Effectiveness of Tailored Dietary Counseling in Treating Malnourished Outpatients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial.

BACKGROUND: Malnutrition in patients with chronic obstructive pulmonary disease (COPD) is common and associated with poor prognosis. Nutrition interventions are necessary, but there is a lack of evidence regarding the effectiveness of tailored nutrition advice. OBJECTIVE: This study investigated whether tailored nutrition counseling could improve dietary intake, nutritional status, functional outcomes, and health-related quality of life (QoL) of malnourished outpatients with COPD. DESIGN: We conducted a randomized controlled trial in which participants were randomly assigned to either the intervention group (IG) or the control group (CG). PARTICIPANTS/SETTING: One hundred and twenty malnourished outpatients with COPD participated in the study between May and November 2017 at the National Lung Hospital, Hanoi, Vietnam. INTERVENTION: The IG received tailored nutrition counseling once per month for 3 months based on a specifically developed written nutrition resource for COPD. The CG received the same educational resource at baseline without any discussion. MAIN OUTCOME MEASURES: The main outcome measures were energy and protein intakes, body weight change, nutritional status (Subjective Global Assessment score), muscle strength, and QoL. STATISTICAL ANALYSES: Differences between groups before and after the intervention were assessed using two-way repeated measures analysis of variance. Generalized estimating equation modeling was used to investigate the differences between groups over time. RESULTS: At baseline, there were no significant differences in outcomes of interest between the two groups. After 3 months of intervention, time-intervention interactions for energy intake, protein intake, and body weight change were significant (945 kcal/day, 95% CI 792 to 1,099 kcal/day, P<0.001; 50.0 g protein/day, 95% CI 43.9 to 56.1 g protein/day, P<0.001; and 1.0 kg, 95% CI 0.5 to 1.5 kg, P<0.001, respectively). Subjective Global Assessment scores improved in the IG and worsened in the CG. Significant improvements were found in inspiratory muscle strength in the IG (5.4 cmH2O, 95% CI 2.3 to 8.6 cmH2O, P=0.001) and significant decreases in handgrip strength were found in the CG after 3 months of the intervention (1.4 kg, 95% CI 0.4 to 2.4 kg, P=0.007). There was a significant interaction effect for all QoL scores (analysis of variance two-way repeated, P≤0.003). The IG also significantly improved all QoL scores from baseline to 3 months (P<0.004). CONCLUSIONS: Tailored nutritional counseling has the potential to improve dietary intakes, nutritional status, functional outcomes, and QoL in malnourished outpatients with COPD.

Disrupting the CD95-PLCγ1 interaction prevents Th17-driven inflammation.

CD95L is a transmembrane ligand (m-CD95L) that is cleaved by metalloproteases to release a soluble ligand (s-CD95L). Unlike m-CD95L, interaction between s-CD95L and CD95 fails to recruit caspase-8 and FADD to trigger apoptosis and instead induces a Ca2+ response via docking of PLCγ1 to the calcium-inducing domain (CID) within CD95. This signaling pathway induces accumulation of inflammatory Th17 cells in damaged organs of lupus patients, thereby aggravating disease pathology. A large-scale screen revealed that the HIV protease inhibitor ritonavir is a potent disruptor of the CD95-PLCγ1 interaction. A structure-activity relationship approach highlighted that ritonavir is a peptidomimetic that shares structural characteristics with CID with respect to docking to PLCγ1. Thus, we synthesized CID peptidomimetics abrogating both the CD95-driven Ca2+ response and transmigration of Th17 cells. Injection of ritonavir and the CID peptidomimetic into lupus mice alleviated clinical symptoms, opening a new avenue for the generation of drugs for lupus patients.