Single-breath Carbon Monoxide Transfer Research Articles

No long-term effect of past Pneumocystis jirovecii pneumonia on pulmonary function in people with HIV.

To assess the impact of past Pneumocystis jirovecii pneumonia (PJP) on the pulmonary diffusion capacity in people with HIV (PWH) with a history of advanced immunodeficiency. Prospective cross-sectional study. Adult PWH with past PJP >1 year ago were included as the study group. The control group consisted of PWH with a nadir CD4+ lymphocyte count <200 cells/mm3, matched by age, sex, smoking status and time since HIV diagnosis. All PWH completed a pulmonary function test (PFT) consisting of pre-bronchodilation spirometry, body plethysmography and single-breath carbon monoxide transfer factor (TLCO) measurement. TLCO, diffusion impairment (defined as a TLCO Z-score <-1.645), total lung capacity (TLC) and forced expiratory volume in one second/forced vital capacity (FEV1/FVC) Z-scores were assessed. Multivariable regression analyses were conducted with Z-scores and odds of diffusion impairment as outcomes. PFTs of 102 participants were analyzed, 51 of whom had past PJP with a median of ten years since PJP. Mean TLCO Z-score and diffusion impairment rate did not differ significantly between groups (P = 0.790; P = 0.650). Past PJP was not independently associated with TLCO Z-score [β = 0.14; 95% confidence interval (CI) -0.30-0.57], diffusion impairment (odds ratio 1.00; 95% CI 0.36-2.75) nor TLC or FEV1/FVC Z-scores, whereas current (vs. never) smoking was associated with more diffusion impairment and lower TLCO Z-scores. In our study, past PJP was not associated with long-term diffusion impairment. Our findings suggest that smoking plays a more important role in persistent pulmonary function impairment whereas PJP-related changes seem to be reversible.

Correlation between Peripheral Blood T-cell Profiles and Clinical and Inflammatory Parameters in Stable COPD

Recent studies suggest that Tc1/Tc2 imbalances are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). The purpose of this study was to clarify the relationship between peripheral blood T-cell profiles and pulmonary function or inflammatory parameters. Thirty-one patients with stable COPD (median age 70 years, 30 males, 15 current smokers and 16 ex-smokers) and 30 healthy control subjects were enrolled in this study. The subjects underwent blood tests, exhaled nitric oxide (eNO) measurement, pulmonary function tests, and sputum induction. Tc1/Tc2 and Th1/Th2 were determined by analyzing intracellular cytokine staining for IFN-gamma and IL-4 in peripheral blood CD8+ and CD4+ T cells using flow cytometry after stimulation with phorbol 12-myristate 13-acetate and ionomycin. There was a significantly increased proportion of IFN-gamma-producing and IL-4-producing CD8+ T cells in patients with COPD compared with control subjects (median [IQR] 73.6% [63.9%-80.7%] vs 62.0% [45.6%-73.8%], p=0.004; and 2.6% [1.1%-6.9%] vs 1.1% [0.6%-2.2%], p=0.002, respectively). In addition, the proportion of IFN-gamma-producing CD4+ T cells was significantly higher in patients with COPD compared with control subjects (25.7% [21.2%-38.0%] vs 22.8% [15.6%-29.2%], p=0.027). The proportion of IFN-gamma-producing CD8+ T cells was correlated negatively with single-breath carbon monoxide transfer coefficient (Kco)(rho=-0.45, p=0.033) and positively with eNO (rho=0.50, p=0.012). The proportion of IL-4-producing CD8+ T cells was positively correlated with body mass index (rho=0.42, p=0.023) and Kco (rho=0.47, p=0.026). It is suggested that Tc1 cells have a detrimental role and that Tc2 cells have a protective role in disease progression.

Pulmonary gas exchange and educational level: a community study.

Socio-economic status (SES) is related to increased risk of airway disease in terms of forced expiratory volume in one second (FEV1) and forced vital capacity. No data are available as to what extent SES predicts alveolar function in a general population. In this cross-sectional study, 1,275 subjects aged 18-73 yrs underwent pulmonary testing, including the single-breath carbon monoxide transfer capacity of the lungs (TL,CO). Educational level was used as an index for SES. Mean +/- SD TL,CO % predicted was 97% among those with primary school education, 99% among those with secondary school education and 104% among those with a university degree. In a multiple linear regression analysis, adjusting for age, height, haemoglobin, carboxyhaemoglobin, smoking habits, occupational exposure, FEV1 and body mass index, TL,CO was significantly related to educational level in males but not in females. Occupational exposure was not significant. In this study, socio-economic status was found to be an independent determinant of TL,CO. Even in an affluent country such as Norway, socio-environmental risk factors may differ based on individuals' SES. Such risk factors may, for instance, be higher exposure to airborne pollutants, poorer housing conditions, or lower consumption of fruit and vegetables. Further exploration is called for.

Pulmonary dysfunction in transfusion-dependent patients with thalassemia major.

Pulmonary function tests were performed on 62 transfusion-dependent patients with thalassemia major, ranging in age from 8 to 33 years, and receiving chelation therapy with desferrioxamine or deferiprone. Percent predicted values for FVC, FEV1, and PEF were significantly reduced, whereas FEV1/FVC and maximal expiratory flow at 25% FVC were within normal limits, indicating a restrictive disease. Both FVC and FEV1 were negatively correlated with transfusional iron burden as indexed by age. Single-breath carbon monoxide transfer factor was reduced, even after correction for low hemoglobin concentration, and was negatively correlated with iron burden and iron overload, as indexed by serum ferritin levels. Owing to low hemoglobin concentration, blood-diffusing capacity was reduced, in spite of increased lung capillary blood volume, which was, however, adequate to normalize blood diffusing capacity when hemoglobin concentration was only partially restored by transfusion. The diffusing capacity of the alveolar-capillary membrane was substantially decreased and negatively correlated with age and serum ferritin, the fall being primarily attributed to increased membrane thickness. These findings suggest that lung fibrosis and/or interstitial edema related to iron overload are the main cause of pulmonary dysfunction observed in patients with thalassemia major.

Short term variability of single breath carbon monoxide transfer factor

BACKGROUNDWhen monitoring patients with chronic lung disease it is important to distinguish genuine changes in gas transfer over time from natural variability. This study aims to define the coefficient of...

Dust exposure, respiratory symptoms, and longitudinal decline of lung function in young coal miners.

To study the role of dust exposure on incidence of respiratory symptoms and decline of lung function in young coal miners. The loss of lung function (forced vital capacity (FVC), forced expiratory volume in one second (FEV1), forced expiratory flow (MEF), carbon monoxide transfer factor (TLCO)) with time and the incidence of respiratory symptoms in 909 Sardinian coal miners (followed up between 1983 and 1993 with seven separate surveys) has been compared with the past and current individual exposures to respirable mixed coal dust. Multiple linear and logistic regression models were used simultaneously controlling for age, smoking, past occupational exposures, and other relevant covariates. According to the relatively low dust exposures experienced during the follow up few abnormal chest x ray films were detected. In the cross sectional analysis of initial data, significant associations between individual cumulative exposure to dust, decrements in FEV1 and MEFs, and increasing prevalence of respiratory symptoms were detected after allowing for the covariates included in the model. The yearly decline of FVC, FEV1, and single breath carbon monoxide transfer factor (TLCO/VA) was still significantly related to the individual exposure to dust experienced during the follow up, even after allowing for age, smoking, initial cumulative exposure to dust, and initial level of each functional variable. In logistic models, dust exposure was a significant predictor of the onset of respiratory symptoms besides age and smoking. The results show that even moderate exposures to mixed coal dust, as in our study, significantly affect lung function and incidence of symptoms of underground miners. Although the frequency of chest x ray examination might be fixed at every three or four years, yearly measurements of lung function (spirometry, MEFs, and TLCO) are recommended for evaluation of the respiratory risk from the coal mine environment to assess the need for further preventive interventions.

Predictive value of serum III procollagen for diagnosis of pulmonary involvement in patients with scleroderma

High resolution computed tomography (HRCT) was recently demonstrated to be as good as open lung biopsy for the diagnosis of pulmonary involvement in patients with scleroderma. Nevertheless, in view of its price and related irradiation, HRCT cannot be recommended as a screening test. Serum III procollagen (sPIIINP) is an aminopropeptide of type III collagen, which is released during conversion into collagen by specific proteases. Increased levels of sPIIINP have been observed in patients with scleroderma. The aim of the present study was to assess the relationship between sPIIINP measurement and pulmonary involvement defined according to HRCT and pulmonary function tests (PFT) with single-breath carbon monoxide transfer capacity (TL,CO) in 28 patients suffering from scleroderma. Patients were divided into two groups for analysis, Group A comprising 16 patients without pulmonary scleroderma and Group B comprising 12 patients with pulmonary scleroderma. All patients had stable cutaneous disease and normal renal and hepatic function. The level of sPIIINP was determined by radioimmunoassay (RIA-gnost P-III-P, Prod. Nr. ODMT; Behring, Marburg, Germany). Mean +/- SD sPIIINP level in Group A was 0.85 +/- 0.21 U.mL-1. Individual values ranged 0.6-1.3 U.mL-1. Mean +/- SD sPIIINP value was 1.30 +/- 0.40 U.mL-1 in Group B and individual values ranged 0.7-1.9 U.mL-1. The difference in mean sPIIINP level between Group A and Group B was significant. Using a cut-off at 1.1 U.mL-1, sensitivity of sPIIINP was 0.66, specificity 0.94, positive predictive value 0.89, negative predictive value 0.79, false positive rate 0.06, and false negative rate 0.33. The value of sPIIINP correlated with HRCT score but not with PFT. This study confirms the relationship between sPIIINP and scleroderma with interstitial lung disease. We suggest that sPIIINP could be measured in patients with scleroderma to screen those patients requiring HRCT. Further studies are necessary to determine the value of sPIIINP in terms of prognosis and follow-up of patients under treatment.

Large lungs and growth hormone: an increased alveolar number?

Previous physiological studies suggest that increased lung growth in patients with acromegaly is associated with either a normal or above normal pulmonary transfer factor. These findings can be interpreted to suggest either alveolar hypertrophy or hyperplasia as the mechanism for lung growth in this condition. Since the ventilated airspaces retain normal elastic properties, we wanted to determine whether the mechanism for lung growth in acromegaly is the result of an increased alveolar number rather than size. Measurements of pulmonary distensibility (K) (an index of alveolar size), elastic recoil, single-breath carbon monoxide transfer factor and carbon monoxide transfer coefficient (KCO), pulmonary capillary blood volume and alveolar membrane diffusing capacity, together with chest width, were compared in nonsmoking, acromegalic and normal men and women, with and without an increased lung size. Pulmonary transfer factor was normal for all groups studied, regardless of lung size. However, KCO was inversely related to total lung capacity (% predicted) for all subjects and KCO (% predicted) was inversely related to chest width in men. Pulmonary capillary blood volume (% predicted) was inversely related to total lung capacity (% predicted) for subjects with large lungs. Pulmonary distensibility (K), membrane diffusing capacity and elastic recoil were within the normal range. These findings suggest normal alveolar size, alveolar membrane surface area and mechanical function in subjects with large lungs. They also suggest that KCO may not be a reliable guide to the interpretation of the mechanism of lung growth in individuals with disproportionately large lungs, and may be reduced because not all the alveoli are perfused. The normal values for pulmonary distensibility found in all our individuals with large lungs, including acromegalics, suggest that lung growth has been achieved by an increased alveolar number rather than size. However, morphometric studies of the lungs of nonsmoking, acromegalic subjects without lung disease, are required to substantiate this finding.

Antiglomerular Basement Membrane Disease: The Long-Term Pulmonary Outcome

We have evaluated long-term pulmonary function in 14 patients who were treated for anti-glomerular basement membrane disease at our institution during the last 17 years. Eight of these patients had evidence of pulmonary involvement, as manifested by hemoptysis, pulmonary infiltrates on chest x-ray film, or anemia. These patients were compared with a control group of 15 patients who had renal disease and who were matched for degree and duration of renal disease, age, smoking history, and method of renal replacement. The following variables were measured in each patient: forced vital capacity, forced expiratory volume in 1 minute, vital capacity, total lung capacity, residual volume, functional residual capacity, single-breath carbon monoxide transfer factor, and single-breath carbon monoxide transfer factor corrected for alveolar volume (KCO). These patients also participated in a graded exercise test and measurements of oxygen uptake, carbon dioxide production, minute ventilation, and oxygen saturation were taken. Patients with anti-glomerular basement membrane disease and a prior history of pulmonary hemorrhage had a significantly reduced KCO (46% +/- 10% v 68.7% +/- 14.7%) compared with the control group. There was no difference in any of the other measured parameters.

Imaging of pulmonary disease in scleroderma with J001X scintigraphy.

J001X is an acylated poly-galactoside isolated from the membrane of Klebsiella and able to interact with macrophages, mainly in their activated state. The aim of the present study was to determine the ability of 99m-labelled technetium (99mTc)-J001X scintigraphy to image pulmonary disease, defined by high resolution computed tomographic scanning and pulmonary function tests, in patients suffering from scleroderma. Patients were considered to have pulmonary disease when they had at least two positive signs on high resolution computed tomography, or a decrease in lung volume and single breath carbon monoxide transfer, or both, with no disease process other than scleroderma in their medical history. Positive J001X scintigraphic imaging was defined by symmetrical bilateral pulmonary fixation three and five hours after inhalation of 99mTc-J001X. J001X scintigraphic results were compared with disease activity as indicated by bronchoalveolar lavage (BAL) fluid lymphocytosis. Seventeen patients were studied, in 12 of whom J001X scintigraphy was positive. There was no correlation between BAL lymphocytosis and J001X scintigraphic findings, nor between BAL and pulmonary scleroderma. This was not surprising because of the high specificity of macrophage targeting by J001X. Follow up of a larger population over a longer period is needed to establish whether there is a prognostic value for positive J001X scintigraphic findings in scleroderma.

Correction of the single breath carbon monoxide transfer factor in exercise for variations in alveolar oxygen pressure.

Carbon monoxide transfer factor (TLCO) varies inversely with the partial pressure of alveolar oxygen (PAO2). During exercise the PAO2 in the alveolar gas sample bag decreases so the TLCO increases more than would be expected from the effects of exercise alone. The effects of PAO2 on the estimation of TLCO during exercise have been investigated and studies have been performed to determine whether it is appropriate to standardise to a PAO2 of 16 kPa. TLCO was estimated at rest and at a single level of exercise in six normal subjects using test gas mixtures of 0.3% carbon monoxide, 14% helium, and oxygen in three different percentages (17%, 21%, and 27%), remainder nitrogen. In three of the subjects an incremental exercise test with estimates of oxygen consumption (VO2) and cardiac frequency (fC) was also performed using a mixture containing 18% oxygen. TLCO decreased as levels of inspired oxygen increased. When standardised to a PAO2 of 16 kPa TLCO became independent of the inspired oxygen concentration. The significance of the curvilinear relations of TLCO and transfer coefficient to VO2 and fC improved. The single breath breath holding TLCO should be standardised to a PAO2 of 16 kPa when estimated during exercise.

Reference values and prediction equations for normal lung function in a non-smoking white urban population.

Prediction equations for normal lung function have been derived from tests on 179 healthy, non-smoking, white urban dwellers. The subjects, 96 women (height 1.46-1.77 m) and 83 men (height 1.61-1.96 m) aged 18-86 years, underwent measurements of spirometric flow and volume, multi-breath helium dilution lung volumes, and single breath carbon monoxide transfer factor and the single breath nitrogen washout test. Regression analysis using height, age, and weight as independent variables was used to provide predicted values for both sexes. Correlation coefficients were similar to those found in previous studies but normal ranges for spirometic measurements were narrower than in many previous studies, and spirometric flow and volume measurements were higher than those obtained in studies that included cigarette smokers, reflecting our more stringent criteria for selecting subjects and the newer standardised technical methods adopted. Multi-breath helium dilution values for total lung capacity were similar to those found in previous studies but the inspiratory vital capacity was larger and the residual volume reduced. Values for carbon monoxide transfer factor and the single breath nitrogen washout did not differ significantly from existing values. A complete set of lung function reference values and prediction equations for both sexes has been derived from a single population. The exclusion of cigarette smokers and subjects with respiratory symptoms has produced values that should have a greater sensitivity in the detection of mild lung disease.

Pulmonary function in chronic renal failure: effects of dialysis and transplantation.

Many possible pulmonary complications of renal disease have been described, but little is known of their physiological importance or the effects on them of different forms of renal replacement therapy. Four groups were recruited, each containing 20 patients. The groups consisted of patients with chronic renal failure before dialysis (group 1); patients receiving continuous ambulatory peritoneal dialysis, never having received a transplant (group 2); patients receiving haemodialysis, never having received a transplant (group 3); and patients after their first successful cadaveric renal transplant (group 4). All were attending the same regional dialysis and transplant unit. None was known to have clinically important lung or chest wall disease. Flow-volume loops were recorded before and after 400 micrograms of salbutamol, and plethysmographic lung volumes and airway conductance and single breath carbon monoxide transfer factor were measured. Only nine of 80 patients had normal lung function. The reductions in spirometric values were minor. Whole lung carbon monoxide transfer factor was reduced in all groups (mean % predicted with 95% confidence intervals: group 1 81.7% (74-89%); group 2 69.7% (62-77%); group 3 87.5% (80-96%); group 4 82.5% (78-87%]. The values were significantly lower in those having continuous ambulatory peritoneal dialysis (group 2). Residual volume was reduced significantly in the group who had undergone renal transplantation (85.7%, 77-94%). There was no correlation between these changes and smoking habit, age, duration or severity of renal failure, duration of treatment, or biochemical derangement. It is concluded that abnormal lung function is common in renal disease. The main change is a reduction in carbon monoxide transfer that persists after transplantation. The likeliest explanation is that subclinical pulmonary oedema progresses to fibrosis before transplantation. The fibrosis may worsen further to cause the reduced residual volume in the recipients of grafts.

Single breath carbon monoxide transfer factor in different forms of chronic airflow obstruction in a general population sample.

The single breath transfer factor for carbon monoxide (TLCO), TLCO/alveolar volume (VA), and standard spirometric indices were measured in a survey of the randomly selected population sample of 1174 subjects enrolled in the Tucson epidemiological study of airways obstructive disease. Subjects were subdivided according to whether the FEV1/FVC ratio was under 65%, 65-75%, or over 75%. The influence of smoking on TLCO was accounted for by expressing TLCO as a percentage of the expected value-that is, of the value expected from the reported cigarette consumption. The 63 subjects who gave a history of physician confirmed asthma in reply to a questionnaire tended to have high values for TLCO, even when FEV1/FVC was reduced. In the absence of a given diagnosis of asthma, however, TLCO and TLCO/VA were reduced when the FEV1/FVC ratio was reduced, whether or not a clinical diagnosis of emphysema had been reported. This suggests that these subjects may have undiagnosed emphysema. This cross sectional analysis of our survey data suggests that subjects in our sample with spirometric evidence of chronic airflow obstruction have different forms of disease, characterised by different physiological features, in addition to the different risk factors and clinical courses reported earlier.

Variability of the single-breath carbon monoxide transfer factor as a function of inspired oxygen pressure

We measured single-breath CO transfer factor (TLCO) and alveolar oxygen partial pressure (PAO2) six times at each of three fractions of inspired oxygen (FIO2) (0.17, 0.21, 0.26) in twelve healthy subjects, to determine whether one FIO2 would have the advantage of producing less variable TLCO results than the others. Measured TLCO was adjusted for the increase in carboxyhaemoglobin during the tests. We found no significant differences in intra- or interindividual variance as a function of test FIO2.

Are Reduced Lung Volumes in IDDM Due to Defect in Connective Tissue?

Lung volumes were measured by spirometry and helium-dilution technique in 28 young adult men with insulin-dependent diabetes mellitus (IDDM) of long duration and compared with 16 age- and height-matched adult men without diabetes. Reduced values for forced expiratory volume at 1 s, vital capacity, functional residual capacity, total lung capacity, residual volume, and single-breath carbon monoxide transfer factor were found for the IDDM patients compared to the control subjects. The results are consistent with reduced lung volumes in IDDM patients and did not correlate with the presence or absence of mild cheiroarthropathy but may relate to duration of diabetes.

Effects of diffuse pleural thickening on respiratory mechanics

Five patients with radiographic and computed tomography (CT) evidence of extensive pleural thickening were studied. All had a restrictive ventilatory defect. The single breath carbon monoxide transfer factor (TLCO) was reduced in each case (mean 76% predicted) but in four patients the transfer coefficient (KCO) was increased (mean 116% predicted), which is consistent with lung 'en cuirasse'. Static pressure-volume curves of the lungs showed that the maximum transpulmonary pressure was greater than normal and pulmonary compliance was reduced; the curves were therefore indistinguishable from those obtained in patients with pulmonary fibrosis. Transdiaphragmatic pressures during maximal inspiratory efforts were moderately impaired and the proportions of each tidal breath contributed by anterposterior (AP) motion of rib cage and abdomen were similar to normal in both erect and supine postures, suggesting that diaphragmatic mobility was well preserved.

Effect of Cold Stimuli on Acute and Chronic Responses of the Single-Breath Carbon Monoxide Transfer Factor (TLCO) and Pulmonary Blood Flow (QC) in Primary Raynauds

Effect of Cold Stimuli on Acute and Chronic Responses of the Single-Breath Carbon Monoxide Transfer Factor (TLCO) and Pulmonary Blood Flow (QC) in Primary Raynauds

The single-breath carbon monoxide transfer test 25 years on: a reappraisal. 2--Clinical considerations.

The single-breath carbon monoxide transfer test 25 years on: a reappraisal. 2--Clinical considerations.

The influence of lung volume on gas transfer in scoliosis

Single-breath carbon monoxide transfer factor (DL co) and diffusion coefficient (K co) have been compared with vital capacity and total lung capacity in 119 subjects with scoliosis, 74 with idiopathic scoliosis, 32 with congenital osteogenic scoliosis and 13 with paralytic scoliosis. In each group mean values of DL co were below, and for K co above, predicted values. Furthermore, in each group, DL co was correlated with lung volume and K co inversely correlated with lung volume. The reduction in DL co is probably due to the reduction in the total alveolar surface area and the increased values for K co probably result from an increase in pulmonary capillary blood volume per unit alveolar volume at low lung volumes.