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Pulmonary diffusing capacity in lambs during the early neonatal period.

A rebreathing method was used to make 53 measurements of pulmonary diffusing capacity (DLco) and functional residual capacity (FRC) in 17 newborn lambs during the first 2 days of life. DLco, FRC, and DLco/FRC all increased in studies made at 24--48 hr of age compared to those at 2--4 hr of age: DLco 0.86 +/- 0.18 to 1.52 +/- 0.09 ml/min/torr; FRC 37 +/- 10 to 60 +/- 8 ml and DLco/FRC 2.52 +/- 0.75 to 2.89 +/- 0.37 ml/min/torr/ml X 10(-2). DLco measured using 0.005% CO in the test gas was not different than that measured using 0.5% CO.

Animals

A chronic pulmonary syndrome associated with graft-versus-host disease after allogeneic marrow transplantation.

Of 143 consecutive patients who survived at least 6 months after bone marrow transplantation (allogeneic [n = 131]; syngeneic [n = 5]; or autologous [n = 7]) and whose pulmonary function was evaluated before and on at least 2 occasions after BMT, 29 (20%) developed a chronic pulmonary syndrome without evidence for an infectious etiology. Twenty-eight (97%) presented with cough and 22 (76%) with dyspnea; abnormal chest signs were crackles in 23 (79%) and wheeze in 22 (76%). Chest roentgenogram showed pulmonary infiltrates in 15 (52%) cases but was normal in 14 (48%). All patients had major reductions in lung volumes (forced expiratory volume in 1 sec [FEV1]; relaxed vital capacity [VC]; and alveolar volume [VA]), and/or diffusing capacity (pulmonary diffusing capacity [TLCO] and single-breath carbon monoxide coefficient [KCO]). The obstructive component varied with only 18 (62%) patients developing overt airways obstruction (FEV1/VC < 75%), and in 6 of this group the fall in lung volumes preceded the onset of airways obstruction. Open lung biopsy (n = 4) showed both bronchiolitis obliterans and chronic patchy interstitial pneumonitis. The development of this syndrome was associated with acute (P < 0.001) and chronic (P < 0.0001) graft-versus-host disease of other organ systems. Twenty-four (83%) patients had a partial or complete response to immunosuppressive agents. Six (21%) have died, five (17%) of pulmonary complications. We suggest that this syndrome may be a manifestation of chronic GVHD involvement of the lung.

Adolescent

Effect of hyperlipidaemia on pulmonary diffusing capacity for carbon monoxide.

There is conflicting evidence on the effect of hyperlipidaemia on pulmonary diffusing capacity for carbon monoxide (DLCO or TLCO) in man. We have measured the carbon monoxide transfer factor per unit alveolar volume (TLCO/VA or KCO) by the single breath method in 25 patients with hyperlipidaemia, and in three normal subjects before and after infusions of an intravenous fat emulsion, Intralipid. Non-smokers with hyperlipidaemia had normal levels of TLCO/VA, whereas some of the smokers showed a slight reduction. In neither group was there any correlation of TLCO/VA with serum triglyceride or cholesterol concentrations. A reduction in triglyceride concentrations of up to five-fold produced by plasma exchange (three studies in two patients) or by dietary manipulation (one patient) had no significant effect on the levels of TLCO/VA. Intralipid infusion in three normal subjects caused a four- to five-fold increase in serum triglyceride concentration but had no effect on TLCO/VA. We conclude that moderate degrees of hyperlipidaemia have no effect on pulmonary diffusion.

Adult

Relationship of mortality, occupation, and pulmonary diffusing capacity to pleural thickening in the First National Health and Nutrition Examination Survey.

We studied the relationship of pleural thickening consistent with asbestos exposure to mortality, career employment in asbestos-related jobs, and pulmonary diffusing capacity among participants in the first National Health and Nutrition Examination Survey. Three "B" readers examined chest X-rays to identify 59 individuals with such pleural abnormalities. From 1975 to 1984, the all-cause mortality rate ratio (RR) comparing males with and without occupational pleural thickening was 1.3 (95% C.I. 0.8-2.2). For lung cancer, the mortality RR for males was 3.0 (95% C.I. 1.0-9.1). Career asbestos work was not associated with occupational pleural thickening among men, probably because some with the condition had only short-term exposure to asbestos. Pulmonary diffusing capacity was lower in those with occupational pleural thickening, taking smoking into account. These results suggest that individuals in the general population who have occupational pleural thickening are at risk for some of the health consequences of asbestos work, including lung cancer, even if they were not career asbestos workers.

Adolescent

Pulmonary diffusing capacity: implications of two-phase blood flow in capillaries.

The classical view of oxygen (O2) uptake in pulmonary capillaries assumes implicitly that capillary blood can be regarded as a continuous homogeneous hemoglobin solution. In this study a theoretical model was used to examine the role played by the particulate (two-phase) nature of blood on pulmonary oxygen exchange. Red cells were modelled as discrete hemoglobin (Hb) containing spheres flowing in single file suspension through a cylindrical capillary surrounded by a uniform annulus of alveolar tissue. The model accounted for the free diffusion of O2 from alveolar air space through tissue and plasma, free and Hb facilitated diffusion of O2 inside red cells, and the intracellular kinetics of O2-Hb binding. Oxygen uptake was driven by a specified O2 tension at the alveolar surface. The computed pulmonary diffusing capacity (DLO2) decreased with increasing spacing (Ls) between red cells. The reduction in DLO2 with increasing Ls was marshalled more by a reduction in membrane diffusing capacity (DMO2), than by the reduction in erythrocyte diffusing capacity (DeO2). The dependence of DMO2 on cell spacing stemmed from the manner in which O2 flowed across the alveolar surface into the discrete sinks (red cells) within the capillaries. The degree to which Ls influenced DMO2 was dependent on tissue and plasma layer thickness relative to red cell dimensions. The results indicate that the functional area of the alveolo-capillary membrane for O2 exchange depends on the red cell content of capillaries. Thus, DMO2 is not dictated solely by the morphology of the exchange apparatus (and physical parameters), but has functional determinants as well.

Capillaries

Comparison of single breath and steady state methods for the measurement of pulmonary diffusing capacity for carbon monoxide in normal subjects, patients with bronchial asthma and chronic obstructive airway disease.

The results of pulmonary diffusing capacity (DLCO) measurements by the steady state (DLCOss) and single breath (DLCOsb) methods were compared in 50 normal subjects (Group A), 50 patients with bronchial asthma (Group B) and 50 patients with chronic obstructive lung disease (COAD) (Group C). A significant correlation was observed between DLCOss and DLCOsb in all the three groups of subjects. This relationship was stronger in Groups A and B as compared to Group C. Both DLCOsb and DLCOss were significantly correlated to parameters of air-flow obstruction. Both measurements of DLCO appear valid in normal subjects and in patients with bronchial asthma. In patients with COAD, on the other hand, DLCOsb may be valid measurement, since it is less likely to be influenced by airways obstruction.

Adult

Pulmonary diffusing capacity disturbances are related to nailfold capillary changes in patients with Raynaud's phenomenon with and without an underlying connective tissue disease.

PURPOSE: The aim of this study was to evaluate whether pulmonary microvascular damage is part of a more generalized involvement of the microvasculature in the spectrum of scleroderma (Scl)-like syndromes. PATIENTS AND METHODS: We studied four groups of patients, all with Raynaud's phenomenon (RP), distinguished by the extent and nature of their underlying connective tissue disease. Twenty-two patients had primary RP (pRP), another 22 patients had RP and an undifferentiated connective tissue disease (uCTD), 15 patients had Scl, and eight patients had the CREST syndrome (CREST). Pulmonary vascular damage in these groups was assessed by measuring the pulmonary diffusing capacity (T1,CO) and its components: the diffusing capacity of the alveolocapillary membrane (Dm) and the pulmonary capillary blood volume (Vc). Results were compared with morphologic abnormalities of the nailfold capillaries, as determined by nailfold capillary microscopy, and related to the presence of antinuclear antibodies. RESULTS: Vc was below normal in 38% and 43% of patients with pRP and uCTD, respectively (versus 52% in patients with Scl or CREST combined). In contrast, Dm was below normal in only 5% and 26% of patients with pRP and uCTD, respectively (versus 61% in patients with Scl or CREST combined). In patients with Scl and CREST, Dm was significantly decreased as compared with the former groups (p less than 0.01). Dm was also the pulmonary function parameter that correlated most strongly with both nailfold capillary abnormalities and the presence of antinuclear antibodies, whereas Vc did not. CONCLUSION: Early pulmonary involvement in Scl syndromes is functionally characterized by a lowered Dm, correlating with morphologic changes of the nailfold capillaries. Decreased Vc is probably a reflection of RP of the pulmonary vasculature.

Adult

[Pulmonary diffusing capacity for CO during breathing of inert gas mixtures with differing physical properties (author's transl)].

In order to study the role of diffusion limitation in alveolar space (stratification) for pulmonary gas exchange function, pulmonary diffusing capacity for CO (Dco) was comparatively measured during breathing of room air and of gas mixtures in which N2 of room air was replaced by He or Ar. Measurements in 15 healthy humans using the single breath method yielded the following mean (+/-SE) values: room air, 22.1+/-1.7; He, 25.1+/-1.3; Ar, 17.4+/-1.0 ml-min-1-Torr-1. The clear negative correlation between Dco and the molecular weight of the gases used is most easily explained on the basis of an airway diffusion resistance limiting CO transfer. For room air breathing this resistance is estimated at about 10% of the total resistance to CO uptake (1/Dco). The alveolar exchange of O2 and CO2 is expected to be affected by the diffusional resistance in airways, particularly at high metabolic levels.

Adolescent

Effects of hemodialysis and anemia on pulmonary diffusing capacity, membrane diffusing capacity and capillary blood volume in uremic patients.

The study aimed at investigating pulmonary function in uremic patients, emphasizing the lung diffusing capacity for CO (DLCO) and its membrane and pulmonary capillary blood volume (Vc) components. The study sample comprised 25 uremic patients without clinical/radiological evidence of lung disease. They were enrolled in a chronic hemodialysis (HD) program and had anemia requiring transfusions. The subjects were tested for their lung function before and after both a first HD and a HD with blood transfusion (BT) that followed a few days later. After HD-induced removal of body fluid, and increase in pre-HD reduced forced vital capacity, alveolar volume and mid-expiratory flow rate (FEF25-75%) was observed. HD-induced DLCO decrease (p less than 0.005) was observed and was related to decreased Vc. The second HD with BT increased DLCO, due to partially normalized Hb. On average, a 7.2% DLCO increase corresponded to each 10-g/l Hb rise. In conclusion, (1) the beneficial effect of HD in uremic patients reverts the small-airway obstruction; (2) the lower values of DLCO in these patients are due to reduced Hb and HD causes further DLCO reduction via decrease of Vc, and (3) HD with BT still increases DLCO because improvement of Hb predominates.

Adult

Comparison of single breath and steady state methods for the measurement of pulmonary diffusing capacity for carbon monoxide in non-homogeneous lungs.

The effect of non-uniformity in the distribution of ventilation and diffusion on the apparent pulmonary diffusing capacity measured by the single breath and steady state techniques has been assessed on the basis of a two-compartmental lung model. Both the methods give reasonable estimates of the true diffusing capacity provided the fast compartment has a greater KCO. The reverse of this results in gross underestimation of the diffusing capacity by both methods. There is a fairly good correlation between the single breath and the steady state results both in theory as well as in practice.

Carbon Monoxide

Effect of lung volume and positional changes on pulmonary diffusing capacity and its components.

Normal subjects have a larger diffusing capacity normalized per liter alveolar volume (DL/VA) in the supine than in the sitting position. Body position changes total lung diffusing capacity (DL), DL/VA, membrane conductance (Dm), and effective pulmonary capillary blood volume (Qc) as a function of alveolar volume (VA). These functions were studied in 37 healthy volunteers. DL/VA vs. VA yields a linear relationship in sitting as well as in supine position. Both have a negative slope but usually do not run parallel. In normal subjects up to 50 yr old DL/VA and DL increased significantly when subjects moved from a sitting to a supine posture at volumes between 50 and 100% of total lung capacity (TLC). In subjects greater than 50 yr old the responses of DL/VA and DL to change in body position were not significant at TLC. Functional residual capacity (FRC) decreases and DL/VA increases in all normal subjects when they change position from sitting to supine. When DL/VA increases more than predicted from the DL/VA vs. VA relationship in a sitting position, we may infer an increase in effective Qc in the supine position. In 56% of the volunteers, supine DL was smaller than sitting DL despite a higher DL/VA at FRC in the supine position because of the relatively larger decrease in FRC. When the positional response at TLC is studied, an estimation obtained accidentally at a volume lower than TLC may influence results. Above 80% of TLC, Dm decreased significantly from sitting to supine. Below this lung volume the decrease was not significant. The relationship between Qc and VA was best described by a second-order polynomial characterized by a maximum Qc at a VA greater than 60% of TLC. Qc was significantly higher in the supine position than in the sitting position, but the difference became smaller with increasing age. In observing the sitting and supine positions, we saw a decrease in maximum Qc normalized per square meter of body surface area with age.

Adolescent