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Evaluation of Diffusing Capacity of the Lung for Carbon Monoxide Normalized per Liter Alveolar Volume (DLCO/VA) as a Parameter for Assessment of Interstitial Lung Diseases Haytham Samy Diab, MD Lecturer of Chest Diseases, Ain Shams University

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Introduction The single-breath test using carbon monoxide (CO) is the most widely used method to measure the pulmonary diffusing capacity. The result usually expressed for the whole lung (DLCO) or per unit alveolar volume DLCO/VA (kco).

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One of the most important clinical indications of DLCO- single breath (SB) technique is assessing interstitial lung diseases (ILDs); as there is thickening of the alveolar membrane and a diminished total lung capacity (TLC) due to interstitial processes which may lead to a severe decline in transfer factor. The acinus is disrupted and the diffusion pathway is increased. Typical diseases are extrinsic allergic alveolitis, pulmonary vasculitis syndromes, systemic lupus erythematosus and of course interstitial fibrosis

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DLCO/VA (kco) represents the diffusing capacity in the available alveolar spaces. In other words DLCO/VA determines whether the currently available alveolar spaces are functioning normally. In healthy adults, DLCO/VA is approximately 4-5ml CO transferred/min/liter of lung volume.

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A normal DLCO/VA cannot exclude ILD. A decreased DLCO/VA, however, strongly suggests parenchymal lung disease (ILD, emphysema) or pulmonary vascular disease (pulmonary hypertension). In healthy volunteers, DLCO decreases and the DLCO/VA increases if VA is decreased.

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Aim of the Work This study aimed to assess the validity of DLCO/VA (kco) interpretation in patients with ILDs.

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Subjects and methods Fifty three consecutive patients referred to perform spirometry and DLCO in the pulmonary function lab of Chest department, Ain Shams University hospital diagnosed as ILDs during period between May 2011 and May 2012 were recruited.

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ILDs diagnosis was based on the the clinical history, radiographic abnormalities, low DLCO, 6 minute walk testing (6MWT) according to an official statement of the: American Thoracic Socity (ATS) European Respiratory Socity (ERS) Japanese Respiratory Socity (JRS) Latin American Thoracic Association (ALAT) (evidence based guidelines for diagnosis and management of idiopathic pulmonary fibrosis)

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The patients performed spirometry: forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), FEV1/FVC, maximal mid-expiratory flow (MMEF), The best results were chosen from three efforts following ATS- ERS guidelines in They also performed DLCO. All data were collected and statistically analyzed.

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Results Fifty three patients with ILD (mean age 47.9 ± 13.7) participated in this study. Of these patients 20 were male and 33 were females.

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Table (1):Descriptive analysis of different parameters NMinimumMaximumMeanStd. Deviation Age HT BMI FEV1/FVC FEV FVC MMEF RV RV/TLC TLC VA DLCO kco FRC Valid N 53

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There was significantly statistical positive correlation between age and FVC and significantly statistical negative correlation between age and residual volume (RV) Table (2): Correlation between age with FVC and RV FVCRV Age r P (sig.) No

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Height showed significantly statistical positive correlation with each of DLCO and FRC Table (3): Correlation between height with DLCO and FRC DLCOFRC Height r P (sig) No

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There was significantly statistical positive correlation between VA and each of the following parameters (TLC, FVC, RV, FRC), while there was significantly statistical negative correlation between VA and kco Table (4): Correlation between VA with other different pulmonary function parameters FVCTLCRVFRCkco VA r P (sig.) No

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This table shows that the FVC was significantly statistical positive correlated with each of TLC by single breath technique, FRC and age. There was significantly statistical negative correlation between FVC and RV/ TLC Table (5): Correlation between FVC with other different pulmonary function parameters and age TLCRV / TLCFRCAge FVC r P (sig) No

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There was no significant correlation between FVC and (DLCO, kco, MMEF, BMI) when statistically tested.

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There was significantly statistical relation between FVC and RV using regression linear analysis. Table (6): Relation between FVC as a dependent variable and all of the following predictors: Height, BMI, MMEF, RV, RV/TLC, TLC, VA, DLCO, KCO, FRC Coefficients a Model Unstandardized Coefficients Standardized Coefficients tSignificance. BStd. ErrorBeta 1Constant HT BMI MMEF RV RV/TLC TLC VA DLCO kco FRC

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There was significantly statistical positive correlation between DLCO and kco. Table (7): Correlation between DLCO and KCO DLCOkco DLCO r P (sig) No ** kco r P (sig) No **

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The results showed that kco was significantly statistical positive correlated to DLCO and significantly statistical negative correlated to TLC using Table (8): Correlation between KCO with DLCO and TLC DLCOTLC kco r P (sig) No

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There was significantly statistical relation between kco and all of DLCO, MMEF, RV/TLC, TLC using Regression Linear Analysis. Table (9): Relation between kco as a dependant variables and all the following predictors: DLCO, FVC, BMI, MMEF, RV, RV/TLC, TLC, FRC Coefficients a Model Unstandardized Coefficients Standardize d Coefficients t Sig. B Std. Error Beta 1(Constant) DLCO FVC BMI MMEF RV RV/TLC TLC FRC

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Clinical implications Firstly we have to point that DLCO and DLCO/VA (kco) are usually compared with predicted values of healthy volunteers, who by definition have a normal TLC. Reduction in alveolar volume by disease processes is the largest potential source of error in interpreting DLCO. So correction for the effect of altered alveolar volume has been tried by reporting the ratio of DLCO/VA (kco).

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DLCO/VA (kco) was introduced in clinical practice mainly to allow for reductions in VA brought about by a loss of pulmonary tissue as for example, following pneumonectomy. The decrease in DLCO following pneumonectomy is of a totally different nature than that caused by a thickened alveolar capillary membrane, as in lung fibrosis, or by lung destruction, as in emphysema.

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Although our study reported a significant statistical positive correlation between DLCO and kco, but kco is proportionally less decreased than DLCO as the mean of kco and DLCO was and respectively. Normally VA represent nearly 10% of TLC and the difference being related to the anatomic dead space and the gas mixture.

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The patients of ILD have low lung volumes, and their VA was near their TLC. In contrast to patients with moderate to severe obstruction where TLC was increased and the VA was lower than TLC being about 50% of TLC. It can be concluded that the VA and TLC-SB can be a good guide for lung volume in patients with interstitial lung disease.

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Our study has two limitations: First, we did not correct the DLCO values for hemoglobin concentration, as this information was not available on all subjects. While this certainly may have changed the DLCO and kco values but it should have changed both equally, and so not affected the primary purpose of our study, which was to compare the two values.

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Second, we accounted on TLC-SB technique rather than TLC measured by Body Plethysmography which is more accurate but with high costs. However, the TLC-SB and VA at low lung volumes gives reproducible results we can account on.

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conclusion In interpretation of DLCO-SB, the DLCO/VA ratio (kco) should not be neglected and should be in coherent with the interpretation of DLCO, as decreased DLCO/VA strongly suggests parenchymal lung disease. However, alone does not provide a valid index of the effect of changes in alveolar volume; it may lead to errors in interpretation of the diffusing capacity.

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VA and TLC-SB could be good indicators of lung volume in patients with Interstitial Lung Disease which needs further investigations on a wide scale.

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Thank You

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