Validity and Reliability of the Fatigue Severity Scale in a Real-World Interstitial Lung Disease Cohort.

Rationale: Fatigue is a common and debilitating symptom for people living with interstitial lung disease (ILD). Studies on fatigue in ILD are limited, and little headway has been made toward developing interventions targeting the alleviation of fatigue. A barrier to progress is a lack of knowledge around the performance characteristics of a patient-reported outcome measure to assess fatigue in patients with ILD. Objectives: To assess the validity and reliability of the Fatigue Severity Scale (FSS) for measuring fatigue in a national cohort of patients with ILD. Methods: FSS scores and several anchors were measured in 1,881 patients from the Pulmonary Fibrosis Foundation Patient Registry. Anchors included the Short Form 6D Health Utility Index (SF-6D) score and a single vitality question from the SF-6D; the University of California, San Diego, Shortness of Breath Questionnaire; FVC; DlCO; and 6-minute-walk distance. Internal consistency reliability, concurrent validity, and known-groups validity were assessed. Structural validity was assessed using confirmatory factor analysis. Measurements and Main Results: The FSS demonstrated high internal consistency (Cronbach's α = 0.96). There were moderate to strong correlations between FSS score and patient-reported anchors (vitality question from the SF-6D [r = 0.55] and University of California, San Diego, Shortness of Breath Questionnaire total score [r = 0.70]) and weak correlations between FSS score and physiological measures (FVC [r = -0.24], percentage predicted DlCO [r = -0.23], and 6-minute-walk distance [r = -0.29]). Higher mean FSS scores, indicating greater fatigue, were observed among patients using supplemental oxygen, those prescribed steroids, and those with lower percentage predicted FVC and percentage predicted DlCO. The confirmatory factor analysis results suggest that the nine questions of the FSS reflect one dimension of fatigue. Conclusions: Fatigue is an important patient-centered outcome in ILD that is poorly correlated with physiological measures of disease severity, including lung function and walk distance. These findings further support the need for a reliable and valid measure of patient-reported fatigue in ILD. The FSS possesses acceptable performance characteristics for assessing fatigue and distinguishing different degrees of fatigue among patients with ILD.

Real-World Clinical Outcomes Based on Body Mass Index and Annualized Weight Change in Patients with Idiopathic Pulmonary Fibrosis.

INTRODUCTION: Identification of clinical characteristics associated with prognosis for idiopathic pulmonary fibrosis (IPF) may help to guide management decisions. This analysis utilized data from the Pulmonary Fibrosis Foundation Patient Registry to examine the relationships between clinical outcomes and both body mass index (BMI) at study enrollment (hereafter referred to as baseline BMI) and annualized percent change in body weight in patients with IPF in a real-world setting. METHODS: The following outcomes over 24 months were stratified by baseline BMI and annualized percent change in body weight: all-cause mortality; annualized change in percent predicted forced vital capacity (%FVC), percent predicted diffusing capacity for carbon monoxide, and 6-min walk distance; all-cause and respiratory-related hospitalizations; and acute exacerbations. RESULTS: Overall, 600 patients with IPF were included (baseline BMI: < 25 kg/m2, n = 120; 25 to < 30 kg/m2, n = 242; ≥ 30 kg/m2, n = 238; annualized percent change in body weight: no loss, n = 95; > 0% to < 5% loss, n = 425; ≥ 5% loss, n = 80). Enrollment demographics and characteristics were generally similar across subgroups. There was no association between mortality and BMI. All-cause mortality was lower among patients who experienced no annualized weight loss versus those with ≥ 5% (OR [95% CI] 3.28 [1.15, 10.95]) or > 0 to < 5% weight loss (OR [95% CI] 2.83 [1.14, 8.62]) over 24 months. Patients with baseline BMI < 25 kg/m2 had a significantly greater estimated annualized decline in %FVC versus patients with baseline BMI ≥ 30 kg/m2 (difference [95% CI] 1.47 [0.01, 2.93]). No relationship was observed between %FVC and weight loss. Other clinical outcomes were generally similar across subgroups. CONCLUSIONS: Some clinical outcomes may be worse in patients with IPF who have a low BMI (< 25 kg/m2) or who experience weight loss over 24 months, but the causation for these relationships is unknown. These results may help to inform management decisions for patients with IPF. GOV IDENTIFIER: NCT02758808.

Stability Analysis of Kernel Quality Traits in Exotic-Derived Doubled Haploid Maize Lines.

Variation in kernel composition across maize ( L.) germplasm is affected by a combination of the plant's genotype, the environment in which it is grown, and the interaction between these two elements. Adapting exotic germplasm to the US Corn Belt is highly dependent on the plant's genotype, the environment where it is grown, and the interaction between these components. Phenotypic plasticity is ill-defined when specific exotic germplasm is moved over large latitudinal distances and for the adapted variants being created. Reduced plasticity (or stability) is desired for the adapted variants, as it allows for a more rapid implementation into breeding programs throughout the Corn Belt. Here, doubled haploid lines derived from exotic maize and adapted through backcrossing exotic germplasm to elite adapted lines were used in conjunction with genome-wide association studies to explore stability in four kernel composition traits. Genotypes demonstrated a response to environments that paralleled the mean response of all genotypes used across all traits, with protein content and kernel density exhibiting the highest levels of Type II stability. Genes such as , , and were identified as potential candidates within quantitative trait locus regions. The findings within this study aid in validating previously identified genomic regions and identified novel genomic regions affecting kernel quality traits.

Association Mapping of Flowering and Height Traits in Germplasm Enhancement of Maize Doubled Haploid (GEM-DH) Lines.

Flowering and height related traits are extensively studied in maize for three main reasons: 1) easily obtained phenotypic measurements, 2) highly heritable, and 3) importance of these traits to adaptation and grain yield. However, variation in flowering and height traits is extensive and findings from previous studies are genotype specific. Herein, a diverse panel of exotic derived doubled haploid lines, in conjunction with genome-wide association analysis, is used to further explore adaptation related trait variation of exotic germplasm for potential use in adapting exotic germplasm to the U.S. Corn-Belt. Phenotypes for the association panel were obtained from six locations across the central-U.S. and genotyping was performed using the genotyping-by-sequencing method. Nineteen flowering time candidate genes were found for three flowering traits. Eighteen candidate genes were found for four height related traits, with the majority of the candidate genes relating to plant hormones auxin and gibberellin. A single gene was discovered for ear height that also had effects on -like flowering gene expression levels. Findings will be used to inform future research efforts of the USDA Germplasm Enhancement of Maize project and eventually aid in the rapid adaptation of exotic germplasm to temperate U.S. environments.