 0.110, p=0.036). However, there were no significant differences in cytokine levels between individuals with a low (<50) versus high (>50) PCS and MCS scores.CONCLUSIONS: Our results validate prior reports of fatigue, cognitive failure, and mental/physical impaired quality of life that displayed no association with circulating Th2 cytokines. Further studies exploring other mediators such as Th1 cytokines and circulating innate immune ligands may provide insight into mechanisms driving these PROs.CLINICAL IMPLICATIONS: Further study of the biologic mediators of PROs in sarcoidosis has the potential to enhance our understanding of these debilitating symptoms and improve patient management in this challenging to treat disease.DISCLOSURES:No relevant relationships by Vitória Fiorinino disclosure on file for Erica Herzog;No relevant relationships by Buqu HuNo relevant relationships by Zara Khanno disclosure on file for John McGovern;No relevant relationships by Changwan RyuNo relevant relationships by Ying Sun SESSION TITLE: Late Breaking Diffuse Lung Disease Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/18/2022 01:30 pm - 02:30 pm PURPOSE: Sarcoidosis is a disease with a highly variable clinical presentation that includes disabling symptoms such as fatigue and cognition dysfunction that impair different facets of quality of life as a result to chronic inflammation. Because currently available treatments are not aimed at improving these patient-related outcomes (PROs), further study thereof may provide novel insight into the psycho-biologic mechanisms of these debilitating symptoms. METHODS: We leveraged our access to the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study, where sarcoidosis subjects (n=195) were administered PRO questionnaires including the Fatigue Assessment Scale (FAS), Cognitive Failure Questionnaire (CFQ), and Short Form Survey (SF-12) to assess physical (PCS) and mental (MCS) quality of life. Next, we quantified Th2 cytokines (IL-4, IL-5, IL-6, IL-9, IL-10, and IL-13) which are associated with fatigue in the available plasma of 150 GRADS subjects and sought statistical correlations between symptoms and cytokines and meaningful differences in cytokine levels in subjects with low and high PRO scores. RESULTS: 99% GRADS subjects met criteria for fatigue and 21% met extreme fatigue levels, with a median FAS score of 33.75 ± interquartile range (IQR) of 7.75. Median FAS Mental Scores were 16.75 ± 3.75 and FAS Physical Scores of 17 ± 4. 22.97% GRADS subjects displayed cognition failure, with a median CFQ score was 32.0 ± 21. 98% GRADS subjects exhibited impaired quality of life in the physical component scale and 59% in the mental component, with a median PCS-12 of 43.30 ± 6.23 and MCS-12 of 53.32 ± 1.83. There was no statistical correlation between FAS scores and cytokines. Moreover, there was no difference in cytokine levels between GRADS participants stratified with fatigue (FAS 22-35) versus extreme fatigue (FAS>35), or between mental versus physical fatigue. There was no statistical correlation between CFQ scores and cytokines, and no difference in cytokines between those with low (≤ 43) versus high (>44) scores. There was a significant correlation between IL-13 and PCS (Spearman r = 0.138, p=0.012) and IL-6 and MCS (Spearman r = 0.110, p=0.036). However, there were no significant differences in cytokine levels between individuals with a low (<50) versus high (>50) PCS and MCS scores. CONCLUSIONS: Our results validate prior reports of fatigue, cognitive failure, and mental/physical impaired quality of life that displayed no association with circulating Th2 cytokines. Further studies exploring other mediators such as Th1 cytokines and circulating innate immune ligands may provide insight into mechanisms driving these PROs. CLINICAL IMPLICATIONS: Further study of the biologic mediators of PROs in sarcoidosis has the potential to enhance our understanding of these debilitating symptoms and improve patient management in this challenging to treat disease. DISCLOSURES: No relevant relationships by Vitória Fiorini no disclosure on file for Erica Herzog; No relevant relationships by Buqu Hu No relevant relationships by Zara Khan no disclosure on file for John McGovern; No relevant relationships by Changwan Ryu No relevant relationships by Ying Sun