Diffusion Capacity Of Lung For Carbon Monoxide Research Articles

Factors associated with heart failure in patients with interstitial lung diseases

Introduction. Investigation of relationships between interstitial lung diseases (ILD) and development of heart failure would be useful for determining target therapy of heart failure (HF) among such patients. Aims.To study intracardiac hemodynamic and factors associated with its dysfunction among patients with ILD. 40 patients including: 34 with Chronic Hypersensitivity Pneumonitis (HP) and 6 with idiopathic pulmonary fibrosis (IPF). Methods. Pulmonary high-resolution computed tomography, echocardiography, spirometry, diffusing lung capacity for carbon monoxide (DLCO), bodypletysmography, blood oxygen (PaO ) were estimated. Results. 55.9% of patients with HP and all patients with IPF had a «cor pulmonale» with diastolic disfunction (DD), and 40% of them also had systolic dysfunction of right ventricle (RV). DD of left ventricle (LV) of I type was found among 10% of patients. 20% of patients were diagnosed with high pulmonary pressure (PP). The basal diameter of right ventricle (BDRV) correlated with DLCO (r=-0,718, p=0,004), PaO (r=-0,690, p=0,006), lung fibrosis (LF) (r=0,602, p=0,002). Tricuspid Annular Plane Systolic Excursion (TAPSE) correlated with mitral E/E’ ratio, tricuspid E/E’ ratio, total lung capacity (TLC) and LF (r=-0,753, p=0,002). Parameters of DD of RV significantly correlated with BDRV, TLC, DLCO, LF. Mitral E/E’ ratio correlated with DLCO and LF. PP corresponded with DLCO, DD of LV, LF (r=0,536, p=0,03) Conclusions. Correlation of LF with parameters of heart failure makes it one of the targets for ILD therapy as well as HF associated with ILD.

Late Effects of High-Dose Chemotherapy and Autologous Hematopoietic Cell Transplantation (HDT-AHCT) in Elderly Patients with Lymphoma

Background: High-dose chemotherapy and autologous hematopoietic cell transplantation (HDT-AHCT) is an established treatment for non-Hodgkin lymphoma (NHL). Incidence of NHL is highest in patients over 60 years of age, however, limited data is available on long-term effects of HDT-AHCT in older patients. This study is conducted to evaluate the late cardiopulmonary effects and overall outcomes of HDT-AHCT in older patients.Methods: This is a single-center, retrospective study examining late cardiopulmonary effects, and overall outcomes of HDT-AHCT in 41 patients age 70 years and older, with NHL, between January 2000 and December 2016. Clinical data and comorbidities were correlated with outcomes. Pre- and post-transplant pulmonary function tests (PFT) and echocardiograms were compared. Overall survival (OS) and progression-free survival (PFS) were analyzed according to age, gender, disease histology, disease stage at diagnosis, number of lines of treatment, Karnofsky Performance Status (KPS), hemoglobin adjusted diffusing capacity of lungs for carbon monoxide (DLCO), left ventricular ejection fraction (LVEF), and hematopoietic cell transplantation comorbidity index (HCT-CI) at the time of HDT-AHCT.Results: A total of 41 patients underwent HDT-AHCT for follicular or diffuse large B-cell lymphoma (FL / DLBCL n=18 44%), mantle cell lymphoma (MCL n=15 37%) and T-cell or other NHL subtypes (n=8 19%). The median age was 72 (range 70-77). Eight (19%), 6 (15%) and 27 (66%) patients had a low (0), intermediate (1-2) and high (≥3) HCT-CI score, respectively, at transplant. All patients except 1, had received anthracycline as part of initial treatment. BEAM and RR-BEAM were the most common conditioning regimens (n=38 93%). Pre-transplant LVEF was within normal range in all patients except 1 (45%). The median (range) pre- and post-transplant LVEF was 63% (45-74%) and 64% (39-71%), respectively. Of the 23 patients who had a post-transplant echocardiogram (median time between the pre- and post-transplant echocardiogram was 423 days), a mild decrease in LVEF was noted in 3. Only 1 patient had a significant decline of 19% in LVEF. Pulmonary artery pressure (PAP) was within normal range pre- and post-transplant in all. The median (range) of pre-transplant DLCO, FEV1 and FVC were 70% (48-125%), 97% (83-141%), and 98% (57-123%), respectively. Of the 10 patients who underwent post-transplant PFT (median time between the pre- and post-transplant PFT was 405 days), DLCO decline of >10% was the most common abnormality, and developed in 4 out of 10 patients. In 5 patients DLCO improvement of >10% was observed. A greater than 15% improvement in FEV1 and FVC was observed in 5 of 10 and 4 of 10 patients respectively. The median improvements in FVC, FEV1 and DLCO were 4%, 6% and 10%, respectively. With a median follow-up of 58 months (range 5-123) for survivors, PFS and OS at 3 years were 84% (95% CI, 67-92%) and 94% (95% CI, 80-99%), respectively. In a univariate analysis, age, gender, histology, disease stage, number of lines of treatment, DLCO, LVEF, and HCT-CI score did not affect OS or PFS. However, KPS ≥90 was associated with worse OS (p=0.008). The small sample size may have been a contributor to this unexpected finding. Relapse occurred in 11 patients (27%), 8 of whom died. Median time to relapse was 38 months (range 26-100). Secondary malignancies developed in 4 patients (8%) which included acute myeloid leukemia in 2, melanoma in 1, and esophageal cancer in 1, and led to death in 3.Conclusion: In this cohort of elderly patients with NHL who underwent HDT-AHCT, the late declines in cardiopulmonary function were minimal, and none resulted in mortality. Secondary malignancy was the only cause of non-relapse mortality. This can be explained by age being the biggest single risk factor for cancer development in general, in addition to the effects of HDT. We show that the most common cause of long-term mortality after HDT-AHCT continues to be lymphoma recurrence. Our data though limited by small number of patients and its retrospective nature, suggest that age alone is not predictive of post-transplant late effects and outcomes, and therefore should not be used to preclude HDT-AHCT in elderly. While prospective studies with larger number of patients are needed to evaluate long-term effects of HDT-AHCT on different organ functions in older adults, strategies to mitigate risk of relapse remain the most important area to improve outcomes. DisclosuresSauter:Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Precision Biosciences: Consultancy; Kite: Consultancy.

Improving Treatment Related Mortality over Time - Data from the Non-Observational Trial on Autologous Stem Cell Transplantation in Systemic Sclerosis By the EBMT Autoimmune Diseases Working Party (ADWP)

Introduction: Systemic sclerosis (SSc) is a chronic autoimmune disease with ongoing high disease related mortality. Three randomized controlled trials proofed efficacy of autologous stem cell transplantation (aHSCT) in patients with severe SSc and superiority over the standard cyclophosphamide pulse therapy. Treatment related mortality is a major point of criticism and different treatment regimen are used in different centers.Methods: This prospective, open, multi-center, non-interventional study of the European Group for Blood and Marrow Transplantation (EBMT) analyzed data for consecutive aHSCT performed in SSc. Every center followed its own local protocol which usually refers to the recent update of the EBMT Guidelines. In order to be eligible for inclusion, patients had to be transplanted for the diagnosis of progressive SSc and aged between 18 and 65 years. Major exclusion criteria were an ejection fraction <40% by cardiac echo, pulmonary arterial hypertension with systolic pulmonary arterial pressure (sPAP) >50mmHg, creatinine clearance <30ml/min, reduced lung function with either FVC <50% or DLCO <30% of predicted values. Concurrent neoplasms, myelodysplasia, severe psychiatric illnesses as well as previously damaged bone marrow had to be ruled out.Progression free survival (PFS) was chosen as primary endpoint. Response to treatment, defined as the number of patients who achieve >25% improvement of the skin thickness, measured by the modified Rodnan Skin score (mRSS; range 0-51) and/or ≥10% improvement in forced vital capacity (FVC) or hemoglobin-adjusted diffusion lung capacity for carbon monoxide (DLCO) and relapse rate as well as safety considerations were secondary endpoints.Results: Between 2013 and 2015, 80 patients from 12 centers were followed for a median of 24.1 (5.97 - 59.8) months. Patients had a median age of 43 years at aHSCT and 70% were female. All patients were mobilized with cyclophosphamide (CYC) with a median of 2g/m2 and granulocyte-colony stimulating factor (GCSF) in 98%. In 45% of transplants stem cells were purified using CD34-positive selection. For conditioning, centers used CYC at 200 mg/kg (50 - 240) in 76 patients (95%) or CYC at 100 mg/kg and thiotepa 10 mg/kg in 4 patients. All patients received additional anti-thymocyte globulin (ATG; different brands were used) over 4-5 days.Progression free survival at 1 year was reached by 83.6% of our patients. Response to treatment at 1 year was achieved by 75% (63.7 - 83.2) and 10.1% relapsed or had further progression despite aHSCT. Figure 1 demonstrates the improvement of skin fibrosis over time. Median mRSS decreased from 24 (2 - 49) at baseline to 13 (0 - 40) at month 12, and 10.5 (0 - 32) at month 24. On multivariate analysis, creatine kinase (CK) levels < 250 U/ml, mRSS <24 and lung crepitation at baseline were significantly associated with response to treatment, but especially CD34-positive selection is a strong positive predictor for response to treatment with a hazard ratio of 2.19 as compared to patients treated with non-selected stem-cell.The 100-day treatment-related mortality for this population was 6.2% (n=5) (CI 2.3 - 13). Three of these 5 patients had a cardiac or cyclophosphamide related event that led to death. During the 24 months of follow up another 3 patients died due to progressive disease, which leads to an overall survival of 91.2% (CI: 85.1 - 97.4) at 2 years.Discussion: Although aHSCT has been proven effective in SSc, we still do not know which regimen is the best. With data from this non-interventional trial we could demonstrate the effectiveness of aHCST in a daily practice setting. Treatment seems to become safer over time with reduction of TRM from 10% in the European phase III Autologous stem cell transplantation international scleroderma trial (ASTIS; JAMA. 2014; 311(24): 2490-8) to 6.2% in our actual study; mainly due to increasing experience of the centers and exclusion of patients with advanced organ damage. Nevertheless indication for aHSCT should also be driven by negative predictive parameters for disease related mortality and it is fairly unlikely to further reduce TRM in these sick patients.We also found a potential value of CD34-selection in these patients. As a retrospective approach demonstrated no benefit to the outcome of SSc patient treated with AHSCT (Bone Marrow Transplant.2016; 51(4): 501-5), these findings have to be confirmed by prospective randomized trials. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Postoperative complications decrease the cost-effectiveness of robotic-assisted lobectomy

BackgroundCost of robotic-assisted (RATS) lobectomy remains a major concern. We sought to define variability in cost and factors associated with increased hospital expenses after RATS lobectomy for early stage non–small cell lung cancer. MethodsWe performed a retrospective review of patients who underwent RATS lobectomy for stages I–IIIA non–small cell lung cancer at a single institution between 2012 and 2014. Clinical outcomes were linked to hospital financial data. Linear regression analysis was used to test the impact of patient factors and postoperative outcomes on cost. ResultsA total of 137 patients underwent RATS lobectomy, predominantly for stage IA (73%, n = 100). Overall in-hospital morbidity was 29.2% (n = 40), median length of stay was 5 days (range 1–27 days). Postoperative cost accounted for approximately 50% of total cost of hospitalization and varied significantly (mean $9,618.38 ± $10,779.65), resulting in an average total hospital cost of $19,565 (±$11,620.42). Male sex and upper lobe predominant disease were independently associated with increased cost, whereas higher preoperative diffusing capacity of lung for carbon monoxide (DLCO) was cost-protective. Hospital expenses associated with prolonged hospitalization were $2,376.23 per day (95% CI $2,178–2,573.60). The most common complication associated with increased cost was atrial fibrillation ($5,609.13; 95% CI $2,095.42–$9,122.84). Postoperative atelectasis requiring bronchoscopy, respiratory failure, pulmonary embolism, and reoperation were seen less frequently in this cohort of patients but were associated with significant additional cost. ConclusionHospital cost of RATS lobectomy can vary significantly. In addition to patient risk factors, differences in cost are mainly driven by postoperative events. Initiatives aimed to reduce common yet expensive complications have the potential to improve overall cost-effectiveness of RATS lobectomy.

Association between Pulmonary Function and Stair-Climbing Test Results after Lung Resection: A Pilot Study.

Background The stair-climbing test was used to assess the exercise capacity before lung resection in subjects with lung cancer. However, few studies have systematically evaluated the role of this exercise methodology as a postoperative test. The aim of the present study was to assess whether the stair-climbing test findings reflect the postoperative decrease in pulmonary function. Methods Twenty subjects with non-small-cell lung cancer who underwent lung resection were enrolled in the study. Perioperative functional evaluation comprised the pulmonary function test, stair-climbing test, and 6-min walk distance test (6MWD). A correlation analysis was performed between the postoperative percentages of pulmonary function with respect to preoperative values and the exercise capacity. Results No correlation was noted between the percentage changes in pulmonary function and those in 6MWD. However, there was a significant correlation between the percentage changes in forced expiratory volume in 1 s and those in the altitude reached in the stair-climbing test (r=0.46, p < 0.05) and between the percentage changes in carbon monoxide lung diffusion capacity and those in the altitude (r=0.54, p < 0.05). Conclusions The stair-climbing test findings might be effective at detecting changes in exercise capacity induced by postoperative decrease in pulmonary function.

Ninety-day hospital costs for anatomic lung resections†.

The study aimed to assess the total cost (TC) and relative cost (RC) of 90-day postoperative care at the hospital after anatomic lung resection. Six hundred and forty lung resections (April 2014-September 2016) were performed at a single centre (547 lobectomies, 55 pneumonectomies and 38 segmentectomies). TC was calculated up to 90 days from the date of surgery and included the postoperative cost of the index hospitalization and the costs of hospital or emergency department readmissions, clinic appointments, medications and radiology post-discharge up to 90 days from the operation. RC was calculated as the difference between the TC and the postoperative cost of the index hospitalization. Bivariate comparisons were performed by using the Mann-Whitney test. Multivariable regression analysis was used to identify the factors associated with TC. Median TC was €12389.5 [interquartile range (IQR) 8455-23043] for pneumonectomy, €9192.1 (IQR 6897-17274) for open lobectomy, €7932.5 (IQR 5806-12697) for video-assisted thoracoscopic surgery (VATS) lobectomy and €6609.9 (IQR 5215-13907) for VATS segmentectomy. Median RCs were €4461.4 (IQR 1240-11828) for pneumonectomy, €3326.8 (IQR 1626-8271) for open lobectomy, €2729.3 (IQR 1348-6312) for VATS lobectomy and €2771.5 (IQR 1229-9705) for segmentectomy. RC accounted for 36% of the TC for pneumonectomy, 36% for open lobectomy, 34% for VATS lobectomy and 42% for segmentectomy. Generalized linear models showed that age (P = 0.024), carbon monoxide lung diffusion capacity (P = 0.030) and body mass index (P = 0.015) were inversely associated with TC, whereas male gender (P = 0.054) was associated with increased cost. Cost-saving measures should be implemented to target not just the in-hospital but also the post-discharge period, particularly in patients with risk factors associated with increased cost.

Interstitial Features at Chest CT Enhance the Deleterious Effects of Emphysema in the COPDGene Cohort.

Purpose To determine if interstitial features at chest CT enhance the effect of emphysema on clinical disease severity in smokers without clinical pulmonary fibrosis. Materials and Methods In this retrospective cohort study, an objective CT analysis tool was used to measure interstitial features (reticular changes, honeycombing, centrilobular nodules, linear scar, nodular changes, subpleural lines, and ground-glass opacities) and emphysema in 8266 participants in a study of chronic obstructive pulmonary disease (COPD) called COPDGene (recruited between October 2006 and January 2011). Additive differences in patients with emphysema with interstitial features and in those without interstitial features were analyzed by using t tests, multivariable linear regression, and Kaplan-Meier analysis. Multivariable linear and Cox regression were used to determine if interstitial features modified the effect of continuously measured emphysema on clinical measures of disease severity and mortality. Results Compared with individuals with emphysema alone, those with emphysema and interstitial features had a higher percentage predicted forced expiratory volume in 1 second (absolute difference, 6.4%; P < .001), a lower percentage predicted diffusing capacity of lung for carbon monoxide (DLCO) (absolute difference, 7.4%; P = .034), a 0.019 higher right ventricular-to-left ventricular (RVLV) volume ratio (P = .029), a 43.2-m shorter 6-minute walk distance (6MWD) (P < .001), a 5.9-point higher St George's Respiratory Questionnaire (SGRQ) score (P < .001), and 82% higher mortality (P < .001). In addition, interstitial features modified the effect of emphysema on percentage predicted DLCO, RVLV volume ratio, 6WMD, SGRQ score, and mortality (P for interaction < .05 for all). Conclusion In smokers, the combined presence of interstitial features and emphysema was associated with worse clinical disease severity and higher mortality than was emphysema alone. In addition, interstitial features enhanced the deleterious effects of emphysema on clinical disease severity and mortality.

Prevalence of interstitial lung disease in patients with gastroesophageal reflux disease

Objective The aim of the study was to investigate the prevalence of interstitial lung diseases in patients with gastroesophageal reflux disease (GERD) and to show the correlation between them. Background Interstitial lung diseases are a common complication in patients with GERD because of repeated aspiration of gastric acid. Patient and methods One hundred patients with GERD (25 patients with GERD grade A, 25 patients with GERD grade B, 25 patients with GERD grade C, and 25 patients with GERD grade D) with no past history of pulmonary diseases, collagen vascular diseases, chronic liver diseases, or ascites were enrolled in this study. All patients were subjected to the following after obtaining their oral consent for participation: complete medical history, examination, laboratory investigations, upper gastrointestinal endoscopy, radiological investigation [plain chest radiography and chest high-resolution computed tomography (HRCT)], and pulmonary function tests [spirometry and diffusing lung capacity of carbon monoxide (DLCO)]. Results When the severity of GERD increased the mean percentage of DLCO decreased (patients with GERD grade D had the lowest DLCO (75.4 ± 26.8). There was a statistically significant negative correlation between the grades of GERD, DLCO, and forced vital capacity%. There was a highly statistically significant difference as regards grades of GERD in relation to chest HRCT results (P Conclusion The present data support and extend the theory of a high incidence of pulmonary involvement in GERD patients even in those patients free of respiratory symptoms.

Use of supplemental oxygen in patients with pulmonary arterial hypertension in REVEAL.

Supplemental low-flow oxygen is recommended by treatment guidelines as supportive therapy for patients with pulmonary arterial hypertension (PAH), based largely on expert opinion. Reduced diffusing capacity of lung carbon monoxide (DLCO) is associated with increased mortality in PAH. Reduced DLCO is also associated with relative hypoxemia, making the effects of supplemental oxygen use of particular interest in this sub-population. Patients in the Registry to Evaluate Early and Long-term PAH Disease Management (REVEAL), a 5-year observational study of Group 1 PAH, were categorized by presence or absence of supplemental oxygen use and by degree of DLCO reduction. Kaplan-Meier survival estimates were calculated by group. Of 3,046 patients, 57% used supplemental oxygen and 43% did not. Supplemental oxygen users had worse prognostic factors and more PAH-specific medication use. Of the 424 patients with severe DLCO reduction (<40% of predicted), 76% used oxygen and 24% did not. Patients with severe DLCO reduction who used supplemental oxygen had a significantly lower risk of all-cause mortality than those who did not (hazard ratio 0.56; 95% confidence interval 0.39 to 0.83; p = 0.0033). This was true for newly diagnosed and previously diagnosed patients. There was no relationship between oxygen use and outcomes in patients with no, mild, or moderate DLCO reduction. In this observational study, the risk of death was significantly lower for patients with severe DLCO reduction who received supplemental oxygen compared with those who did not. A randomized trial is warranted to further investigate the relationship between supplemental oxygen use and outcomes in PAH.

Association between values of preoperative 6-min walk test and surgical outcomes in lung cancer patients with decreased predicted postoperative pulmonary function.

We retrospectively investigated the possibility that the 6-min walk test (6MWT) could predict surgical outcomes in lung cancer patients with decreased predicted postoperative (ppo) lung function. Patients were enrolled based on their preoperative spirometry: <60% of the ppo forced expiratory volume in 1s (FEV1.0) or < 60% of the ppo lung carbon monoxide diffusion capacity (DLco). Morbidity, oxygen inhalation required > 10days, home oxygen therapy (HOT) requirement, unexpected readmission within 90days, and 90-day mortality were included as surgical outcomes. The correlations with walking distance and the minimum SpO2 (SpO2min) and maximum decrease in SpO2 (ΔSpO2) during the 6MWT were analyzed using logistic regression analysis, adjusting for age, sex, and surgical procedure. Altogether, 121 patients were analyzed. Logistic regression analysis revealed that higher ΔSpO2 and lower SpO2min were significantly correlated with a higher risk of prolonged need for oxygen inhalation and HOT, surgical morbidity, and 90-day mortality. Cut-off values of > 4% for ΔSpO2 were significant for prolonged oxygen inhalation and surgical morbidity. Cut-off values of < 89-91% for SpO2min were also significant for the need for prolonged oxygen inhalation, surgical morbidity, and HOT requirement. There were no significant correlations between walking distance and each surgical outcome. Oxygen desaturation during 6MWT was a good predictor for poor surgical outcomes in lung cancer patients with decreased ppo pulmonary function.

The effect of selective internal radiation therapy with yttrium-90 resin microspheres on lung carbon monoxide diffusion capacity

BackgroundSelective internal radiation therapy (SIRT) with embolization of branches of the hepatic artery is a valuable therapeutic tool for patients with hepatic malignancies; however, it is also associated with lung injury risk due to shunting. Diffusion capacity of the lungs for carbon monoxide (DLCO) is a clinically significant lung function test, and worsening in DLCO is suggested to reflect a limited gas exchange reserve caused by the potential toxicity of chemoradiotherapy or it may be a marker of related lung injury. This study aimed to examine the changes in DLCO during SIRT with resin microspheres in newly treated and retreated patients. Forty consecutive patients who received SIRT for a variety of malignant conditions were included. All subjects were treated with Yttrium-90 labelled resin microspheres. DLCO tests were performed after the procedures. In addition, patients were specifically followed for radiation pneumonitis.ResultsThe mean DLCO did not significantly change after the first (82.8 ± 19.4 vs. 83.1 ± 20.9, p = 0.921) and the second treatments (87.4 ± 19.7 vs. 88.6 ± 23.2, p = 0.256). Proportion of patients with impaired DLCO at baseline was not altered significantly after the first (37.5 vs. 45.0%, p = 0.581) and the second treatments (27.3 vs. 27.3%, p = 1.000). Also, percent change in DLCO values did not correlate with radiation dose, lung shunt fraction, or lung exposure dose (p > 0.05 for all comparisons). None of the patients developed radiation pneumonitis.ConclusionsOur results suggest that no significant change in DLCO in association with SIRT occurs, both after the first or the second treatment sessions. Further larger studies possibly with different protocols are warranted to better delineate DLCO changes after SIRT in a larger spectrum of patients.

Multi-Dimensional Assessment in Idiopathic Pulmonary Fibrosis

SESSION TITLE: Diffuse Lung Disease 1 SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, November 1, 2017 at 01:30 PM - 02:30 PM PURPOSE: Purpose. The clinical course of idiopathic pulmonary fibrosis (IPF) is difficult to predict. Perceived dyspnea, exercise capacity, and lung physiology have all been associated with mortality outcomes in IPF, but the significance of this relationship is unclear. We sought to investigate the strength of the relationship between these variables and their independent predictive capability in determining mortality outcomes. METHODS: Methods. Four-hundred-thirty-seven patients from 3 different centers (Western University, University of Toronto, University of Rome) with IPF were included in the study. Medical Research Council dyspnea score (MRCDS), 6-minute walk distance percent predicted (6MWD %pred) and pulmonary function tests, including calculation of the composite physiologic index (CPI), were determined at baseline. The endpoint was 18-month mortality/lung transplant (LTx). RESULTS: Results. Correlations between MRCDS, 6MWD % pred, forced vital capacity (FVC) and diffusing lung capacity for carbon monoxide (DLCO) were weak (r<0.5). Collinearity between variables, measured by variance inflation factors, was low. At the end of the observation period, 165 patients were alive, 167 had been transplanted, and 105 had died. Univariate regression analysis and c-statistics identified MRCDS (H.R=1.89, AUC=0.74), 6MWD % pred (H.R.=0.97, AUC=0.79), FVC (H.R.=0.97, AUC=0.76), and CPI (H.R.=1.05, AUC=0.78) as significant predictors of 18-month mortality/LTx. Multivariate regression analysis retained MRCDS (H.R.=1.33), 6MWD % pred (H.R.=0.982) and FVC %pred (H.R.=0.99) or MRCDS (H.R.=1.33), 6MWD % pred (H.R.=0.98), and CPI (H.R.=1.02) as independent predictors of outcome. CONCLUSIONS: Conclusion. Baseline dyspnea, exercise capacity and physiology are weakly correlated to each other, translating in low collinearity among variables. MRCDS, 6MWD % pred and CPI (or FVC) are significant, independent predictors of outcome. CLINICAL IMPLICATIONS: Clinical Implications. MRCDS, 6MWD%pred and CPI (or FVC) provide independent prognostic information, suggesting that a multi-dimensional assessment of mortality in patients with IPF is feasible and advantageous. DISCLOSURE: The following authors have nothing to disclose: Hana Serajeddini, Marco Mura, Paola Rogliani No Product/Research Disclosure Information

Statistical Commentary

Brunelli and colleagues [1Brunelli A. Dinesh P. Woodcock-Shaw J. Littlechild D. Pompili C. Ninety-day mortality after video-assisted thoracoscopic lobectomy: incidence and risk factors.Ann Thorac Surg. 2017; 104: 1020-1026Abstract Full Text Full Text PDF PubMed Scopus (37) Google Scholar] evaluate the factors associated with 90-day mortality in a cohort of 733 patients who underwent lobectomy by video-assisted thoracic surgery from 2012 to 2016. They report that Dlco (carbon monoxide lung diffusion capacity) below 60%, operative time longer than 2.5 hours, and male sex were statistically significant predictors of 90-day mortality. Despite a small sample size, the authors build a model to predict mortality from the coefficients in this data set. The purpose of such a model is for use in counseling patients and guiding treatment decisions. Like other models in cardiothoracic surgery, key concerns are a clear definition of the purpose of the model and its time of use in the clinical care pathway. In the current article, using operative time to counsel patients preoperatively has practical limitations, needing “what if” considerations. For a model to be most useful, all variables should be measured preoperatively if the purpose is to predict operative outcomes and use the tool in decision making. As described, the score cannot be developed and applied prospectively to counsel patients. Clear definition of purpose and the final application setting should help guide choices for factors considered in building a prediction model. The field of risk prediction has grown rapidly over the past decade. Although internal validation is more easily included in the model development phase, it leaves the user with concern about applicability in other settings. Risk models should be developed and then validated in a separate independent cohort before use in clinic. Extensive literature reports set forth the methods to follow through this process [2Moons K.G. Altman D.G. Vergouwe Y. Royston P. Prognosis and prognostic research: application and impact of prognostic models in clinical practice.BMJ. 2009; 338: b606Crossref PubMed Scopus (621) Google Scholar, 3Moons K.G. Kengne A.P. Grobbee D.E. et al.Risk prediction models: II. External validation, model updating, and impact assessment.Heart. 2012; 98: 691-698Crossref PubMed Scopus (678) Google Scholar, 4Moons K.G. Kengne A.P. Woodward M. et al.Risk prediction models: I. Development, internal validation, and assessing the incremental value of a new (bio)marker.Heart. 2012; 98: 683-690Crossref PubMed Scopus (568) Google Scholar]. Finally, presentation of the output from prediction models, scores, and scales is positioned as helping guide clinical decision making. Attention to how the scale is summarized for ease of use should again be a focus from early in the development. This can then ensure a presentation that is easy for patient and provider to comprehend, resulting in meaningful use for decision making. Ninety-Day Mortality After Video-Assisted Thoracoscopic Lobectomy: Incidence and Risk FactorsThe Annals of Thoracic SurgeryVol. 104Issue 3PreviewWe evaluated the incidence and risk factors of 90-day mortality rate after video-assisted thoracoscopic (VATS) lobectomy. Full-Text PDF

Shrinking lung syndrome in systemic lupus erythematosus: a single-centre experience

Introduction Shrinking lung syndrome (SLS) is a rare manifestation of systemic lupus erythematosus (SLE), characterized by decreased lung volumes and extra-pulmonary restriction. The aim of this study was to describe the characteristics of SLS in our lupus cohort with emphasis on prevalence, presentation, treatment and outcomes. Patients and methods Patients attending the Toronto Lupus Clinic since 1980 ( n = 1439) and who had pulmonary function tests (PFTs) performed during follow-up were enrolled ( n = 278). PFT records were reviewed to characterize the pattern of pulmonary disease. SLS definition was based on a restrictive ventilatory defect with normal or slightly reduced corrected diffusing lung capacity for carbon monoxide (DLCO) in the presence of suggestive clinical (dyspnea, chest pain) and radiological (elevated diaphragm) manifestations. Data on clinical symptoms, functional abnormalities, imaging, treatment and outcomes were extracted in a dedicated data retrieval form. Results Twenty-two patients (20 females) were identified with SLS for a prevalence of 1.53%. Their mean age was 29.5 ± 13.3 years at SLE and 35.7 ± 14.6 years at SLS diagnosis. Main clinical manifestations included dyspnea (21/22, 95.5%) and pleuritic chest pain (20/22, 90.9%). PFTs were available in 20 patients; 16 (80%) had decreased maximal inspiratory (MIP) and/or expiratory pressure (MEP). Elevated hemidiaphragm was demonstrated in 12 patients (60%). Treatment with prednisone and/or immunosuppressives led to clinical improvement in 19/20 cases (95%), while spirometrical improvement was observed in 14/16 patients and was mostly partial. Conclusions SLS prevalence in SLE was 1.53%. Treatment with glucocorticosteroids and immunosuppressives was generally effective. However, a chronic restrictive ventilatory defect usually persisted.

Ninety-Day Mortality After Video-Assisted Thoracoscopic Lobectomy: Incidence and Risk Factors

We evaluated the incidence and risk factors of 90-day mortality rate after video-assisted thoracoscopic (VATS) lobectomy. Retrospective analysis on 733 VATS lobectomies or segmentectomies (January 2012 to February 2016), including 66 operations converted to open operation. Several patient-related and surgical variables were tested to verify their association with 90-day mortality using univariable and logistic regression analyses. A score was assigned to each variable in the final model by proportionally weighting the regression odds ratios (ORs) and assigning 1 point to the smallest one. A total score was generated for each patient by adding the individual points. The patients were finally grouped into classes of risk. In-hospital/30-day mortality rate was 1.9% (14patients). Additionally, 4 patients died after discharge between 30 and 90 days. Total 90-day mortality rate was 2.5% (18 patients). Regression analysis showed that factors significantly associated with 90-day mortality were male sex (OR 12, p= 0.001), carbon monoxide lung diffusion capacity (Dlco) less than 60% (OR 4.8, p=0.001), and operative time longer than 150 minutes (OR 4.2, p= 0.03). A score was developed assigning 1 point to the variables Dlco and operative time and 3 points to the variable male sex. The total score ranged from 0 (155 patients) to 5 points (32 patients). Patients were grouped into five risk classes showing an incremental 90-day mortality rate (class A, 0; class B, 0.38%; class C, 0.93%; class D, 5.65%; class E, 18.75%, p < 0.0001). Our results represent important information to be shared with the patients during surgical counseling. It can also assist multidisciplinary tumor board discussion about treatment selection.

Evaluation of the questionnaires\u2019 validity in assessing the severity of idiopathic pulmonary fibrosis in correlation with high-resolution computed tomography, lung diffusion, and cardiopulmonary exercise tests

IntroductionHealth-related quality-of-life questionnaires need to be incorporated into the evaluations of idiopathic pulmonary fibrosis (IPF) patients to assess their influence.AimThe aim of the study was to evaluate the validity of generic and specific questionnaires in assessing the severity of IPF in correlation with high-resolution computed tomography (HRCT), diffusion lung capacity for carbon monoxide (DLCO), and cardiopulmonary exercise testing (CPET).Patients and methodsForty stable IPF patients were prospectively recruited and categorized on the basis of spirometry, DLCO, HRCT, and CPET. The results were correlated with a generic International Physical Activity Questionnaire (IPAQ) and a Specific Saint George Respiratory Questionnaire (SGRQ).ResultsIPF patients showed restrictive pattern with impairment of diffusion capacity (forced vital capacity (FVC)= 56±14.8% and DLCO=48.5±20% of predicted value) with a total semiquantitative scoring of HRCT 16.6±8. The mean total score of the SGRQ questionnaire for all studied cases was 56.5+21 and categorical scoring of IPAQ showed that 45, 42.5, and 12.5% of patients were in moderate, severe, and mild categories, respectively. There was a negative correlation between the total score of SGRQ and VO2max (ml/kg/min) (maximum oxygen consumption) (r=−0.35) and VE’ (l/min) (minute ventilation) (r=−0.39) on CPET, as well as with DLCO (r=−0.53), and a positive correlation with HRCT score (r=0.63). There was a highly significant correlation between IPAQ and VO2max (χ2=28), VE’ (χ2=14.8) and desaturation percentage variables of CPET, DLCO (r=0.61), and HRCT score (r=−0.68).ConclusionCorrelations between physiological parameters including DLCO and CPET, radiological parameters in the form of HRCT, and health-related quality-of-life assessment using SGRQ and IPAQ were strong and it was possible to distinguish IPF patients with severely impaired lung functions.

Riskfactors for acute exacerbation of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic disease limited to the lungs. The course of disease varies widely, with some patients experiencing acute respiratory deterioration, a condition called acute exacerbations of IPF (AE-IPF). The risk factors contributing to AE-IPF are unclear. This systematic review and meta-analysis investigated the risk factors for AE-IPF. Studies of risk factors for AE-IPF were identified in Medline, EMBASE and Cochrane databases. Fixed effects models were used to calculate pooled relative risks and weighted mean differences (WMD).The meta-analysis included seven articles involving 14 risk factors for AE-IPF. Risk factors for AE included reductions in vital capacity (VC; WMD - 10.58, 95% confidence interval (CI) -17.17 to - 3.99), forced vital capacity (FVC; WMD -6.02, 95%CI - 8.58 to - 3.47), total lung capacity (TLC; WMD -4.88, 95%CI -7.59 to - 2.17), and PaO2 (WMD -4.19, 95%CI -7.66 to -0.71) and a higher alveolar-arterial oxygen difference (AaDO2 ; WMD 4.4, 95%CI 0.24 to 8.57). Mechanical procedures, higher serum KL-6 concentration and secondary pulmonary hypertension, might be risk factors for AE-IPF. In contrast, age, sex, body mass index (BMI), differences in diffusing lung capacity for carbon monoxide (DLCO), exposure to seasonal variations and air pollution, and virus infection might be unrelated to AE-IPF. Poor pulmonary function, mechanical procedures, higher serum KL-6 and secondary pulmonary hypertension were associated with increased risks of AE-IPF.

Risk for pulmonary late effects in childhood Hodgkin lymphoma survivors.

112 Background: Survivors of Hodgkin lymphoma (HL) are at risk for pulmonary late effects, including pulmonary fibrosis (PF). Established risk factors such as younger age at diagnosis and specific therapeutic exposures explain a fraction of the risk for these outcomes. Notably, systemic inflammation and impaired telomere maintenance are associated with adverse pulmonary outcomes in adult populations, but have not been explored in cancer survivors. Our aim was to identify pulmonary diffusion defects in HL survivors, and evaluate the impact of short lymphocyte telomere length (LTL) and systemic inflammation on these outcomes. Methods: Blood samples, demographic and treatment data, and lung carbon monoxide diffusion capacity corrected for hemoglobin and alveolar volume (DLCO) were obtained from HL survivors ≥6 months off therapy and without history of relapse or transplant. LTL was measured by telomere flow FISH (Repeat Diagnostics), and age-based percentiles determined from population controls. Plasma elevations in pro-inflammatory cytokines (HCYTMAG panel, EMD Millipore) were detected on a Luminex platform. Associations between clinical features and most recent DLCO were determined by linear regression, adjusted for age, sex, radiation, and race/ethnicity. In a subset of subjects, cytokine levels and LTL were compared in survivors with DLCO above or below the mean using a Student t-test or Fisher’s Exact test, respectively. Results: Seventy-two HL survivors met inclusion criteria (mean age at diagnosis=14 years, range: 3-18 years). Mean off-therapy DLCO was 75% (range: 52-98%), below the lower limit of normal (76%) in healthy populations. DLCO was inversely associated with female sex (p = 0.002). Five of 24 survivors (21%) had LTL ≤10th percentile for age, but there was no difference in LTL relative to DLCO. Survivors with DLCO ≤75% had higher IL1α and IL1β levels (n = 30, p = 0.07). Conclusions: HL survivors had lower than expected DLCO, with females at highest risk for impaired pulmonary diffusion. Twice as many survivors as expected had LTL ≤10th percentile, and PF-related cytokine profiles were observed in survivors with lower DLCO, suggesting inflammation and telomere maintenance defects may contribute to late effects in HL survivors.

A study of pulmonary function test, diffusing capacity of lungs for carbon monoxide and hematological parameters among petrol pump workers

Background: Currently, air pollution is one of the crucial issues with growing concern. Automobile exhaust consists of mixture of soot, gases including oxides of sulfur and of nitrogen, carbon monoxide and liquid aerosols and particles. It leads to various lung disorders, carcinogenesis and changes in hematological parameters. Aims and Objective: To detect the presence and extent of changes in pulmonary function tests and changes in hematological parameters in petrol pump workers. Materials and Methods: It was a cross-sectional study. Study subjects comprised 60 males working at different petrol pumps. Healthy counterparts were taken as controls. The study subjects were given pre-designed questionnaire, and data were collected in preformed case record form. Investigations such as sputum for acid fast bacilli, spirometry, diffusing capacity of lungs for carbon monoxide (DLCO), and hematological parameters like hemoglobin (Hb)% and packed cell volume (PCV) were done. Data for all parameters were analyzed by software Microsoft excel and Graph pad prism5. Results: There was no statistical difference in the baseline characters of study and control groups. There was a significant decline in Hb% and PCV in petrol pump workers as compared to control group. Decrease in values of forced vital capacity, forced expired volume 1, and forced expiratory flow 25-75% is noted in petrol pump workers. Values of DLCO% predicted were mildly decreased in Group II and mild to moderately in Group III. Conclusions: The lung function tests and hematological tests (Hb, PCV) in petrol pump workers were significantly lower than control group. Lack of awareness and protective measures during duty hours by these workers may have led to lung function abnormality and hematological changes among them.

SC08.01 Impact and Management of Co-Morbidities

SC08.01 Impact and Management of Co-Morbidities