Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

Reverse Halo Sign on Chest Imaging in a Renal Transplant Recipient.

Without proper treatment, the mortality of pulmonary mucormycosis is nearly 100%. Although the diagnosis is often made histologically, it can be suspected when patients have a reverse halo sign on computed tomography (CT) of the chest, along with the right clinical findings. We describe the case of a woman 7 months post renal transplant who presented with fevers, malaise, and chest pain. Her chest CT revealed a round, focal area of ground-glass attenuation surrounded by a complete rim of consolidation in the left upper lobe, consistent with the reverse halo sign. Pulmonary mucormycosis was diagnosed by transbronchial lung biopsy. She was successfully treated with combined medical and surgical therapies. In the context of this case, we provide a brief review of the diagnosis of pulmonary mucormycosis, with a focus on radiographic and pathologic findings

Air Current Applied to the Face Improves Exercise Performance in Patients with COPD

Purpose: Improving dyspnea and exercise performance are goals of COPD therapy. We tested the hypothesis that air current applied to the face would lessen dyspnea and improve exercise performance in moderate-severe COPD patients.Methods: We recruited 10 COPD patients (5 men, age 62 ± 6 years, FEV1 0.93 ± 0.11 L (34 ± 3 % predicted), TLC 107 ± 6 %, RV 172 ± 18 %) naïve to the study hypothesis. Each patient was randomized in a crossover fashion to lower extremity ergometry at constant submaximal workload with a 12-diameter fan directed at the patients face or exposed leg. Each patients\u27 studies were separated by at least 1 week. Inspiratory capacity and Borg dyspnea score were measured every 2 min and at maximal exercise.Results: Total exercise time was longer when the fan was directed to the face (14.3 ± 12 vs. 9.4 ± 7.6 min, face vs. leg, respectively, p = 0.03). Inspiratory capacity tended to be greater with the fan directed to the face (1.4 (0.6-3.25) vs. 1.26 (0.56-2.89) L, p = 0.06). There was a reduction in dynamic hyperinflation, as reflected by higher IRV area in the fan on face group (553 ± 562 a.u. vs. 328 ± 319 a.u., p = 0.047). There was a significant improvement in the Borg dyspnea score at maximal exercise (5.0 (0-10) vs. 6.5 (0-10), p = 0.03), despite exercising for 34 % longer with the fan directed to the face.Conclusions: Air current applied to the face improves exercise performance in COPD. Possible mechanisms include an alteration in breathing pattern that diminishes development of dynamic hyperinflation or to a change in perception of breathlessness