Project description:A decreased lung diffusing capacity for carbon monoxide (DLCO ) in systemic sclerosis (SSc) is considered to reflect losses of alveolar membrane diffusive conductance for CO (DMCO ), due to interstitial lung disease, and/or pulmonary capillary blood volume (VC ), due to vasculopathy. However, standard DLCO does not allow separate DMCO from VC . Lung diffusing capacity for nitric oxide (DLNO ) is considered to be more sensitive to decrement of alveolar membrane diffusive conductance than DLCO . Standard DLCO and DLNO were compared in 96 SSc subjects with or without lung restriction. Data showed that DLNO was reduced in 22% of subjects with normal lung volumes and DLCO , whereas DLCO was normal in 30% of those with decreased DLNO . In 30 subjects with available computed tomography of the chest, both DLCO and DLNO were negatively correlated with the extent of pulmonary fibrosis. However, DLNO but not DLCO was always reduced in subjects with ≥ 5% fibrosis, and also decreased in some subjects with < 5% fibrosis. DMCO and VC partitioning and Doppler ultrasound-determined systolic pulmonary artery pressure could not explain individual differences in DLCO and DLNO . DLNO may be of clinical value in SSc because it is more sensitive to DMCO loss than standard DLCO , even in nonrestricted subjects without fibrosis, whereas DLCO partitioning into its subcomponents does not provide information on whether diffusion limitation is primarily due to vascular or interstitial lung disease in individual subjects. Moreover, decreased DLCO in the absence of lung restriction does not allow to suspect pulmonary arterial hypertension without fibrosis.
Project description:ObjectivesFibrotic interstitial lung disease (ILD) includes a large group of conditions that lead to scarring of the lungs. The lack of available 5-level EuroQol 5D (EQ5D) data has limited the ability to conduct economic evaluations in ILD. The purpose of this study was to develop and validate a mapping algorithm that predicts EQ5D utilities from commonly collected pulmonary function measurements (forced vital capacity [FVC] and diffusing capacity of the lung for carbon monoxide [DLCO]) in fibrotic ILDs.MethodsEQ5D utility and pulmonary function measurements from the Canadian Registry for Pulmonary Fibrosis were included. Ordinary least squares (OLS), beta regression, two-part, and tobit models were used to map EQ5D utilities from FVC or DLCO. Model performance was assessed by comparing the predicted and observed utilities. Subgroup analyses were also conducted to test how well models performed across different patient characteristics. The models were then externally validated in the Australian Idiopathic Pulmonary Fibrosis Registry.ResultsThe OLS model performed as well as other more complex models (root mean squared error: 0.17 for FVC and 0.16 for DLCO). As with the other models, the OLS algorithm performed well across the different subgroups (except for EQ5D utilities < 0.5) and in the external validation cohort.ConclusionWe developed a mapping algorithm that predicts EQ5D utilities from FVC and DLCO, with the intent that this algorithm can be applied to clinical trial populations and real-world cohorts that have not prioritized collection of health-related utilities. The mapping algorithm can be used in future economic evaluations of potential ILD therapies.
Project description:Thalamic nuclei have been implicated in neurodegenerative and neuropsychiatric disorders. Normative models for thalamic nuclear volumes have not been proposed thus far. The aim of this work was to establish normative models of thalamic nuclear volumes and subsequently investigate changes in thalamic nuclei in cognitive and psychiatric disorders. Volumes of the bilateral thalami and 12 nuclear regions were generated from T1 MRI data using a novel segmentation method (HIPS-THOMAS) in healthy control subjects (n=2374) and non-control subjects (n=695) with early and late mild cognitive impairment (EMCI, LMCI), Alzheimer's disease (AD), Early psychosis and Schizophrenia, Bipolar disorder, and Attention deficit hyperactivity disorder. Three different normative modelling methods were evaluated while controlling for sex, intracranial volume, and site. Z-scores and extreme z-score deviations were calculated and compared across phenotypes. GAMLSS models performed the best. Statistically significant shifts in z-score distributions consistent with atrophy were observed for most phenotypes. Shifts of progressively increasing magnitude were observed bilaterally from EMCI to AD with larger shifts in the left thalamic regions. Heterogeneous shifts were observed in psychiatric diagnoses with a predilection for the right thalamic regions. Here we present the first normative models of thalamic nuclear volumes and highlight their utility in evaluating heterogenous disorders such as Schizophrenia.
Project description:RationaleAmerican Thoracic Society guidelines state that a 10% or greater intersession change in diffusing capacity of the lung (DL(CO)) should be considered clinically significant. However, little is known about the short-term intersession variability in DL(CO) in untrained subjects or how variability is affected by rigorous external quality control.ObjectivesTo characterize the intersession variability of DL(CO) and the effect of different quality control methods in untrained individuals without significant lung disease.MethodsData were pooled from the comparator arms of 14 preregistration trials of inhaled insulin that included nonsmoking diabetic patients without significant lung disease. A total of 699 participants performed repeated DL(CO) measurements using a highly standardized technique. A total of 948 participants performed repeated measurements using routine clinical testing.Measurements and main resultsThe mean intersession absolute change in DL(CO) using the highly standardized method was 1.45 ml/minute/mm Hg (5.64%) compared with 2.49 ml/minute/mm Hg (9.52%) in the routine testing group (P < 0.0001 for both absolute and percent difference). The variability in absolute intersession change in DL(CO) increased with increasing baseline DL(CO) values, whereas the absolute percentage of intersession change was stable across baseline values. Depending on the method, 15.5 to 35.5% of participants had an intersession change of 10% or greater. A 20% or greater threshold would reduce this percentage of patients to 1 to 10%.ConclusionsIntersession variability in DL(CO) measurement is dependent on the method of testing used and baseline DL(CO). Using a more liberal threshold to define meaningful intersession change may reduce the misclassification of normal variation as abnormal change.
Project description:We studied whether in patients with COPD the use of metformin for diabetes treatment was linked to a pattern of lung function decline consistent with the hypothesis of anti-aging effects of metformin. Patients of GOLD grades 1-4 of the COSYCONET cohort with follow-up data of up to 4.5 y were included. The annual decline in lung function (FEV1, FVC) and CO diffusing capacity (KCO, TLCO) in %predicted at baseline was evaluated for associations with age, sex, BMI, pack-years, smoking status, baseline lung function, exacerbation risk, respiratory symptoms, cardiac disease, as well as metformin-containing therapy compared to patients without diabetes and metformin. Among 2741 patients, 1541 (mean age 64.4 y, 601 female) fulfilled the inclusion criteria. In the group with metformin treatment vs. non-diabetes the mean annual decline in KCO and TLCO was significantly lower (0.2 vs 2.3, 0.8 vs. 2.8%predicted, respectively; p < 0.05 each), but not the decline of FEV1 and FVC. These results were confirmed using multiple regression and propensity score analyses. Our findings demonstrate an association between the annual decline of lung diffusing capacity and the intake of metformin in patients with COPD consistent with the hypothesis of anti-aging effects of metformin as reflected in a surrogate marker of emphysema.
Project description:A decreased lung diffusing capacity for carbon monoxide (DLCO ) has been reported in a variable proportion of subjects over the first 3 months of recovery from severe coronavirus disease 2019 (COVID-19). In this study, we investigated whether measurement of lung diffusing capacity for nitric oxide (DLNO ) offers additional insights on the presence and mechanisms of gas transport abnormalities. In 94 subjects, recovering from mild-to-severe COVID-19 pneumonia, we measured DLNO and DLCO between 10 and 266 days after each patient was tested negative for severe acute respiratory syndrome coronavirus 2. In 38 subjects, a chest computed tomography (CT) was available for semiquantitative analysis at six axial levels and automatic quantitative analysis of entire lungs. DLNO was abnormal in 57% of subjects, independent of time of lung function testing and severity of COVID-19, whereas standard DLCO was reduced in only 20% and mostly within the first 3 months. These differences were not associated with changes of simultaneous DLNO /DLCO ratio, while DLCO /VA and DLNO /VA were within normal range or slightly decreased. DLCO but not DLNO positively correlated with recovery time and DLCO was within the normal range in about 90% of cases after 3 months, while DLNO was reduced in more than half of subjects. Both DLNO and DLCO inversely correlated with persisting CT ground glass opacities and mean lung attenuation, but these were more frequently associated with DLNO than DLCO decrease. These data show that an impairment of DLNO exceeding standard DLCO may be present during the recovery from COVID-19, possibly due to loss of alveolar units with alveolar membrane damage, but relatively preserved capillary volume. Alterations of gas transport may be present even in subjects who had mild COVID-19 pneumonia and no or minimal persisting CT abnormalities. TRIAL REGISTRY: ClinicalTrials.gov PRS: No.: NCT04610554 Unique Protocol ID: SARS-CoV-2_DLNO 2020.
Project description:Background and objectiveCurrently there is paucity of evidence in the literature in relation to normative values for diffusing capacity of carbon monoxide (DLCO) and total lung capacity (TLC) among Indigenous Australians. Hence, in this study we assessed the DLCO and TLC parameters among Indigenous Australians in comparison to Australian Caucasian counterparts.MethodsDLCO and TLC values were assessed and compared between Indigenous Australians and Australian Caucasians matched for age, sex and body mass index, with normal chest radiology.ResultsOf the 1350 and 5634 pulmonary function tests assessed in Indigenous Australian and Australian Caucasian adults respectively, a total of 129 Indigenous Australians and 197 Australian Caucasians met the inclusion criteria. Absolute DLCO and TLC values for Indigenous Australians were a mean 4.3 ml/min/mmHg (95% CI 2.86, 5.74) and 1.03 L (95% CI 0.78, 1.27) lower than Australian Caucasians (p<0.01). Percentage predicted values were 15.38 (95% CI 11.59, 19.17) and 16.63 (95% CI 13.59, 19.68) points lower for DLCO and TLC, respectively. Lower limit of normal (LLN) values did not significantly differ between groups, however a significantly greater proportion of Indigenous Australians recorded values below the LLN in comparison to Australian Caucasians for DLCO (64 vs. 25%, p<0.01) and TLC (66 vs. 21%, p<0.01). Significant differences for the interaction of sex on DLCO and TLC were noted in Australian Caucasians, with reduced or absent sex differentiation among Indigenous Australians.ConclusionsThere are significant differences in DLCO and TLC parameters between Indigenous Australian compared to Australian Caucasians. Appropriate DLCO and TLC norms need to be established for Indigenous Australians.
Project description:Aims and objectivesTo examine agreement between Minimum Data Set clinician ratings and researcher assessments of depression among ethnically diverse nursing home residents using the 9-item Patient Health Questionnaire.BackgroundAlthough depression is common among nursing homes residents, its recognition remains a challenge.DesignObservational baseline data from a longitudinal intervention study.MethodsSample of 155 residents from 12 long-term care units in one US facility; 50 were interviewed in Spanish. Convergence between clinician and researcher ratings was examined for (i) self-report capacity, (ii) suicidal ideation, (iii) at least moderate depression, (iv) Patient Health Questionnaire severity scores. Experiences by clinical raters using the depression assessment were analysed. The intraclass correlation coefficient was used to examine concordance and Cohen's kappa to examine agreement between clinicians and researchers.ResultsModerate agreement (κ = 0.52) was observed in determination of capacity and poor to fair agreement in reporting suicidal ideation (κ = 0.10-0.37) across time intervals. Poor agreement was observed in classification of at least moderate depression (κ = -0.02 to 0.24), lower than the maximum kappa obtainable (0.58-0.85). Eight assessors indicated problems assessing Spanish-speaking residents. Among Spanish speakers, researchers identified 16% with Patient Health Questionnaire scores of 10 or greater, and 14% with thoughts of self-harm whilst clinicians identified 6% and 0%, respectively.ConclusionThis study advances the field of depression recognition in long-term care by identification of possible challenges in assessing Spanish speakers.Relevance to clinical practiceUse of the Patient Health Questionnaire requires further investigation, particularly among non-English speakers. Depression screening for ethnically diverse nursing home residents is required, as underreporting of depression and suicidal ideation among Spanish speakers may result in lack of depression recognition and referral for evaluation and treatment. Training in depression recognition is imperative to improve the recognition, evaluation and treatment of depression in older people living in nursing homes.
Project description:BackgroundIt is essential to embed patient and public perspectives into every stage of the research journey, including setting the future research agenda. The substantial gaps in our understanding of prematurity-associated lung disease presented a timely opportunity to determine the community's research priorities.ObjectiveTo conduct a priority setting partnership (PSP) to determine the top 10 research priorities for preterm lung health.DesignWe undertook a modified James Lind Alliance methodology comprising three main stages: (1) an idea generating survey with open questions to ascertain the community's most important ideas for future preterm lung health research, (2) prioritisation survey to distill the main themes into a shortlist of 20 and (3) consensus workshop where participants were tasked with ranking their final top 10. This PSP is reflective of the view of preterm-born individuals, parents of preterm children and healthcare professionals in an Australian healthcare setting.ResultsWe collated 144 submissions from the idea generating survey from which 27 prioritisation themes were developed. From the 150 prioritisation survey responses, the 20 themes receiving the most votes were taken to the consensus workshop. Participants identified the following top 10: (1) lifelong impacts; (2) interventions, treatments or supports; (3) ongoing lung health follow-up; (4) diagnostic tools, resources and education for primary healthcare providers; (5) resources to inform and empower families; (6) relationship to physical health and developmental issues; (7) preventing and/or treating lung infections; (8) additional supports, resources and research for minority groups; (9) impact on mental well-being; and (10) likelihood of asthma diagnosis.ConclusionPriorities identified through the PSP will be invaluable in informing future research into prematurity-associated lung disease.