Significant Difference In DLCO Research Articles

Effect of barometric pressure on single-breath carbon monoxide diffusing capacity

BackgroundSingle-breath diffusing capacity for carbon monoxide (DLCO) quantifies gas transfer in the lungs. DLCO measurement is affected by barometric pressure (Pb) and alveolar partial pressure of oxygen (PAO2). The current equations for adjusting DLCO for Pb and PAO2 may not be accurate given advances in test performance and technology. We quantify changes in DLCO with alterations in Pb in normal and COPD subjects, determine the accuracy of the current Pb and PAO2 adjustment equations and develop updated adjustment equations. MethodsWe measured DLCO in 13 normal and 10 COPD subjects at 1330 m altitude and in a hypobaric/hyperbaric chamber at altitudes of sea-level and 2500 m; six normal subjects were tested at 3600 m. We determined if there were significant differences in DLCO between altitudes. We developed an equation for adjusting DLCO for changes in Pb from sea-level. We compared this equation with the existing Pb adjustment equation in normal and COPD subjects. We determined the accuracy of the current PAO2 adjustment equation and developed a new PAO2 adjustment equation. ResultsDLCO significantly increased with decreasing Pb. We developed a Pb adjustment equation that adjusts DLCO measured at altitudes between 1330 m and 3600 m to sea-level values. This Pb adjustment equation yields DLCO results that are not significantly different than the currently recommended equation. We developed a more accurate PAO2 adjustment equation. ConclusionDLCO measurement is significantly affected by altitude. We developed equations that accurately adjust DLCO for changes in Pb and PAO2 in normal and COPD subjects.

A Randomized Phase II Trial Comparing BeEAM with BEAM As Conditioning Regimen for Autologous Stem Cell Transplantation in Lymphoma Patients

Introduction BCNU containing BEAM (BCNU, etoposide, cytarabine, melphalan) is one of the most commonly used conditioning regimens in lymphoma patients before autologous stem cell transplantation (ASCT). A frequently observed non-hematological complication of high-dose BCNU containing regimens is pulmonary toxicity that might lead to permanent damage with a reported incidence varying from 2% to 64%. Replacing BCNU with bendamustine in the BeEAM regimen has shown to be effective and feasible in phase II trials. So far, no randomized clinical trial has compared the established BEAM protocol with the BeEAM regimen. Here we present the results of a randomized phase II clinical trial (EudraCT2014-003629-16). Methods In this multicentre Austrian Swiss trial, 108 patients were enrolled from January 2015 to December 2018 and randomly assigned to the BeEAM (N=53) or BEAM (N=55) arm as a conditioning regimen. Patients enrolled had either mantle cell lymphoma (MCL) (N=39), diffuse large B-cell lymphoma (DLBCL) (N=57) or follicular lymphoma (FL) (N=12). The conditioning regimen was administered according to the standard BEAM protocol (BCNU: 300mg/m2) and the BeEAM regimen was given according the regimen first published by Giuseppe Visani et al. 2011 (bendamustine: 2x200mg/m2 on consecutive days). Hematological engraftment after ASCT was defined as the first day of neutrophil counts above 0.5 x 109/l, and of platelet counts above 20 x 109/l in the absence of platelet transfusion in the previous 3 days. The primary endpoint of the study was to evaluate whether replacement of BCNU by bendamustine could reduce lung toxicity defined, as a decrease of the diffusion capacity of the lung for carbon monoxide (DLCO) by at least 20%, at 3 months after ASCT. Secondary endpoints included overall survival (OS) and progression-free survival (PFS), acute toxicity, hematological recovery and engraftment, pulmonary function parameters as assessed by spiro- and ergometry from diagnosis until 1-year after ASCT and quality of life according to the EORTC-Q30 questionnaire. ResultsAge, disease status and remission status were well balanced and did not differ between the two study groups. Engraftment: Median number of infused CD34+ cells x 106/kg was 4.3 in the BeEAM vs. 4.6 in the BEAM arm. All patients engrafted and there was no difference in time to engraftment between the BeEAM and BEAM group. Respiratory function: The primary endpoint was achieved in 8/41(19.5%) in the BeEAM and in 9/43 (20.9%) in the BEAM group. There was no significant difference in DLCO and spiro- and ergometry in the BeEAM and BEAM group during the whole study period (Table 1). Although 2 patients died because of treatment related lung toxicity in the BEAM arm, we did not observe any functional detoriation in the patients who received the BCNU-containing BEAM regimen. Additionally, blood gas analysis revealed similar results in both study arms at screening, 3 months and 1-year after ASCT. Toxicity: Acute toxicity grade 3-5 according to CTCAE v4.0 was observed in 43.4% of the patients in the BeEAM arm and in 34.5% of the patients in the BEAM arm in the category any adverse event (p =0.43). Infections and infestations were observed in 9.4% of patients in the BeEAM arm and in 14.5% in the BEAM arm (p=0.56). Respiratory, thoracic and mediastinal disorders were only detected in the BEAM arm (5.5%) (p=0.24). In contrast to previous trials, grade 3-5 renal toxicity was low, both in the BeEAM and BEAM arm, respectively (1.9% vs. 1.8%) (p=1.00). Gastrointestinal toxicity occurred more frequently in the BeEAM arm (13.2%) than in the BEAM arm (5.5%) (p=0.20). Median follow-up was 369 days (15-540 days). In the BeEAM arm 4 out of 53 patients died during the observational period, 6 out of 55 in the BEAM arm (log-rank test p=0.54, Figure 1). Ten patients in each group had a progression or died during the observational period (log-rank test p=0.89). Quality of life: There was no statistical difference in the assessment of quality of life in the two study arms. Conclusion BeEAM is a feasible, well tolerated regimen resulting in similar clinical results as observed with the BEAM regimen. Interestingly we did not see any difference in impairment of pulmonary function, however 2 patients died in the BEAM arm of lung toxicity and no lung related deaths were observed in the BeEAM group. In our conclusion, BeEAM is a reasonable alternative to the BEAM regimen. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Forced expiratory flows and diffusion capacity in infants born from mothers with pre-eclampsia.

Animal models suggest pre-eclampsia (Pre-E) affects alveolar development, but data from humans are lacking. Assess the impact of Pre-E on airway function, diffusion capacity, and respiratory morbidity in preterm and term infants born from mothers with Pre-E. Infants born from mothers with and without Pre-E were recruited for this study; term and preterm infants were included in both cohorts. Respiratory morbidity in the first 12 months of life was assessed through monthly phone surveys. Raised volume rapid thoracoabdominal compression and measurement of diffusion capacity of the lung to carbon monoxide (DLCO) were performed at 6 months corrected age. There were 146 infants in the Pre-E cohort and 143 in the control cohort. The Pre-E cohort was further divided into nonsevere (N = 41) and severe (N = 105) groups. There was no significant difference in DLCO and DLCO/alveolar volume amongthe three groups. Forced vital capacity was similar amongthe three groups, but the nonsevere Pre-E group had significantly higher forced expiratory flows than the other two groups. After adjusting for multiple covariates including prematurity, the severe Pre-E group had a lower risk for wheezing in the first year of life compared to the other two groups. Pre-E is not associated with reduced DLCO, lower forced expiratory flows, or increased wheezing in the first year of life. These results differ from animal models and highlight the complex relationships between Pre-E and lung function and respiratory morbidity in human infants.

Comparison of diffusing capacity of carbon monoxide (DLCO) and total lung capacity (TLC) between Indigenous Australians and Australian Caucasian adults.

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.

The Effect of a Pulmonary Rehabilitation on Lung Function and Exercise Capacity in Patients with Burn: A Prospective Randomized Single-Blind Study.

We performed pulmonary function (PF) tests and factors affecting PF evaluation in 120 patients with inhalation injury to evaluate the effects of pulmonary rehabilitation (PR) in burn patients with inhalation injury. Patients were randomized into pulmonary rehabilitation (PR) group and conventional rehabilitation (CON) group. PF tests, including forced vital capacity (FVC), 1-s forced expiratory volume FEV1), maximum voluntary ventilation (MVV), and respiratory muscles strength (maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP)), were measured by mouth pressure meter in the sitting position. Diffusing capacity for carbon monoxide (DLco) was determined by the single-breath carbon monoxide technique. Peak cough flow (PCF) was measured by a peak flow meter. Diaphragmatic mobility (DM) was evaluated on anteroposterior fluoroscopy. All evaluations were performed in all groups at baseline and after 12 weeks. There were no differences in evaluations between the PR group and CON group before the intervention. There were significant improvements in the PCF and MIP (%) changes, taken before and after rehabilitation in the PR group, compared with the changes in the CON group (p = 0.01, and p = 0.04). There were no significant changes in the other parameters in the PR group compared with the changes in the CON group (p > 0.05). There were significant differences in DLco (%), MIP, MIP (%), and DM between the PR group and the CON group (p = 0.02, p = 0.005, and p = 0.001) after 12 weeks of rehabilitation. There were no differences between the PR group and CON group after 12 weeks rehabilitation in the other parameters (p > 0.05). PR for patients with major burns and smoke inhalation induced improved PCF, MIP, MIP (%), DLco (%), and DM. These results show that PR should be a fundamental component of the treatment program for patients with burns.

Significance of the lobe-specific emphysema index to predict prolonged air leak after anatomical segmentectomy.

Prolonged air leak (PAL) is a major complication of pulmonary resection. Emphysema quantification with computed tomography is regarded as an important predictor of PAL for patients undergoing lobectomy. Therefore, we investigated whether this predictor might be applicable for segmentectomy. Herein, we characterized the factors that influence PAL in early stage lung cancer patients undergoing anatomical segmentectomy. Forty-one patients who underwent anatomical segmentectomy for early lung cancer between January 2014 and July 2017 were included for analysis. Several baseline and surgical variables were evaluated. In particular, the emphysema index (EI, %) and lobe-specific emphysema index (LEI, %) were assessed by using three-dimensional volumetric CT scan. PAL was observed in 13 patients (31.7%). There were statistically significant differences in DLCO (97.3% ± 18.3% vs. 111.7% ± 15.9%, p = 0.014), EI (4.61% ± 4.66% vs. 1.17% ± 1.76%, p = 0.023), and LEI (5.81% ± 5.78% vs. 0.76% ± 1.17%, p = 0.009) between patients with and without PAL. According to logistic regression analysis, both EI and LEI were significantly associated with PAL (p = 0.028 and p < 0.001, respectively). We found that EI and LEI significantly influenced the development of PAL after pulmonary resection. In particular, LEI showed stronger association with PAL, compared with EI, suggesting the importance of LEI in the prediction of PAL after anatomical segmentectomy.

Cardiopulmonary exercise testing and second-line pulmonary function tests to detect obstructive pattern in symptomatic smokers with borderline spirometry

BackgroundThe need for additional research on symptomatic smokers with normal spirometry has been recently emphasized. Albeit not meeting criteria for Chronic obstructive pulmonary disease (COPD) diagnosis, symptomatic smokers may experience activity limitation, evidence of airway disease, and exacerbations. We, therefore, evaluated whether symptomatic smokers with borderline spirometry (post-bronchodilator FEV1/FVC ratio between 5th to 20th percentile of predicted values) have pulmonary function abnormalities at rest and ventilatory constraints during exercise. Methods48 subjects (aged 60 ± 8 years, mean ± SD, 73% males, 16 healthy, and 17 symptomatic smokers) underwent cardiopulmonary exercise testing (CPET), body plethysmography, nitrogen single-breath washout test (N2SBW), lung diffusion for carbon monoxide (DLCO), and forced oscillation technique (FOT). ResultsCompared to healthy subjects, symptomatic smokers showed: 1) reduced breathing reserve (36 ± 17 vs. 49 ± 12%, P = 0.050); 2) exercise induced dynamic hyperinflation (−0.20 ± 0.17 vs. −0.03 ± 0.21 L, P = 0.043); 3) higher residual volume (158 ± 22 vs. 112 ± 22%, P < 0.001); 4) phase 3 slope at N2SBW (4.7 ± 2.1 vs. 1.4 ± 0.6%, P < 0.001); 5) no significant differences in DLCO and FOT results. ConclusionsIn smokers with borderline spirometry, CPET and second-line pulmonary function tests may detect obstructive pattern. These subjects should be referred for second line testing, to obtain a diagnosis, or at least to clarify the mechanisms underlying symptoms. Whether the natural history of these patients is similar to COPD, and they deserve a similar therapeutic approach is worth investigating.

Pulmonary diffusing capacity in healthy African-American and Caucasian children.

Previous studies of pulmonary diffusing capacity in healthy children primarily focused upon Caucasian (C) subjects. Since lung volumes in African-Americans (AA) are smaller than lung volumes in C subjects of the same height, diffusing capacity values in AA children might be interpreted as low or abnormal using currently available equations without adjusting for race. Healthy AA (N = 151) and C (N = 301) children between 5 and 18 years of age performed acceptable measurements of single breath pulmonary diffusing capacity for carbon monoxide (DLCO ) and alveolar volume (VA ) according to current ATS/ERS guidelines. The natural log of DLCO and VA were associated with height, gender, age, and race; AA children had lower DLCO and VA compared to C children. Adjustment of DLCO for Hemoglobin (Hgb) resulted in no significant difference in DLCO among these healthy subjects with normal Hgb. In summary, we report prediction equations for DLCO and VA that include adjustment for race (C; AA) demonstrating that AA have lower DLCO and VA compared to C children for the same height, gender, and age.

Effects of antifibrotic agents on TGF- β1, CTGF and IFN- γ expression in patients with idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a deadly disease, largely unresponsive to treatment with corticosteroids and immunosuppressives. The aim of this randomized, prospective, open-label study was to characterize the molecular effects of IFN-gamma-1b and colchicine, on biomarkers expression associated with fibrosis (TGF-beta, CTGF) and immunomodulatory/antimicrobial activity (IFN-gamma), in the lungs of patients with IPF. Fourteen (14) patients with an established diagnosis of IPF received either 200 microg of IFN-gamma-1b subcutaneously three times per week, or 1mg of oral colchicine per day, for 24 months. Using RT-PCR assay, we evaluated the transcription levels of transforming growth factor beta1 (TGF-beta1), connective-tissue growth factor (CTGF), and interferon-gamma (IFN-gamma) genes in lung tissue before and after treatment with IFN-gamma-1b or colchicine. Marked mRNA expression of TGF-beta1 and CTGF, but complete lack of interferon-gamma was detected in fibrotic lung tissue at entry. After treatment, both groups exhibited increased expression of IFN-gamma gene at 6 months that was sustained at 24 months. The expression of CTGF and TGF-beta1 remained almost stable before and after treatment, in the IFN-gamma-1b group, while TGF-beta1 was statistically decreased after therapy, in the colchicine group (p=0.0002). Significant difference in DLCO (% pred), was found between the two treatment groups in favor of IFN-gamma-1b group (p=0.04). In addition, the IFN-gamma-1b group showed stability in arterial PO2 while the colchicine group significantly deteriorated (p=0.02). In conclusion, we report the effect of antifibrotic agents (IFN-gamma-1b and colchicine) in TGF-beta, CTGF, and endogenous IFN-gamma gene expression, in human fibrosis. However, extended studies are needed to verify the pathophysiological consequences of these findings.

EFFECTS OF INHALED IRON OXIDE PARTICLES ON ALVEOLAR EPITHELIAL PERMEABILITY IN NORMAL SUBJECTS

Pulmonary inflammation secondary to oxidant generation catalyzed by transition metals associated with inhaled particles is one factor postulated to underlie the acute health effects of particulate air pollution. We postulated that inhaled iron oxide particles with associated amounts of soluble iron should induce mild pulmonary inflammation and lead to altered alveolar epithelial integrity and altered gas exchange. To test this hypothesis we examined the effects of inhaled iron oxide particles on alveolar epithelial permeability. Sixteen healthy subjects inhaled aerosols of iron oxide particles (1.5 µm mass median aerodynamic diameter) having either high or low water-soluble iron content [3.26 ± 0.25 (SE) and 0.14 ± 0.04 µg soluble iron/mg of particles, respectively] for 30 min at an average mass concentration of 12.7 mg/m 3. Alveolar epithelial permeability was assessed by measuring the pulmonary clearance of an inhaled radiolabeled tracer molecule (99m Tc-DTPA, diethylene triamine pentaacetic acid) using a gamma camera at ½ h and 24 h post particle exposure. Carbon monoxide lung diffusing capacity (DL CO) and spirometry were also performed before and after breathing the iron oxide. As a control, on a separate day, the procedures were duplicated except that the subject breathed particle-free air. For those subjects breathing aerosols with high soluble iron, we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at ½ h (97.4 ± 15.4 vs. 116.1 ± 15.5 min, respectively) or 24 h postinhalation (105.1 ± 13.8 vs. 106.9 ± 12.9 min, respectively). Likewise, for those subjects breathing aerosols with low soluble iron content we found no significant difference in DTPA clearance half-times after breathing particles versus particle-free air either at ½ h (108.6 ± 31.9 vs. 95.6 ± 10.8 min, respectively) or 24 h postinhalation (130.0 ± 18.0 vs. 105.8 ± 13.7 min, respectively). We found no significant differences in DL CO between particle exposures and air exposures. Minor differences in spirometric measurements were noted but were not statistically significant. We conclude that inhalation of iron oxide particles did not cause an appreciable alteration of alveolar epithelial permeability, lung diffusing capacity, or pulmonary function in healthy subjects under the studied conditions.