Rationale: Surgical lung biopsy can help to determine a specific diagnosis in interstitial lung disease but has associated risks. Most currently available mortality data are derived from case series and may not be generalizable to broader populations.Objectives: To assess in-hospital mortality after surgical lung biopsy for interstitial lung disease in a national secondary care dataset from the United States.Methods: Data were obtained from the 2000–2011 Nationwide Inpatient Sample. Cases were identified using International Classification of Diseases codes for interstitial lung disease and surgical lung biopsies. Lung resections and cases of lung cancer were excluded. Weighted data were used to estimate numbers of biopsies nationwide and in-hospital mortality, and multivariable logistic regression was used to adjust for sex, age, geographic region, comorbidity, type of operation, and provisional diagnosis.Measurements and Main Results: We estimated there to be around 12,000 surgical lung biopsies performed annually for interstitial lung disease in the United States, two-thirds of which were performed electively. In-hospital mortality was 1.7% for elective procedures but significantly higher for nonelective procedures (16.0%). Male sex, increasing age, increasing comorbidity, open surgery, and a provisional diagnosis of idiopathic pulmonary fibrosis or connective tissue disease–related interstitial lung disease were risk factors for increased mortality.Conclusions: In-hospital mortality after elective surgical lung biopsy for interstitial lung disease is just under 2% but significantly higher for nonelective procedures. Identified risk factors for death should be taken into account when counseling patients on whether to pursue a histologic diagnosis.
No studies have investigated the immediate impact of receiving an allogeneic hematopoietic stem cell transplant (HSCT) on pulmonary inflammation or lung function.Using a prospective study design, we quantified the changes in these outcome measures in eligible adult individuals in the first six months after receiving an allogeneic hematopoietic stem cell transplant.Between January 2007 and December 2008, 72 patients were eligible to participate in the cohort, and of these 68 (94%) were included in the study. Compared to baseline, pulmonary inflammation as measured by exhaled nitric oxide increased after receiving a HSCT with the largest increment seen at three months (+6.0 ppb, 95%CI: +0.4 to +11.5), and this was sustained at six months. Percent predicted forced expiratory volume in one second decreased over the same period, with the largest decrease observed at six weeks (-5.9%, 95% CI: -8.9 to -2.9), and this was also sustained over a six month period. Similar associations were observed for FVC. A larger increase in exhaled nitric oxide from baseline at six weeks and three months may be associated with decreased mortality (p=0.06, p=0.04 respectively).Our data demonstrate that recipients of an allogeneic HSCT experience an increase in biomarkers of pulmonary inflammation and a decrease in lung function in the first six months after the procedure. If independently validated in other study populations, these observations could have potential as a prognostic biomarker for this patient group.
Abstract Background Idiopathic pulmonary fibrosis (IPF) is an incurable disease characterised by progressive scarring of the lungs. This leads to the lungs becoming stiffer, reducing lung capacity, and impeding gas transfer. We aimed to identify genetic variants associated with either declining lung capacity or gas transfer after diagnosis of IPF. Methods We performed a genome-wide meta-analysis of longitudinal measures of forced vital capacity (FVC) and diffusing capacity for lung of carbon monoxide (DLco) in individuals diagnosed with IPF from three studies. Suggestively significant variants were investigated further in an additional study. Variants were defined as significantly associated if they had a meta-analysis p<5×10 −8 , had consistent direction of effects across all studies and were nominally significant (p<0.05) in each study. Findings 1,048 individuals with measures of longitudinal FVC and 729 individuals with longitudinal measures of DLco passed quality control. In total, 4,560 measures of FVC and 2,795 measures of DLco and over 7 million genetic variants were included in the analysis. One variant located in an antisense RNA gene for Protein Kinase N2 ( PKN2 ) showed a genome-wide significant association with FVC decline (−140 ml/year per risk allele, 95% CI [−180, −100], p=9.14×10 −12 ). Interpretation These results identify a possible druggable target involved in promoting IPF disease progression. Funding Action for Pulmonary Fibrosis, Medical Research Council, Wellcome Trust, National Institute of Health/National Heart, Lung and Blood Institute Research in context Evidence before this study Idiopathic pulmonary fibrosis (IPF) is a devastating disease where the lungs become scarred, this scarring leads to a reduced lung capacity, poorer rates of gas transfer and is eventually fatal. However, disease progression is highly variable and it is not clear why this is. To date, genome-wide association studies (GWAS) have identified 20 genetic loci associated with susceptibility to IPF. These genetic loci implicate genes involved with host defence, regulation of TGFβ signalling, telomere maintenance, cell-cell adhesion and spindle assembly as important biological processes involved in the pathogenesis of IPF. The GWAS variant with the strongest effect on disease risk is found in the promoter region of the MUC5B gene (rs35705950). Generally, the variants associated with IPF susceptibility show little or no association with disease progression, apart from the risk allele at rs35705950 which has been reported as having an association with improved survival times. Added value of this study Although genetic variants associated with disease risk have been widely studied, little has been reported to investigate the effect of genetics on progression of IPF. Here we present a GWAS of progressive IPF by identifying genetic variants associated longitudinal measures of lung health after diagnosis of IPF. We identify a genetic locus associated with a more rapid decline in lung capacity that lies in the RNA antisense gene of PKN2 . Implications of all available evidence The novel genetic locus associated with a more rapid decline in lung capacity in individuals with IPF implicates a Rho/RAC effector protein. Effective treatments for IPF are desperately needed. There are currently PKN2 inhibitors under development meaning this analysis highlights a potential therapeutic target for IPF. We also show the genetic determinants of IPF progression appear to be distinct from those that drive IPF susceptibility.
Summary Background: A 15‐fold increased risk of gastrointestinal bleeding has been reported with concurrent use of selective serotonin reuptake inhibitors and non‐steroidal anti‐inflammatory drugs. Recent guidance cautions against concurrent prescription, particularly in older people. Aim: To quantify the risk of gastrointestinal bleeding associated with current exposure to non‐steroidal anti‐inflammatory drugs, selective serotonin reuptake inhibitors, and both drugs concurrently. Methods: We conducted a case–control analysis of 11 261 cases with upper gastrointestinal bleeding and 53 156 controls matched by gender, age and general practice from computerized primary care data. We coupled this with self‐controlled case series analysis. Results: Both drugs were associated with a twofold increased risk of gastrointestinal bleeding (odds ratio =2.38, 95% confidence interval 2.08–2.72 for selective serotonin reuptake inhibitors and odds ratio = 2.15, 95% confidence interval 2.02–2.28 for non‐steroidal anti‐inflammatory drugs). This increased risk was marginally higher for concurrent prescription (odds ratio = 2.93, 95%confidence interval 2.25–3.82). The self‐controlled analysis showed a greater incidence rate ratio for gastrointestinal bleeding with non‐steroidal anti‐inflammatory drugs (2.71, 95% confidence interval 2.51–2.91) and lower incidence rate ratio with selective serotonin reuptake inhibitors (1.71, 95% confidence interval 1.48–1.98). The incidence rate ratio when both drugs were combined was 3.25, 95% confidence interval 1.95–5.42. Estimates were similar after restricting to people over 80 years of age. Increased risk of gastrointestinal bleeding was not specifically related to class of non‐steroidal anti‐inflammatory drugs and was similar when we looked at tricyclic anti‐depressants. Conclusions: Our study suggests that the risk of gastrointestinal bleeding is not substantially increased when non‐steroidal anti‐inflammatory drugs and selective serotonin reuptake inhibitors are prescribed together, compared with their use alone.
There is an unmet need for identification of additional prognostic markers for lung cancer. The aim of this study was to identify novel clinical and immunological predictors of prognosis in lung cancer patients.Lymphocyte subsets CD3+, CD4+, CD8+, CD4+/8+, CD25+, CD69+, CD44+ and CD54+ were quantified in peripheral blood using flow cytometry, for 203 newly diagnosed lung cancer patients and 120 healthy controls.The levels of CD3+, CD4+, CD8+, CD4+/CD8+ and CD69+ lymphocytes were significantly lower in patients with lung cancer compared with the healthy control group, while CD54+ and CD44+ lymphocytes were significantly higher. In stage III/IV patients with lymph node metastasis or distant metastasis, the levels of CD44+ and CD54+ lymphocytes were significantly increased compared with patients with stage I/II disease (p<0.05). The levels of CD44+ and CD54+ lymphocytes markedly reduced after chemotherapy, and follow-up analysis indicated that patients found without increase of CD44+ and CD54+ lymphocytes after chemotherapy had survival advantages. Independent predictors of survival in lung cancer patients included clinical stage (hazard ratio [HR] = 2.791; 95% confidence interval [95% CI], 1.42-3.54, p<0.001), CD44+ lymphocytes (HR = 1.282; 95% CI, 1.02-1.49, p = 0.002) and CD54+ lymphocytes (HR = 1.475; 95% CI, 1.22-1.73, p = 0.003). Elevated levels of CD44+ and CD54+ lymphocytes correlated with poor prognosis in lung cancer patients.Peripheral blood lymphocyte subsets in patients with lung cancer are different from those in healthy people, and circulating CD44+ and CD54+ lymphocytes seem to be a promising criterion to predict survival in lung cancer patients undergoing chemotherapy.
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