Automatic CPAP (auto-CPAP) is engineered to automatically provide a positive pressure to the upper airway in response to apnea, hypopnea, airflow limitation, or snoring in patients with the sleep apnea/ hypopnea syndrome (SAHS). Self-adjusted CPAP has theoretical advantages over traditional fixed CPAP. We investigated the value of auto-CPAP regulation in 20 patients with SAHS in order to predict future fixed-level CPAP needs, as an alternative method to conventional polysomnographically (PSG)-controlled CPAP titration. This was accomplished through comparison of the optimal CPAP level obtained with PSG with that obtained with auto-CPAP. There were no significant differences between the optimal CPAP level achieved with full PSG or with auto-CPAP. As a secondary analysis, we analyzed auto-CPAP performance with regard to sleep-stage distribution and arousals in a group of nine male patients, and compared it with the previous group of 20 patients in which manually CPAP titration was guided by PSG. After adequate CPAP was reached, upward and downward fluctuations in the CPAP level had no significant effect on sleep architecture or fragmentation. We conclude that auto-CPAP permits the prediction of future fixed-level CPAP needs, and does so without sleep disruption.

Pharmacogenetics is the study of variations in DNA sequence related to drug response. Moreover, the evolution of biotechnology and the sequencing of human DNA have allowed the creation of pharmacogenomics, a branch of genetics that analyzes human genes, the RNAs and proteins encoded by them, and the inter-and intra-individual variations in expression and function in relation to drug response. Pharmacogenetics and pharmacogenomics are being used to search for biomarkers that can predict response to systemic treatments, including those for moderate-to-severe psoriasis. Psoriasis is a chronic inflammatory disease with an autoimmune contribution. Although its etiology remains unknown, genetic, epigenetic, and environmental factors play a role in its development. Diverse systemic and biologic therapies are used to treat moderate-to-severe psoriasis. However, these treatments are not curative, and patients exhibit a wide range of responses to them. Moderate-to-severe psoriasis is usually treated with systemic immunomodulators such as acitretin, ciclosporin, and methotrexate. Anti-tumor necrosis factor (TNF) drugs (adalimumab, etanercept, or infliximab) are the first-line treatment for patients resistant to conventional systemic therapies. Although these therapies are very efficient, around 30-50% of patients have inadequate response. Ustekinumab is a monoclonal antibody that targets interleukin (IL)-12 and IL-23 and is used for moderate-to-severe psoriasis. New drugs (apremilast, brodalumab, guselkumab, ixekizumab, and secukinumab) have recently been approved for psoriasis. However, response rates to systemic treatments for moderate-to-severe psoriasis range from 35 to 80%, so it is necessary to identify non-invasive biomarkers that could help predict treatment outcomes of these therapies and individualize care for patients with psoriasis. These biomarkers could improve patient quality of life and reduce health costs and potential side effects. Pharmacogenetic studies have identified potential biomarkers for response to biologic treatments for moderate-to-severe psoriasis. These biomarkers need to be validated in clinical trials involving large cohorts of patients before they can be translated to the clinic. We review pharmacogenetics and pharmacogenomics studies for the treatment of moderate-to-severe plaque psoriasis.

Figure 1 a) Patient 4. Confluent maculopapular exanthem affecting predominantly the trunk and proximal extremities. b) Patient 1. More extensive involvement of the trunk, with areas of unaffected skin. c) HE stain 920. Mild superficial perivascular lympohcytic infiltrate, spongiosis and interface dermatitis. d) HE 940. Mild superficial perivascular lymphocytic infiltrate.

Because successful medical treatment of obstructive sleep apnea/hypopnea syndrome (SAHS) depends on adequate CPAP treatment, we have analyzed in nine SAHS patients the behavior of respiratory and neurological parameters during a stepwise, polysomnography-controlled CPAP titration to achieve an optimal CPAP. Particularly, we have focused on which simple variable could predict the optimal CPAP pressure and could better define a distinctive optimal-suboptimal pattern. Main parameters analyzed through the CPAP titration procedure were respiratory events (apnea, hypopnea), the contour of inspiratory flow, the pleural pressure behavior, the thoraco-abdominal motion, oximetry, arousals, and sleep stage. During the CPAP titration we observed: (1) a rounded shape in the inspiratory flow contour was associated with the lowest esophageal pressure; (2) during stepwise increases in CPAP, almost all apnea events changed to hypopnea periods, followed by prolonged periods of limited inspiratory flow with still high esophageal pressure but without arousals (probably suboptimal CPAP); and (3) as CPAP reached suboptimal levels, sleep stage moved to deeper stages without arousals. We conclude that if during CPAP titration the end point is the disappearance of arousals, most patients with SAHS will still exhibit periods of high intrathoracic pressures with limited inspiratory flow. Alternatively, if the end point to be reached is the lowest esophageal pressure, higher CPAP levels will be needed. The contour of inspiratory flow appears as the simplest variable that best correlates with lowest esophageal pressure during CPAP titration.

Introduction Epigenetic factors play an important role in psoriasis onset and development. Biological drugs are used to treat moderate‐to‐severe psoriasis patients resistant to conventional systemic drugs. Although they are safe and effective, some patients do not respond to them. Therefore, it is necessary to find biomarkers that could predict response to these therapies. Objective To find epigenetic biomarkers that could predict response to biological drugs (ustekinumab, secukinumab, adalimumab, ixekizumab). Materials and methods Peripheral blood mononuclear cells (PBMCs) were isolated from 39 psoriasis patients treated with biological therapies before and after drug administration and from 42 healthy subjects. Afterwards, histones were extracted from PBMCs. Four histone modifications (H3 and H4 acetylation, H3K4 and H3K27 methylation) were determined by ELISA. Data were analysed by IBM‐SPSS v.23. Results and conclusions Psoriasis patients presented reduced levels of acetylated H3 and H4 and increased levels of methylated H3K4 compared to controls. Non‐significant changes were observed after treatment administration in any of the histone modifications analysed. Nevertheless, significant changes in methylated H3K27 were found between responders and non‐responders to biological drugs at 3 months. As 28% of these patients also presented psoriatic arthritis (PsA), the former analysis was repeated in the subsets of patients with or without PsA. In patients without PsA, significant changes in methylated H3K4 were found between responders and non‐responders to biological drugs at 3 and 6 months. Although further studies should confirm these results, these findings suggest that H3K27 and H3K4 methylation may contribute to patients’ response to biological drugs in psoriasis.

No abstract

BackgroundBullous pemphigoid (BP) has been associated with dipeptidyl peptidase‐4 inhibitors (DPP4i). Clinical features, outcomes, and risk of BP for new DPP4i (linagliptin, saxagliptin, and alopgliptin) are not well established. Comparison of risk of BP appearance for DPP4i and other oral antidiabetic drugs (OADs) such as sodium glucose cotransporter 2 inhibitors has not been studied to date.ObjectivesTo describe the prevalence, sociodemographic, clinical, and histopathological characteristics, and outcome after drug withdrawal in DPP‐4i‐associated BP cases from our hospital. To review all Spanish spontaneous notifications of BP where DPP4i or OADs were included as suspected drugs and calculate the reporting odds ratios (RORs).MethodsA retrospective observational study was performed examining the association between DDP4i and BP. Clinical features and RORs were analyzed. Data from the Spanish Pharmacovigilance System (SEFV) are included.ResultsIn our center, 28 of 89 patients with BP (31.5%) were under DPP4i treatment; 53.6% were male, and mean age was 80.8 years. BP debuted the first year after DPP4i in 57.2%. BP control was achieved within 3.7 months after drug withdrawal. Regarding SEFV, 22 of 972 spontaneous notifications were related to BP and DPP4i. RORs were superior for DPP4i compared to other OADs. Vildagliptin had the highest ROR.ConclusionsWe present the largest DPP4i‐induced BP case series in a single center, with a detailed study of the sociodemographic, clinical, and histopathological characteristics of each patient, and their treatment and outcome. Vildagliptin had the highest risk. DPP4i‐associated BP does not seem to have specific clinical characteristics.

While anti-TNF therapies are effective against psoriasis, 30%-50% of patients do not show an adequate response to these drugs. Different candidate-gene pharmacogenetics studies have identified single nucleotide polymorphisms that may predict anti-TNF drugs response in psoriasis. Nevertheless, only one paper has undertaken a pharmacogenomic approach failing to find significant biomarkers of biological drug response along the whole genome. Furthermore, most of the pharmacogenetic candidate biomarkers identified previously have not been confirmed in a different cohort of patients. The objective of this study was to find biomarkers that could predict anti-TNF drugs response along the whole genome and validate biomarkers identified previously. A genome-wide association study (GWAS) was performed using the Human Omni Express-8 v1.2 Beadchips in 243 psoriasis patients treated with anti-TNF drugs. This study was multicentric and did not interfere with clinical practice. Associations between single nucleotide polymorphisms (SNP) and PASI75 (a 75% reduction with respect to baseline PASI) at 3 months were evaluated. Imputation was performed using SNPs with R 2 > 0.7. There were two SNPs located in NPFFR2 that were close to the significant threshold of 5 × 10 −8. These data suggest that NPFFR2 might be associated with anti-TNF drug response. However, further How to cite this article: Ovejero-Benito MC, Muñoz-Aceituno E, Sabador D, et al. Genome-wide association analysis of psoriasis patients treated with anti-TNF drugs.