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PubMed1982

A model for the study of diffusion and perfusion limitation.

On the basis of a very simple model for the association of diffusion and perfusion, an association common to many respiratory gas transfers, a simple equation is described that defines gas partial pressure equilibration in diffusion-perfusion-limited systems as a function of the ratio of D to beta bQ(D = diffusing capacity, beta b = blood capacitance coefficient, Q = perfusion). The equation applies to steady-state conditions and assumes D, beta b, and Q to be independent of gas partial pressures. In spite of the fact that this assumption may represent a gross simplification, the equation can be regarded as a powerful conceptual tool in the analysis of most gas exchange systems.

Animals↗

PubMed2002

Retrospective analysis of the results of liver transplantation for adults with severe hepatopulmonary syndrome.

The hepatopulmonary syndrome (HPS), consisting of elevated alveolar-arterial oxygen gradient and intrapulmonary vascular abnormalities in the presence of advanced liver disease, is associated with high mortality. Liver transplantation (LT) has been used for the treatment of HPS; however, the success of LT for the treatment of HPS is not uniformly documented. We reviewed our experience over a 5-year period and identified eight adult patients with incapacitating respiratory symptoms compatible with HPS. Inclusion criteria included hypoxemia, normal lung volumes, reduced oxygen diffusing capacity (D(L)CO), and the presence of intrapulmonary shunting. Underlying liver disease was caused by hepatitis C (2 patients), primary biliary cirrhosis (1 patient), cryptogenic cirrhosis (1 patient), alcohol (2 patients), and hepatitis C with alcohol (2 patients). Six out of eight patients required preoperative oxygen support. Severe hypoxemia was present in seven patients (Pa(O2) 51.5 +/- 8.2 mm Hg). Three patients had complicating pulmonary hypertension. All patients exhibited a severely reduced D(L)CO (44.6 +/- 12.2% of predicted value). Six patients were transplanted, with five requiring oxygen support at the time of discharge. Resolution of oxygen dependency occurred in all patients but was delayed in the two patients exhibiting complicating pulmonary hypertension (288.5 +/- 37.4 v 53.5 +/- 35.7 days). All patients exhibited O2 saturations greater than 98% on room air. Currently, three patients are alive and off oxygen. The current report documents successful resolution of hypoxemia after LT in this pilot cohort. This supports the newly implemented United Network for Organ Sharing (UNOS) criteria, that LT for HPS may be extended to include patients with Pa(O2) < 60 mm Hg.

Aged↗

PubMed1996

Long-term pulmonary toxicity of multiagent chemotherapy including bleomycin and cyclophosphamide in osteosarcoma survivors.

PURPOSE: To assess long-term pulmonary effects of multiagent chemotherapy, we studied serial pulmonary function tests (PFTs) of 35 children with osteosarcoma up to 12 years after diagnosis. PATIENTS AND METHODS: We analyzed 84 sets of PFTs from 35 patients diagnosed with osteosarcoma between 1981 and 1991. They received bleomycin, cyclophosphamide, methotrexate, doxorubicin, cisplatin, and actinomycin D over 9-12 months and we performed PFTs from 3 days to 152 months after diagnosis. Time period I included 36 PFTs (43%) performed between 1 and 5 months from diagnosis, time period II included 20 PFTs (24%) performed between 8 and 12 months from diagnosis, and time period III included 28 PFTs (33%) performed between 12 and 119 months from diagnosis. Total lung capacity (TLC), forced vital capacity (FVC), forced expiratory volume in 1 second (FEV1), and carbon monoxide diffusing capacity (DLCO) were analyzed. Maximal respiratory pressures and arterial blood gases were measured to assess muscle weakness and gas exchange, respectively. Mean differences in PFTs were compared among the three time periods and between time period pairs. RESULTS: All mean PFT values showed significant differences among time periods. Significant decline in DLCO; (P=.012), TLC (P=.020), and FEV1 (P=.028) between time periods I and II were noted followed by a trend towards recovery between time periods II and III. Time periods I and III were not significantly different from one another. Mean PFTs performed after 2 years of diagnosis were not different from mean PFTs performed from diagnosis at 2 years. CONCLUSION: This dosage regimen of multi-agent chemotherapy for osteosarcoma patients caused a transient, but significant, decline in PFTs within 8-12 months after administration but appears to cause no significant long-term pulmonary function abnormalities.

Adolescent↗

PubMedDate not supplied

Severe acute respiratory syndrome: thin-section computed tomography features, temporal changes, and clinicoradiologic correlation during the convalescent period.

OBJECTIVE: To evaluate thin-section computed tomography findings of patients with severe acute respiratory syndrome (SARS) in the convalescent period and to correlate the results with clinical parameters and lung function tests. METHODS: Ninety-nine severe acute respiratory syndrome patients with persistent changes on follow-up chest radiography were included. One hundred seventy computed tomography examinations at baseline (n=70), 3 months (n=56), and 6 months (n=44) were retrospectively evaluated to determine the extent of ground-glass opacification, reticulation, and total parenchymal involvement. Patients' demographic information, clinical information during treatment, and results of lung function tests at 3 and 6 months were correlated with computed tomography findings. RESULTS: A significant serial improvement in the extent of overall ground-glass opacification, overall reticulation, and total parenchymal involvement was observed (P <0.01). Advanced age, previous intensive care unit admission, mechanical ventilation, alternative treatment, higher peak lactate dehydrogenase, and peak radiographic involvement during treatment showed a positive correlation with overall reticulation and total parenchymal involvement at 6 months. There was a significant negative correlation between overall reticulation and total parenchymal involvement with diffusion capacity adjusted for hemoglobin at 3 and 6 months (P <0.01). CONCLUSION: Lung changes on thin-section computed tomography of severe acute respiratory syndrome patients improved with time during the convalescent period and showed a significant correlation with advanced age, parameters indicating severe illness, and diffusion capacity adjusted for hemoglobin on follow-up.

Adult↗

PubMed2007

Decline of neuroadrenergic bronchial innervation and respiratory function in type 1 diabetes mellitus: a longitudinal study.

BACKGROUND AND AIM: Type 1 diabetes mellitus complicated by autonomic neuropathy (AN) is characterized by depressed cholinergic bronchomotor tone and neuroadrenergic denervation of the lung. We explored the effects of AN on the rate of decline of pulmonary sympathetic innervation and respiratory function during a 5-year follow-up. METHODS: Twenty diabetic patients, 11 with AN, were enrolled in 1998 and then followed-up until 2003. During follow-up, glycosylated haemoglobin (HbA1c) was measured every 3 months. In 1998 and 2003 the patients underwent respiratory function tests and a ventilatory scintigraphic study of neuroadrenergic bronchial innervation using 123I-MIBG. RESULTS: During follow-up 4 patients, all with AN, were lost, and 1 developed AN. Forced vital capacity (FVC), and diffusing capacity of the lung for carbon monoxide (DLCO) showed comparable rates of decrease in patients with and without AN. The yearly decline of forced expiratory volume in 1 s (FEV1) was about double the physiologic rate, in both AN and AN-free patients. The MIBG clearance significantly increased both in patients with AN (T1/2: 118.88 +/- 30.14 min at baseline and 92.10 +/- 24.52 min at the end of follow-up) and without AN (135.14 +/- 17.09 min and 92.68 +/- 13.52 min, respectively), indicating a rapidly progressive neuroadrenergic denervation. The rate of the neuroadrenergic denervation was inversely related to the severity of autonomic dysfunction at baseline (Spearman's rho - 0.62, p = 0.017). Neither respiratory function indexes nor MIBG clearance changes correlated with the overall HbA1c values. CONCLUSIONS: Neuroadrenergic denervation of the lung parallels the decline of respiratory function indexes in diabetic patients both with and without AN and seems to be independent from the quality of glycemic control.

3-Iodobenzylguanidine↗

PubMed1992

Isolated diffusing capacity reduction in systemic sclerosis.

OBJECTIVE: To determine the long-term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLCO) at the time of initial evaluation. METHODS: Patients with an isolated reduction in DLCO (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV1] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined. RESULTS: An isolated reduction in DLCO, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLCO (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLCO of less than 55% of predicted normal and a FVC (% predicted)/DLCO (% predicted) ratio of greater than 1.4. Among all patients in whom this ratio was greater than 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was less than 1.4 (P less than 0.01). Of the 152 patients with isolated DLCO reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0-13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLCO demonstrated a significant improvement (greater than 20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit. CONCLUSION: Isolated reduction in DLCO is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLCO (less than 55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.

Carbon Monoxide↗

PubMedDate not supplied

[Respiratory parameters in pneumoconiotic miners in the north French coal district (author's transl)].

The authors examine the respiratory tests performed during a two years-period in 676 pneumoconiotic miners. Spirography was normal in 8% of the cases; a mixed ventilatory impairment, with an obstructive prevalence of variable extent, was present in 2/3 of the cases. Pharmacodynamic tests in 353 subjects showed a frequent non-specific bronchial sensitivity (34.2% of the whole group). Hypoxaemia (PaO2 below 75 mmHg) with normo- or hypocapnia was observed in 379 patients; hypercapnia was relatively uncommon (9.9%) and occurred mainly in bronchitic patients. The breath holding CO lung transfer test was very often disturbed, as the diffusing capacity (DLCO) was below the predicted value in about 80% of the population. Radiofunctional comparisons were carried out in an homogeneous group of 212 subjects. The data clearly demonstrate that functional abnormalities were not exclusively seen in extensive radiological forms. As far as it goes beyond a simple ventilatory study, the measurement of the breath holding lung transfer factor for CO has proved to be a valuable element in the functional statement of anthracosilicosis. The polymorphism of the pulmonary repercussions of dust exposure explains individual differences between the results of the main investigations, and this emphasizes the need for a series of diversified tests.

Adult↗

PubMed1997

Relationship between loss in parenchymal elastic recoil pressure and maximal airway narrowing in subjects with alpha1-antitrypsin deficiency.

Airway hyperresponsiveness is characterized by an increase in sensitivity and excessive airway narrowing to inhaled bronchoconstrictor stimuli. There is experimental evidence that maximal airway narrowing is related to lung elasticity in normal and asthmatic subjects. We hypothesized that reduced lung elasticity by parenchymal destruction increases the level of maximal airway narrowing in subjects with alpha1-antitrypsin deficiency. To that end, we measured complete dose-response curves to methacholine, quasistatic pressure-volume (P-V) curves, diffusion capacity for carbon monoxide per unit lung volume (DLCO/VA), and mean lung density by spirometrically controlled computed tomography (CT) scan in eight non- or ex-smoking subjects with alpha1-antitrypsin deficiency. Methacholine dose-response curves were expressed as the provocative concentration causing 20% fall in FEV1 (PC20). A maximal response plateau was considered if > or = 3 highest doses fell within a 5% response range, the maximal response (MFEV1) being the average value on the plateau. The P-V curves were characterized by an index of compliance (exponent K), and elastic recoil pressures at 90, and 100% of TLC (PL90 and PLmax). In all subjects a complete dose-response curve to methacholine could be recorded. MFEV1 was significantly correlated with logPC20 (r = -0.94, p < 0.001), but not with baseline FEV1 (r = -0.53, p > 0.15). There was a significant relationship between MFEV1 and PL90 (r = -0.79, p < 0.02), PLmax (r = -0.87, p < 0.005), and K (r = 0.79, p < 0.02). Furthermore MFEV1 was significantly correlated with DLCO/VA (r = -0.76, p < 0.03) and with lung density (r = 0.78, p < 0.04). We conclude that in subjects with alpha1-antitrypsin deficiency the level of maximal airway narrowing increases with loss in lung elasticity, with reduction in diffusing capacity, and with lowered mean lung density. This suggests that loss in elastic recoil pressure secondary to parenchymal destruction contributes to excessive airway narrowing in humans in vivo.

Adult↗

PubMed1985

Reference equations for the single-breath diffusing capacity. A cross-sectional analysis and effect of body size and age.

A longitudinal study was implemented in an unpolluted rural area of northern Italy (near Venice), before the start of the operation of a large oil-burning thermoelectric power plant, in order to investigate the effects of the future exposure to air pollution and to elucidate the natural history of obstructive airways diseases. During the first cross-sectional survey, a sample of the general population (n=3,300, 8 to 64 yr of age) performed several lung function tests, and information on risk factors and on the presence of respiratory symptoms were obtained by a standardized questionnaire. There were 712 subjects who were classified as normal on the basis of rigid criteria and who were able to perform satisfactorily a single-breath CO diffusing capacity (DLCOsb) test. The DLCOsb values showed an increase with height and age early in life and a later decrease with age. Two age groups were selected to determine an age at which DLCOsb stopped increasing and began to decline. Reference equations were computed (using age and height) in these 2 different age groups in each of the sexes. Similar equations were calculated for the total lung capacity derived from single-breath helium dilution measurements. The DLCOsb values in this study were higher than reported by other investigators. The method of selection of the study population, the strict criteria for normal, as well as technical, differences probably explain this finding. Reference equations for diffusing capacity corrected to lung volume (DL/VA) were computed only for adults (much greater than 20) in both sexes, because age and height coefficients in young subjects were insignificant.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

PubMed1995

Relationship of rheumatoid factor to lung diffusion capacity in smoking and non-smoking patients with rheumatoid arthritis.

We studied the relationship of serum rheumatoid factor (RF) and certain other variables to lung diffusion capacity for carbon monoxide (DLCO) in patients with rheumatoid arthritis (RA). In non-smoking patients none of the examined variables correlated significantly to DLCO whereas in smokers RF showed a significant (p < 0.01) negative correlation in this respect. These results indicate that smoking in connection with RF may contribute to reduced DLCO in RA patients.

Adult↗

PubMed2006

Pulmonary function testing in idiopathic interstitial pneumonias.

Diffuse parenchymal lung diseases are a group of disorders that involve the space between the epithelial and endothelial basement membranes and are generally segregated into four major categories. These include the idiopathic interstitial pneumonias, which are further categorized into seven clinical/radiologic/pathologic subsets. These disorders generally share a common pattern of physiologic abnormality characterized by a restrictive ventilatory defect and reduced diffusing capacity (DLCO). Pulmonary function testing is often used and recommended in their assessment and management. The potential clinical application of physiologic testing includes to aid in diagnosis, although its value in differential diagnosis is limited. Pulmonary function testing also aids in establishing disease severity and in defining prognosis. In nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis, severely decreased DLCO has proven valuable in this regard. Similarly, exertional desaturation to less than 88% at baseline testing and a decrease in FVC (greater than 10%) over the course of short-term follow-up identify patients at particular risk of mortality. Finally, physiologic testing, especially spirometry and DLCO, have demonstrated value in monitoring response to therapy and identifying disease progression.

Diagnosis, Differential↗

PubMed1982

The influence of lung volume on gas transfer in scoliosis.

Single-breath carbon monoxide transfer factor (DLCO) and diffusion coefficient (KCO) 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 DLCO were below, and for KCO above, predicted values. Furthermore, in each group, DLCO was correlated with lung volume and KCO inversely correlated with lung volume. The reduction in DLCO is probably due to the reduction in the total alveolar surface area and the increased values for KCO probably result from an increase in pulmonary capillary blood volume per unit alveolar volume at low lung volumes.

Adolescent↗

PubMed1981

Serial estimations of carbon monoxide diffusing capacity in intrapulmonary haemorrhage.

1. Serial estimations of the diffusing capacity for carbon monoxide, with a standard single-breath technique, were used to assist the monitoring of disease activity in patients at risk from intrapulmonary haemorrhage. 2. A reversible rise in diffusing capacity for carbon monoxide per unit alveolar volume (DLCO/VA) of 50% or more above baseline values was detected on 61 occasions and in the diffusing capacity for carbon monoxide (DLCO) alone on 45 occasions in 39 patients. 3. Concurrent with these rises in DLCO/VA or DLCO, two or more traditional indicators of intrapulmonary haemorrhage (haemoptysis, abrupt fall in haemoglobin concentration, chest X-ray opacities) were found on 47 occasions. 4. In the appropriate clinical context, acute reversible rises in DLCO/VA or DLCO reflect active intrapulmonary haemorrhage.

Adult↗

PubMed1982

[Carbon monoxide tests in a steady state. Uptake and transfer capacity, normal values and lower limits].

The aim of this study was to establish data which would best demonstrate the variations of different tests using Carbon Monoxide as a tracer gas (total and partial functional uptake coefficient and transfer capacity) to establish mean values and lower limits of normal of these tests. Multivariate statistical analysis was used; in the first stage a connection was sought between the fractional uptake coefficient (partial and total) to other parameters, comparing subjects and data. In the second stage the comparison was refined by eliminating the least useful data, trying, despite a small loss of material, to reveal the most important connections, linear or otherwise. The fractional uptake coefficients varied according to sex, also the variation of the partial alveolar-expired fractional uptake equivalent (DuACO) was largely a function of respiratory rate and tidal volume. The alveolar-arterial partial fractional uptake equivalent (DuaCO) depended more on respiratory frequency and age. Finally the total fractional uptake coefficient (DuCO) and the transfer capacity corrected per liter of ventilation (TLCO/V) were functions of these parameters. The last stage of this work, after taking account of the statistical observations consistent with the facts of these physiological hypotheses led to a search for a better way of approaching the laws linking the collected data to the fractional uptake coefficient. The lower limits of normal were arbitrarily defined, separating those 5% of subjects deviating most strongly from the mean. As a result, the relationship between the lower limit of normal and the theoretical mean value was 90% for the partial and total fractional uptake coefficient and 70% for the transfer capacity corrected per liter of ventilation.

Adolescent↗

PubMed1981

Effect of prolonged recombency on pulmonary blood volume in normal humans.

We have observed a progressive decrease in pulmonary blood volume during sustained recumbency measured using two independent methods. Pulmonary capillary blood volume (Vc) was estimated by the method of Roughton and Forster (J. Appl. Physiol. 11: 290, 1957). We measured regional pulmonary blood volume (PBVR) using 99mTc-labeled erythrocytes (Gorin et al., J. Appl. Physiol.: Respirat. Environ. Exercise Physiol. 45: 225, 1978). In 21 studies in 19 normal subjects, we measured pulmonary CO diffusing capacity by the single-breath technique and calculated Vc with the subjects seated and at fixed times after lying down. After 5 min in the recumbent position, there was a mean 49% increase in Vc over the value in the seated position. With sustained recumbency Vc decreased 18.3%/h over 90 min. In 12 studies in 8 normal subjects, PBVR declined 16.7%/h with prolonged recumbency in studies lasting 60-90 min. The initial increase in Vc after subjects assumed a supine position has been well described. The subsequent fall in pulmonary blood volume to levels equal to or below that measured with the subject seated has not previously been reported.

Adolescent↗

PubMed2003

Retinoic acid-induced alveolar cellular growth does not improve function after right pneumonectomy.

To determine whether all-trans retinoic acid (RA) treatment enhances lung function during 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 3 mo, transpulmonary pressure (TPP)-lung volume relationship, diffusing capacities for carbon monoxide and nitric oxide, cardiac output, and septal volume (V(tiss-RB)) were measured under anesthesia by a rebreathing technique at two lung volumes. Lung air and tissue volumes (V(air-CT) and V(tiss-CT)) were also measured from high-resolution computerized tomographic (CT) scans at a constant TPP. In RA-treated dogs compared with controls, TPP-lung volume relationships were similar. Diffusing capacities for carbon monoxide and nitric oxide were significantly impaired at a lower lung volume but similar at a high lung volume. Whereas V(tiss-RB) was significantly lower at both lung volumes in RA-treated animals, V(air-CT) and V(tiss-CT) were not different between groups; results suggest uneven distribution of ventilation consistent with distortion of alveolar geometry and/or altered small airway function induced by RA. We conclude that RA does not improve resting pulmonary function during the early months after R-PNX despite histological evidence of its action in enhancing alveolar cellular growth in the remaining lung.

Animals↗

PubMed1988

C1q and C3 in bronchoalveolar lavage fluid from patients with summer-type hypersensitivity pneumonitis.

Immune complexes have been thought to participate in the pathogenesis of hypersensitivity pneumonitis, but the role of complement components is not defined. In our study of nine patients with summer-type hypersensitivity pneumonitis (summer-type HP), C1q in bronchoalveolar lavage fluid (BALF) was strikingly increased (mean 3.7, range 0.4 to 10 micrograms/ml). The value of C1q/albumin was several to 20 times greater in BALF than in serum samples from individual patients. In contrast, BALF samples from control subjects (ten patients with sarcoidosis and nine normal subjects) contained an undetectable amount (less than 0.02 micrograms/ml) of C1q. C3 in BALF also increased in the summer-type HP patients. Furthermore, C1q (as well as specific IgG and IgA antibody activities to Trichosporon cutaneum antigen) in BALF correlated with clinical symptoms and diffusing capacity (DCO), while the BAL lymphocytosis or the change of OKT4/OKT8 ratio did not. These findings are indicative of local secretion or concentration mechanism of C1q and C3, supporting the involvement of immune complexes in the respiratory tract of the patients.

Alveolitis, Extrinsic Allergic↗

PubMed1983

Maturation of lung function in children with hypopituitarism.

To identify factors that bring about maturation of the respiratory system, we studied pulmonary function in 18 patients 9 to 19 yr of age with severe growth retardation caused by hypopituitarism. In 6 we measured pulmonary pressure-volume (P-V) curves before and after a 4 to 6 yr period of human growth-hormone-induced catch-up growth. Even when size-corrected according to total lung capacity (TLC), all measurements were more appropriate for height than for age. The ratio of functional residual capacity to TLC was low for age (less than 2 SD in 8 of 18 patients), and the ratio of closing capacity to TLC was slightly high for age (108% of predicted, p less than 0.05). The diffusion constant for carbon monoxide and the slope of the nitrogen washout alveolar plateau were both high for age. Lung elastic recoil was low for age; Pst(L) at 60% TLC was less than 2 SD in 3 of the 6 patients studied. During the period of catch-up growth, TLC increased appropriately for height, the slope of the alveolar plateau decreased (1.9 to 1.0% N2 L, p less than 0.01) and Pst(L) at 60% TLC increased (6.3 to 7.9 cm H2O, p less than 0.02). The P-V results indicate that growth of the lungs per se causes the increase in lung elastic recoil previously observed during childhood.

Adolescent↗