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Diffusing capacity, specific diffusing capacity and interpretation of diffusion defects.

Six pathophysiologic mechanisms of a reduced single breath CO diffusing capacity are discussed and the usefulness of relating carbon monoxide (CO) uptake to the functioning alveolar volume (DL/VA, specific diffusing capacity) is illustrated for several pulmonary diseases. In patients with emphysema and pulmonary emboli (pulmonary vascular occlusive disease), reduced CO uptake is associated with significantly reduced DL/VA and is compatible with reduction of pulmonary capillary bed. In patients with pulmonary alveolar proteinosis, improvement in CO uptake and DL/VA follows lung lavage and suggests that lung units partially filled with proteinaceous material are responsible for hypoxemia, reduced CO uptake and reduced DL/VA. In most cases of radiation fibrosis, sarcoidosis and miscellaneous interstitial fibrosis, reduced CO uptake is associated with a normal DL/VA and suggests that loss of alveolar units, both capillaries and alveoli, has occurred. New regression equations for DL and DL/VA are established for children and adults. DL/VA is linearly related to height and independent of age and sex, while different predictive equations must be used for DL for the 5 through 17 and 18 through 76 age groups. The new regression equations for DL show better correlation in adults we studied over 50 years of age than previous regression equations which use a constant reduction of 2 to 3 ml CO per minute per mm of mercury for each 10 years of adult aging.

Adolescent↗

Conductive and acinar lung-zone contributions to ventilation inhomogeneity in COPD.

We investigated ventilation inhomogeneity in patients with chronic obstructive pulmonary disease (COPD) through use of the multiple breath N2 washout test (MBW). From an alveolar slope analysis throughout the MBW, we derived two indices, S(cond) and S(acin), as a measure of ventilation inhomogeneity in conductive and acinar zones of the lungs, respectively (J. Appl. Physiol. 1997;83:1807-1816). We evaluated the relationship of S(cond) and S(acin) to standard lung-function indices by means of a principal-components factor analysis, which linked correlated indices to independent factors accounting for 81% of the total variance within the COPD group. S(acin) was linked to the so-called acinar lung-zone factor, which also comprises diffusion capacity measurements. S(cond) was linked to the so-called conductive lung-zone factor, which also comprises specific airway conductance (S(Gaw)) and forced expiratory flows. FEV1 divided by FVC (FEV1/FVC) was the only variable linked to both the conductive and the acinar lung-zone factors. The fact that S(cond) and S(acin) were linked to independent factors provides statistical confirmation of the hypothesis that S(cond) and S(acin) reflect independent lung alterations, whereas FEV1/FVC behavior indicates a combined conductive and acinar contribution to airways obstruction.

Airway Resistance↗

Diffusing capacity in the clinical assessment of chronic airflow limitation.

CAL remains an important cause of morbidity and mortality. The diffusing capacity has ranked high in the assessment of CAL because it represents the best pulmonary function test to assess the integrity of the pulmonary capillary bed. Unfortunately, numerous physiologic, pathologic, and technical factors affect the test, thus limiting its sensitivity and specificity. HRCT techniques offer the potential to assess the extent of emphysema more accurately, but the technique requires greater standardization and is more expensive and less noninvasive than DLcoSB testing. Although the CIBA symposium considered DLcoSB "essential" in the investigation of the CAL patient, 16 the use of conventional DLcoSB testing in the seated position at rest is not currently advised as a routine screening procedure. The test must be performed in a center with high degree of quality control, and the results can be of value only by integrating the result into a comprehensive clinical assessment. Within this context, conventional DLcoSB testing may provide limited information about the extent of emphysema because reductions in DLcoSB correlate with the extent of emphysema by HRCT. When DLcoSB is normal, it may point in the direction of considering asthma as the cause of the airflow limitation. It may also provide information about disease severity and prognosis in O2-dependent CAL patients. The test should be a part of the investigation of the patient with unexplained dyspnea. It remains controversial how emphysema correlates with the degree of impairment in CAL, and further work needs to be done to clarify this relationship. This requires a reexamination of current CT methods 110 and the relationship between DLcoSB, structural changes in the lung, and HRCT evidence of emphysema. Refinements in DLcoSB testing methods, such as the measurement of DLcoSB-3EQ are linked to rapidly responding CO analyzers and computer-driven software, which will potentially improve the accuracy and reproducibility of the test, particularly in the presence of airway obstruction and nonuniform distribution of ventilation. Such refinements, which offer the possibility that tests of diffusion could become more useful markers of disease, include measuring DLcoSB when the pulmonary capillary recruitment is near maximal (head-down position, exercise), enhancing the sensitivity of the test to alterations in the lung periphery, standardizing previous volume history, developing more precise corrections for Hb and COHb, and developing an index of diffusion nonuniformity.

Cystic Fibrosis↗

Diffusing capacity of the lung for carbon monoxide.

The measurement of co uptake (VCO and DLCO) from alveolar gas is a unique way to noninvasively assess pulmonary vascular function, specifically the functional volume of the pulmonary capillary bed. Proper interpretation of results, however, needs to account for inherent assumptions regarding co distribution and timing procedures. Moreover, reasonable airway mechanics, lung volumes, and patient cooperation are required for accurate measurements. Potential clinical utility may be increased if measurements are made in different positions or under exercise conditions.

Capillary Permeability↗

Effects of abnormal hemoglobin concentration in human blood on membrane diffusing capacity of the lung and on pulmonary capillary blood volume.

In 13 patients with chronic anemia or polycythemia but normal lung function, and in 7 healthy students a statistically significant correlation between hemoglobin concentration and membrane diffusing capacity of the lung for CO was found. A membrane diffusing constant resulting from extrapolation for hemoglobin concentration 0 g/ was 13.4% of the predicted value (100% for Hb = 14.5 g%). A change of 1 g hemoglobin/100 ml changes membrane diffusing capacity for 6.3% of the predicted value. This result confirms the theory of Koyama and Mochizuki that the diffusing capacity of the pulmonary membrane is a function of the hemoglobin concentration of pulmonary capillary blood. In 3 healthy subjects with normal hemoglobin concentration the effect of DL/VA inhomogenities in the lung on single-breath diffusing capacity and its subdivisions was examined. An increase of DLCO for 20% of predicted normal at decreasing apnea time (tA = 5 sec) resulted from an increased pulmonary capillary blood volume for 50--90% of the predicted value (at tA = 10 sec), whereas membrane diffusing capacity remained unchanged over the range of apnea times. The reasons for this finding are still unknown; alteration of pulmonary perfusion at changing apnea time is taken into account.

Anemia↗

Diaphragm function and lung involvement in systemic lupus erythematosus.

Lung involvement was assessed in 30 consecutive patients with systemic lupus erythematosus (SLE), not selected by respiratory symptoms. Pulmonary function tests revealed a higher rate of abnormality than either clinical history or radiography. The single breath carbon monoxide diffusing capacity was below 80 per cent of the predicted value in 24 patients (80 per cent), and a reduced total lung capacity was present in 13 (43 per cent). There was a weak correlation between the severity of the functional defect and disease activity, assessed antinuclear factor and DNA binding. No correlation was found with serum complement of Clq precipitation. Since pulmonary fibrosis in SLE is uncommon it cannot account for the high frequency of abnormal findings, and the pathogenesis of the functional changes is probably multifactorial. In seven of the patients with the smallest lung volumes, measurements of static pressure volume curves and of maximum respiratory pressures indicated extrapulmonary volume restriction. In five of these patients, diaphragm function was specifically assessed and found to be grossly abnormal in four. The inability of the diaphragm to generate normal pressure may be due to either severe weakness or immobility following extensive pleural adhesions. The well recognized syndrome of "shrinking lungs" and high "sluggish" diaphragms with clear lung fields on radiography is probably due to dysfunction of the diaphragm rather than to primary intrapulmonary pathology.

Adolescent↗

Pulmonary function testing and pulmonary Langerhans cell histiocytosis.

In a long-term single-center follow-up (median 16-years), we studied high-resolution computed tomography (HRCT) and pulmonary function testing (PFT) in pulmonary LCH. Diffusing capacity corrected for alveolar volume (K(CO)) and total lung capacity (TLC) were significantly decreased (P=0.016 and P=0.030, respectively) in patients with extensive HRCT abnormalities. Patients with late stage disease on HRCT had increased forced expiratory volume (FEV1.0)(P=0.037) and vital capacity (VC)(P=0.036). Disease monitoring is important in pulmonary LCH, and since PFT with diffusing capacity provides a measurement of the current lung function, it may be a valuable tool in monitoring pulmonary LCH, and a good complement to imaging.

Adolescent↗

Pulmonary physiology in interstitial lung disease: recent developments in diagnostic and prognostic implications.

Pulmonary function changes in interstitial lung disease are characterized by loss of lung volume, increase in ratio of forced expiratory volume in 1 second to forced vital capacity, and decrease in carbon monoxide diffusion capacity. Recent developments in the assessment of respiratory mechanics in infiltrative lung disease have elucidated volume and flow dependence of lung and total respiratory resistance and elastance related to the viscoelastic properties of the respiratory system. A new, simple test of applying negative expiratory pressure at the mouth during tidal expiration can be used to generate expiratory flow-volume curves to detect flow limitation in patients with restrictive as well as obstructive disorders. This method is useful in patients who are weak, uncoordinated, or who cough during forced maneuvers. Poor prognostic signs in interstitial lung disease include male gender, paucity of lymphocytes on bronchoalveolar lavage, extensive radiographic infiltration, absence of cellular histologic findings on lung biopsy, presence of right-axis deviation, persistent or progressive decrease in lung volumes, and diffusion capacity of carbon monoxide.

Airway Resistance↗

Hindrance to diffusive gas mixing in the lung in hyperbaric environments.

Diffusivity of a gas is inversely proportional to atmospheric pressure. We studied pulmonary gas mixing in hyperbaric environments (5.5 and 9.5 ATA) as a means of understanding the role played by diffusion in normal situations and also as a means of determining whether persons in hyperbaric environments will be handicapped by poor diffusive mixing. Our subjects took single breaths of a mixture of indicator gases (5% each of SF6, Ar, Ne, and He; 20% O2, balance N2). Recordings of expired volumes and concentrations showed that heavier indicators were less well mixed than lighter ones, as evidenced by a slower fall during the transition between dead space and "alveolar" gas and a steeper slope of the alveolar plateau. Differences between light and heavy gases increased as pressure increased. Amounts of the indicators retained in the functional residual capacity (FRC) or residual volume after a single breath had a weak positive relation to diffusivity; the amounts (A) in the FRC (as fraction of inspired amounts) were well fitted by a simple equation. ARFC/AI = 0.55 - (0.0010/D), where D is molecular diffusivity. We conclude that the changes of distribution of inspired gas that occur with large changes of diffusivity have only a minor effect on the amount of gas exchanged between the inspirate and residual gas in the FRC.

Atmospheric Pressure↗

Pulmonary function in thalassemia major.

Pulmonary function tests were evaluated in 28 Chinese patients with beta-thalassemia major receiving regular transfusions and desferoxamine, and in 34 height-matched normal Chinese children. Comparison of lung function using analysis of covariance with reference to standing height showed that patients with thalassemia had a proportional decrease in forced vital capacity and forced expiratory flow volume in 1 second, whereas their expiratory flow rates, residual volume, and total lung capacity were comparable to those in normal children. The single-breath carbon monoxide diffusion capacity was normal. Our findings suggest that children with thalassemia major have mild restrictive lung disease. The previous controversy regarding the presence of restrictive or obstructive lung disease in patients with thalassemia may be related to the use of inappropriate control values.

Adolescent↗