Deep Learning Classification of Usual Interstitial Pneumonia Predicts Outcomes.

Rationale: Computed tomography (CT) enables noninvasive diagnosis of usual interstitial pneumonia (UIP), but enhanced image analyses are needed to overcome the limitations of visual assessment. Objectives: Apply multiple instance learning (MIL) to develop an explainable deep learning algorithm for prediction of UIP from CT and validate its performance in independent cohorts. Methods: We trained an MIL algorithm using a pooled dataset (n = 2,143) and tested it in three independent populations: data from a prior publication (n = 127), a single-institution clinical cohort (n = 239), and a national registry of patients with pulmonary fibrosis (n = 979). We tested UIP classification performance using receiver operating characteristic analysis, with histologic UIP as ground truth. Cox proportional hazards and linear mixed-effects models were used to examine associations between MIL predictions and survival or longitudinal FVC. Measurements and Main Results: In two cohorts with biopsy data, MIL improved accuracy for histologic UIP (area under the curve, 0.77 [n = 127] and 0.79 [n = 239]) compared with visual assessment (area under the curve, 0.65 and 0.71). In cohorts with survival data, MIL-UIP classifications were significant for mortality (n = 239, mortality to April 2021: unadjusted hazard ratio, 3.1; 95% confidence interval [CI], 1.96-4.91; P < 0.001; and n = 979, mortality to July 2022: unadjusted hazard ratio, 3.64; 95% CI, 2.66-4.97; P < 0.001). Individuals classified as UIP positive by the algorithm had a significantly greater annual decline in FVC than those classified as UIP negative (-88 ml/yr vs. -45 ml/yr; n = 979; P < 0.01), adjusting for extent of lung fibrosis. Conclusions: Computerized assessment using MIL identifies clinically significant features of UIP on CT. Such a method could improve confidence in radiologic assessment of patients with interstitial lung disease, potentially enabling earlier and more precise diagnosis.

Enantioselective Syntheses of Wickerols A and B.

The evolution of a successful strategy for the synthesis of the strained, cage-like antiviral diterpenoids wickerols A and B is described. Initial attempts to access the carbocyclic core were surprisingly challenging and in retrospect, presaged the many detours needed to ultimately arrive at the fully adorned wickerol architecture. In most cases, conditions to trigger desired outcomes with respect to both reactivity and stereochemistry were hard-won. The successful synthesis ultimately leveraged alkenes in virtually all productive bond-forming events. A series of conjugate addition reactions generated the fused tricyclic core, a Claisen rearrangement was used to install an otherwise unmanageable methyl-bearing stereogenic center, and a Prins cyclization closed the strained bridging ring. This final reaction proved enormously interesting because the strain of the ring system permitted diversion of the presumed initial Prins product into several different scaffolds.

Tobacco smoking is associated with combined pulmonary fibrosis and emphysema and worse outcomes in interstitial lung disease.

Tobacco smoking is an established cause of pulmonary disease whose contribution to interstitial lung disease (ILD) is incompletely characterized. We hypothesized that compared with nonsmokers, subjects who smoked tobacco would differ in their clinical phenotype and have greater mortality. We performed a retrospective cohort study of tobacco smoking in ILD. We evaluated demographic and clinical characteristics, time to clinically meaningful lung function decline (LFD), and mortality in patients stratified by tobacco smoking status (ever vs. never) within a tertiary center ILD registry (2006-2021) and replicated mortality outcomes across four nontertiary medical centers. Data were analyzed by two-sided t tests, Poisson generalized linear models, and Cox proportional hazard models adjusted for age, sex, forced vital capacity (FVC), diffusion capacity of the lung for carbon monoxide (DLCO), ILD subtype, antifibrotic therapy, and hospital center. Of 1,163 study participants, 651 were tobacco smokers. Smokers were more likely to be older, male, have idiopathic pulmonary fibrosis (IPF), coronary artery disease, CT honeycombing and emphysema, higher FVC, and lower DLCO than nonsmokers (P < 0.01). Time to LFD in smokers was shorter (19.7 ± 20 mo vs. 24.8 ± 29 mo; P = 0.038) and survival time was decreased [10.75 (10.08-11.50) yr vs. 20 (18.67-21.25) yr; adjusted mortality HR = 1.50, 95%CI 1.17-1.92; P < 0.0001] compared with nonsmokers. Smokers had 12% greater odds of death for every additional 10 pack yr of smoking (P < 0.0001). Mortality outcomes remained consistent in the nontertiary cohort (HR = 1.51, 95%CI = 1.03-2.23; P = 0.036). Tobacco smokers with ILD have a distinct clinical phenotype strongly associated with the syndrome of combined PF and emphysema, shorter time to LFD, and decreased survival. Smoking prevention may improve ILD outcomes.NEW & NOTEWORTHY Smoking in ILD is associated with combined pulmonary fibrosis and emphysema and worse clinical outcomes.

TrackSOM: Mapping immune response dynamics through clustering of time-course cytometry data.

Mapping the dynamics of immune cell populations over time or disease-course is key to understanding immunopathogenesis and devising putative interventions. We present TrackSOM, a novel method for delineating cellular populations and tracking their development over a time- or disease-course cytometry datasets. We demonstrate TrackSOM-enabled elucidation of the immune response to West Nile Virus infection in mice, uncovering heterogeneous subpopulations of immune cells and relating their functional evolution to disease severity. TrackSOM is easy to use, encompasses few parameters, is quick to execute, and enables an integrative and dynamic overview of the immune system kinetics that underlie disease progression and/or resolution.

How Three Self-Secreted Biofilm Exopolysaccharides of Pseudomonas aeruginosa, Psl, Pel, and Alginate, Can Each Be Exploited for Antibiotic Adjuvant Effects in Cystic Fibrosis Lung Infection.

In cystic fibrosis (CF), pulmonary infection with Pseudomonas aeruginosa is a cause of increased morbidity and mortality, especially in patients for whom infection becomes chronic and there is reliance on long-term suppressive therapies. Current antimicrobials, though varied mechanistically and by mode of delivery, are inadequate not only due to their failure to eradicate infection but also because they do not halt the progression of lung function decline over time. One of the reasons for this failure is thought to be the biofilm mode of growth of P. aeruginosa, wherein self-secreted exopolysaccharides (EPSs) provide physical protection against antibiotics and an array of niches with resulting metabolic and phenotypic heterogeneity. The three biofilm-associated EPSs secreted by P. aeruginosa (alginate, Psl, and Pel) are each under investigation and are being exploited in ways that potentiate antibiotics. In this review, we describe the development and structure of P. aeruginosa biofilms before examining each EPS as a potential therapeutic target for combating pulmonary infection with P. aeruginosa in CF, with a particular focus on the current evidence for these emerging therapies and barriers to bringing these therapies into clinic.

Multilevel Body Composition Analysis on Chest Computed Tomography Predicts Hospital Length of Stay and Complications After Lobectomy for Lung Cancer: A Multicenter Study.

OBJECTIVE: To investigate the impact of thoracic body composition on outcomes after lobectomy for lung cancer. SUMMARY AND BACKGROUND DATA: Preoperative identification of patients at risk for adverse outcomes permits treatment modification. The impact of body composition on lung resection outcomes has not been investigated in a multicenter setting. METHODS: A total of 958 consecutive patients undergoing lobectomy for lung cancer at 3 centers from 2014 to 2017 were retrospectively analyzed. Muscle and adipose tissue cross-sectional area at the fifth, eighth, and tenth thoracic vertebral body was quantified. Prospectively collected outcomes from a national database were abstracted to characterize the association between sums of muscle and adipose tissue and hospital length of stay (LOS), number of any postoperative complications, and number of respiratory postoperative complications using multivariate regression. A priori determined covariates were forced expiratory volume in 1 second and diffusion capacity of the lungs for carbon monoxide predicted, age, sex, body mass index, race, surgical approach, smoking status, Zubrod and American Society of Anesthesiologists scores. RESULTS: Mean patient age was 67 years, body mass index 27.4 kg/m2 and 65% had stage i disease. Sixty-three percent underwent minimally invasive lobectomy. Median LOS was 4 days and 34% of patients experienced complications. Muscle (using 30 cm2 increments) was an independent predictor of LOS (adjusted coefficient 0.972; P = 0.002), any postoperative complications (odds ratio 0.897; P = 0.007) and postoperative respiratory complications (odds ratio 0.860; P = 0.010). Sarcopenic obesity was also associated with LOS and adverse outcomes. CONCLUSIONS: Body composition on preoperative chest computed tomography is an independent predictor of LOS and postoperative complications after lobectomy for lung cancer.

Utility of a Molecular Classifier as a Complement to High-Resolution Computed Tomography to Identify Usual Interstitial Pneumonia.

Rationale: Usual interstitial pneumonia (UIP) is the defining morphology of idiopathic pulmonary fibrosis (IPF). Guidelines for IPF diagnosis conditionally recommend surgical lung biopsy for histopathology diagnosis of UIP when radiology and clinical context are not definitive. A "molecular diagnosis of UIP" in transbronchial lung biopsy, the Envisia Genomic Classifier, accurately predicted histopathologic UIP.Objectives: We evaluated the combined accuracy of the Envisia Genomic Classifier and local radiology in the detection of UIP pattern.Methods: Ninety-six patients who had diagnostic lung pathology as well as a transbronchial lung biopsy for molecular testing with Envisia Genomic Classifier were included in this analysis. The classifier results were scored against reference pathology. UIP identified on high-resolution computed tomography (HRCT) as documented by features in local radiologists' reports was compared with histopathology.Measurements and Main Results: In 96 patients, the Envisia Classifier achieved a specificity of 92.1% (confidence interval [CI],78.6-98.3%) and a sensitivity of 60.3% (CI, 46.6-73.0%) for histology-proven UIP pattern. Local radiologists identified UIP in 18 of 53 patients with UIP histopathology, with a sensitivity of 34.0% (CI, 21.5-48.3%) and a specificity of 96.9% (CI, 83.8-100%). In conjunction with HRCT patterns of UIP, the Envisia Classifier results identified 24 additional patients with UIP (sensitivity 79.2%; specificity 90.6%).Conclusions: In 96 patients with suspected interstitial lung disease, the Envisia Genomic Classifier identified UIP regardless of HRCT pattern. These results suggest that recognition of a UIP pattern by the Envisia Genomic Classifier combined with HRCT and clinical factors in a multidisciplinary discussion may assist clinicians in making an interstitial lung disease (especially IPF) diagnosis without the need for a surgical lung biopsy.

Vessel-related structures predict UIP pathology in those with a non-IPF pattern on CT.

OBJECTIVES: To determine if a quantitative imaging variable (vessel-related structures [VRS]) could identify subjects with a non-IPF diagnosis CT pattern who were highly likely to have UIP histologically. METHODS: Subjects with a multidisciplinary diagnosis of interstitial lung disease including surgical lung biopsy and chest CT within 1 year of each other were included in the study. Non-contrast CT scans were analyzed using the Computer-Aided Lung Informatics for Pathology Evaluation and Rating (CALIPER) program, which quantifies the amount of various abnormal CT patterns on chest CT. Quantitative data were analyzed relative to pathological diagnosis as well as the qualitative CT pattern. RESULTS: CALIPER-derived volumes of reticulation (p = 0.012), honeycombing (p = 0.017), and VRS (p < 0.001) were associated with a UIP pattern on pathology on univariate analysis but only VRS was associated with a UIP pathology on multivariable analysis (p = 0.013). Using a VRS cut-off of 173 cm3, the sensitivity and specificity for pathological UIP were similar to those for standard qualitative CT assessment (55.9% and 80.4% compared to 60.6% and 80.4%, respectively). VRS differentiated pathological UIP cases in those with a non-IPF diagnosis CT category (p < 0.001) but not in other qualitative CT patterns (typical UIP, probable UIP, and indeterminate for UIP). The rate of pathological UIP in those with VRS greater than 173 cm3 (84.2%) was nearly identical to those who had a qualitative CT pattern of probable UIP (88.9%). CONCLUSIONS: VRS may be an adjunct to CT in predicting pathology in patients with interstitial lung disease. KEY POINTS: • Volume of vessel-related structures (VRS) was associated with usual interstitial pneumonia (UIP) on pathology. • This differentiation arose from those with CT scans with a non-IPF diagnosis imaging pattern. • Higher VRS has similar diagnostic ramifications for UIP as probable UIP, transitively suggesting in patients with high VRS, pathology may be obviated.

Computed Tomography Findings Suggestive of Connective Tissue Disease in the Setting of Usual Interstitial Pneumonia.

PURPOSE: A usual interstitial pneumonia (UIP) pattern is common in idiopathic pulmonary fibrosis (IPF) and connective tissue disease-related interstitial lung disease (CTD-ILD). The purpose of the study was to validate imaging findings differentiating CTD-ILD from IPF in UIP. METHODS: Patients with a multidisciplinary diagnosis of CTD-ILD or IPF and a UIP pattern on computed tomography and/or pathology were included in this study. Prevalence of 3 computed tomography findings shown to be associated with CTD-ILD (the straight edge sign [SES], the exuberant honeycombing sign, and the anterior upper lobe sign [AULS]) were tabulated in CTD-ILD and IPF subjects. The ability of each of these signs to discriminate between CTD-ILD and IPF was evaluated. Survival analysis was also performed using log-rank analysis. RESULTS: The study cohort included 50 CTD-ILD and 100 IPF subjects with UIP. The SES and the AULS were more common in CTD-ILD than IPF (prevalence, 36.0% and 34.9% in CTD-ILD vs 8.3% and 17.2% in IPF, respectively [P = 0.0105 - <0.001]). The highest specificity (95.7%) of CTD-ILD diagnosis was seen with bilateral SES. Moreover, the SES was associated with improved survival (P = 0.0383), which appeared to be largely because of improvement in survival in IPF subjects. The presence of AULS was associated with pulmonary functional abnormalities. CONCLUSIONS: A radiographic UIP pattern with evidence of SES or the AULS should raise suspicion for CTD-ILD rather than IPF. Patients with IPF and SES have an attenuated disease course and might represent a different phenotype than those without the SES.

Diagnosis of Hypersensitivity Pneumonitis in Adults. An Official ATS/JRS/ALAT Clinical Practice Guideline.

Background: This guideline addresses the diagnosis of hypersensitivity pneumonitis (HP). It represents a collaborative effort among the American Thoracic Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax.Methods: Systematic reviews were performed for six questions. The evidence was discussed, and then recommendations were formulated by a multidisciplinary committee of experts in the field of interstitial lung disease and HP using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach.Results: The guideline committee defined HP, and clinical, radiographic, and pathological features were described. HP was classified into nonfibrotic and fibrotic phenotypes. There was limited evidence that was directly applicable to all questions. The need for a thorough history and a validated questionnaire to identify potential exposures was agreed on. Serum IgG testing against potential antigens associated with HP was suggested to identify potential exposures. For patients with nonfibrotic HP, a recommendation was made in favor of obtaining bronchoalveolar lavage (BAL) fluid for lymphocyte cellular analysis, and suggestions for transbronchial lung biopsy and surgical lung biopsy were also made. For patients with fibrotic HP, suggestions were made in favor of obtaining BAL for lymphocyte cellular analysis, transbronchial lung cryobiopsy, and surgical lung biopsy. Diagnostic criteria were established, and a diagnostic algorithm was created by expert consensus. Knowledge gaps were identified as future research directions.Conclusions: The guideline committee developed a systematic approach to the diagnosis of HP. The approach should be reevaluated as new evidence accumulates.

Myositis-specific Antibodies Identify A Distinct Interstitial Pneumonia with Autoimmune Features Phenotype.

Interstitial pneumonia with autoimmune features (IPAF) characterises individuals with interstitial lung disease (ILD) and features of connective tissue disease (CTD) who fail to satisfy CTD criteria. Inclusion of myositis-specific antibodies (MSAs) in the IPAF criteria has generated controversy, as these patients also meet proposed criteria for an anti-synthetase syndrome. Whether MSAs and myositis associated antibodies (MAA) identify phenotypically distinct IPAF subgroups remains unclear.A multi-center, retrospective investigation was conducted to assess clinical features and outcomes in patients meeting IPAF criteria stratified by the presence of MSAs and MAAs. IPAF subgroups were compared to cohorts of patients with idiopathic inflammatory myopathy-ILD (IIM-ILD), idiopathic pulmonary fibrosis (IPF) and non-IIM CTD-ILDs. The primary endpoint assessed was three-year transplant-free survival. Two hundred sixty-nine patients met IPAF criteria, including 35 (13%) with MSAs and 65 (24.2%) with MAAs. Survival was highest among patients with IPAF-MSA and closely approximated those with IIM-ILD. Survival did not differ between IPAF-MAA and IPAF without MSA/MAA cohorts. Usual interstitial pneumonia (UIP) morphology was associated with differential outcome risk, with IPAF patients with non-UIP morphology approximating survival observed in non-IIM CTD-ILDs. MSAs, but not MAAs identified a unique IPAF phenotype characterised by clinical features and outcomes similar to IIM-ILD. UIP morphology was a strong predictor of outcome in others meeting IPAF criteria. Because IPAF is a research classification without clear treatment approach, these findings suggest MSAs should be removed from the IPAF criteria and such patients should be managed as an IIM-ILD.

Percutaneous Ultrasound Gastrostomy: First-in-Human Experience with the PUMA-G System.

Percutaneous ultrasound gastrostomy (PUG) technique was developed to allow for gastrostomy tube insertion to be performed solely under ultrasound guidance without need for fluoroscopy or endoscopy. This report discusses the new device, proposed PUG technique, and the first-in-human experience. Five patients had PUG tube insertion performed as part of a Health Canada approved investigational study. All procedures were successful with no complications within 30 days postprocedure. Mean total procedure time was 50 ± 13 minutes. Two of 5 procedures required temporary fluoroscopy use to localize the orogastric balloon position within the stomach to achieve magnetic gastropexy.

Sarcoidosis: A Diagnosis of Exclusion.

OBJECTIVE. This article will review the typical and atypical imaging features of sarcoidosis, identify entities that may be mistaken for sarcoidosis, and discuss patterns and clinical scenarios that suggest an alternative diagnosis. CONCLUSION. Radiologists must be familiar with the characteristic findings in sarcoidosis and be attentive to situations that suggest alternative diagnoses. The radiologist plays a major role in prompt diagnosis and one that may help reduce patient morbidity and mortality.

Performance of the right ventricular outflow tract/aortic diameter as a novel predictor of risk in patients with acute pulmonary embolism.

Right ventricular (RV) enlargement, determined via the ratio of the right to left ventricular diameters (RV/LV) by CT imaging is used to classify the severity of acute pulmonary embolism (PE) and impacts treatment decisions. The RV/LV ratio may be an unreliable marker of RV dysfunction, due in part to the complex RV geometry. This study compared the RV/LV ratio to a novel metric, the ratio of the right ventricular to aortic outflow tract diameters (RVOT/Ao) in patients with acute PE treated with catheter-directed therapies (CDT). RVOT/Ao and RV/LV ratios were measured on CT images from 103 patients who received CDT for acute submassive or massive PE and were compared to RV dysfunction severity determined by transthoracic echocardiography. Ratios and biomarkers on admission were assessed for correlation with invasively-measured hemodynamics [right atrial (RA) pressure, mean pulmonary artery (PA) pressure, cardiac output (CO)]. RVOT/Ao but not RV/LV ratios were increased in patients with moderate or severe RV dysfunction compared to those without RV dysfunction (p < 0.05). Neither ratio showed significant correlation with RA (r = 0.09 vs 0.055, p > 0.05), mean PA pressure (r = 0.167 vs 0.146, p > 0.05), or CO (r = 0.021 vs - 0.183, p > 0.05). proBNP correlated with mean PA pressure (r = 0.377, p < 0.05). The RVOT/Ao ratio may be better at assessing RV dysfunction than the RV/LV ratio in patients presenting with acute PE. Although currently accepted protocols rely on the RV/LV ratio in determining when CDT are of benefit, the RVOT/Ao ratio may be a more useful tool in identifying high risk patients.

Diffuse Pulmonary Ossification on High-Resolution Computed Tomography in Idiopathic Pulmonary Fibrosis, Systemic Sclerosis-Related Interstitial Lung Disease, and Chronic Hypersensitivity Pneumonitis: A Comparative Study.

OBJECTIVE: The aim of the study was to compare the prevalence of diffuse pulmonary ossification (DPO) in idiopathic pulmonary fibrosis (IPF), systemic sclerosis (SSc)-related interstitial lung disease (ILD), and chronic hypersensitivity pneumonitis (HP). METHODS: High-resolution computed tomography (HRCT) from 71 IPF, 67 SSc-ILD, and 75 HP cases were independently evaluated by 2 thoracic radiologists blinded to patient data. Studies were assessed for the presence of DPO, HRCT scanning pattern, stigmata of granulomatous infection, and honeycombing. RESULTS: The prevalence of DPO was significantly higher in cases of IPF and SSc compared with HP, although there was no significant difference in prevalence between the IPF and SSc groups, even when accounting for the presence of prior granulomatous infection. Interobserver agreement for the presence of DPO was substantial. CONCLUSIONS: Although prevalence DPO on HRCT varies between some forms of ILD, the use of DPO to influence characterization of ILD should be considered with caution.

Prognosticating Outcomes in Interstitial Lung Disease by Mediastinal Lymph Node Assessment. An Observational Cohort Study with Independent Validation.

RATIONALE: Mediastinal lymph node (MLN) enlargement on chest computed tomography (CT) is prevalent in patients with interstitial lung disease (ILD) and may reflect immunologic activation and subsequent cytokine-mediated immune cell trafficking. OBJECTIVES: We aimed to determine whether MLN enlargement on chest CT predicts clinical outcomes and circulating cytokine levels in ILD. METHODS: MLN measurements were obtained from chest CT scans of patients with ILD at baseline evaluation over a 10-year period. Patients with sarcoidosis and drug toxicity-related ILD were excluded. MLN diameter and location were assessed. Plasma cytokine levels were analyzed in a subset of patients. The primary outcome was transplant-free survival (TFS). Secondary outcomes included all-cause and respiratory hospitalizations, lung function, and plasma cytokine concentrations. Cox regression was used to assess mortality risk. Outcomes were assessed in three independent ILD cohorts. MEASUREMENTS AND MAIN RESULTS: Chest CT scans were assessed in 1,094 patients (mean age, 64 yr; 52% male). MLN enlargement (≥10 mm) was present in 66% (n = 726) and strongly predicted TFS (hazard ratio [HR], 1.53; 95% confidence interval [CI], 1.12-2.10; P = 0.008) and risk of all-cause and respiratory hospitalizations (internal rate of return [IRR], 1.52; 95% CI, 1.17-1.98; P = 0.002; and IRR, 1.71; 95% CI, 1.15-2.53; P = 0.008, respectively) when compared with subjects with MLN <10 mm. Patients with MLN enlargement had lower lung function and decreased plasma concentrations of soluble CD40L (376 pg/ml vs. 505 pg/ml, P = 0.001) compared with those without MLN enlargement. Plasma IL-10 concentration >45 pg/ml predicted mortality (HR, 4.21; 95% CI, 1.21-14.68; P = 0.024). Independent analysis of external datasets confirmed these findings. CONCLUSIONS: MLN enlargement predicts TFS and hospitalization risk in ILD and is associated with decreased levels of a key circulating cytokine, soluble CD40L. Incorporating MLN and cytokine findings into current prediction models might improve ILD prognostication.

MUC5B variant is associated with visually and quantitatively detected preclinical pulmonary fibrosis.

BACKGROUND: Relatives of patients with familial interstitial pneumonia (FIP) are at increased risk for pulmonary fibrosis. We assessed the prevalence and risk factors for preclinical pulmonary fibrosis (PrePF) in first-degree relatives of patients with FIP and determined the utility of deep learning in detecting PrePF on CT. METHODS: First-degree relatives of patients with FIP over 40 years of age who believed themselves to be unaffected by pulmonary fibrosis underwent CT scans of the chest. Images were visually reviewed, and a deep learning algorithm was used to quantify lung fibrosis. Genotyping for common idiopathic pulmonary fibrosis risk variants in MUC5B and TERT was performed. FINDINGS: In 494 relatives of patients with FIP from 263 families of patients with FIP, the prevalence of PrePF on visual CT evaluation was 15.6% (95% CI 12.6 to 19.0). Compared with visual CT evaluation, deep learning quantitative CT analysis had 84% sensitivity (95% CI 0.72 to 0.89) and 86% sensitivity (95% CI 0.83 to 0.89) for discriminating subjects with visual PrePF diagnosis. Subjects with PrePF were older (65.9, SD 10.1 years) than subjects without fibrosis (55.8 SD 8.7 years), more likely to be male (49% vs 37%), more likely to have smoked (44% vs 27%) and more likely to have the MUC5B promoter variant rs35705950 (minor allele frequency 0.29 vs 0.21). MUC5B variant carriers had higher quantitative CT fibrosis scores (mean difference of 0.36%), a difference that remains significant when controlling for age and sex. INTERPRETATION: PrePF is common in relatives of patients with FIP. Its prevalence increases with age and the presence of a common MUC5B promoter variant. Quantitative CT analysis can detect these imaging abnormalities.

Diagnostic test interpretation and referral delay in patients with interstitial lung disease.

BACKGROUND: Diagnostic delays are common in patients with interstitial lung disease (ILD). A substantial percentage of patients experience a diagnostic delay in the primary care setting, but the factors underpinning this observation remain unclear. In this multi-center investigation, we assessed ILD reporting on diagnostic test interpretation and its association with subsequent pulmonology referral by a primary care physician (PCP). METHODS: A retrospective cohort analysis of patients referred to the ILD programs at UC-Davis and University of Chicago by a PCP within each institution was performed. Computed tomography (CT) of the chest and abdomen and pulmonary function test (PFT) were reviewed to identify the date ILD features were first present and determine the time from diagnostic test to pulmonology referral. The association between ILD reporting on diagnostic test interpretation and pulmonology referral was assessed, as was the association between years of diagnostic delay and changes in fibrotic features on longitudinal chest CT. RESULTS: One hundred and forty-six patients were included in the final analysis. Prior to pulmonology referral, 66% (n = 97) of patients underwent chest CT, 15% (n = 21) underwent PFT and 15% (n = 21) underwent abdominal CT. ILD features were reported on 84, 62 and 33% of chest CT, PFT and abdominal CT interpretations, respectively. ILD reporting was associated with shorter time to pulmonology referral when undergoing chest CT (1.3 vs 15.1 months, respectively; p = 0.02), but not PFT or abdominal CT. ILD reporting was associated with increased likelihood of pulmonology referral within 6 months of diagnostic test when undergoing chest CT (rate ratio 2.17, 95% CI 1.03-4.56; p = 0.04), but not PFT or abdominal CT. Each year of diagnostic delay was associated with a 1.8% increase in percent fibrosis on chest CT. Patients with documented dyspnea had shorter time to chest CT acquisition and pulmonology referral than patients with documented cough and lung crackles. CONCLUSIONS: Determinants of ILD diagnostic delays in the primary care setting include underreporting of ILD features on diagnostic testing and prolonged time to pulmonology referral even when ILD is reported. Interventions to modulate these factors may reduce ILD diagnostic delays in the primary care setting.

Attention, novelty preference and the visual paired comparison task.

The innate ability of humans to identify, process and ascribe greater attentional resources (attention bias) to novel stimuli is essential for exploring new opportunities and consequently adapt to changing environments. One of the most common tests to assess attention bias to novel stimuli (Novelty Preference - NP) is the visual paired comparison task (VPC). In the VPC task subjects are presented with novel and previously seen images (repeated images) and NP is measured by parameters that describe visual scanning patterns on these images. The main objective of this study is to evaluate the effects of divided attention on NP. NP was measured in 26 healthy young individuals under two test conditions. In the first condition, subjects performed the VPC task and an audio task simultaneously (divided attention test condition), while in the second condition subjects performed only the VPC task (undivided attention test condition). For each test condition, repeated images were presented after delays ranging from 1.0 to 219.5 s and NP was measured by the mean difference between the relative fixation times on novel and repeated images at each delay. In the divided attention test condition, there were significant differences (p < 0.037) between the magnitudes of NPs for long delays (≥ 162 s) and short delays (≤12.5 s). Such differences were not detected in the undivided attention test condition. Analysis of variance revealed significant differences between the measured NPs during the divided and undivided attention test conditions (F(1, 25) = 18.38, p < 0.001, η2 = 0.424) and significant interaction effects between delays and testing conditions (F(5,125) = 2.88, p = 0.017, η2 = 0.103). Post-hoc t-tests showed significant differences between the measured NPs during the divided attention and undivided attention test conditions for long delays (162.0 and 219.5 s) but not for short delays (1.0 and 12.5 s). The results of the study are consistent with the hypothesis that for longer delays between the presentations of repeated images in the VPC task, NP is dependent on the recollection-based item recognition memory system, while for shorter delays NP is dependent on the automatic, familiarity-based item recognition memory system.