Pharmacodynamic monitoring by residual gene expression of the nuclear factor of activated T cell-regulated genes in lung transplant recipients and its correlation with tacrolimus blood levels.

Introduction: Trough blood levels (C0) of tacrolimus are used to adjust drug dosage, but they do not consistently correlate with clinical outcomes. Measurement of residual gene expression of nuclear factor of activated T cell (NFAT)-regulated genes (NFAT-RGE) has been proposed as a pharmacodynamic biomarker to assess the degree of immunosuppression in certain solid organ transplantations, but little is known regarding lung transplant recipients (LTR). Our primary objective is to correlate tacrolimus blood levels with NFAT-RGE. Methods: NFAT-RGE and tacrolimus C0 and peak (C1.5) levels were determined in 42 patients at three, six and 12 months post-transplantation. Results: Tacrolimus C0 did not exhibit a correlation with NFAT-RGE, whereas C1.5 did. Besides, over 20% of measurements indicated high levels of immunosuppression based on the below 30% NFAT-RGE threshold observed in many studies. Among those measurements within the therapeutic range, 19% had an NFAT-RGE<30%. Conclusion: Consequently, a subset of patients within the tacrolimus therapeutic range may be more susceptible to infection or cancer, potentially benefiting from NFAT-RGE and tacrolimus peak level monitoring to tailor their dosage. Further quantitative risk assessment studies are needed to elucidate the relationship between NFAT-RGE and the risk of infection, cancer, or rejection.

Obstructive sleep apnea in adults with Down syndrome.

Patients with Down syndrome (DS) often have a high occurrence of obstructive sleep apnea-hypopnea (OSA) syndrome. We studied a large cohort of adults with DS attended due to clinical suspicion of OSA. A standardized questionnaire and full medical assessment were conducted, including a sleep study. One hundred and fifty-seven DS individuals were studied, with a mean ± SD age of 36 ± 10 years, 40.7% women, BMI 29.4 ± 5.6 kg/m2 . The main clinical symptom was daytime sleepiness (64.9%). A sleep study was conducted in 114 patients. All 114 DS patients were diagnosed with OSA, with a predominance of obstructive and hypopnea events, (apnea-hypopnoea index, AHI, 35.0 ± 26.6), with an oxygen desaturation index of 32.9, and a Tc90% of 24.7%. Continuous positive airway pressure (CPAP) treatment was implemented in 75 (65.8%) of subjects. Tolerance was considered good in 75% of them, with a high compliance of 79.2% >4 hr/day (mean 7.1 hr/day), resulting in a symptomatic improvement in 58.7% of them. Obstructive sleep apnea is frequently confirmed in patients with DS when it clinically suspected. Treatment with CPAP in DS is feasible, and with higher adherence than in adults with normal cognitive functioning.