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Biomedical subjects

R M Cherniack

Publications and source records attributed to R M Cherniack.

At least 55 records · Page 3Linked to original sources
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↗
PubMed1989

Circadian variations in theophylline concentrations and the treatment of nocturnal asthma.

The nocturnal worsening of asthma is a common problem that can be difficult to treat. Two different sustained-release theophylline preparations were used to determine (1) if the serum theophylline concentrations (STC) depend on the type and dosing schedule of the preparation, (2) the relationship between STC and the circadian variations in asthma, and (3) the effect of STC on sleep quality and respiratory patterns during the night. In 16 subjects with nocturnal asthma, the STC were significantly higher during the daytime on twice-daily versus once-daily theophylline preparations given at 7 P.M., but the FEV1 values were similar. During the night, the STC were significantly higher with the once-daily regimen, and the awakening FEV1 value was also improved (p less than 0.05). All polysomnographic variables were similar between the two preparations, except that with the once-daily preparation there was a decreased number of hypopneas (p less than 0.05) and fewer minutes below an oxygen saturation of 90% (p less than 0.05). We conclude that patients with nocturnal asthma need their treatment focused on the nocturnal portion of the circadian cycle and that higher STC during this critical time period are beneficial without interfering with sleep quality.

Adult↗
PubMed1989

Hard-rock mining exposures affect smokers and nonsmokers differently. Results of a community prevalence study.

The physiologic consequences of occupational dust exposure, their relation to smoking, and their reversibility with cessation of exposure remain controversial. To address these questions, we studied a random sample of male residents of Leadville, Colorado when the major employer, a hard-rock mine, had been closed for 5 to 11 months. Subjects were interviewed for respiratory symptoms and occupational history, underwent plethysmographic measurements of lung volume and airflow, and performed a single breath diffusing capacity procedure. Dyspnea was the only respiratory symptom exacerbated by mining exposures. Cumulative dust exposure, estimated with historic respirable dust measurements for mining job titles and weighted by time at the job, was associated with decreases in maximal expiratory flow rates when controlled for smoking, age, and height. However, determinations of plethysmographic lung volume that allowed calculation of flow rates at equivalent absolute lung volume indicated that dust effects differed in never-smokers and smokers. In never-smokers, dust exposure was associated with decreased lung volume, increased flow rates, and increased DLCO/VA. In smokers, dust exposure was associated with increased lung volume, lower flow rates, and lower DLCO/VA than that accounted for by smoking. We suggest that hard-rock mining exposures result in irreversible pulmonary function changes of airflow limitation in smokers and of a restrictive nature in never-smokers.

Adult↗
PubMed1989

Efficiency of the respiratory muscles in healthy individuals.

We evaluated respiratory muscle performance by determining the energy cost of breathing against incremental threshold loads and calculating the efficiency of the respiratory apparatus for handling the added work. In five subjects, the energy cost of breathing against the loads, and thus the calculated efficiency of the respiratory muscles, was reproducible on repeated measurements. In all subjects, the calculated efficiency varied while breathing with low loads but was relatively constant at loads that resulted in a mouth pressure of 20 to 60% of the subjects' maximal static inspiratory pressure (PImax). The mean efficiency calculated between 20 to 60% of PImax in 30 normal subjects (15 males and 15 females) ranged between 1.54 and 7.98%. It was significantly greater in males (5.41 +/- 0.43%) (mean +/- SEM) than in females (2.41 +/- 0.17%). There was no relationship between efficiency and body size, but the efficiency correlated with inspiratory muscle strength (PImax). We suggest that measurement of the efficiency of the respiratory muscles over a spectrum of incremental threshold loads is a simple, noninvasive, and reproducible method of assessing respiratory muscle performance and may have clinical application.

Adolescent↗
PubMed1989

111Indium-labeled neutrophil migration into the lungs of bleomycin-treated rabbits assessed noninvasively by external scintigraphy.

Factors controlling neutrophil migration into the lung are poorly understood, but their identification is important for our understanding of the pathogenesis of inflammatory lung diseases. Pulmonary inflammation is difficult to quantify, and neutrophils in tissues and BAL may not accurately represent cell migration. In this study, intravenously delivered pulses of rabbit neutrophils labeled with Indium-111 (111In-neutrophils) were used to monitor neutrophil migration into the lungs. Radioactivity quantified in the lung "region of interest" (ROI) of external gamma camera scintigrams recorded 24 h after intravenous 111In-neutrophil injection accurately reflected the actual neutrophil-associated lung tissue radioactivity. ROI radioactivity at 24 h also correlated closely with the percent of 111In-neutrophils that had migrated into lavageable air spaces, and this parameter therefore provided an index of total lung 111In-neutrophil migration. Using 24-h ROI radioactivity and percent of injected 111In-neutrophils recovered in BAL at 24 h as indices of neutrophil migration into the lung, it was found that intratracheal saline caused only a transient neutrophil migration, whereas 10 U/kg intratracheal bleomycin induced migration that persisted for as long as 3 wk. 111In-neutrophil migration into the lung, assessed by external scintigraphy, correlated with total neutrophils quantified in histologic sections (r = 0.71, p = 0.006). The data suggest that this approach will be valuable in investigating mechanisms controlling neutrophil migration in lung inflammation, and that 111In-neutrophil scintigraphy may provide a noninvasive index of total lung neutrophil load that might be useful in staging inflammation in patchy diseases such as idiopathic pulmonary fibrosis.

Animals↗
PubMed1989

Efficacy of a pulsed oxygen delivery device during exercise in patients with chronic respiratory disease.

The ability of a pulsed oxygen delivery system (Puritan-Bennett Companion Oxygen Saver (COS-5) to track respiratory rate during exercise and the oxygenation achieved during the exercise while oxygen was being delivered by this system was compared to that attained while oxygen was delivered continuously in six patients with chronic obstructive pulmonary disease (COPD) and six patients with idiopathic pulmonary fibrosis (IPF). The COS-5 appeared to respond appropriately at respiratory rates between 15 and 45, even when there were minimal pressure changes at the nose. There was an excellent correlation in PaO2 at equivalent flow settings during the exercise in the patients with COPD and IPF. There were six instances (in four patients) of the 31 comparisons in which the PaO2 differed by more than 5 mm Hg. The PaO2 was higher with continuous oxygen delivery on two occasions in a patient with COPD who utilized pursed-lip breathing during the exercise. The PaO2 was higher with COS-5 delivery on two occasions in a patient with IPF who was breathing at the highest respiratory rates (44 and 45/min) during the exercise.

Adult↗
PubMed1988

Gas exchange at a given degree of volume restriction is different in sarcoidosis and idiopathic pulmonary fibrosis.

PURPOSE: It is likely that the relationship between lung volume changes and gas exchange in patients with idiopathic pulmonary fibrosis (IPF) and patients with sarcoidosis is different since the two conditions vary widely in histopathology and prognosis. Few studies, however, have examined this relationship. The goal of this investigation was to measure diffusing capacity and gas exchange in patients with IPF and sarcoidosis in whom the reduction of lung volume was equivalent. PATIENTS AND METHODS: In 21 patients with IPF and 20 patients with pulmonary sarcoidosis with comparable reductions in lung volume, the single breath diffusing capacity for carbon monoxide and gas exchange at rest and during exercise were compared. RESULTS: The relationship between lung volume and gas transfer differed in the two groups of patients. Resting and exercise gas exchange tended to be relatively normal and the diffusing capacity was higher in patients with sarcoidosis than in those with IPF. These differences could not be attributed to disparities in race, age, smoking habits, or the radiographic stage of sarcoidosis. CONCLUSION: The preservation of gas exchange in sarcoidosis as opposed to IPF, despite equivalent degrees of volume restriction, suggests that different pathophysiologic mechanism underlie the volume loss and gas exchange defects seen in these disorders. Furthermore, these findings suggest that diffusing capacity may not be a sensitive indicator of pulmonary pathology in sarcoidosis since lung volume can be altered independently of abnormalities in the diffusing capacity.

Adult↗
PubMed1988

The intensity of chronic lung inflammation and fibrosis after bleomycin is directly related to the severity of acute injury.

Interstitial lung disease is thought to result from progression of an initial lung injury and alveolitis into a chronic inflammatory process that produces fibrosis. However, the relationship between the severity of the initial phase of acute injury and alveolitis and the amount of subsequent chronic inflammation and fibrosis remains unclear. We induced a wide spectrum of acute lung injury in rabbits by using various amounts of intratracheal bleomycin (5 or 10 U/kg) with and without oxygen supplementation (100% O2 for 2 min). The arterial oxygen tension on Day 12 after the bleomycin correlated with the extent of acute lung injury, as well as with the amount of chronic inflammation and fibrosis present on Day 56, as determined by physiologic parameters (lung volume, DLCO/VA, and PO2), and morphometry (volume proportions abnormal parenchyma made up of intra-alveolar macrophages, intra-alveolar granulocytes, abnormal alveoli, abnormal airways, fibrosis, consolidation, and honeycombing). We conclude that in bleomycin-induced interstitial lung disease in the rabbit, there is a direct relationship between the severity of acute lung injury after intratracheal bleomycin and the amount of subsequent chronic inflammation and fibrosis. This suggests that the mechanisms regulating the development of fibrosis are directly influenced by the extent of initial injury.

Acute Disease↗
PubMed1987

Idiopathic pulmonary fibrosis. Pretreatment bronchoalveolar lavage cellular constituents and their relationships with lung histopathology and clinical response to therapy.

Analysis of bronchoalveolar lavage cellular constituents has been recommended as a valuable method for the characterization of the inflammatory cellular population and for studying cellular interactions in the lower respiratory tract of patients with idiopathic pulmonary fibrosis (IPF). However, the clinical relevance of the enumeration of cells in bronchoalveolar lavage fluid (BALF) from patients with IPF remains controversial. We therefore examined the correlations between BALF cellular constituents and both the histopathologic abnormalities and the subsequent clinical response to corticosteroid therapy in 26 newly diagnosed, untreated patients with IPF. The BALF lymphocytosis was associated with moderate-to-severe alveolar septal inflammation (p less than 0.0005) and with a relative lack of histologic honeycombing (p less than 0.05). On the other hand, BALF neutrophil and eosinophil contents did not significantly correlate with any of eleven particular histopathologic abnormalities, and BALF neutrophil and lymphocyte contents did not correlate with the degree of clinical impairment (quantitated by a composite score based on dyspnea, radiographic abnormalities, and physiologic impairment) upon presentation. However, BALF eosinophil content correlated significantly with the severity of clinical impairment, higher eosinophil counts being associated with more severe initial clinical impairment (p less than 0.01). Neither pretreatment BALF neutrophil nor eosinophil content was related to the frequency or magnitude of subsequent clinical change in 20 patients evaluated before and after 1 yr of corticosteroid therapy. In contrast, pretreatment BALF lymphocytosis was associated with significant subsequent clinical improvement (p less than 0.002).(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1986

Bronchoalveolar lavage fluid neutrophils increase after corticosteroid therapy in smokers with idiopathic pulmonary fibrosis.

Patients with idiopathic pulmonary fibrosis (IPF) are often cigarette smokers and are often being treated with corticosteroids at the time of bronchoalveolar lavage. We addressed the question of whether or not the bronchoalveolar lavage fluid (BALF) neutrophil content of patients with IPF undergoes changes in smokers different from those in nonsmokers after institution of corticosteroids. Eighteen patients were studied (10 smokers and 8 nonsmokers). Fourteen patients (6 smokers and 8 nonsmokers) were treated orally with prednisone. The histologic assessment of alveolar inflammation and inflammatory small airways disease was no different in smokers than in nonsmokers. None of the smokers treated with prednisone had pathologic evidence of emphysema in addition to IPF. Five of 6 smokers showed an increase in BALF neutrophils after 3 months of prednisone (p less than 0.05), whereas the nonsmokers' BALF neutrophils decreased or remained unchanged. This increase in BALF neutrophils in smokers was not associated with concomitant or subsequent clinical deterioration but, in fact, with clinical improvement after 3 months of therapy. These data indicate that the combination of cigarette smoking and corticosteroid therapy influences the BALF neutrophil content in patients with IPF and suggest that interval changes in BALF neutrophil content may not reflect the status of the inflammatory process or structural derangements in the lungs of some patients with IPF.

Aged↗
PubMed1986

A clinical, radiographic, and physiologic scoring system for the longitudinal assessment of patients with idiopathic pulmonary fibrosis.

In order to develop a reproducible, quantifiable means of assessment of the clinical status of patients with idiopathic pulmonary fibrosis (IPF), a composite clinical-radiographic-physiologic (CRP) scoring system was devised, using 7 variables: dyspnea, chest radiograph, spirometry, lung volume, diffusion capacity, resting alveolar-arterial PO2, and exercise O2 saturation. To assess this scoring system, we examined the relationships between CRP scores and histopathologic findings, including a cellular pathology score composed of abnormalities deemed to be potentially reversible, a fibrotic pathology score based on abnormalities felt to be essentially irreversible, and an index of overall pathologic derangement (total pathology score), derived from the sum of the cellular and fibrotic scores. The initial CRP determination at the time of open lung biopsy correlated significantly with the total pathology score (r = 0.61, p less than 0.001). The CRP score determined after 6 months of corticosteroid therapy showed a significant correlation with the fibrotic pathology score present on open lung biopsy (r = 0.76, p less than 0.001). The change in CRP after 6 months of corticosteroid therapy tended to reflect the cellular histopathologic component of the open lung biopsy (r = -0.43, p less than 0.10). Moreover, in none of these relationships did any individual component of the CRP score correlate better with the respective histopathologic index than did the CRP score itself. These data suggest that this CRP score is useful for the estimation of the severity of underlying pathologic derangement and for the longitudinal quantitative assessment of clinical impairment in patients with IPF.

Adult↗
PubMed1986

The effect of topical ophthalmic instillation of timolol and betaxolol on lung function in asthmatic subjects.

The propensity of systemic beta-adrenergic blockers to cause bronchoconstriction in patients with reactive airway disease is well recognized. A study was carried out to determine the prevalence of sensitivity to ophthalmic timolol in 24 asthmatic subjects at our institution and to determine the effect of ophthalmic betaxolol, a cardioselective beta-blocker efficacious in the treatment of glaucoma, in 8 subjects who were timolol-sensitive. Subjects received topical timolol 0.5%; ventilatory function, blood pressure, and heart rate were monitored over a 90-min period. The mean FEV1 fell from 2.47 to 1.93 L by 30 min after drug treatment to a minimal value of 1.86 L (-27.8%). There was a corresponding fall in FVC from 3.68 to 3.09 L by 30 min with a minimal value of 3.00 L(-20.7%). FEV1/FVC ratio also fell from 66.9 to 61.0% by 30 min, reaching a minimum of 60.0%. In 14 subjects (58.3%), the fall in FEV1 was greater than or equal to 20%, with a mean fall of 38.7% by 30 min and a maximal fall of 44.9%. The severity of timolol-sensitivity correlated with the extent of reduction in baseline percent predicted FEV1 and FVC and with exercise-induced bronchospasm. In addition, the administration of timolol reduced the bronchodilator response to below the pretimolol value. In 8 of the timolol-sensitive patients who underwent a double-blind crossover challenge with ocular instillation of betaxolol 1% and saline, betaxolol was well-tolerated and did not affect ventilatory function over a 4-h observation period. In addition, it did not prevent the FEV1 response to inhaled bronchodilator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Laryngeal dysfunction and pulmonary disorder.

The normal respiratory function of the larynx has been described in detailed reports in both the otolaryngology and the respiratory physiology literature. The role of the posterior cricoarytenoid muscle in vocal cord abduction has been shown to be paramount in laryngeal respiratory function. However, only in recent reports has attention been directed toward disordered laryngeal function as evidenced in pulmonary disorders, such as asthma, or in association with underlying pulmonary disorders, such as asthma (ROAD) or emphysema (COPD). In this article, cases will be presented to demonstrate the role of disordered laryngeal function appearing as pulmonary disease and associated with various degrees of underlying pulmonary disease. The effect on pulmonary function tests and the role of treatment will be discussed.

Adult↗