The psychometric properties of the King's Brief Interstitial Lung Disease questionnaire and thresholds for meaningful treatment response in patients with progressive fibrosing interstitial lung diseases

There is a lack of fully validated patient-reported outcome measures for progressive fibrosing interstitial lung disease (PF-ILD). We aimed to validate the King's Brief Interstitial Lung Disease questionnaire (KBILD) for measuring health-related quality of life (HRQoL) in these patients. We also estimated the meaningful change threshold for interpreting stabilisation of HRQoL as a clinical endpoint in PF-ILD, where the current goal of treatment is disease stability and slowing progression. This analysis evaluated data from 663 patients with PF-ILD other than idiopathic pulmonary fibrosis from the INBUILD trial. Validation of the measurement properties was assessed for internal consistency, test-retest reliability, construct validity, known-groups validity, and responsiveness. We calculated meaningful change thresholds for treatment response using anchor-based (within-patient) and distribution-based methods. The KBILD had strong internal consistency (Cronbach alpha was 0.94 for total score, 0.88 for KBILD domain breathlessness and activities, 0.91 for psychological and 0.79 for chest symptoms). Test-retest reliability intraclass correlation coefficient was 0.74 for KBILD total score. The KBILD demonstrated weak correlations with forced vital capacity (FVC)% predicted. Known-groups validity showed significant differences in KBILD scores for patient groups with different disease severity based on use of supplemental oxygen or baseline FVC% predicted (<70 or >70%). We estimated a meaningful change threshold of ≥–2 for the KBILD total score for defining patients who remain stable/improved versus those with progressive deterioration. Our results validate the KBILD as a tool for assessing HRQoL in patients with PF-ILD and set a meaningful change threshold of ≥–2 for KBILD total score.

Validation of a visual analog scale for assessing cough severity in patients with chronic cough

Introduction: Patients with chronic cough experience considerable burden. The cough severity visual analog scale (VAS) records patients’ assessment of cough severity on a 100-mm linear scale ranging from “no cough” (0 mm) to “worst cough” (100 mm). Although cough severity scales are widely used in clinical practice and research, their use in patients with refractory or unexplained chronic cough has not been formally validated. Methods: This analysis includes data from a phase 2b randomized controlled trial of the P2X3-receptor antagonist gefapixant for treatment of refractory or unexplained chronic cough (NCT02612610). Cough severity VAS scores were assessed at baseline and Weeks 4, 8, and 12. The cough severity VAS was validated using several outcomes, including the Cough Severity Diary (CSD), Leicester Cough Questionnaire (LCQ), patient global impression of change (PGIC) scale, and objective cough frequency. Validation metrics included test–retest reliability, convergent and known-groups validity, responsiveness, and score interpretation (i.e., clinically meaningful change threshold). Results: The analysis included 253 patients (median age, 61.0 years; females, 76%). Test–retest reliability of the cough severity VAS was moderate (intraclass correlation coefficient, 0.51). The cough severity VAS had acceptable convergent validity with other related measures (Pearson r of 0.53 and -0.41 for CSD and LCQ total scores, respectively; p < 0.0001 for each). Known-groups validity was supported by significant differences in mean cough severity VAS scores across severity groups defined using CSD, LCQ, and cough frequency tertiles. A large effect size was observed in patients with the greatest improvements in PGIC (Cohen d = -1.8). A ⩾ 30-mm reduction in the cough severity VAS was estimated as a clinically meaningful change threshold for clinical trials in chronic cough. Conclusions: The cough severity VAS is a valid and responsive measure. A cough severity VAS reduction of ⩾ 30 mm can discriminate clinically meaningful changes in chronic cough severity in clinical studies.

Changes in Proteome and Protein Phosphorylation Reveal the Protective Roles of Exogenous Nitrogen in Alleviating Cadmium Toxicity in Poplar Plants

Phytoremediation soil polluted by cadmium has drawn worldwide attention. However, how to improve the efficiency of plant remediation of cadmium contaminated soil remains unknown. Previous studies showed that nitrogen (N) significantly enhances cadmium uptake and accumulation in poplar plants. In order to explore the important role of nitrogen in plants’ responses to cadmium stress, this study investigates the poplar proteome and phosphoproteome difference between Cd stress and Cd + N treatment. In total, 6573 proteins were identified, and 5838 of them were quantified. With a fold-change threshold of > 1.3, and a p-value < 0.05, 375 and 108 proteins were up- and down-regulated by Cd stress when compared to the control, respectively. Compared to the Cd stress group, 42 and 89 proteins were up- and down-regulated by Cd + N treatment, respectively. Moreover, 522 and 127 proteins were up- and down-regulated by Cd + N treatment compared to the CK group. In addition, 1471 phosphosites in 721 proteins were identified. Based on a fold-change threshold of > 1.2, and a p-value < 0.05, the Cd stress up-regulated eight proteins containing eight phosphosites, and down-regulated 58 proteins containing 69 phosphosites, whereas N + Cd treatment up-regulated 86 proteins containing 95 phosphosites, and down-regulated 17 proteins containing 17 phosphosites, when compared to Cd stress alone. N + Cd treatment up-regulated 60 proteins containing 74 phosphosites and down-regulated 37 proteins containing 42 phosphosites, when compared to the control. Several putative responses to stress proteins, as well as transcriptional and translational regulation factors, were up-regulated by the addition of exogenous nitrogen following Cd stress. Especially, heat shock protein 70 (HSP70), 14-3-3 protein, peroxidase (POD), zinc finger protein (ZFP), ABC transporter protein, eukaryotic translation initiation factor (elF) and splicing factor 3 B subunit 1-like (SF3BI) were up-regulated by Cd + N treatment at both the proteome and the phosphoproteome levels. Combing the proteomic data and phosphoproteomics data, the mechanism by which exogenous nitrogen can alleviate cadmium toxicity in poplar plants was explained at the molecular level. The results of this study will establish the solid molecular foundation of the phytoremediation method to improve cadmium-contaminated soil.

Abbott ARCHITECT STAT Contemporary Troponin I Outlier Detection and Prevention of Erroneous Outlier Result Reporting Using an Immediate Repeat Testing Protocol: A 1-Year Summary

Objectives The laboratory sought to monitor and eliminate reported patient cardiac troponin outlier results using the Abbott ARCHITECT STAT Contemporary Troponin-I test. Methods The laboratory implemented an immediate repeat test for all patient samples yielding an Abbott ARCHITECT STAT contemporary Troponin I concentration greater than the combined male and female 99th percentile of 28 ng/L. The lower troponin concentration of the paired testing was reported. Samples with reference range troponin concentration were reported without repeat testing. Blood collected in Becton Dickinson Vacutainer PST Gel and Lithium Heparin tubes was centrifuged using a HemoCue StatSpin Express 4 centrifuge 4,000 g × 5 minutes and immediately tested on the primary tube. Troponin outliers were defined as paired samples showing a percentage change based on the low value of the pair exceeding the significant change threshold of 4.7x%CVanalytical for brackets of troponin concentrations (P0.0005), representing a significant change value for serial tests of 1.41xZxCVa%, where Z is 3.3. Critical troponin outliers were sample pairs with one result exceeding and one result within the 99th percentile reference range. Turnaround time was defined as time of receipt to time of verification. Results The outlier rate, based on 4,575 troponin tests performed on 3,797 patient samples, was 0.48% (N = 22) of troponin determinations, 0.58% of test samples, and critical outliers 0.13% (N = 6) of troponin determinations, 0.16% of test samples. The significant change threshold at 28 ng/L was 37%. The worst outlier pair was 5,978 ng/L, true value 3,184 ng/L; critical outlier pair 146 ng/L, true value of 14 ng/L. Twenty-one percent of test samples were tested in duplicate; 777 samples had troponin concentration >28 ng/L. Median and mean turnaround time were 32 minutes; 90% of orders completed in 54 minutes. Conclusion The laboratory detected and prevented reporting erroneously high outlier troponin results in 0.58% and critical outlier troponin results in 0.16% of test samples using an immediate repeat testing protocol.

Mapping Mangrove Extent and Change: A Globally Applicable Approach

This study demonstrates a globally applicable method for monitoring mangrove forest extent at high spatial resolution. A 2010 mangrove baseline was classified for 16 study areas using a combination of ALOS PALSAR and Landsat composite imagery within a random forests classifier. A novel map-to-image change method was used to detect annual and decadal changes in extent using ALOS PALSAR/JERS-1 imagery. The map-to-image method presented makes fewer assumptions of the data than existing methods, is less sensitive to variation between scenes due to environmental factors (e.g., tide or soil moisture) and is able to automatically identify a change threshold. Change maps were derived from the 2010 baseline to 1996 using JERS-1 SAR and to 2007, 2008 and 2009 using ALOS PALSAR. This study demonstrated results for 16 known hotspots of mangrove change distributed globally, with a total mangrove area of 2,529,760 ha. The method was demonstrated to have accuracies consistently in excess of 90% (overall accuracy: 92.2–93.3%, kappa: 0.86) for mapping baseline extent. The accuracies of the change maps were more variable and were dependent upon the time period between images and number of change features. Total change from 1996 to 2010 was 204,850 ha (127,990 ha gain, 76,860 ha loss), with the highest gains observed in French Guiana (15,570 ha) and the highest losses observed in East Kalimantan, Indonesia (23,003 ha). Changes in mangrove extent were the consequence of both natural and anthropogenic drivers, yielding net increases or decreases in extent dependent upon the study site. These updated maps are of importance to the mangrove research community, particularly as the continual updating of the baseline with currently available and anticipated spaceborne sensors. It is recommended that mangrove baselines are updated on at least a 5-year interval to suit the requirements of policy makers.