GDF15 as a potential biomarker to distinguish fibrotic from non-fibrotic hypersensitivity pneumonitis.

Hypersensitivity Pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) characterized by fibrotic HP (fHP) or non-fibrotic HP (non-fHP). Fibrosis is associated with poor prognosis, emphasizing the need for biomarkers to distinguish fHP from non-fHP. This study aimed to determine the plasma levels of GDF15 in HP patients and assess its association with lung function and phenotype classification. GDF15 levels were quantified by ELISA in HP (n = 64), idiopathic pulmonary fibrosis (n = 54), and healthy control (n = 128) groups. Clinical, demographic, and functional data were obtained from medical records. High-resolution chest CT scans were used to classify HP patients into fHP and non-fHP groups. In addition, receiver operating characteristic analysis was performed to determine the cut-off point, sensitivity, and specificity. Our results revealed significantly elevated GDF15 levels in fHP compared to non-fHP (2539 ± 821 pg/ml versus 1783 ± 801 pg/ml; p = 0.009). The estimated cut-off point for plasma GDF15 levels to distinguish fHP from non-fHP was 2193.4 pg/ml (AUC 0.75). These findings suggest that GDF15 may serve as a valuable biomarker for differentiating between fHP and non-fHP, potentially indicating its involvement in lung fibrosis development in HP.

Cardiovascular and Respiratory Interactions in Idiopathic Pulmonary Fibrosis by Extended Partial Directed Coherence: Short-term Effects of Supplemental Oxygen.

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease that can lead to chronic arterial hypoxemia, hypercapnia, and dyspnea. To improve clinical symptoms in IPF patients, supplemental oxygen (SupplO2) has been prescribed with the aim to maintain SpO2 level, and consequently to relieve dyspnea, increase physical activity and improve quality of life. In this study, we investigated the effect of disease and short-term SupplO2 on cardiovascular and respiratory autonomic regulation. Linear and nonlinear indices were extracted from the beat-to-beat variability of heart rate (HR), systolic (SYS) blood pressure and respiration (RESP) in IPF patients and healthy subjects spontaneously breathing ambient air (AA) and during SupplO2 at 3 L/min. It was found that the effects on autonomic nervous systems (ANS) regulation were better demonstrated by the Granger causality (GC) method. GC was significantly higher (p<0.01) in patients compared to controls for the interactions RESP→SYS and BBI→SYS.Clinical Relevance-Short-term SupplO2 in IPF could adversely affect systolic blood pressure variability in particular. This study may help in the management of SupplO2 administration.

Genetic variants associated with severe pneumonia in A/H1N1 influenza infection.

The A/H1N1 influenza strain isolated in Mexico in 2009 caused severe pulmonary illness in a small number of exposed individuals. Our objective was to determine the influence of genetic factors on their susceptibility. We carried out a case-control association study genotyping 91 patients with confirmed severe pneumonia from A/H1N1 infection and 98 exposed but asymptomatic household contacts, using the HumanCVD BeadChip (Illumina, San Diego, CA, USA). Four risk single-nucleotide polymorphisms were significantly (p<0.0001) associated with severe pneumonia: rs1801274 (Fc fragment of immunoglobulin G, low-affinity IIA, receptor (FCGR2A) gene, chromosome 1; OR 2.68, 95% CI 1.69-4.25); rs9856661 (gene unknown, chromosome 3; OR 2.62, 95% CI 1.64-4.18); rs8070740 (RPA interacting protein (RPAIN) gene, chromosome 17; OR 2.67, 95% CI 1.63-4.39); and rs3786054 (complement component 1, q subcomponent binding protein (C1QBP) gene, chromosome 17; OR 3.13, 95% CI 1.89-5.17). All SNP associations remained significant after adjustment for sex and comorbidities. The SNPs on chromosome 17 were in linkage disequilibrium. These findings revealed that gene polymorphisms located in chromosomes 1 and 17 might influence susceptibility to development of severe pneumonia in A/H1N1 infection. Two of these SNPs are mapped within genes (FCGR2A, C1QBP) involved in the handling of immune complexes and complement activation, respectively, suggesting that these genes may confer risk due to increased activation of host immunity.

Self-mutilation in the Lesch-Nyhan syndrome: a corporal consciousness problem?--a new hypothesis.

The Lesch-Nyhan syndrome (LNS) has been extensively studied from the genetic and biochemical point of view. The main characteristic of the syndrome is the self-mutilation feature, which has been poorly studied and understood. We propose a new hypothesis about the self-mutilation physiopathology, which is related to the supersensitivity of the dopaminergic D1 receptors in the neuromatrix found in the cingulum cortex region. The LNS shows an increase of uric acid levels as a result of the deficiency of hypoxanthine phosphoribosyltransferase enzyme. This increase could induce damage to dopaminergic neurons. As a consequence, a decrease in dopamine synthesis during gestation and the early postnatal period could occur, producing a functional dopaminergic denervation of the D1 receptors, located on the prefrontal cortex, specifically in the cingulum bundle projections. This phenomenon could induce a codification disturbance in the 'genetic body' of the neuromatrix, that could be expressed functionally as anosognosia, giving rise to self-mutilation. We suggest that this self-mutilation is a pain consciousness problem.