Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven cases of single lung transplantation are reported. The recipients were all below 60 years of age and severely disabled with end-stage lung disease. Transplantation was performed according to ABO blood group compatibility and negative lymphocytotoxic cross-match between donor and recipient irrespective of HLA mismatch. Recipients' diagnoses were sarcoidosis (3), alfa-1 antitrypsin deficiency (3), and idiopathic emphysema (1). Mean recipient age was 48 +/- 2.4 years (range 45-52). Donor age was 29.7 +/- 5.6 years (range 16-49). The immunosuppressive regimen included cyclosporin A, azathioprine, steroids and rabbit antithymocyte globulin. Excellent graft function was achieved. Six patients survived the postoperative period and are alive 4-18 months posttransplant. One patient died after the operation due to pneumonia with respiratory distress syndrome. Graft function was also monitored by transbronchial biopsy, and 57 biopsy procedures were performed without fatal complications. Acute cellular rejection was seen in 16 biopsy specimens from 5 recipients (grade 1 and 2 rejection in 14, grade 3 rejection in 2). Neither severe rejection with septal necrosis (grade 4) nor obliterative bronchiolitis was seen. The rejection rate was 0.03 episodes per patient/month. In contrast to other reports, episodes of cellular rejection occurred throughout the observation period, and were not mainly limited to the first 4 months posttransplant. Graft vascular occlusive disease or chronic vascular rejection was found in 6 biopsy specimens from one recipient. Five patients experienced 7 episodes of cytomegalovirus infection. The cytomegalovirus infection rate was 0.01 episodes per patient/month. The incidence of infection was significantly lower compared to previous studies of rejection in other lung graft combinations. Both infections and rejection episodes may contribute to the development of obliterative bronchiolitis. Almost one third of the specimens (30%) showed lymphocytic bronchitis without perivascular inflammation. The absence of perivascular infiltrates and exclusion of infectious agents leaves in question the aetiology of this inflammation. The lymphocytic bronchitis could be ischaemic, related to aspiration, or represent recurrent sarcoidosis, or, in fact, express bronchial rejection. All biopsy specimens regarded as rejection with cellular infiltrates in the lung parenchyma also showed a lymphocytic bronchitis. The impact of HLA mismatch on cellular and vascular rejection is unclear. Transbronchial biopsy is a reasonably safe and reliable method in the diagnosis of rejection and infection in single lung transplantation.
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PMID:Single lung transplantation. Morphological surveillance by transbronchial biopsy. 839 61

To present an overview of the surgical issues in lung transplantation, including the historical context and the rationale for choosing a particular procedure for a specific patient, we reviewed and summarized the current medical literature and our personal experience. Several surgical options are available, including single lung transplantation; double lung transplantation; heart-lung transplantation; bilateral, sequential single lung transplantation; and (recently) single lobe transplantation. Although single lung transplantation is preferred for maximal use of the available organs, bilateral lung transplantation is necessary for septic lung diseases and may be appropriate for pulmonary hypertension and bullous emphysema. Heart-lung transplantation is performed for Eisenmenger's syndrome and for primary pulmonary hypertension with severe right ventricular failure. General factors for consideration in assessment of compatibility of the donor and potential recipient include ABO blood group, height (the donor should be within +/- 20% of the recipient's height), and length of the lungs (determined on an anteroposterior chest roentgenogram). Graft preservation and minimal duration of ischemia are important. Complications associated with airway healing are related to ischemia of the donor bronchus. We have addressed the issue of donor bronchial ischemia by direct revascularization of the donor bronchial arteries with use of the recipient's internal thoracic artery. Currently, lung transplantation offers a realistic therapeutic option to patients with end-stage pulmonary parenchymal or vascular disease.
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PMID:Surgical issues in lung transplantation: options, donor selection, graft preservation, and airway healing. 900 92

Because the number of ideal brain-dead donors is limited, active use of marginal donors is currently one of the major issues discussed in regard to lung transplantation. We report a case in which the patient underwent single-lung transplantation for chronic pulmonary emphysema. The lung came from a marginal, ABO blood group nonidentical, compatible donor. Because the donor was marginal (pneumonia in the right lung and lobar atelectasis in both lungs), all recipient candidates with ABO blood group identical declined. Thus, a nonidentical, compatible recipient had a chance to receive a lung transplant. This 49-year-old man underwent single-lung transplantation for chronic pulmonary emphysema with severe respiratory failure. He had a good postoperative clinical course.
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PMID:Single-lung transplantation in a chronic pulmonary emphysema patient with a marginal donor who was ABO blood group nonidentical but compatible. 2245 44

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 < 8 X 10-10) pQTLs in 38 (43%) of blood proteins tested. Most pQTL SNPs were novel with low overlap to eQTL SNPs. The pQTL SNPs explained >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.
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PMID:Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD. 2753 55