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PubMed1982

Serial pulmonary function in systemic sclerosis.

The natural history of the pulmonary involvement in systemic sclerosis is not well studied. Reported here are the serial measurements of pulmonary function in a well defined population of patients with systemic sclerosis followed over a mean of 63 months. The mean rate of loss of vital capacity (0.10 liters per year) for the 38 patients serially studied was more than three times the expected rate of loss for a normal population. The mean rate of loss of diffusing capacity (0.33 ml/min/mm Hg per year) for the 27 patients serially studied was similar to that for a normal population. The percent forced vital capacity expired in the first second increased 0.53 percent per year consistent with a progressive restrictive ventilatory defect. Smokers tended to lose vital capacity at a slightly greater rate than nonsmokers (p = 0.069). Individual variability in the course of pulmonary function was observed. Although the overall trend in our population was towards a slowly progressive restrictive ventilatory defect, pulmonary function in the nonsmokers did not change at rates different from those in a nonsmoking reference population.

Adolescent↗
PubMed2001

Esophageal hypomotility in systemic sclerosis: close relationship with pulmonary involvement.

PURPOSE: Esophageal motility was assessed in patients with systemic sclerosis (SSc) by scintigraphy and compared with (i) extent of scleroderma, (ii) duration of disease, (iii) index of anti-topoisomerase I antibody (topo I), and (iv) pulmonary involvement. METHODS: A multiple-swallow test was performed in 47 patients with SSc in the supine position with 99mTc-DTPA. A region of interest on the entire esophagus was defined and the retention ratio (RR) was calculated from a time-activity curve. RESULTS: Patients with diffuse scleroderma had higher RRs than those with limited scleroderma (48.8% vs. 30.0%; p < 0.05). There was no correlation between the RRs and the duration of disease. Patients with positive topo I had higher RRs than those who were negative (53.8% vs. 29.7%; p < 0.05). Patients with reduced % diffusion capacity for carbon monoxide (%DLCO) had higher RRs than those with normal %DLCO (40.5% vs. 19.6%; p = 0.03). Patients with reduced % vital capacity (%VC) had higher RRs than those with normal %VC (54.6% vs. 25.0%; p < 0.005). Patients with pulmonary fibrosis had higher RRs than those who were negative (58.5% vs. 20.3%; p < 0.00005). CONCLUSION: Esophageal dysfunction in patients with SSc showed a correlation with the extent of scleroderma, positive topo I, and pulmonary involvement. The RR can be an objective clinical marker for the severity of organ fibrosis.

Adolescent↗
PubMed1987

A simple method of correcting diffusing capacity for alveolar volume reduction in restrictive lung diseases.

We studied the discriminative power of the transfer factor (TLCO), KCO (TLCO/Va) and ZCO (a corrected TLCO according to alveolar volume measured (Va), introduced by our group), in order to differentiate diffuse interstitial disease from other restrictive diseases. Measurements were taken in 46 subjects, divided into two groups: Pure restriction (group 1: normal subjects with voluntary restriction and diseased subjects) and (2) diffuse interstitial restriction (group 2). There were no statistical differences in Va between groups 1 and 2. TLCO was statistically lower in groups 1 and 2 in comparison with the control group (normal values of our laboratory in test with Va greater than 90% of predicted) and showed a significant difference when group 1 was compared with group 2. Similar results (but with higher values than those of the control group) were found for KCO. A similar difference exists in ZCO only when group 2 is compared with group 1, but not when group 1 is compared with the control group. The corrected diffusion capacity ZCO yields the highest discriminative power.

Humans↗
PubMed1975

[Interdependence between the main hemodynamic indices and alveolar-capillary diffusion in mitral stenosis patients].

The basic hemodynamics indices were studied in 100 patients with mitral stenosis as well as the lung diffusion capacity (DLCO) with its components--membrane component (DM) and blood volume in lung capillaries (VC). Certain correlation dependence between the indicies were studied the correlation coefficients were calculated and the regression lines plotted. The author established that the indices of blood output has a considerably direct correlation with blood component (VC) and with the diffusion capacity (DLCO). A moderately expressed reverse correlation exists between VC and the general peripheral resistance. The circulation times have a moderately manifested reverse mutual dependence with diffusion capacity. It is better manifested with DLCO and DM and decreased with VC.

Adolescent↗
PubMed2003

Retinoic acid induces nonuniform alveolar septal growth after right pneumonectomy.

To determine whether all-trans retinoic acid (RA) enhances compensatory lung growth in fully mature animals, adult male dogs (n = 4) received 2 mg x kg(-1) x day(-1) po RA 4 days/wk beginning the day after right pneumonectomy (R-PNX, 55-58% resection). Litter-matched male R-PNX controls (n = 4) received placebo. After 4 mo, the remaining lung was fixed by tracheal instillation of fixatives at a constant airway pressure for detailed morphometric analysis. After RA treatment compared with placebo, lung volume was slightly but not significantly lower. Volume density of septum to lung was 37% higher because of a 50 and 25% higher volume density of capillary and septal tissue, respectively. Mean septal thickness was 27% higher. Absolute volumes of endothelial cells and capillary blood were 31-37% higher, whereas epithelial and interstitial volumes were not different between groups. Absolute alveolar-capillary surface areas did not differ between groups, and alveolar septal surface-to-volume ratio was 20% lower in RA-treated animals. RA treatment exaggerated interlobar differences in morphometric indexes and caused alveolar capillary morphology to revert to a more immature state. Thus RA treatment during early post-R-PNX adaptation preferentially enhanced alveolar capillary and endothelial cell volumes consistent with formation of new capillaries, but the associated septal distortion precluded a corresponding increase in gas-exchange surface or morphometric estimates of lung diffusing capacity.

Animals↗
PubMed1979

Resting ventilatory pattern, mouth occlusion pressure, and the effects of aminophylline in asthma and chronic airways obstruction.

Patients with obstruction of the airways can maintain normocapnia either by increasing the central inspiratory neuromuscular output or by altering the central timing of each breath. This point and the effects of administration of aminophylline on ventilatory regulation were studied in six normal subjects, seven asthmatic patients, and eight patients with unresponsive chronic obstruction of the airways. Spirometric and body plethysmographic values, the ventilatory pattern, and the mouth occlusion pressure did not differ between the two groups of patients. The results indicate that in these patients, normocapnia is maintained at rest by increased central inspiratory neuromuscular output; central respiratory timing is not altered. Intravenous administration of aminophylline (5.6 mg/kg of body weight) increased alveolar ventilation in all three groups, without increasing the uptake of oxygen. In normal subjects, there was no significant effect on ventilatory regulation or drive. In asthmatic patients the central timing of each breath was altered, with no significant effect on central inspiratory output. In unresponsive obstruction of the airways, the central inspiratory output increased transiently, with no effect on central timing.

Adult↗
PubMed1993

Factors contributing to dyspnoea during bronchoconstriction and exercise in asthmatic subjects.

The purpose of the present study was to identify: 1) whether dyspnoea during bronchoconstriction and exercise is related, in asthmatic subjects; and 2) to what extent baseline pulmonary function and respiratory muscle strength contribute to dyspnoea under both conditions. One hundred and seventy five consecutive subjects, referred with suspected asthma, rated the intensity of dyspnoea (Borg scale 0-10): 1) during the administration of doubling concentrations of methacholine to 32 mg.ml-1 methacholine, or until the baseline forced expiratory volume in one second (FEV1) was reduced by 20%; and 2) during incremental cycle ergometry (100 kpm.min-1 each minute) to maximal capacity. 138/175 subjects achieved a 20% reduction in their baseline FEV1; 18 of the 138 were excluded, 2 children and 16 with complicating pulmonary disorders (diffusing capacity of the lung for carbon monoxide (DLCO) and/or total lung capacity (TLC) < 70% predicted). The remaining 120 out of 175 constituted the study population. Dyspnoea following a 20% reduction in the baseline FEV1 (Dys20%) was linearly interpolated, using the rating of dyspnoea and the FEV1 at the two final concentrations of methacholine. In the 120 asthmatic subjects, the mean intensity of dyspnoea was "moderate" (2.9, SD 1.91; Borg 0-10) and the intensity across subjects was not significantly related to baseline FEV1, vital capacity (VC), FEV1/VC, DLCO, TLC and maximal static inspiratory pressure (MIP), alone or in combination.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2004

Pulmonary artery occlusion increases the ratio of diffusing capacity for nitric oxide to carbon monoxide in prone sheep.

OBJECTIVE: To test the hypothesis that the ratio of diffusing capacity of the lung for nitric oxide (DLno) to diffusing capacity of the lung for carbon monoxide (DLco) would be affected by occlusion of a fraction of the pulmonary vascular bed. DESIGN: Interventional physiologic study. SETTING: Animal laboratory of a university hospital. SUBJECTS: Thirteen sheep. INTERVENTIONS: We simultaneously measured single-breath DLno and DLco in anesthetized and mechanically ventilated sheep (fraction of inspired oxygen [Fio(2)] of 1.0) before and after pulmonary artery occlusion by inflation of a balloon (n = 6), and by autologous clot embolism (n = 4). To see if the effect also occurred on Fio(2) of 0.21, four animals were studied during ventilation with room air, one of which was also in the Fio(2) of 1.0 group (14 total experiments with 13 sheep). RESULTS: On Fio(2) of 1.0, the mean DLno/Dlco ratio rose by 35% from 4.76 +/- 0.41 in control to 6.42 +/- 0.82 after balloon occlusion (p = 0.002), and by 54% from 7.55 +/- 2.09 to 11.6 +/- 2.61 (p = 0.005) after autologous clot embolism (+/- SD). An equivalent relative increase of 27% took place during ventilation with room air, but the DLno/DLco ratio was lower (3.14 +/- 0.22 in control and 3.98 +/- 0.38 after balloon occlusion). Independent of the method of obstruction or Fio(2), the increase in DLno/DLco ratio was mostly due to a drop in DLco. The DLno/Dlco ratio reduced much of the intersubject variability of either DLno or DLco alone. CONCLUSION: The DLno/DLco ratio increased after pulmonary artery occlusion regardless of the method of occlusion or Fio(2). This increase may be a result of a greater sensitivity of DLco than DLno to a regional reduction in capillary blood flow.

Animals↗
PubMed1986

Effect of ritodrine and betamethasone on metabolism, respiration, and circulation.

In order to obtain information on pharmacologic side effects of the most commonly used betamimetic in obstetrics, ritodrine (R) was infused under standardized, controlled conditions in one male and four nonpregnant female volunteers in increasing doses from 0.9 to 7.2 micrograms/kg/min. In second series, the same was done after premedication with 12 mg betamethasone (B), intravenously, 30 minutes before the start of the R infusion. Ritodrine caused increases in cardiac and respiratory work that were associated with rises in energy requirements and impaired efficiency of breathing. Premedication with betamethasone potentiated all side effects with the exception of diffusion capacity.

Adult↗
PubMed1986

Hysteresis of the alveolar capillary membrane in normal subjects.

Weibel and associates (Respir. Physiol. 18: 285-308, 1973), using morphometric techniques, demonstrated in the rat that changes in lung volume related to inflation and deflation caused a hysteretic variation in alveolar capillary membrane which is locally pleated at low pulmonary volume, unfolds during inflation but does not immediately refold during deflation, possibly enhancing the CO diffusion throughout the membrane. The present study was conducted to verify the existence of this hysteresis in human lungs in vivo. Single-breath diffusing capacity for CO (DLCO) was measured in five healthy seated subjects before and 0, 0.5, 1, 3, and 7 min after an inflation-deflation maneuver (IDM) in 6 separate days. The value of mean DLCO was 36.4 +/- 3 (SD) before and 42.1 +/- 2.9, 41.6 +/- 3.3, 40.3 +/- 3.3, 39.2 +/- 3.2, and 38.1 +/- 2.7 ml X min-1 X Torr-1 after the IDM. Two mechanisms can explain our findings: an active filling of the capillary bed, or an unfolding of the alveolar capillary membrane. The first mechanism should be accompanied by changes in pulmonary circulation. Therefore, right-heart catheterization was performed in two normal subjects and in four patients examined for a chest pain syndrome. At the end of the IDM, the values for the pulmonary artery pressure and capillary wedge pressure had returned to control levels. This suggests that the capillary bed is not directly involved in the DLCO increase observed from 0.5 to 7 min after the IDM. The unfolding of the alveolar capillary membrane appears to better explain our findings.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Volume↗
PubMed2003

Effects of radiotherapy and chemotherapy on lung function in patients with non-small-cell lung cancer.

PURPOSE: To evaluate the effects of chemoradiation on objective tests of pulmonary function. MATERIALS AND METHODS: One hundred lung cancer patients treated in five protocols between 1992 and 2000 with combinations of thoracic radiotherapy (RT) and chemotherapy were evaluated with pre- and post-RT pulmonary function tests. The pulmonary function tests were analyzed for changes in measures of obstruction (forced expiratory volume in 1 s per unit of vital capacity [FEV(1)/VC]), restriction (total lung capacity [TLC]), and diffusing capacity (diffusing capacity for carbon monoxide [DLCO]). The use and timing of chemotherapy and RT, as well as patient, tumor, and treatment factors, were evaluated using univariate and multivariate analyses. RESULTS: No treatment or patient factors were significantly associated with changes in FEV(1)/VC. Chemotherapy with RT, compared with RT alone, was associated with a lower post-RT TLC (92% vs. 107%, p = 0.002). Nodal status (N2-N3 vs. N1), tumor location (central vs. peripheral), use of >/=6 treatment fields, and tumor volume >/=100 cm(3) were also associated with a significantly lower post-RT TLC. On univariate analysis, the use of any chemotherapy (p = 0.029) and the use of concurrent vs. sequential chemotherapy (p = 0.028) were predictive of a lower post-RT DLCO. Patient age >/=60 years, nodal status (N2-N3 vs. N0-N1), tumor volume >/=100 cm(3), tumor location (central vs. peripheral), and use of >/=6 treatment fields were also associated with a significantly lower post-RT DLCO. The fractional volume of irradiated normal lung correlated with the decrease in DLCO (p <0.001), with a 1.3% DLCO decline for each 1% of total lung volume that received >20 Gy. CONCLUSIONS: The addition of chemotherapy to RT significantly exacerbates the post-RT decrease in TLC and DLCO. The greatest decrease in DLCO occurs in patients treated with concurrent chemoradiation.

Adult↗
PubMed2003

[Role of single-breath carbon monoxide-diffusing capacity in monitoring the bleomycin-induced lung toxicity in human].

OBJECTIVE: To investigate if the carbon monoxide-diffusing capacity (D(LCO)) could be the early indictor monitoring the bleomycin-induced lung toxicity (BILT) with retrospection of the influence of bleomycin cumulative dose on the pulmonary functions. METHODS: During June 1985 to October 2000, 42 patients with malignant tumor of ovarian germ cells received chemotherapy containing bleomycin in the department of Obstetrics and Gynecology of Peking Union Medical College Hospital. Twenty three patients (54.76%) among them had >or= 2 courses of chemotherapy with bleomycin and performed >or= 2 measurements of lung function. These 23 patients were included in the study. The forced expiratory volume in one second (FEV(1)), forced vital capacity (FVC), total lung capacity (TLC) and D(LCO) were measured and recorded as % of predicted. The D(LCO) was corrected by hemoglobin concentration [D(LCO) corrected = D(LCO) measured x (9.38 + Hb) divided by (1.76 x Hb)]. All the data were divided into 4 groups according to the cumulative dose of bleomycin (pre-treatment group, < 100 mg group, 101 - 200 mg group and > 201 mg group). The relationship between D(LCO) and bleomycin cumulative dose was examined by linear regression analysis and t-test. RESULTS: The values of FEV(1%)predicted in the 4 groups were 99.83 +/- 16.41 (14), 101.43 +/- 12.32 (42), 99.41 +/- 10.22 (23), and 90.96 +/- 13.63 (12), respectively. The FVC%predicted were 97.74 +/- 18.23 (14), 101.11 +/- 13.95 (42), 96.49 +/- 12.04 (23) and 89.63 +/- 18.20 (12), respectively. The TLC%predicted were 101.22 +/- 10.68 (13), 106.14 +/- 12.16 (40), 102.13 +/- 11.33 (23) and 95.05 +/- 14.06 (11), respectively. There were no statistical significant differences in the parameters among the 4 groups. The D(LCO%)predicted of the 4 groups were 93.27 +/- 12.75 (14), 94.51 +/- 12.50 (40), 80.93 +/- 10.05 (24) and 70.99 +/- 11.69 (15), respectively, and the D(LCO) of the last group (> 201 mg group) was significantly decreased as compared to that of the other groups (P < 0.05). A bleomycin dose-related fall in D(LCO) was observed, y = 100.59 - 0.11x, r = -0.649, P < 0.001. CONCLUSION: The D(LCO) might be the most sensitive indicator of subclinical BILT. However, the cumulative dose of bleomycin did not show significant influence on the FEV(1), FVC and TLC.

Adolescent↗
PubMed1985

Role of carbon monoxide diffusing capacity in the early detection of major bleomycin-induced pulmonary toxicity.

Fifteen patients with malignant teratoma and twelve with squamous cancer of the head and neck received treatment with bleomycin. Routine measurements of carbon monoxide diffusing capacity (DLco) were performed. Both groups showed a gradual fall of similar magnitude in their DLco measurements during treatment. No patient in the group with squamous cancer developed clinical or radiological evidence of major pulmonary toxicity. Two of the teratoma patients suffered fatal pulmonary toxicity and their DLco measurements before any signs of major pulmonary toxicity were no different from the measurements of those patients who remained free of major clinical toxicity. The two patients who died both showed a sustained reduction in renal function during chemotherapy which may have been a major risk factor in the development of severe clinical toxicity. The magnitude of the decline in DLco in this series was not a useful predictor of those patients who developed severe and radiological toxicity.

Adolescent↗
PubMed1976

Extracorporeal membrane oxygenation during bronchopulmonary lavage.

Extracorporeal membrane oxygenation (ECMO) in a venoarterial perfusion circuit was used to provide support of gas exchange during bronchopulmonary lavage in a 32-year-old man with pulmonary alveolar proteinosis and severe arterial hypoxemia. Prior to the lavage, Pao2 during mechanical ventilation with 100% oxygen and positive end-expiratory pressure was only 125 mm Hg. Extracorporeal perfusion at a flow rate of 3 liters/min, with oxygen delivery of 244 ml/min, increased the Pao2 to 227 mmHg and lowered the mean pulmonary artery pressure from 28 to 24 mm Hg. During bronchopulmonary lavage and ECMO, the Pao2 ranged between 46 and 96 mm Hg. After the procedure, pulmonary performance decidely improved. By reducing the chances of fatal hypoxemia, ECMO allowed treatment to be instituted for this potentially reversible disorder and proved helpful as a form of support during the management of pulmonary alveolar proteinosis when severe hypoxemia may have other wise precluded bronchopulmonary lavage.

Adult↗
PubMed1979

Pulmonary function in identical twins: comparison of nonsmokers and smokers.

Forty-five apparently normal pairs of identical twins were given pulmonary function tests to determine the role of genetics in bronchial susceptibility to cigarette smoke. Maximal expiratory flow at 60 per cent of total lung capacity (Vmax60) was the best discriminator of smokers from nonsmokers among pairs in which one member smoked and the other did not. The intrapair difference of Vmax60 values in pairs in which both members smoked was the same as in pairs in which both members did not smoke. These data support the view that genetic factors are important in determining the vulnerability of the airways to cigarette smoke.

Adult↗
PubMed1986

Approaches to assessing pulmonary dysfunction and susceptibility in workers.

Indices of the maximal forced expiration are the most widely adopted method of screening for occupational lung disease because of their ease of measurement, employee acceptability, and reproducibility. However, these indices may lack sensitivity, specificity, or validity in detecting cases of some occupational lung diseases at asymptomatic stages when intervention may affect outcome. In populations at increased risk for occupational asthma, pneumoconiosis, or hypersensitivity pneumonitis, three other types of screening are being evaluated in field settings: tests for bronchial hyperreactivity, barriers to diffusion, and abnormalities in gas distribution in the lung. The potential methods of screening--cold air challenge, methacholine challenge, peak flow logs, diffusing capacity, and single breath nitrogen tests--await clinical trials in industrial settings to evaluate whether early case finding of susceptible subjects can result in prevention of morbidity.

Cold Temperature↗
PubMed1989

Retrosternal pain is an early indicator of oxygen toxicity.

To determine the most sensitive early indicator of toxicity from exposure to O2, we measured respiratory clearance of 99mTc-diethylenetriamine pentaacetate (Tc-DTPA), pulmonary function, serum Factor VIII antigen, and plasma fibronectin values and monitored symptoms in six normal volunteers who breathed 21, 40, and 100% O2, administered in random order, for 17 h at least 1 wk apart. Twenty minutes after beginning O2, arterial PO2 differed among the three exposure groups. After exposure to the three concentrations of O2, there were no differences in Tc-DTPA clearance, vital capacity, FEV1/FVC, diffusing capacity, Factor VIII antigen, or fibronectin concentration. In contrast, all subjects complained of retrosternal pain during and after breathing 100% O2 (p less than 0.001). We conclude that with exposure to 100% O2, retrosternal pain, presumably from tracheal inflammation, occurs before detectable abnormalities of epithelial solute permeability (Tc-DTPA clearance), endothelial O2 injury (fibronectin concentration and Factor VIII), or pulmonary function. These findings indicate that symptoms are more sensitive than signs in detecting early O2 toxicity.

Adult↗