Referential equations for pulmonary diffusing capacity using GAMLSS models derived from Japanese individuals with near-normal lung function.
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ABSTRACT: Objective
To generate appropriate reference values for the single-breath diffusing capacity of the lungs for carbon monoxide (DLCO), alveolar volume (VA), and the transfer coefficient of the lungs for carbon monoxide (KCO, often denoted as DLCO/VA) in the Japanese population. We also intended to assess the applicability of these values for the Japanese population by comparing them to those published by the Global Lung Function Initiative in 2017 (GLI-2017) and previous values.Methods
In this retrospective study, we measured the spirometric indices, DLCO, VA, and KCO of the Japanese population aged 16-85 years. The lambda, mu, and sigma (LMS) method and the generalized additive models for the location, scale, and shape program in R were used to generate the reference values.Results
We conducted a total of 390 tests. The GLI-2017 z-scores of DLCO were approximately zero, whereas those of KCO and VA were far from zero. In the present study, the mean square errors of the DLCO, VA, and KCO reference values were lower than the reference values derived from GLI-2017 and previous linear regression equations.Conclusions
Reference values obtained in this study were more appropriate for our sample than those reported in GLI-2017. Differences between the two equations were attributed to underestimating KCO (DLCO / VA) and overestimating VA, respectively, by the GLI-2017 for the Japanese population.
SUBMITTER: Wada Y
PROVIDER: S-EPMC9302824 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundReference equations from the Global Lung Function Initiative (GLI) are now available for both spirometry and diffusion. However, respiratory phenotypes defined by GLI-based measures of diffusion have not yet been evaluated in GLI-based normal-for-age spirometry or spirometric impairments.MethodsWe evaluated cross-sectional data from 2100 Caucasians, aged 40-85 years. GLI-based spirometric categories included normal-for-age and the impairments of restrictive-pattern and three-level severity of airflow-obstruction (mild, moderate, severe). GLI-based diffusion included diffusing capacity of the lung for carbon monoxide (DLCO) and measured components of alveolar volume (VA) and transfer coefficient (KCO): DLCO = [VA]x[KCO]. Using multivariable regression models, adjusted odds ratios (adjORs) for DLCO, VA, and KCO < lower limit of normal (LLN) were calculated for spirometric impairments, relative to normal-for-age spirometry.ResultsRelative to normal-for-age spirometry, the restrictive-pattern increased the adjORs (95% confidence intervals) for DLCO and VA < LLN-4.61 (3.62, 5.85) and 15.53 (11.8, 20.4), respectively, but not for KCO < LLN-1.02 (0.79, 1.33). Also relative to normal-for-age spirometry, airflow-obstruction from mild to severe increased the adjORs for DLCO < LLN-from 1.22 (0.80, 1.86) to 6.63 (4.91, 8.95), for VA < LLN-from 1.37 (0.85, 2.18) to 7.01 (5.20, 9.43), and for KCO < LLN-from 2.04 (1.33, 3.14) to 3.03 (2.29, 3.99). Notably, in normal-for-age spirometry, 34.5%, 19.7%, and 25.3% of participants had DLCO, VA, or KCO < LLN, respectively.ConclusionAbnormal diffusion is most prevalent in spirometric impairments but also occurs in normal-for-age spirometry. These results further inform the respiratory phenotypes of GLI-based spirometric categories and, in turn, the spirometric evaluation of respiratory disease.
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Project description:To achieve a multidimensional evaluation of chronic obstructive pulmonary disease (COPD) patients, the spirometry measures are supplemented by assessment of symptoms, risk of exacerbations, and CT imaging. However, the measurement of diffusing capacity of the lung for carbon monoxide (DLCO) is not included in most common used models of COPD assessment. Here, we conducted a meta-analysis to evaluate the role of DLCO in COPD assessment.The studies were identified by searching the terms "diffusing capacity" OR "diffusing capacity for carbon monoxide" or "DLCO" AND "COPD" AND "assessment" in Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and Web of Science databases. The mean difference of DLCO % predict was assessed in COPD patient with different severity (according to GOLD stage and GOLD group), between COPD patients with or without with frequent exacerbation, between survivors and non-survivors, between emphysema dominant and non-emphysema dominant COPD patients, and between COPD patients with or without pulmonary hypertension.43 studies were included in the meta-analysis. DLCO % predicted was significantly lower in COPD patients with more severe airflow limitation (stage II/IV), more symptoms (group B/D), and high exacerbation risk (group C/D). Lower DLCO % predicted was also found in exacerbation patients and non-survivors. Low DLCO % predicted was related to emphysema dominant phenotype, and COPD patients with PH.The current meta-analysis suggested that DLCO % predicted might be an important measurement for COPD patients in terms of severity, exacerbation risk, mortality, emphysema domination, and presence of pulmonary hypertension. As diffusion capacity reflects pulmonary ventilation and perfusion at the same time, the predictive value of DLCO or DLCO combined with other criteria worth further exploration.
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Project description:BackgroundPatients with COPD who experience pulmonary hypertension (PH) have worse mortality than those with COPD alone. Predictors of poor outcomes in COPD-PH are not well-described. Diffusing capacity of the lung (Dlco) assesses the integrity of the alveolar-capillary interface and thus may be a useful prognostic tool among those with COPD-PH.Research questionUsing a single center registry, we sought to evaluate Dlco as a predictor of mortality in a cohort of patients with COPD-PH.Study design and methodsThis retrospective cohort study analyzed 71 COPD-PH patients from the Johns Hopkins Pulmonary Hypertension Registry with right-sided heart catheterization (RHC)-proven PH and pulmonary function testing data within one year of diagnostic RHC. Transplant-free survival was calculated from index RHC. Adjusted transplant-free survival was modelled using Cox proportional hazard methods; age, pulmonary vascular resistance, FEV1, oxygen use, and N-terminal pro-brain natriuretic peptide were included as covariates.ResultsOverall unadjusted transplant-free 1-, 3-, and 5-year survivals were 87%, 60%, and 51%, respectively. Survival was associated with reduced Dlco across the observed range of pulmonary artery pressures and pulmonary vascular resistance. Severe Dlco impairment was associated with poorer survival (log-rank χ2 13.07) (P < .001); adjusting for covariates, for every percent predicted decrease in Dlco, mortality rates increased by 4% (hazard ratio, 1.04; 95% CI, 1.01-1.07).InterpretationAmong patients with COPD-PH, severe gas transfer impairment is associated with higher mortality, even with adjustment for airflow obstruction and hemodynamics, which suggests that Dlco may be a useful prognostic marker in this population. Future studies are needed to further investigate the association between Dlco and morbidity and to determine the utility of Dlco as a biomarker for disease risk and severity in COPD-PH.
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Project description:Background: The hemodynamic results of balloon pulmonary angioplasty vary among patients with inoperable chronic thromboembolic pulmonary hypertension (CTEPH). Previous studies revealed that microvasculopathy accounted for residual pulmonary hypertension after pulmonary endarterectomy, which could be reflected by the diffusing capacity for carbon monoxide (DLCO). We aimed to identify whether the DLCO could predict the BPA response. Materials and Methods: We retrospectively analyzed 75 consecutive patients with inoperable CTEPH who underwent BPA from May 2018 to January 2021 at Fuwai Hospital. According to the hemodynamics at follow-up after the last BPA, patients were classified as "BPA responders" (defined as a mean pulmonary arterial pressure ≤ 30 mmHg and/or a reduction of pulmonary vascular resistance ≥ 30%) or "BPA nonresponders." Results: At the baseline, BPA responders had significantly higher DLCO values than nonresponders, although the other variables were comparable. In BPA responders, the DLCO decreased after the first BPA session and then returned to a level similar to the baseline at follow-up. Conversely, the DLCO increased constantly from the baseline to follow-up in nonresponders. Multivariate logistic analysis showed that a baseline DLCO of <70% and a percent change in DLCO between the baseline and the period within 7 days after the first BPA session (ΔDLCO) of > 6% were both independent predictors of an unfavorable response to BPA. Receiver operator characteristic analysis showed that the combination of a baseline DLCO < 70% and ΔDLCO > 6% demonstrated a better area under the curve than either of these two variables used alone. Conclusions: A baseline DLCO < 70% and ΔDLCO > 6% could independently predict unfavorable responses to BPA. Measuring the DLCO dynamically facilitates the identification of patients who might have unsatisfactory hemodynamic results after BPA.
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Project description:ObjectivePeople with HIV (PWH) are at greater risk of developing lung diseases even when they are antiretroviral therapy (ART)-adherent and virally suppressed. The most common pulmonary function abnormality in PWH is that of impaired diffusing capacity of the lungs for carbon monoxide (DL CO ), which is an independent risk factor for increased mortality in PWH. Earlier work has identified several plasma biomarkers of inflammation and immune activation to be associated with decreased DL CO . However, the underpinning molecular mechanisms of HIV-associated impaired DL CO are largely unknown.DesignCross-sectional pilot study with PWH with normal DL CO (values greater than or equal to the lower limit of normal, DL CO ≥ LLN, N = 9) or abnormal DL CO (DL CO < LLN, N = 9).MethodsWe compared the gene expression levels of over 900 inflammation and immune exhaustion genes in PBMCs from PWH with normal vs. abnormal DL CO using the NanoString technology.ResultsWe found that 26 genes were differentially expressed in the impaired DL CO group. These genes belong to 4 categories: 1. Nine genes in inflammation and immune activation pathways, 2. seven upregulated genes that are direct targets of the interferon signaling pathway, 3. seven B-cell specific genes that are downregulated, and 4. three miscellaneous genes. These results were corroborated using the bioinformatics tools DAVID (Database for Annotation, Visualization and Integrated Discovery) and GSEA (Gene Sets Enrichment Analysis).ConclusionThe data provides preliminary evidence for the involvement of sustained interferon signaling as a molecular mechanism for impaired DL CO in PWH.
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Project description:BackgroundDiffusing capacity of the lung for carbon monoxide (Dlco) is inconsistently obtained in patients with COPD, and the added benefit of Dlco testing beyond that of more common tools is unknown.ObjectiveThe goal of this study was to determine whether lower Dlco is associated with increased COPD morbidity independent of emphysema assessed via spirometry and CT imaging.MethodsData for 1,806 participants with COPD from the Genetic Epidemiology of COPD (COPDGene) study 5-year visit were analyzed, including pulmonary function testing, quality of life, symptoms, exercise performance, and exacerbation rates. Dlco percent predicted was primarily analyzed as a continuous variable and additionally categorized into four groups: (1) Dlco and FEV1 > 50% (reference); (2) only Dlco ≤ 50%; (3) only FEV1 ≤ 50%; and (4) both ≤ 50% predicted. Outcomes were modeled by using multivariable linear and negative binomial regression, including emphysema and FEV1 percent predicted among other confounders.ResultsIn multivariable analyses, every 10% predicted decrease in Dlco was associated with symptoms and quality of life (COPD Assessment Test, 0.53 [P < .001]; St. George's Respiratory Questionnaire, 1.67 [P < .001]; Medical Outcomes Study Short Form 36 Physical Function, -0.89 [P < .001]), exercise performance (6-min walk distance, -45.35 feet; P < .001), and severe exacerbation rate (rate ratio, 1.14; P < .001). When categorized, severe impairment in Dlco alone, FEV1 alone, or both Dlco and FEV1 were associated with significantly worse morbidity compared with the reference group (P < .05 for all outcomes).ConclusionsImpairment in Dlco was associated with increased COPD symptoms, reduced exercise performance, and severe exacerbation risk even after accounting for spirometry and CT evidence of emphysema. These findings suggest that Dlco should be considered for inclusion in future multidimensional tools assessing COPD.
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Project description: Not available
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