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PubMed1995

Abnormalities of pulmonary function tests after marrow transplantation predict nonrelapse mortality.

To determine whether pulmonary function test (PFT) results after marrow transplantation were predictive of nonrelapse mortality, a review was made of prospective, nonrandomized PFT results for association with nonrelapse mortality by log-rank test and Cox proportional hazards modeling. The setting was a tertiary referral center. The patients were all marrow recipients who performed PFT between Days 60 and 120 after marrow transplantation between July 1, 1983 and December 31, 1990 (n = 906). At 3 mo after transplantation, the mean values for total lung capacity (TLC) and diffusing capacity decreased, and restrictive ventilatory defects (TLC < 80% of predicted) were noted in 34% of the cohort. Airflow rates (FEV1/FVC) were unchanged. A restrictive lung defect at 3 mo after transplant or a significant decline (> or = 15%) in TLC from baseline despite remaining within the normal range was associated with a twofold increased risk of nonrelapse mortality. Neither airflow obstruction nor impairment in diffusing capacity was associated with an increased risk. Abnormalities of the TLC at 3 mo after transplant were associated with death with respiratory failure, but not with an increased risk of chronic graft-versus-host disease (GVHD). There is an increase in the nonrelapse mortality rate associated with either the presence of a restrictive defect 3 mo after marrow transplantation or a significant decline in lung volume compared with baseline. This effect is most pronounced more than 1 yr after marrow transplant and appears to be a result of an increase in the rate of death with respiratory failure, not chronic GVHD.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

The clearance rate of alveolar epithelium using 99mTc-DTPA in patients with diffuse infiltrative lung diseases.

The early diagnosis of diffuse infiltrative lung disease (DILD) is important in prognosis and it is necessary to develop a noninvasive, inexpensive, and rapid diagnostic tool for suspected cases of DILD. Thus, we measured the epithelial permeability via radioisotope (99mTc-DTPA) in 22 patients with DILD for clinical application of the clearance rate (T1/2LB) of radioisotope on the early diagnosis of DILD. We divided the patients with DILD into the early and late stages according to the derangements of the diffusion capacity for carbon monoxide. The T1/2LB in patients with DILD were significantly shorter when compared with those with normal control in all lobes. However, 40 to 58 percent of T1/2LB in patients with DILD overlapped normal values (2 SDs of mean of T1/2LB of normal control) dependent on specific lung regions. The T1/2LB of patients with early-stage DILD was longer than that of patients with late-stage DILD in right upper and middle lobes. Although T1/2LB of 99mTc-DTPA, the index of alveolar epithelial permeability, was shortened in patients with DILD with normal diffusing capacity, it was difficult to detect early-stage DILD by measuring alveolar epithelial permeability because of many overlaps of T1/2LB between early-stage DILD and normal control.

Adult↗
PubMed1979

Farmer's lung disease: long-term clinical and physiologic outcome.

To determine the long-term effects of farmer's lung disease and the factors influening the outcome, 141 patients with farmer's lung disease were evaluated. At the time of the last follow-up, 29 patients had died and 92 (mean age, 54 years) were studied clinically, physiologically, and radiologically. The mean length of disease was 14.8 years (range, 2.25 to 40 years). Symptoms at the time of the last follow-up included complaints of cough (33 per cent of the patients), breathlessness while walking on the level (20 per cent), breathlessness on minor exertion (14 per cent), and breathlessness while at rest (3 per cent). Twenty-eight per cent had chronic bronchitis. Thirty-nine per cent (36 of 92 patients) had some evidence of interstitial changes on roentgenogram. Abnormal vital capacity was present in 11 patients (12 per cent), abnormal total lung capacity in 11 (12 per cent), and abnormal CO difussing capacity in 27 (30 per cent). The ratio of one-sec forced expiratory volume to forced vital capacity was abnormal in 23 patients (25 per cent), and arterial PO2 was abnormal in 39 (40 per cent). Patients with a history of 5 or more symptomatic recurrences had significantly smaller values (P less than 0.05) for vital capacity, total lung capacity, and CO diffusing capacity than did those patients with less than 5 recurrences. There was no significant relation between continued farming or length of disease and lung function. On the basis of several measurements of airway function, 34 of the patients (58 per cent) were found to have some abnormality, It is concluded that symptomatic recurrences may be the most important factor in determining the danger of progressive disease. Persistently positive precipitins were correlated with decreased CO diffusing capacity. Moreover, airway disease is relatively uncommon but does occur, and in some cases it is a possible consequence of farmer's lung disease.

Adult↗
PubMed1998

Pseudophysiologic emphysema resulting from severe small-airways disease.

Loss of lung elastic recoil causing hyperinflation with increased TLC and decreased diffusing capacity and expiratory airflow are physiologic hallmarks of emphysema. We studied lung mechanics in 10 patients (seven men and three women) aged 69 +/- 9 yr (mean +/- SD) who had fixed, severe expiratory airflow limitation with a mean FEV1 = 0.73 +/- 0.1 L (mean +/- SD) (32 +/- 7% predicted) and lung computed tomographic picture grade score <= 20, indicating no or trivial emphysema. Three patients died, in whom whole-lung emphysema scores were 15 each and small airways were abnormal. Marked hyperinflation was present in all 10 patients studied, with TLC 7.3 +/- 1.1 L (140 +/- 12% predicted); FRC 5.6 +/- 0.8 L (177 +/- 30% predicted); and RV 5.2 +/- 0.8 L (242 +/- 28% predicted). Diffusing capacity of carbon monoxide (DLCO was reduced, at 12 +/- 6 ml/min/mm Hg (61 +/- 29% predicted). The pressure-volume curves of the lung were markedly abnormal. Pst(L) at TLC was 11.6 +/- 1.4 cm H2O. Transdiaphragmatic pressure (Pdi) in five patients was 66 +/- 13 cm H2O. These results indicate that severe small-airways disease with no or trivial emphysema may cause a spurious reduction in diffusing capacity as well as severe loss of lung elastic recoil resulting in marked hyperinflation, increased TLC, and decreased Pdi and expiratory airflow.

Aged↗
PubMed1975

Pulmonary involvement in patients with rheumatoid arthritis.

Vital capacity (VC) and single-breath diffusing capacity for carbon monoxide of the lungs (Dco) were measured and chest X-ray evaluated in 129 patients with rheumatoid arthritis (RA). 123 of them represented average RA patients, either hospitalized (84 patients, Group I) or outpatient material (39 patients, Group II). The remaining six patients (Group III) represented cases with marked changes in chest X-ray detected in an earlier study. Deviating findings in the 123 cases of Groups I and II were observed as follows: in one the lung function tests or X-ray examinations, 35%; abnormal X-rays, 18%; reduced VC or Dco, 28%; simultaneously low VC and Dco, 7%; and pathological findings in all three tests, 2%. Group III showed extremely low VC and Dco values. Changes in respiratory function involved restrictive impairment and diffusion defects, and the results further implied that restrictive changes develop early, whereas decreased diffusing capacity is associated with more advanced "rheumatoid lung". The disparity abnormal findings in chest X-ray changes and in lung function tests suggests that in examining pulmonary manifestations in patients witu RA, both radiographic methods and pulmonary function tests should be used for relevant evaluation.

Adult↗
PubMed1986

The aging lung.

Structural changes occur in the respiratory system with advancing age. Lung elasticity decreases, stiffness of the chest wall increases, and respiratory muscle strength declines. These alterations contribute to gradual, but progressive, reductions in forced vital capacity, expiratory flow rates, diffusing capacity, gas exchange, ventilatory drive, and respiratory sensation. Cigarette smoking accelerates the age-related decline in flow rates. Understanding the effects of aging on the lung is important in order to distinguish pathologic changes from changes that are part of the normal aging process.

Adult↗
PubMed2006

Oral cyclophosphamide improves pulmonary function in scleroderma patients with fibrosing alveolitis: experience in one centre.

Lung involvement constitutes nowadays the major cause of morbidity and mortality in scleroderma patients. Pulmonary fibrosis in systemic sclerosis (SSc) is thought to be the consequence of interstitial inflammation. Early diagnosis and treatment of active alveolitis is essential to prevent the deterioration of pulmonary function, improving outcome in SSc patients. The aim of the study was to investigate the effect of 1-year treatment with oral cyclophosphamide (CYC) on the evolution of interstitial lung disease in scleroderma patients with a diagnosis of active alveolitis. An open-label one-arm monocenteric study was conducted on 33 scleroderma patients with active alveolitis--defined as the presence of areas of 'ground-glass attenuation' on high-resolution computed tomography and a recent deterioration in lung function-treated with oral CYC 2 mg kg-1 day-1 for 1 year and medium-low dose steroids (prednisone 25 mg for 3 months and then tapered to 5 mg/day). Results showed that diffusing capacity for carbon monoxide (DLco) values remained stable after 6 months of treatment and significantly increased after 12 months (2.06+/-1.38, 2.21+/-1.62 and 2.39+/-1.64 mmol/min/kPa, at baseline/6/12 months, respectively; p<0.001 12th month vs baseline) vital capacity (VC) values slightly increased (i.e. stabilised) in the same time frame (2.46+/-0.71, 2.41+/-0.76 and 2.56+/-0.75 l). Accordingly, the vast majority of our patients (n=29, 87.9%) presented a DLco and/or a VC improvement or stabilisation with respect to baseline. Favourable results were more likely to be observed in patients with a lower Wells' radiological grade (grade I). In 25 patients followed up for further 12 months after the interruption of therapy, VC and DLco remained stable. Thus, long-term therapy with oral CYC is effective in ameliorating and/or stabilising lung function in scleroderma patients with active alveolitis, with beneficial effects lasting up to 1 year after interruption. The higher efficacy in those patients with an early pulmonary disease stage and a lower radiological grade underlies the importance of an early diagnosis and intervention.

Administration, Oral↗
PubMed2004

Results of lung volume reduction surgery in patients meeting a national emphysema treatment trial high-risk criterion.

OBJECTIVES: A report from the National Emphysema Treatment Trial indicated that lung volume reduction candidates with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value were at high risk for mortality and were unlikely to benefit from surgical intervention. This article examines the applicability of the National Emphysema Treatment Trial findings to our own patients. METHODS: We reviewed 280 patients who underwent bilateral lung volume reduction surgery at our institution between January 1993 and December 2001. All patients met our selection criteria, including heterogeneous distribution of emphysema. Of these 280 patients, 20 patients had both a preoperative forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of less than or equal to 20% of the predicted normal values, thus meeting one National Emphysema Treatment Trial criterion for high risk. Outcomes of the 20 patients were assessed through 5 years after the operation. The survival of the 20 patient cohort was compared with that of the 260 patients not meeting the National Emphysema Treatment Trial high-risk criterion. RESULTS: Ninety-day operative mortality included 1 (5%) patient. In all patients the forced expiratory volume in 1 second increased from 0.46 L (17%) to 0.78 L (32%), a 73% change; the diffusing capacity of carbon monoxide increased from 16% to 27%, a 70% improvement; residual volume decreased from 6.33 L (305%) to 4.26 L (205%), a 33% improvement; and room air arterial partial pressure of oxygen increased from 55 mm Hg to 64 mm Hg. Kaplan-Meier 5-year survivals did not differ between the high-risk and non-high-risk groups. CONCLUSIONS: Patients with a forced expiratory volume in 1 second and a diffusing capacity of carbon monoxide of 20% or less of predicted value might experience improvements in lung function, exercise tolerance, and quality of life with acceptable morbidity and mortality after lung volume reduction surgery.

Aged↗
PubMed1983

Nutritional status and lung function in patients with emphysema and chronic bronchitis.

This study compared the nutritional status of patients with emphysema and chronic bronchitis and examined the relationship between lung dysfunction and nutritional depletion in patients with emphysema. There was no evidence of nutritional depletion in patients with chronic bronchitis (n = 4). In contrast, patients with emphysema (n = 14) were somatically depleted. They exhibited lower values for percent ideal body weight (%IBW), arm muscle circumference (AMC), and triceps skin fold thickness (TSF) (p less than 0.05) than did patients with chronic bronchitis. The creatinine height index (CHI) was also lower in this group, but the difference was not significant (p = 0.08). In patients with emphysema, there was a good correlation between the degree of airflow obstruction and of somatic depletion (FEV1 vs %IBW, r = 0.699, p less than 0.001). The single-breath diffusing capacity (DCO) also correlated well with %IBW (r = 0.6052, p less than 0.019). These results confirm that patients with emphysema are frequently nutritionally depleted and suggest that nutritional depletion contributes to lung dysfunction in emphysema.

Aged↗
PubMed1986

Lung function abnormalities in different connective tissue diseases.

Lung volumes, forced expiratory flow-volume curves, diffusing capacity indexes, and arterial blood gases were measured in 72 non-smoking patients with various connective tissue diseases (13 with rheumatoid arthritis, 17 with systemic lupus erythematosus, 25 with progressive systemic sclerosis, 10 with primary Sjögren's syndrome, 4 with polymyositis, and 3 with mixed connective tissue disease). Small airways disease and a diffusion capacity impairment were the most frequent and marked functional abnormalities in the whole group, and were often present in asymptomatic patients. Different lung function defects seemed to be present in each disease group. In fact, large airway obstruction was prevalent in progressive systemic sclerosis, diffusion capacity impairment in systemic lupus erythematosus, and small airways disease in rheumatoid arthritis. In contrast, primary Sjögren's syndrome appeared to be the connective tissue disease in which lung function abnormalities were less frequent and less pronounced.

Adolescent↗
PubMed2003

Evaluation of oxygen uptake kinetics and oxygen kinetics of peripheral skeletal muscle during recovery from exercise in patients with chronic obstructive pulmonary disease.

The biochemical features of skeletal muscle and its contribution to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD) is under active investigation. Near-infrared spectroscopy (NIRS) can non-invasively provide information on the oxidative capacity of muscle. To clarify whether oxygenation of peripheral muscle is one determinant of exercise tolerance, we simultaneously examined the oxygen uptake (V O 2off) kinetics and oxygen kinetics of peripheral skeletal muscle evaluated by NIRS during recovery from exercise in COPD patients. Fifteen patients with COPD and five normal control subjects performed a symptom-limited incremental exercise test. On the following day, all patients performed a constant work rate exercise test while being monitored using NIRS continuously for changes in concentration of oxygenated haemoglobin (HbO2) and during expired gas analysis. We found that the time constant of during recovery from constant work rate exercise (V O 2off) and the time constant of V O 2off during recovery (tau V O 2off) were significantly longer in COPD patients than in normal control subjects. was inversely correlated with absolute values of forced expiratory volume in 1 s (FEV1.0) and FEV1.0 (% predicted). However, no significant correlation was found between and FVC (forced vital capacity), FEV1.0/FVC, or diffusing capacity of the lung for CO (DLCO). Moreover, was inversely correlated with maximal V O 2off and maximal work rate. In contrast, exhibited a significant positive correlation with tau V O 2off. These results indicate that V O 2off kinetics during recovery is related to re-oxygenation of peripheral skeletal muscle evaluated by NIRS in patients with COPD. Therefore, NIRS may be a useful tool to estimate the impairment of cardiopulmonary responses and re-oxygenation of peripheral skeletal muscle during the immediate recovery phase after exercise in COPD patients.

Aged↗
PubMed1994

Determinants of progression in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive form of lung disease with a median survival of less than 5 yr. To address the progressive nature of this disease process, we investigated the determinants of decrements in lung function in patients with IPF. We prospectively evaluated 39 subjects with IPF. Our study subjects were followed for an average of 2 yr (range, 49 to 1,883 days) and lung function was measured on at least two separate occasions (mean = 9.1 separate tests) during the follow-up period. Since IPF is characterized by reduced lung volume and abnormal gas exchange, our analysis focused on the determinants of total lung capacity (TLC) and diffusing capacity of carbon monoxide (DLCO) during the period of observation. Although, on average, there was a 5.3% increase in the TLC and a 9.8% increase in DLCO between the first and last measure of lung function, 25% of the study population experienced a decline in the TLC and 28% of the study population experienced a decline in the DLCO. Decrements in TLC were independently associated with severe dyspnea (p = 0.01) and treatment with cyclophosphamide (p = 0.03). Decrements in DLCO were significantly and independently associated with more pack-years of cigarette smoking (p = 0.02), moderate (p = 0.03) or severe (p = 0.02) dyspnea, and treatment with cyclophosphamide (p = 0.0002). These findings indicate that several clinical characteristics are independently associated with subsequent declines in TLC and DLCO in patients with IPF.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchoalveolar Lavage Fluid↗
PubMed1998

Effects of hypoxia, blood P(CO2) and flow on O2 transport in excised rabbit lungs.

In previous studies using isolated perfused rabbit lungs, an O2 deficit measured by an alveolar gas-to-end capillary blood P(O2) difference (A-aD(O2)) was absent at blood flows (Q) consistent with severe exercise. Thus factors such as VA/Q heterogeneity, shunt and diffusion limitation that contribute to an O2 deficit in vivo were absent. Here we attempted to increase diffusion limitation to O2 transport by reducing the equilibration coefficient D/(betaQ), the ratio of the diffusing capacity (D) to the product of Q and the capacitance coefficient (beta, the slope of the blood O2 content-P(O2) curve). First, we used hypoxic (10% O2) ventilation in conjunction with a low PV(O2) (approximately 25 mmHg) because beta is largest in this region of the O2 dissociation curve. Second, we increased beta by decreasing blood P(CO2) which shifts the O2 dissociation curve to the left (Bohr effect). Third, we increased Q to three times control to reduce D/Q. CO diffusing capacity was measured as a function of blood flow and blood P(O2). A deficit in O2 transport as measured by a significant A-aD(O2) was measured only under conditions of hypoxia and high blood flow. The measured O2 deficit matched the predictions from the equilibration coefficients D/(betaQ) based on measurements of beta, D and Q.

Animals↗
PubMed1997

Pulmonary tissue volume, cardiac output, and diffusing capacity in sustained microgravity.

In microgravity (microG) humans have marked changes in body fluids, with a combination of an overall fluid loss and a redistribution of fluids in the cranial direction. We investigated whether interstitial pulmonary edema develops as a result of a headward fluid shift or whether pulmonary tissue fluid volume is reduced as a result of the overall loss of body fluid. We measured pulmonary tissue volume (Vti), capillary blood flow, and diffusing capacity in four subjects before, during, and after 10 days of exposure to microG during spaceflight. Measurements were made by rebreathing a gas mixture containing small amounts of acetylene, carbon monoxide, and argon. Measurements made early in flight in two subjects showed no change in Vti despite large increases in stroke volume (40%) and diffusing capacity (13%) consistent with increased pulmonary capillary blood volume. Late in-flight measurements in four subjects showed a 25% reduction in Vti compared with preflight controls (P < 0.001). There was a concomittant reduction in stroke volume, to the extent that it was no longer significantly different from preflight control. Diffusing capacity remained elevated (11%; P < 0.05) late in flight. These findings suggest that, despite increased pulmonary perfusion and pulmonary capillary blood volume, interstitial pulmonary edema does not result from exposure to microG.

Blood Gas Analysis↗
PubMed1980

Reflection spectrophotometric measurement of O2 uptake in pulmonary arterioles of cats.

We have attempted to determine both experimentally and theoretically whether a significant quantity of oxygen enters the pulmonary blood before it reaches the alveolar wall capillaries. We built a microspectrophotometer that allowed us to record oxyhemoglobin saturation values with light reflected from transected frozen pulmonary arteries as small as 100 microns in diameter. We prepared anesthetized cats to provide optimal conditions for precapillary oxygenation, quickly froze their lungs with chilled liquid propane, and removed these lungs. We examined lung cross sections with the microspectrophotometer and recorded data indicating the presence of precapillary oxygenation. These data did not tell us how much this process normally contributes to total lung oxygenation because propane did not freeze the lungs fast enough to capture conditions exactly as they are in life. We therefore made several calculations to estimate the extent of precapillary oxygenation using available data on pulmonary arterial geometry and diffusing capacity. We concluded that pulmonary arterial blood may be as much as 15% oxygenated by this process at rest and as much as 100% during oxygen breathing.

Animals↗
PubMedDate not supplied

Lung function in children and adolescents with idiopathic interstitial pulmonary fibrosis.

Lung function of 65 patients who had idiopathic interstitial pulmonary fibrosis (IIPF) that had been treated with prednisone was evaluated by tests of ventilatory function, lung mechanics, and gas exchange at rest and during exercise. Ages on initial investigation ranged from 5 to 20 years. In 35 of 65 patients the studies were repeated an average of four times over a period of 1 to 9 years. Results of the first testing were as follows: vital capacity (VC)-significantly reduced in all patients; inspiratory capacity (IC)-significantly reduced in all patients; total lung capacity (TLC)-reduced in 91%; functional residual capacity (FRC)-reduced in 31%; residual volume (RV)-reduced in 6%; elastic recoil of the lungs (Pstl)-significantly increased in 97% at 100% TLC, significantly increased in 52% at 90% TLC, reduced in 68% at 60% TLC; 7) static compliance (Cst)-reduced in 83%; 8) dynamic compliance (Cdyn)-reduced in 88%; 9) specific airway conductance at FRC level (Gaw/TGVex)-significantly increased in 50%; 10) maximum expiratory flow rates at 60% TLC (Vmax 60% TLC, in TLC/s)-significantly reduced in 33%; 11) upstream airway conductance (Gus 60% TLC, in TLC/s/cm H2O)-reduced in 32%; 12) diffusing capacity of the lungs for carbon monoxide (DLco) related to body-surface area-abnormal in 58% (when corrected for lung size, i.e., DLco/TLC, abnormal in only 8%); 13) PaO2 at rest and after 6 minutes submaximal exercise-reduced in 25% and 63%, respectively. Changes in lung function that occurred with growth were assessed in terms of percentages of predicted values. Results showed that the VC and IC remained significantly reduced. An actual reduction of TLC, FRC, RV, breathing frequency, DLCO, and Pstl at 100% and 90% TLC was observed. Increases were seen in Pstl at 60% TLC, Gaw/TGVex, Vmax, and Cst. Indices of lung elasticity suggested that regions of fibrosis and emphysema had become present. Smaller patients were also noted to have stiffer lungs.

Adolescent↗
PubMed1986

Interstitial vasculitis--interstitial lung disease: case studies.

Six patients with interstitial lung disease were tested in a serial fashion to determine response to medications. All patients had biopsy-proven interstitial lung disease. Exercise testing with measurements of PaO2, PaCO2, and DLCO (the diffusing capacity to carbon monoxide) were made before and after exercise to determine the response to medications. Three patients were treated with corticosteroids and three patients with cytotoxic medications. Results of serial testing of gas transfer correlated with improvement of interstitial lung disease as characterized by resting PaO2, symptoms, and maximal duration of exercise. The value of serial exercise testing is of great help in some, but not all patients. The value of serial testing of patients with interstitial lung disease is discussed.

Adult↗
PubMed2002

[Alveolar-capillary dysfunction in heart failure].

Heart failure increases the resistance to gas transfer across the alveolar-capillary interface. In different experimental conditions of vascular capillary injury, peculiar anatomical and functional abnormalities of the alveolar unit have been reported and consist of a disruption of its anatomical configuration and of a loss of fluid-flux regulation and gas exchange efficiency (i.e. "stress failure" of the alveolar-capillary membrane). In heart failure, the pathophysiological relevance of these changes has been only recently appreciated. Alveolar-capillary membrane conductance and capillary blood volume are subcomponents of lung diffusion capacity. A reduction of the former with an increase of the latter and consequent impairment of gas exchange are typical of heart failure syndrome. Alveolar-capillary membrane conductance abnormalities have been shown to be a sensitive index of the underlying lung tissue damage, bring an independent prognostic information and play a significant role in the pathogenesis of exercise limitation and ventilatory abnormalities. This review examines the current knowledge on this topic.

Adult↗