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Biomedical subjects

R M Cherniack

Publications and source records attributed to R M Cherniack.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of respiratory function in health and disease.

From a conceptual standpoint, the tests of pulmonary function can be divided into those that assess the ventilatory function of the lungs and those concerned with gas exchange. Tests of ventilatory function reflect alterations of the elastic resistance and flow resistance of the respiratory apparatus. The elastic properties of the lungs are assessed by determining the position and shape of the curve representing the relationship between the pressure across the lungs and absolute lung volume. When there is reduced distensibility of either the lungs or the chest wall, the volume-pressure curve is shifted down and to the right. The slope of the curve is reduced in the patient with pulmonary fibrosis, while it is normal in the patient with obesity. In asthma (or chronic bronchitis) and emphysema, the volume-pressure curve is shifted up and to the left. In emphysema, the slope of the curve is increased, while it is normal in patients with asthma or bronchitis. In practice, lung volume is used as an index of alterations of the volume-pressure characteristics of the lungs and/or chest wall. The vital capacity is often used as a surrogate for the TLC but it is lower than expected in both restrictive and obstructive disorders. The FEV1.0 reflects the degree of expiratory flow limitation. In a restrictive disorder, lung volume and the FEV1.0 are reduced, but the FEV1.0/FVC ratio is normal. In airflow limitation, lung volume, the FEV1.0, and the FEV1.0/FVC ratio are lower than expected. In airflow limitation, the reversibility with inhaled bronchodilator should be determined. Tests of airway responsiveness are indicated when evaluating patients with unexplained chronic cough, chest tightness, or wheezing, particularly if other lung function tests are normal. The adequacy of gas exchange is assessed by determining the arterial blood gas tensions--PaO2 and PaCO2--and the alveoloarterial pO2 gradient--P(A-a)O2. A lower-than-expected PaO2 can result from several different physiologic disturbances. When alveolar hypoventilation is the sole disturbance, the oxygen in the alveoli and in the blood perfusing them virtually comes into equilibrium, so that the P(A-a)O2 is normal. An elevated P(A-a)O2 is caused by either mismatching of ventilation and perfusion, true venous admixture, a diffusion abnormality, or a combination of these disturbances. Because dyspnea on exertion is a cardinal symptom of respiratory disease, exercise tolerance should be assessed. A reduced exercise tolerance may result from ventilatory limitation, impaired gas exchange, cardiac impairment, impaired delivery of the oxygen to the working muscles, or an inability to use the energy.

Acid-Base Imbalance↗
PubMed1992

Inflammatory cells and eicosanoid mediators in subjects with late asthmatic responses and increases in airway responsiveness.

To determine the relationship of inflammatory cells and eicosanoid mediators to the pathogenesis of the late asthmatic response (LAR) and increases in nonspecific airway responsiveness, we studied bronchoalveolar lavage (BAL) cells and fluid in 27 subjects 12 hours after inhaled antigen challenge. Methacholine challenge was performed before antigen challenge and 24 hours later (12 hours after BAL). Eight subjects had no LAR (-LAR, less than or equal to 10% fall in FEV1), nine subjects had an equivocal LAR (+/- LAR, 11% 25% fall in FEV1), and 10 subjects had a definite LAR (+LAR, greater than 25% fall in FEV1). Subjects developing +LAR had increased airway responsiveness at baseline compared with that of subjects developing an +/- LAR, but not with subjects having -LAR. If airway responsiveness was markedly increased at baseline, further increases after antigen challenge were often not observed. We found that both percent neutrophils and eosinophils increased in BAL as the severity of the LAR increased, but significant differences between the groups with -LAR and +LAR were only observed when both cell types were considered together. In addition, there was a significant correlation between the combined cell percentages and the severity of the LAR as determined by fall in FEV1. Likewise, increases in airway responsiveness were associated with significant increases in both neutrophil and eosinophil numbers, but only neutrophils correlated with the change in airway responsiveness after antigen challenge. However, despite the significant physiologic and cellular differences that we found between our groups, no significant differences could be found in BAL eicosanoid-mediator concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

Airway Resistance↗
PubMed1992

Idiopathic pulmonary fibrosis. Quantitative assessment of lung pathology. Comparison of a semiquantitative and a morphometric histopathologic scoring system.

The objective of this study was to determine the accuracy of a semiquantitative method of assessing the relative degree of cellularity and fibrosis compared with a morphometric analysis of specific histopathologic features in idiopathic pulmonary fibrosis (IPF). Morphometric analysis was performed on biopsy tissue from 20 patients. Morphometry showed that approximately 70% of parenchymal tissue was abnormal: 35% cellular consolidation and fibrosis, 20% honeycomb changes, 10% thick alveolar septa, and 5% small airways within abnormal parenchymal tissue. The prominent components of the abnormal parenchymal tissue were extracellular fibers, an abundance of interstitial cells, and epithelial cell hyperplasia. Correlation between four groupings of pathologic features, identified by a semiquantitative analysis, and each of the components of the parenchymal lesions showed significant correlations between (1) the fibrotic or reparative factor (alveolar wall metaplasia, fibrosis, honeycombing, and smooth muscle and vascular changes) and components of honeycomb lesions (extracellular fibers, interstitial cells, and epithelial injury and repair), and (2) the inflammatory and exudative factor and extracellular fibers in the lesions. These results support that the scoring system used by the pathology panel provides an accurate assessment of pathologic features useful in the assessment of the extent and severity of the histopathologic lesions of IPF.

Biopsy↗
PubMed1992

The utility of spirometry in the diagnosis of reversible airways obstruction.

Patients with suspected reversible airways obstruction (RAO) sometimes report subjective benefit after bronchodilator treatment despite no objective spirometric improvement. One possible explanation for this is improvement in volume-related or plethysmographic parameters in the absence of spirometric improvement. One hundred patients with RAO were assessed before and after inhaled bronchodilator to determine the prevalence of improvement by plethysmographic parameters in the absence of improvement in spirometric parameters. Spirometry alone (FEV1, FVC, and FEF25-75%) identified reversibility of airflow limitation in 82 patients. Reversibility was identified by body plethysmography (specific conductance [SGaw], thoracic gas volume [TGV], and isovolume maximum expiratory flow rates [IVMEF]) in 15 of the remaining patients. The percent predicted FEF25-75% at baseline was higher in patients who required plethysmography to identify reversibility, but could not be used to predict the lack of a spirometric response for any individual patient. We conclude that spirometry alone fails to identify reversibility in approximately 15 percent of patients, and that most of these patients can be identified by additional plethysmographic measurements of volume-related parameters. At any one point in time, multiple tests must be used together to adequately identify the majority of patients with reversible airways obstruction. Improvement in volume-related parameters may explain why some patients with RAO improve subjectively with bronchodilators but show no spirometric improvement.

Adrenergic beta-Agonists↗
PubMed1992

Prolonged monocyte accumulation in the lung during bleomycin-induced pulmonary fibrosis. A noninvasive assessment of monocyte kinetics by scintigraphy.

It has become more evident that monocytes, macrophages, and their products interact in a complex manner with various cell types in the lung, and may under the proper set of conditions contribute to the pathogenesis of pulmonary fibrosis. Current methods used to assess the lung content of mononuclear cells, which include tissue immunohistochemistry and bronchoalveolar lavage fluid analysis, sample the lung at one point in time and therefore provide only a "snapshot" of dynamic process. We utilized external imaging (scintigraphy) to provide a dynamic assessment of the trafficking patterns of radiolabeled monocytes in the lungs of rabbits in conjunction with lung tissue morphometry and bronchoalveolar lavage fluid analysis to determine the kinetics of neutrophil and monocyte accumulation in the alveolar walls and alveolar spaces of the lung during bleomycin-induced pulmonary fibrosis. We found that scintigraphy accurately reflected the accumulation of monocyte-associated radioactivity in the alveolar walls over time as well as the subsequent migration of these cells into alveolar spaces during the acute phase of bleomycin-induced lung injury (days 0 to 14) when compared with lung tissue morphometry. The scintigraphy, lavage, and morphometry data together showed that neutrophil influx into both of these lung compartments preceded that of monocytes by days, and that the influx of monocytes accounted for a major proportion of mononuclear cells found in the alveolar walls and alveolar spaces of the lung during this acute phase of inflammation. The increased numbers of neutrophils and mononuclear cells in alveolar spaces normalized by days 14 and 28 respectively, but in contrast to the normalization of neutrophil content in alveolar walls by day 10, increased numbers of mononuclear cells persisted in alveolar walls for up to 56 days, a time when there was a significant increase in the hydroxyproline content of these lungs. These data also show that the increased number of mononuclear cells present in the alveolar walls on days 28 and 56 was not due to a persistent influx of blood monocytes. These data suggest: (a) that differential pathways of efflux existed for alveolar wall versus alveolar space mononuclear cells, (b) that a delay in efflux from the alveolar walls occurred and/or that an increase in the local proliferation of mononuclear cells in this compartment may have been occurring during the later phases of bleomycin-induced lung injury, and (c) that this prolonged residence of mononuclear cells in the alveolar walls occurred concurrently with the development of pulmonary fibrosis.

Animals↗
PubMed1991

Sustained improvement in gas exchange after negative pressure ventilation for 8 hours per day on 2 successive days in chronic airflow limitation.

Negative pressure ventilation (NPV) was applied for 6 to 8 h/day for 2 consecutive days in 13 patients with severe airflow limitation and chronic respiratory failure. After cessation of NPV, the mean arterial blood gases were improved in 10 patients, and this improvement was sustained for the nex 2 days in eight patients, for 3 days in seven patients, and was still present in four patients on the fourth day. Respiratory muscle strength improved in all patients, but there was no relationship between the increase in strength and sustained improvement in gas exchange. Ventilation and respiratory pattern were unchanged in all patients, but the mean VD/VT fell and VA rose while the VO2 and VCO2 fell. The ventilatory responses to hypoxia and hypercapnia increased in patients who demonstrated sustained improvement in blood gases. The mechanism underlying the sustained improvement in gas exchange following NPV is not clear but is likely multifactorial.

Aged↗
PubMed1991

Quantitative assessment of lung pathology in idiopathic pulmonary fibrosis. The BAL Cooperative Group Steering Committee.

The diagnosis and classification of most interstitial lung diseases requires histologic evaluation of lung tissue, obtained by an open lung biopsy to confirm the diagnosis. In addition, it is generally accepted that response to therapy in idiopathic pulmonary fibrosis (IPF) is related to the relative degree of cellularity and fibrosis present. Because only a qualitative assessment of the relative extent and severity of these changes is generally provided, correlation with clinical and physiologic alterations is difficult. This report describes results of a semiquantitative assessment by four pathologists of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, in addition to an overall assessment of cellularity and fibrosis in 50 patients with IPF. In 10 randomly selected biopsies examined twice in a blinded fashion, absolute agreement between assessments for a given pathologist varied between 54 and 64% (mean = 57.5%) and in the majority of instances the agreement was greater than would have occurred by chance. There was good agreement for most variables across the four raters on the 101 samples. The mean score for some of the parameters reported by a given rater deviated occasionally from those of the other raters, but no single rater was consistently different from the other raters. A principal component factor analysis revealed that the pathologic features fell into four general groupings: alveolar wall metaplasia, fibrosis, honeycombing, smooth muscle, and vascular changes fell into one group; severity and extent of cellularity in the alveolar wall into a second group; severity and extent of cellularity in the alveolar space into a third group; and interstitial young connective tissue along with granulation tissue in the airways formed the fourth group.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1991

The impact of smoking on mechanical properties of the lungs in idiopathic pulmonary fibrosis and sarcoidosis.

Interstitial lung disease is characterized by interstitial inflammatory cell infiltration and fibrosis, a reduction in lung volumes, an increase in lung elastic recoil, and rapid shallow respirations. However, the alterations in lung volumes and elastic recoil as well as in breathing pattern are extremely variable, and the values are normal in a number of patients. In order to determine whether the effects of smoking could account for the variability in lung volumes and breathing pattern, we evaluated the elastic properties of the lung and the respiratory frequency at rest and during exercise in smokers and in nonsmokers with idiopathic pulmonary fibrosis (IPF) or with sarcoidosis. The volume-pressure curve in patients with IPF who smoked was positioned upwards and to the left when compared with that in nonsmokers. Conversely, the volume-pressure curve in patients with sarcoidosis who smoked was shifted downwards and to the right. In both conditions the respiratory rate while at rest and during exercise was greater in the group of patients who demonstrated the lower positioning of volume-pressure curves of the lungs (i.e., nonsmokers with IPF and smokers with sarcoidosis). We conclude that the impact of smoking may account, at least in part, for the variability in lung volume and volume-pressure characteristics of the lungs as well as the variability in respiratory rates in patients with interstitial lung disease.

Adult↗
PubMed1990

Surface and tissue forces, surfactant protein A, and the phospholipid components of pulmonary surfactant in bleomycin-induced pulmonary fibrosis in the rat.

Administration of bleomycin to animals results in an alteration of the pressure-volume relationship of the lungs with an increased elastic recoil at any given volume. We sought to evaluate the relative importance of surface forces to elastic recoil by comparing the differences between the air and saline pressure-volume curves. The difference in elastic recoil between air- and saline-filled lungs was altered in bleomycin-treated rats when elastic recoil was compared at 35% of predicted TLC or at 80% of observed TLC. This pressure difference was present both during the early phase (Days 4 and 7) of the injury and acute inflammation as well as during the later phase (Days 14 to 28) when there was chronic inflammation and an elevation in the lung hydroxyproline content. The total amount of phospholipids recovered in lavage was decreased at Day 4 and increased more than 2.5-fold over saline-instilled control animals at Days 21 and 28. The percentage of phosphatidylglycerol was reduced and that of phosphatidylinositol increased. There was no consistent change in the percentage of phosphatidylcholine that was disaturated. The amount of surfactant protein A (SP-A) did not change during the course of the experiment and was not a useful independent marker of alveolar injury or changes in pulmonary compliance. The ratio of SP-A to total phospholipid decreased 14 to 28 days after instillation of bleomycin. These results support the hypothesis that individual components of surfactant are independently regulated and indicate that SP-A content in lavage is insensitive to lung injury and repair.

Animals↗
PubMed1990

Relationship of diaphragm glycogen, lactate, and function to respiratory failure.

Diaphragmatic function and biochemical changes were studied during respiratory failure induced by incremental inspiratory threshold loading in anesthetized rabbits (1) who were unbound and spontaneously breathing, (2) during lower thoracic and abdominal binding, and (3) while bound and undergoing transvenous phrenic nerve pacing of the diaphragm. There was no evidence of contractile fatigue or alterations in glycogen or lactate concentrations in the diaphragm of unbound spontaneously breathing animals. With thoracoabdominal binding, there was a fall in maximal transdiaphragmatic pressure (Pdimax) and the ratio of diaphragmatic force divided by neural input (Pdi/Edi ratio); there was no change in diaphragm glycogen, but there was a significant rise in lactate. In the bound and phrenic-paced animals Pdimax and Pdi/Edi ratio fell, and there was significant glycogen depletion and lactate accumulation. There was a significant correlation between diaphragm function and the levels of diaphragm glycogen and lactate at the point of respiratory failure. We conclude that (1) respiratory failure induced by incremental inspiratory threshold loading was not associated with either contractile fatigue of the diaphragm or diaphragmatic biochemical changes in unbound spontaneously breathing animals, (2) when mechanisms that preserve diaphragmatic function are circumvented by phrenic pacing and/or thoracoabdominal binding, diaphragm fatigue and biochemical changes occur, and (3) there is a significant relationship between in vivo evidence of contractile fatigue of the diaphragm and diaphragmatic glycogen depletion and lactate accumulation.

Acid-Base Equilibrium↗
PubMed1990

The effect of hyperinflation on respiratory muscle strength and efficiency in healthy subjects and patients with asthma.

We evaluated respiratory muscle strength and efficiency in 15 patients with asthma. There was a significant reduction in mean Plmax (89.3 +/- 4.7 versus 110.5 +/- 9.4 cm H2O, p less than 0.001) and efficiency (2.41 +/- 0.2 versus 4.2 +/- 0.6%, p less than 0.01). This reduction in strength and efficiency was seen only in the male patients. Following bronchodilator, there was a significant increase in Plmax (from 89.3 +/- 4.7 to 96.2 +/- 5.4 cm H2O, p less than 0.005) and efficiency (from 2.41 +/- 0.2 to 3.22 +/- 0.2%, p less than 0.001). There was no correlation between the change in strength and efficiency and the degree of improvement in FEV1 following bronchodilator. However, there was a significant correlation with the fall in lung volume. To determine whether hyperinflation would result in a reduction in respiratory muscle strength and efficiency, we induced a mean increase in end-expiratory lung volume of 0.66 L by applying continuous negative pressure around the chest in 10 healthy individuals. This was associated with a significant fall in Plmax (from 110.5 +/- 9.4 to 100.5 +/- 8.93 cm H2O, p less than 0.001) and efficiency (from 4.2 +/- 0.6 to 2.6 +/- 0.5%, p less than 0.005). The data suggest that the strength and efficiency of the respiratory muscles are reduced in asthmatic males but not in the females. The strength and efficiency of the respiratory muscles improve significantly following bronchodilator, and this improvement is related to reduction in lung volume.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Agonists↗
PubMed1990

Effect of corticosteroids on respiratory muscle histopathology.

Pathologic alterations induced by corticosteroid administration were evaluated in the respiratory muscles and compared to those in the peripheral skeletal muscles of the rabbit. Alterations in gross and microscopic pathology as well as histochemistry were determined in the diaphragm, intercostal, sternocleidomastoid, extensor digitorum longus, and soleus muscles following 3 wk of intramuscular cortisone injections. Corticosteroid administration induced significant pathologic changes in all the muscles except the soleus. Although gross pathologic changes were greatest in the extensor digitorum longus, microscopic changes were greatest in the diaphragm. Reductions in total muscle fiber volume were similar in the diaphragm, sternocleidomastoid, and extensor digitorum longus muscles. The composition of muscle fiber types and the number of fibers in a muscle were not altered in any of the muscles studied following corticosteroids. There was significant atrophy of individual muscle fibers in all the muscles except the soleus. In the diaphragm, corticosteroids induced atrophy of all fiber types, including type I fibers. Atrophy of type I fibers was not present in the peripheral skeletal muscles or the other respiratory muscles. On the other hand, corticosteroids induced selective atrophy of type IIb muscle fibers in the intercostal and sternocleidomastoid muscles similar to that in the peripheral skeletal muscles. These findings suggest that the effect of corticosteroids on the diaphragm is unique, and one cannot extrapolate form the effect of corticosteroids on peripheral skeletal muscles to that in the diaphragm. In addition, these pathologic changes may have functional relevance, since atrophy of type I fibers may result in a reduction in muscle endurance.

Animals↗
PubMed1990

Attenuation of the metabisulfite-induced bronchoconstrictive response by pretreatment with cromolyn.

In a retrospective analysis of 1,544 patients who underwent provocative challenge with metabisulfite at the National Jewish Center between 1983 and 1987, an abnormal airway response to metabisulfite was found in 52 patients, an incidence of 3.4 percent. There was no relationship between this abnormal airway responsiveness to metabisulfite and the degree of airway obstruction present, or the degree of airway reactivity as assessed by the response to inhaled bronchodilator or exercise testing. In a pilot study, we found that the administration of cromolyn sodium prior to metabisulfite challenge markedly attenuated the abnormal bronchoconstrictive response in nine of ten patients. We conclude that a metabisulfite-induced bronchoconstrictive response cannot be predicted on the basis of the degree of airway obstruction or airway reactivity and that pretreatment with cromolyn sodium may attenuate the abnormal response.

Adolescent↗
PubMed1979

Relationship between the single-breath N test and age, sex, and smoking habit in three North American cities.

This report describes a collaborative study conducted in Montreal, Canada, Portland, Ore., and Winnipeg, Canada, to establish the relationship between the single-breath N2 test and age, sex, and smoking and to determine the prevalence of functional abnormalities in these populations. In nonsmokers, age-related regressions for closing volume, closing capacity, and the slope of phase III obtained from the single-breath N2 test, plus the ratio of the I-s forced expiratory volume to the forced vital capacity had very similar slopes, suggesting that differences in geographic location, climate, air pollution, and occupation had no effect on lung function detectable by these tests. Among the 6 city/six groups there was no systematic difference in the prevalence of functional abnormalities between the cities, but closing capacity expressed as a percentage of total lung capacity was abnormal most often in men and the slope of the alveolar plateau was abnormal most often in women. The prevalence of respiratory symptoms within different smoking categories was similar in the 3 cities. Although the number of cigarettes smoked had a significant effect on every test except the ratio of the I-s forced expiratory volume to forced vital capacity in men, the effect of age was considerably greater than the effect of smoking, and the dose-response relationship was weak. We conclude that additional factors may interact with smoking to place a smoker at risk of developing chronic airflow limitation.

Adult↗
PubMed1978

Alpha1-antitrypsin phenotypes and lung function in a moderately polluted northern Ontario community.

To determine whether persons with intermediate value alpha1-antitrypsin phenotypes living in a polluted environment manifest significant abnormalities in lung function, a study was undertaken of an age-, sex- and smoking-stratified sample of 391 persons from the town of Fort Frances, Ont., which has elevated values of total dustfall, suspended particulates and hydrogen sulfide. Indices of pulmonary function were derived from the maximum expiratory flow and the single breath expiratory flow and the single breath expiratory nitrogen washout curves. The percentage frequency of the M, MS and MZ pheontypes was 91.7, 7.3 and 0.8, respectively. There was no significant difference between the M and MS groups as indicated by the nitrogen washout curve and maximum expiratory flow curve. There was no significant difference between the three MZ subjects and the M group. In both M and MS groups smokers displayed evidence of airflow obstruction when compared with nonsmokers. It would appear that, when compared with M subjects, persons with the MS phenotype living in a moderately polluted area show no changes in indicators of pulmonary function, including tests of early airway disease, that cannot be attributed to their smoking habit.

Adult↗
PubMed1978

Mechanical properties of the lung in extrinsic allergic alveolitis.

The lung function of 14 patients with extrinsic allergic alveolitis caused by exposure to mouldy hay (farmer's lung) or to birds (bird fancier's lung) was studied one week and four to six weeks after the last exposure to antigen. These data, together with lung mechanics measured four weeks after antigen exposure, were compared with measurements in 34 healthy non-smoking control subjects. Shortly after exposure to antigen there were reduction in lung volumes, increased elastic recoil (reduced compliance), and varied effects on expiratory flow and reduced gas transfer. With time, lung volumes and gas transfer improved, but expiratory flow often remained decreased. The data on lung mechanics showed that reduced compliance was often found, but this increased recoil did not always produce high airflow indicating increased upstream airways resistance. Patients with a longer duration of the illness tended to have increased compliance (reduced recoil) and low airflow. These results show that the described pathological changes of airway involvement, fibrosis, and emphysema in allergic alveolitis are manifest in the lung function of patients with the disease.

Adult↗
PubMed1978

Prevalence of respiratory abnormalities in a rural and an urban community.

Population samples stratified on sex, age and smoking habits were studied in a rural and an urban community with a low level of air pollution to establish "normal" values of parameters derived from the single-breath N2 curve, the effect of smoking on these parameters, and any differences related to an urban or rural environment. Respiratory symptoms and past illnesses, smoking habits, and residential as well as occupational history were obtained by a respiratory questionnair. Pulmonary function was assessed by the single-breath N2 test and the forced vital capacity maneuver. In "healthy" nonsmokers, residual volume/total lung capacity, closing volume/vital capacity on expiration, and closing capacity/total lung capacity were significantly related to age. The slope of phase III was related to neither height nor age. There was no significant difference in prediction equations between the 2 communities for any of these parameters. Multiple regression analysis indicated that smoking had an effect on residual volume/total lung capacity, closing volume/vital capacity on expiration, closing capacity/total lung capacity, and the slope of phase III in both sexes. Abnormal values were more prevalent among male than female smokers in both communities, the highest prevalence being found in the slope of phase III in both sexes (35 to 40 per cent). The slope of phase III and closing capacity/total lung capacity were consistently related to the current number of cigarettes smoked per day.

Adult↗