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Relatives of patients with familial interstitial pneumonia are at increased risk for pulmonary fibrosis, and develop preclinical pulmonary fibrosis (PrePF).We defined the incidence and progression of new onset PrePF; its relationship to survival among first degree relatives of families with familial interstitial pneumonia.This is a cohort study of family members with familial interstitial pneumonia who were initially screened with a questionnaire and chest HRCT scan, and approximately 4 years later, the evaluation was repeated. 493 asymptomatic first-degree relatives of patients with familial interstitial pneumonia were evaluated at baseline, and 296 (60%) of the original subjects participated in subsequent evaluation.The median interval between HRCTs was 3.9 years (IQ range 3.5-4.4). 252 subjects who agreed to repeat evaluation were originally determined not to have PrePF at baseline; 16 developed PrePF. A conservative estimate of the annual incidence of PrePF is 1,023 per 100, 000 person years (95% CI 511-1831). Of 44 subjects with PrePF at baseline, 38.4% subjects had worsening dyspnea compared to 15.4% of those without PrePF (P=0.002). Usual interstitial pneumonia (UIP) by HRCT (P0.0002) and baseline quantitative fibrosis score (P0.001) are also associated with worsening dyspnea. PrePF at the initial screen is associated with decreased survival (P0.001).The incidence of PrePF in this at-risk population is at least 100-fold higher than that reported for sporadic idiopathic pulmonary fibrosis (IPF). While PrePF and IPF represent distinct entities, our study demonstrates that PrePF, like IPF, is progressive and associated with decreased survival.

Rationale: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict...

PURPOSE We noted incidental findings on chest computed tomography (CT) imaging of expiratory central airway collapse (ECAC) in dyspneic patients after military deployment to southwest Asia (mainly Iraq and Afghanistan). We developed a standardized chest CT protocol with dynamic expiration to enhance diagnostic reliability and investigated demographic, clinical, and deployment characteristics possibly associated with ECAC. MATERIALS AND METHODS We calculated ECAC in 62 consecutive post-9/11 deployers with dyspnea who underwent multi-detector chest CT acquisition. ECAC was defined as ≥70% reduction in the cross-sectional tracheal area at dynamic expiration. We compared demographics (age, smoking, body mass index), comorbid conditions (gastroesophageal reflux, obstructive sleep apnea [OSA]), and clinical findings (air trapping, forced expiratory volume in 1 second percent predicted) in deployers with and without ECAC. We examined associations between ECAC and forced expiratory volume in 1 second percent predicted, air trapping, OSA, deployment duration, and blast exposure. RESULTS Among 62 consecutive deployers with persistent dyspnea, 37% had ECAC. Three had severe (>85%) collapse. Those with ECAC were older (mean age 46 vs. 40 y, P=0.02), but no other demographic or clinical characteristics were statistically different among the groups. Although not statistically significant, ECAC odds were 1.5 times higher (95% confidence interval: 0.9, 2.5) for each additional year of southwest Asia deployment. Deployers with ECAC had 1.6 times greater odds (95% confidence interval: 0.5, 4.8) of OSA. CONCLUSIONS Findings suggest that ECAC is common in symptomatic southwest Asia deployers. Chest high-resolution CT with dynamic expiration may provide an insight into the causes of dyspnea in this population, although risk factors for ECAC remain to be determined. A standardized semiquantitative approach to CT-based assessment of ECAC should improve reliable diagnosis in dyspneic patients.

Abdullah Alismail,1,2,* Brett Schaeffer,2,* Andrea Oh,1 Saba Hamiduzzaman,3 Noha Daher,4 Hae-Young Song,2 Brian Furukawa,3 Laren D Tan1– 3 1Department of Cardiopulmonary Sciences, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA; 2Department of Medicine, School of Medicine, Loma Linda University, Loma Linda, CA, USA; 3Division of Pulmonary, Critical Care, Hyperbaric, Allergy and Sleep Medicine, Loma Linda University Health, Loma Linda, CA, USA; 4Department of Allied Health Studies, School of Allied Health Professions, Loma Linda University, Loma Linda, CA, USA*These authors contributed equally to this workCorrespondence: Laren D TanDivision of Pulmonary, Critical Care, Hyperbaric, Allergy and Sleep Medicine, Loma Linda University Health, 11234 Anderson Street, Suite 6439, Loma Linda, CA 92354, USATel/Fax +1 909 558-8081Email LaTan@llu.eduIntroduction: Patient satisfaction has become an essential metric in addition to the type of care they receive. Phone calls, emails, and text to patients after their healthcare visit are the typical way of obtaining the data reflecting patient satisfaction. The purpose of this retrospective quality improvement study is to compare the traditional post-outpatient clinic survey method with an onsite concise two-question survey using a tablet method immediately after the patient visit using Net Promoter Score (NPS) questions.Methods: Data were collected retrospectively from February to August 2018 from an outpatient subspecialty clinic in southern California using an existing database from two different sources: the traditional method (TM) and the tablet-based tool (TBT), using NPS. The TM data were obtained from a third-party company using two questions via phone, email, and text collected 2– 4 weeks after the patient’s visit. The TBT has only two questions that were given to patients upon their visit check-out. These two questions assessed both provider and clinic’s performance using the NPS method.Results: In total, there were 1708 patients seen from February to August 2018. In the TM, the total outgoing messages during this period were 580 (34.0%) with 156 responses (27%). In the TBT, 648 out of 1708 (37.9%) surveys were collected with a 100% response rate. The NPS score showed that 99.2% of the providers were promoters. The NPS score for the clinic was 96% which reflects a promoter score.Conclusion: Our results indicate that when using the TBT immediately after their visit to the clinic, a higher response rate was noted. In addition, both methods had similar outcomes in terms of patient satisfaction NPS scores. Future prospective studies with a larger sample size are warranted to evaluate the effectiveness of the TBT tool in assessing patient satisfaction.Keywords: patient satisfaction, NPS, Net Promoter Score

COPD is a heterogeneous syndrome. Many COPD subtypes have been proposed, but there is not yet consensus on how many COPD subtypes there are and how they should be defined. The COPD Genetic Epidemiology Study (COPDGene), which has generated 10-year longitudinal chest imaging, spirometry, and molecular data, is a rich resource for relating COPD phenotypes to underlying genetic and molecular mechanisms. In this article, we place COPDGene clustering studies in context with other highly cited COPD clustering studies, and summarize the main COPD subtype findings from COPDGene. First, most manifestations of COPD occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods. Second, continuous COPD-related measures can be used to create subgroups through the use of predictive models to define cut-points, and we review COPDGene research on blood eosinophil count thresholds as a specific example. Third, COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD. Fourth, trajectory-based COPD subtyping captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity. Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes.

RATIONALE: Multiple studies have demonstrated an increased risk of chronic obstructive pulmonary disease (COPD) in heterozygous carriers of the AAT (alpha-1 antitrypsin) Z allele. However, it is not known if MZ subjects with COPD are phenotypically different from noncarriers (MM genotype) with COPD. OBJECTIVES: To assess if MZ subjects with COPD have different clinical features compared with MM subjects with COPD. METHODS: Genotypes of SERPINA1 were ascertained by using whole-genome sequencing data in three independent studies. We compared outcomes between MM subjects with COPD and MZ subjects with COPD in each study and combined the results in a meta-analysis. We performed longitudinal and survival analyses to compare outcomes in MM and MZ subjects with COPD over time. MEASUREMENTS AND MAIN RESULTS: We included 290 MZ subjects with COPD and 6,184 MM subjects with COPD across the three studies. MZ subjects had a lower FEV(1)% predicted and greater quantitative emphysema on chest computed tomography scans compared with MM subjects. In a meta-analysis, the FEV(1) was 3.9% lower (95% confidence interval [CI], −6.55% to −1.26%) and emphysema (the percentage of lung attenuation areas

Objective: To explore the presence of small airway disease (SAD) and emphysema in scleroderma-related interstitial lung disease (SSc-ILD) and to evaluate the physiologic and clinical correlates of SAD in SSc-ILD. Methods: Thoracic high-resolution computed tomography (HRCT) images obtained from the Scleroderma Lung Study II (SLSII) participants were reviewed by a group of thoracic radiologists. The presence of SAD was assessed by visual assessment for air trapping. HRCT scans were also evaluated for the presence of emphysema. The association of the presence of air trapping and emphysema with physiological measures of airway disease and clinical variables was evaluated. Results: A total of 155 baseline HRCT scans were reviewed. For assessment of air trapping, images needed to be adequate end-expiratory examinations, leaving 123 scans. Air trapping was seen in 13/123 (10.6%) of the SSc-ILD cohort and was independent of smoking history, asthma or the presence of gastroesophageal reflux. Air trapping on HRCT was not associated with physiologic evidence of SAD. We also identified 8/155 (5.2%) patients with emphysema on HRCT, which was independent of SAD and found mostly in prior smokers. Conclusion: We report the first study of air trapping on standardized, high-quality HRCT images as a reflection of SAD in a relatively large, well characterized SSc-ILD cohort. The presence of SAD in non-smoking SSc-ILD patients supports that SSc may cause not only restrictive lung disease (SSc-ILD), but also, to a lesser extent, obstructive disease. Physiologic measures alone may be inadequate to detect airway disease in patients with SSc-ILD.

BackgroundBody composition measures, specifically low weight or reduced muscle mass, are associated with mortality in COPD, but the effect of longitudinal body composition changes is undefined.Research questionIs the longitudinal loss of fat-free mass (FFM) associated with increased mortality, including in those with initially normal or elevated body composition metrics?Study design and methodsParticipants with complete data for at least one visit in the COPDGene study (n= 9,268) and the ECLIPSE study (n= 1,760) were included and monitored for 12 and 8 years, respectively. Pectoralis muscle area (PMA) was derived from thoracic CT scans and used as a proxy for FFM. A longitudinal mixed submodel for PMA and a Cox proportional hazards submodel for survival were fitted on a joint distribution, using a shared random intercept parameter and Markov chain Monte Carlo parameter estimation.ResultsBoth cohorts demonstrated a left-shifted distribution of baseline FFM, not reflected in BMI, and an increase in all-cause mortality risk associated with longitudinal loss of PMA. For each 1-cm2 PMA loss, mortality increased 3.1%(95%CI, 2.4%-3.7%; P< .001) in COPDGene, and 2.4%(95%CI, 0.9%-4.0%; P< .001) in ECLIPSE. Increased mortality risk was independent of enrollment values for BMI and disease severity [BODE (body mass, airflow obstruction, dyspnea, and exercise capacity) index quartiles] and was significant even in participants with initially greater than average PMA.InterpretationLongitudinal loss of PMA is associated with increased all-cause mortality, regardless of BMI or initial muscle mass. Consideration of novel screening tests and further research into mechanisms contributing to muscle decline may improve risk stratification and identify novel therapeutic targets in ever smokers.

Background Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV1 progression in current smokers. Research Question Is use of ACEi and ARB associated with less progression of emphysema and FEV1 decline among individuals with COPD or baseline emphysema? Methods Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume Results Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV1 % predicted, 0.83; 95% CI, –0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV1 % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema. Interpretation Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline. Trial Registry ClinicalTrials.gov ; No.: NCT00608764; URL: www.clinicaltrials.gov

Rationale and Objectives: The current paradigm of cancer diagnosis involves uncoordinated communication of findings from radiology and pathology to downstream physicians. Discordance between these findings can require additional time from downstream users to resolve, or given incorrect resolution, may adversely impact treatment decisions. To mitigate this problem, we developed a webbased system, called RadPath, for correlating and integrating radiology and pathology reporting. Materials and Methods: RadPath includes interfaces to our institution’s clinical information systems, which are used to retrieve reports, images, and test results that are structured into an interactive compendium for a diagnostic patient case. The system includes an editing interface for physicians, allowing for the inclusion of additional clinical data, as well as the ability to retrospectively correlate and contextualize imaging findings following pathology diagnosis. Results: During pilot deployment and testing over the course of 1 year, physicians at our institution have completed 60 RadPath cases, requiring an average of 128 seconds from a radiologist and an average of 93 seconds from a pathologist per case. Several technical and workflow challenges were encountered during development, including interfacing with diverse clinical information systems, automatically structuring report contents, and determining the appropriate physicians to create RadPath summaries. Reaction to RadPath has been positive, with users valuing the system’s ability to consolidate diagnostic information. Conclusions: With the increasing complexity of medicine and the movement toward team-based disease management, there is a need for improved clinical communication and information exchange. RadPath provides a platform for generating coherent and correlated diagnostic summaries in cancer diagnosis with minimal additional effort from physicians.

Rationale and Objectives The purpose of this study was to quantify the degree of imaging–histologic discordance in a cohort of patients undergoing computed tomography (CT)–guided lung biopsy for focal lung disease. Materials and Methods A retrospective review was performed of 186 patients who underwent percutaneous lung biopsy of a parenchymal lesion at our institution between January and December 2009. Diagnostic radiology reports of CT or positron emission tomography–CTs performed before biopsy were used to classify the lesion as malignant or benign by five readers. Pathology reports of the biopsied lesions were classified by three readers. Inter-reader agreement and imaging–histologic concordance were quantified using kappa statistics. Discordant benign cases were then revisited to determine downstream effects. Results Inter-reader agreement on report content was substantial or almost perfect with kappas >0.783. Kappas for concordance were as follows: malignant (0.448), primary lung cancer (0.517), metastatic disease to lung (0.449), benign (0.510), and overall agreement (0.381). Of the twelve discordant benign cases that were revisited, four were found to be false negatives, resulting in a delay in diagnosis. Conclusions Our study of imaging–histologic discordance in percutaneous biopsy of lung lesions supports the need for imaging report standardization and improved integration and communication between the fields of radiology and pathology.

This paper describes the information retrieval step in Casama (Contextualized Semantic Maps), a project that summarizes and contextualizes current research papers on driver mutations in non-small cell lung cancer. Casama?s representation of lung cancer studies aims to capture elements that will assist an end-user in retrieving studies and, importantly, judging their strength. This paper focuses on two types of study metadata: study objective and study design. 430 abstracts on EGFR and ALK mutations in lung cancer were annotated manually. Casama?s support vector machine (SVM) automatically classified the abstracts by study objective with as much as 129% higher F-scores compared to PubMed?s built-in filters. A second SVM classified the abstracts by epidemiological study design, suggesting strength of evidence at a more granular level than in previous work. The classification results and the top features determined by the classifiers suggest that this scheme would be generalizable to other mutations in lung cancer, as well as studies on driver mutations in other cancer domains. HighlightsWe propose to improve retrieval by representing and extracting study metadata.Multiple expert readers produced a gold standard of 430 abstracts on lung cancer.Automatic classification performed better than or comparable to PubMed?s filters.Study design classification was robust to differences in vocabulary across corpora.Top-ranked features were not domain-specific and could generalize to other domains.

A topic model with three different parameter settings is fit to a large collection of clinical reports.The interpretability of discovered topics is evaluated by clinicians and laypersons.Clinicians are significantly more capable of interpreting topics than laypersons.Topics hold potential for applications in automatic summarization. Background and objectiveProbabilistic topic models provide an unsupervised method for analyzing unstructured text. These models discover semantically coherent combinations of words (topics) that could be integrated in a clinical automatic summarization system for primary care physicians performing chart review. However, the human interpretability of topics discovered from clinical reports is unknown. Our objective is to assess the coherence of topics and their ability to represent the contents of clinical reports from a primary care physician's point of view. MethodsThree latent Dirichlet allocation models (50 topics, 100 topics, and 150 topics) were fit to a large collection of clinical reports. Topics were manually evaluated by primary care physicians and graduate students. Wilcoxon Signed-Rank Tests for Paired Samples were used to evaluate differences between different topic models, while differences in performance between students and primary care physicians (PCPs) were tested using Mann-Whitney U tests for each of the tasks. ResultsWhile the 150-topic model produced the best log likelihood, participants were most accurate at identifying words that did not belong in topics learned by the 100-topic model, suggesting that 100 topics provides better relative granularity of discovered semantic themes for the data set used in this study. Models were comparable in their ability to represent the contents of documents. Primary care physicians significantly outperformed students in both tasks. ConclusionThis work establishes a baseline of interpretability for topic models trained with clinical reports, and provides insights on the appropriateness of using topic models for informatics applications. Our results indicate that PCPs find discovered topics more coherent and representative of clinical reports relative to students, warranting further research into their use for automatic summarization.

The current paradigm of cancer diagnosis involves uncoordinated communication of findings from radiology and pathology to downstream physicians. Discordance between these findings can require additional time from downstream users to resolve, or given incorrect resolution, may adversely impact treatment decisions. To mitigate this problem, we developed a web-based system, called RadPath, for correlating and integrating radiology and pathology reporting.RadPath includes interfaces to our institution's clinical information systems, which are used to retrieve reports, images, and test results that are structured into an interactive compendium for a diagnostic patient case. The system includes an editing interface for physicians, allowing for the inclusion of additional clinical data, as well as the ability to retrospectively correlate and contextualize imaging findings following pathology diagnosis.During pilot deployment and testing over the course of 1 year, physicians at our institution have completed 60 RadPath cases, requiring an average of 128 seconds from a radiologist and an average of 93 seconds from a pathologist per case. Several technical and workflow challenges were encountered during development, including interfacing with diverse clinical information systems, automatically structuring report contents, and determining the appropriate physicians to create RadPath summaries. Reaction to RadPath has been positive, with users valuing the system's ability to consolidate diagnostic information.With the increasing complexity of medicine and the movement toward team-based disease management, there is a need for improved clinical communication and information exchange. RadPath provides a platform for generating coherent and correlated diagnostic summaries in cancer diagnosis with minimal additional effort from physicians.

Background While mammalian cortical granules are important in fertilization, their biochemical composition and functions are not fully understood. We previously showed that the ABL2 antibody, made against zona free mouse blastocysts, binds to a 75-kDa cortical granule protein (p75) present in a subpopulation of mouse cortical granules. The purpose of this study was to identify and characterize p75, examine its distribution in unfertilized oocytes and preimplantation embryos, and investigate its biological role in fertilization. Results To identify p75, the protein was immunoprecipitated from ovarian lysates with the ABL2 antibody and analyzed by tandem mass spectrometry (MS/MS). A partial amino acid sequence (VLIGGSFY) was obtained, searched against the NCBI nonredundant database using two independent programs, and matched to mouse peptidylarginine deiminase (PAD). When PAD antibody was used to probe western blots of p75, the antibody detected a single protein band with a molecular weight of 75 kDa, confirming our mass spectrometric identification of p75. Immunohistochemistry demonstrated that PAD was present in the cortical granules of unfertilized oocytes and was released from activated and in vivo fertilized oocytes. After its release, PAD was observed in the perivitelline space, and some PAD remained associated with the oolemma and blastomeres' plasma membranes as a peripheral membrane protein until the blastocyst stage of development. In vitro treatment of 2-cell embryos with the ABL2 antibody or a PAD specific antibody retarded preimplantation development, suggesting that cortical granule PAD plays a role after its release in preimplantation cleavage and early embryonic development. Conclusion Our data showed that PAD is present in the cortical granules of mouse oocytes, is released extracellularly during the cortical reaction, and remains associated with the blastomeres' surfaces as a peripheral membrane protein until the blastocyst stage of development. Our in vitro study supports the idea that extracellular PAD functions in preimplantation development.