MRC chronic Dyspnea Scale: Relationships with cardiopulmonary exercise testing and 6-minute walk test in idiopathic pulmonary fibrosis patients: a prospective study

<p>Abstract</p> <p>Background</p> <p>Exertional dyspnea is the most prominent and disabling feature in idiopathic pulmonary fibrosis (IPF). The Medical Research Chronic (MRC) chronic dyspnea score as well as physiological measurements obtained during cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) are shown to provide information on the severity and survival of disease.</p> <p>Methods</p> <p>We prospectively recruited IPF patients and examined the relationship between the MRC score and either CPET or 6MWT parameters known to reflect physiologic derangements limiting exercise capacity in IPF patients</p> <p>Results</p> <p>Twenty-five patients with IPF were included in the study. Significant correlations were found between the MRC score and the distance (r = -.781, p < 0.001), the SPO₂at the initiation and the end (r = -.542, p = 0.005 and r = -.713, p < 0.001 respectively) and the desaturation index (r = .634, p = 0.001) for the 6MWT; the MRC score and <it>V</it>O₂peak/kg (r = -.731, p < 0.001), SPO₂at peak exercise (r = -. 682, p < 0.001), VE/VCO₂slope (r = .731, p < 0.001), VE/VCO₂at AT (r = .630, p = 0.002) and the Borg scale at peak exercise (r = .50, p = 0.01) for the CPET. In multiple logistic regression analysis, the only variable independently related to the MRC is the distance walked at the 6MWT.</p> <p>Conclusion</p> <p>In this population of IPF patients a good correlation was found between the MRC chronic dyspnoea score and physiological parameters obtained during maximal and submaximal exercise testing known to reflect ventilatory impairment and exercise limitation as well as disease severity and survival. This finding is described for the first time in the literature in this group of patients as far as we know and could explain why a simple chronic dyspnea score provides reliable prognostic information on IPF.</p

Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family

Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca2+ stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10-7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease

Genome-wide physical activity interactions in adiposity. A meta-analysis of 200,452 adults

Physical activity (PA) may modify the genetic effects that give rise to increased risk of obesity. To identify adiposity loci whose effects are modified by PA, we performed genome-wide interaction meta-analyses of BMI and BMI-adjusted waist circumference and waist-hip ratio from up to 200,452 adults of European (n = 180,423) or other ancestry (n = 20,029). We standardized PA by categorizing it into a dichotomous variable where, on average, 23% of participants were categorized as inactive and 77% as physically active. While we replicate the interaction with PA for the strongest known obesity-risk locus in the FTO gene, of which the effect is attenuated by similar to 30% in physically active individuals compared to inactive individuals, we do not identify additional loci that are sensitive to PA. In additional genome-wide meta-analyses adjusting for PA and interaction with PA, we identify 11 novel adiposity loci, suggesting that accounting for PA or other environmental factors that contribute to variation in adiposity may facilitate gene discovery.Peer reviewe

Meta-analysis of exome array data identifies six novel genetic loci for lung function

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease.Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV1), forced vital capacity (FVC) and the ratio of FEV1 to FVC (FEV1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals.Results: We identified significant (PRPAP1, which is predicted to be damaging, three intronic SNPs (SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU.Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.</p