Citations

Abstract In order to select samples that are optimally informative for sequence analysis, studies for the Genetic Epidemiology Consortium, we implemented three strategies for analysis, taking into account the known family histories of lung cancer. Susceptibility for lung cancer arises from a complex interplay between largely unknown genetic factors and smoking behavior. In order to optimize our ability to identify genetic factors for lung cancer we have recruited individuals with extensive family histories of lung cancer and also collected information about their smoking behaviors. For this study, we have modeled family history to identify individuals to select for sequencing using three approaches. First, we used an expert opinion approach in which multiple investigators evaluated pedigree structures with family history to reach a consensus priority in selecting individuals. Second we developed an approximation that assumes a low penetrance among noncarriers and uses known cancer status in first degree relatives. Third, we used the cancer, smoking behaviors and family information along with a likelihood that models penetrance according to genetic susceptibility and an interaction with smoking to estimate the probabilities individuals carry susceptibility factors. In this analysis we compare results among these methods. We evaluate effectiveness of these methods using simulation-based approaches. Citation Format: Christopher Amos, Joan Bailey-Wilson, Susan Pinney, Maria de Andrada, Colette Gaba, Diptasri Mandal, Ming You, Margaret Spitz, Marshall Anderson. Optimal strategies for selecting samples for sequencing families with a common cancer: The Genetic Epidemiology of Lung Cancer Consortium. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A106.

AbstractIntroductionSolid organ transplant recipients have a higher frequency of tuberculosis (TB) than the general population, with mortality rates of approximately 30%. Although donor‐derived TB is reported to account for <5% of TB in solid organ transplants, the source of Mycobacterium tuberculosis infection is infrequently determined.MethodsWe report 3 new cases of pulmonary TB in lung transplant recipients attributed to donor infection, and review the 12 previously reported cases to assess whether cases could have been prevented and whether any cases that might occur in the future could be detected and investigated more quickly. Specifically, we evaluate whether opportunities existed to determine TB risk on the basis of routine donor history, to expedite diagnosis through routine mycobacterial smears and cultures of respiratory specimens early post transplant, and to utilize molecular tools to investigate infection sources epidemiologically.FindingsOn review, donor TB risk was present among 7 cases. Routine smears and cultures diagnosed 4 asymptomatic cases. Genotyping was used to support epidemiologic findings in 6 cases.ConclusionValidated screening protocols, including microbiological testing and newer technologies (e.g., interferon‐gamma release assays) to identify unrecognized M. tuberculosis infection in deceased donors, are warranted.

Purpose: Oxygen saturation to fraction of inspired oxygen ratio (SpO 2 /FiO 2 ) has been validated as a surrogate marker for partial pressure of oxygen to fraction of inspired oxygen ratio among mechanically ventilated patients with acute respiratory distress syndrome (ARDS). The validity of SpO 2 /FiO 2 measurements in predicting ARDS has not been studied. Recently, a Lung Injury Prediction Score (LIPS) has been developed to help identify patients at risk of developing ARDS. Methods: This was a secondary analysis of the LIPS-1 cohort. A multivariate logistic regression included all established variables for LIPS, Acute Physiology and Chronic Health Evaluation 2, age, and comorbid conditions that could affect SpO 2 /FiO 2 . The primary outcome was development of ARDS in the hospital. The secondary outcomes included hospital mortality, hospital day of ARDS development, and hospital day of death. Results: Of the 5584 patients, we evaluated all 4646 with recorded SpO 2 /FiO 2 values. Median SpO 2 /FiO 2 in those who did and did not develop ARDS was 254 (100, 438) and 452 (329, 467), respectively. There was a significant association between SpO 2 /FiO 2 and ARDS ( P ≤ .001). The SpO 2 /FiO 2 was found to be an independent predictor of ARDS in a “dose-dependent” manner; for SpO 2 /FiO 2 < 100—odds ratios (OR) 2.49 (1.69-3.64, P < .001), for SpO 2 /FiO 2 100 < 200—OR 1.75 (1.16-2.58, P = .007), and for SpO 2 /FiO 2 200 < 300—OR 1.62 (1.06-2.42, P = .025). The discriminatory characteristics of the multivariable model and SpO 2 /FiO 2 as a single variable demonstrated area under the curve (AUC) of 0.81 and AUC of 0.74, respectively. Conclusions: The SpO 2 /FiO 2 , measured within the first 6 hours after hospital admission, is an independent indicator of ARDS development among patients at risk.

Background— Reduced low forced expiratory volume in 1 second (FEV 1 ) is reportedly associated with an increased risk of atrial fibrillation (AF). Extant reports do not provide separate estimates for never smokers or for blacks, who incongruously have lower AF incidence than whites. Methods and Results— We examined 15 004 middle-aged blacks and whites enrolled in the Atherosclerosis Risk in Communities (ARIC) cohort study. Standardized spirometry data were collected at the baseline examination. Incident AF was identified from the first among the following: International Classification of Diseases codes for AF on hospital discharge records or death certificates or 12-lead ECGs performed during 3 triennial follow-up visits. Over an average follow-up of 17.5 years, a total of 1691 participants (11%) developed new-onset AF. The rate of incident AF was inversely associated with FEV 1 in each of the 4 race and sex groups. After multivariable adjustment for traditional cardiovascular disease risk factors and height, hazard ratios of AF comparing the lowest with the highest quartile of FEV 1 were 1.37 (95% confidence interval, 1.02–1.83) for white women, 1.49 (95% confidence interval, 1.16–1.91) for white men, 1.63 (95% confidence interval, 1.00–2.66) for black women, and 2.36 (95% confidence interval, 1.30–4.29) for black men. The above associations were observed across all smoking status categories. Moderate/severe airflow obstruction (FEV 1 /forced vital capacity <0.70 and FEV 1 < 80% of predicted value) was also associated with higher AF incidence. Conclusions— In this large population-based study with a long-term follow-up, reduced FEV 1 and obstructive respiratory disease were associated with a higher AF incidence after adjustment for measured confounders.

Objective A very few studies describe the epidemiology of primary Sjögren's syndrome (pSS). The reported frequency of pulmonary involvement in pSS varies widely depending on the detection method employed, and consists mainly of various forms of airways disease. We aimed to evaluate the incidence and mortality of pSS and of lung disease in pSS, focusing on interstitial lung disease (ILD). Methods A population-based incidence cohort of patients diagnosed with pSS in 1976–2005 was assembled. Diagnosis was based on the 2002 American-European Consensus Group criteria for pSS. Cumulative incidence adjusted for the competing risk of death was estimated. A Cox model with a time-dependent covariate was used to determine the incidence and the standardised mortality HR of pSS. Results 85 patients with pSS were identified (mean age 59.9 years; 91% women). The annual incidence of pSS was 4.2, 95% CI (3.3 to 5.1)/100 000 population and it increased with higher age at pSS diagnosis (18–44 years: 2.1/100 000 vs ≥75 years: 12.3/100 000). Standardised mortality ratio in pSS compared with the general population was 0.92, 95% CI (0.57 to 1.41). A total of 105 patients with pSS and ILD were identified (mean age 58.1 years; 91% women). Among patients with pSS without prior ILD, the cumulative incidence of ILD in patients with pSS was 10% (±3%) at 1 year after diagnosis of pSS and increased to 20% (±4%) by 5 years after pSS. The development of lung disease in pSS was associated with poor survival (HR 2.16; 95% CI 0.99 to 4.74). Conclusions pSS incidence seems to be almost the same as was reported in a previous study conducted among Olmsted County Minnesota population. Survival among patients with pSS and general population does not differ substantially. However, patients with pSS who have ILD likely have increased premature mortality.

Purpose To develop a rapid proton MR elastography (MRE) technique that can quantify the absolute shear stiffness of lung parenchyma, to investigate the ability to differentiate respiration‐dependent stiffness variations of the lung, and to demonstrate clinical feasibility. Materials and Methods A spin‐echo echo planar imaging MRE sequence (SE‐EPI MRE) with a very short echo time was developed and tested in a series of five healthy volunteers at three different lung volumes: (i) residual volume (RV), (ii) total lung capacity (TLC), (iii) and midway between RV and TLC (MID). At each volume, lung density was quantified using a MR‐based density mapping sequence. For reference, data were acquired using the previously described spin‐echo lung MRE sequence (SE‐MRE). MRE data were also acquired in a patient with proven Idiopathic Pulmonary Fibrosis (IPF) to test clinical feasibility. Results The SE‐EPIMRE sequence reduced total acquisition time by a factor of 2 compared with the SE‐MRE sequence. Lung parenchyma median shear stiffness for the 5 volunteers quantified with the SE‐EPI MRE sequence was 0.9 kPa, 1.1 kPa, and 1.6 kPa at RV, MID, and TLC, respectively. The corresponding values obtained with the SE‐MRE sequence were 0.9 kPa, 1.1 kPa, and 1.5 kPa. Absolute shear stiffness was also successfully measured in the IPF patient. Conclusion The results indicate that stiffness variations due to respiration could be measured with the SE‐EPIMRE technique and were equivalent to values generated by the previously described SE‐MRE approach. Preliminary data obtained from the patient demonstrate clinical feasibility. J. Magn. Reson. Imaging 2014;40:1230–1237 . © 2013 Wiley Periodicals, Inc .