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Biomedical subjects

D E Griffith

Publications and source records attributed to D E Griffith.

At least 55 records · Page 3Linked to original sources
PubMed1994

Alterations in lung defense and unusual infections in chronic bronchitis.

Cigarette smoking is the primary irritant responsible for the syndrome of chronic bronchitis. In addition to the symptoms of cough and sputum production, smoking leads to structural changes and immunologic alterations that place the patient with chronic bronchitis at increased risk for tracheobronchial infections. This article reviews the modifications in lung defenses that occur as a result of chronic bronchitis. The uncommon infectious agents that are seen in chronic bronchitis are also discussed including clinical presentation, diagnosis, and treatment.

Aspergillosis↗
PubMed1994

Changing strategies for treatment of chronic bronchitis.

There has been a recent re-examination of the therapeutic approach to chronic bronchitis, with or without airflow obstruction, partly as a result of intense interest in asthma therapy. Although the mainstay of therapy in chronic bronchitis is still smoking cessation, there has been a shift in importance and use of therapeutic interventions based on pathophysiological considerations. The presence of airway inflammation and bronchial hyperreactivity in chronic bronchitis, analogous to asthma, has spurred interest in the use of anti-inflammatory agents such as inhaled steroids, with the hope that these drugs will have the same favorable effects on airflow obstruction as in asthma. Recognition of the relative importance of cholinergic stimulation in airflow obstruction associated with chronic bronchitis has elevated the role of anticholinergic agents to primary therapy. And lastly, evolving understanding of the role of infectious agents in exacerbations of chronic bronchitis is having an impact on the perceived importance of antibiotics in this setting. This article will discuss the rationale, evidence of efficacy, and current role for each of these treatment modalities in chronic bronchitis.

Administration, Inhalation↗
PubMed1993

Airflow obstruction in nonsmoking, asbestos- and mixed dust-exposed workers.

Obstructive changes in small airways have been described in patients exposed to asbestos and other mineral dusts. The physiologic significance of these small airways abnormalities and their relationship to dust burden and alveolitis remain unclear. We performed bronchoalveolar lavage (BAL) in 30 nonsmoking and 30 age-matched smoking subjects, all with mild asbestos and mixed dust exposure, to determine if parameters of lung dust burden correlated with spirometric evidence of airflow obstruction. Seventeen of 30 nonsmoking subjects and 24 of 30 smoking subjects met spirometric criteria for airflow obstruction. There were significantly more obstructed subjects in both dust exposed groups (P < 0.05) than in an age-matched nondust exposed group. There was, however, no significant difference in the number of obstructed subjects between the smoking and nonsmoking groups. There was no correlation in either group between airflow obstruction and total or differential cell counts, ferruginous bodies, total asbestos fibers, or the percent of free silica in the particulate fraction recovered by BAL. We conclude that evidence of small airways obstruction occurs commonly in occupationally dust exposed subjects and appears to be related to dust exposure per se and not to alveolar inflammation or fiber retention, important factors in the development of alveolitis and interstitial lung disease.

Asbestos↗
PubMed1993

Analysis of ferruginous bodies in bronchoalveolar lavage from foundry workers.

Classical ferruginous bodies in tissue samples are considered to be markers of past exposure to asbestos. Recent studies have shown that the presence of ferruginous bodies in bronchoalveolar lavage (BAL) fluid correlates with past exposure to asbestos and offers a more sensitive reference than occupational history. Lavage samples from five subjects who had worked in foundries were evaluated by light microscopy for the presence of ferruginous bodies and by transmission electron microscopy for both characterisation of the uncoated fibre burden and analysis of the cores of the ferruginous bodies. All samples at lower magnification (light microscopy (200 x)) contained ferruginous bodies that were externally consistent with asbestos bodies. At higher magnification (400 x), a separate population from this group could be identified by the presence of a thin black ribbon. Transmission electron microscopy of the core materials of ferruginous bodies and comparable uncoated particulates supported the reliability of higher magnification light microscopy for distinguishing most of those non-asbestos cores; however, a population of transparent non-asbestos cored ferruginous bodies were also shown to exist.

Aged↗
PubMed1993

Single-cycle bronchoalveolar lavage to determine solute concentrations in epithelial lining fluid.

An accurate and reproducible measure of solute concentration of lung epithelial lining fluid (ELF) by bronchoalveolar lavage would be valuable in lung research and in patient care. Measurements of the albumin/total protein ratio in a previously proposed rewash lavage procedure showed that albumin enters the lavage fluid. Therefore, the rewash lavage may measure ELF volume accurately, but it overestimates ELF protein concentration (PELF). To avoid problems of solute exchange, we examined five sequential fractions of lavage fluid obtained from sheep after a single 60-ml lavage containing a 99mTcO4- tracer. Assays of albumin, 99mTcO4-, total protein, and endogenous urea concentrations allowed calculation of PELF from each fraction. PELF was 8 +/- 4 mg/ml when calculated from dilution of either endogenous urea or 99mTcO4- in fractions collected after the first 15 to 20 ml. Paired lavages provided a reproducible measure of PELF (SD, 1.2 mg/ml) that was unaffected by any solute exchange that occurred during the 40-s procedure. Accuracy was verified by comparisons of lung lymph and ELF protein concentrations during high pressure lung edema in anesthetized sheep. The single-cycle lavage procedure is an accurate and reproducible procedure for measuring PELF.

Albumins↗
PubMed1993

Clinical features of pulmonary disease caused by rapidly growing mycobacteria. An analysis of 154 patients.

The role of rapidly growing mycobacteria (RGM) as pulmonary pathogens has been unclear. We identified 154 cases of lung disease caused by RGM using the microbiologic and radiographic criteria of the American Thoracic Society (ATS) and availability of the causative organism for study. More than one third of patients had positive lung biopsy cultures. Patients were predominantly white (83%), female (65%) nonsmokers (66%), and they had prolonged periods from onset of symptoms to diagnosis of their disease. Cough was an almost universal presenting symptom, whereas constitutional symptoms became more important with progression of disease. Upper lobe infiltrates were most common (88%), with 77% of patients developing bilateral disease. Cavitation was present in only 16% of the patients. Specific underlying diseases were infrequent, but they included previously treated mycobacterial disease (18%), coexistent Mycobacterium avium complex (8%), cystic fibrosis (6%), and gastroesophageal disorders with chronic vomiting (6%). The majority of isolates (82%) were M. abscessus (formerly M. chelonae subsp. abscessus). Effective treatment for M. fortuitum long disease was accomplished with drug therapy, whereas surgical resection of localized disease was the only effective long-term therapy for M. abscessus. Although the disease was generally slowly progressive, 21 of 154 (14%) patients died as a consequence of progressive RGM lung disease and respiratory failure. RGM should be recognized as a cause of chronic mycobacterial lung disease, and respiratory isolates should be assessed carefully.

Adolescent↗
PubMed1993

Chronic bronchitis. Key points in evaluation.

Thorough history taking is essential in evaluation of chronic bronchitis. Patients often reveal key symptoms that help define the disorder and provide information about contributing factors, such as cigarette smoking, that can be eliminated. Useful baseline data can be collected through pulmonary function studies, electrocardiogram, chest radiographs, complete blood cell count, and measurement of electrolyte levels.

Bronchitis↗
PubMed1993

Chronic bronchitis. Choosing the optimal treatment.

Among the various therapies for chronic bronchitis none is more important, both for relieving symptoms and for preserving pulmonary function, than cessation of cigarette smoking. Unfortunately, even when patients are motivated and programs are aggressive, results are unspectacular. Chronic bronchitis often responds favorably to bronchodilating agents. For initial therapy, ipratropium bromide (Atrovent) is the agent of choice because of its efficacy and safety. The role of antiinflammatory drugs is not yet clear, although inhaled steroids are beneficial in some patients. Most patients improve with smoking cessation and/or judicious pharmacologic intervention.

Acute Disease↗
PubMed1992

Hyperoxic exposure in humans. Effects of 50 percent oxygen on alveolar macrophage leukotriene B4 synthesis.

The pathogenesis of oxygen toxicity remains unknown but may involve leukocyte mediated injury. The effects of hyperoxia on several lower respiratory tract parameters were examined in bronchoalveolar lavage fluid of normal nonsmoking subjects who inhaled a fractional inspired oxygen concentration of 50 percent (mean exposure: 44 h). Evidence that 50 percent O2 produced oxidative stress in the lung included recovery of fluorescent products of lipid peroxidation and partial oxidation of alpha 1-antitrypsin in BAL fluid obtained after O2 exposure. To examine whether alveolar macrophage-derived leukotriene B4 may be generated in response to 50 percent O2, AM were isolated from O2-exposed subjects and compared with AM recovered from subjects breathing room air. Leukotriene B4 levels were elevated in supernatants from both unstimulated and arachidonic acid-stimulated AM obtained from hyperoxia-exposed subjects. In hyperoxia-exposed individuals, LTB4 levels were also elevated in extracted BAL fluid. The percentage of BAL neutrophils was also significantly increased after O2 exposure (2.8 +/- 0.6 vs 1.2 +/- 0.4 percent, p = 0.05). We conclude that an FIO2 of 50 percent inhaled for 44 h is associated with enhanced oxidative stress, stimulation of AM to release LTB4, and a small but significantly increased percentage of neutrophils recovered in BAL fluid.

Adolescent↗
PubMed1991

The usefulness of bronchoalveolar lavage in identifying past occupational exposure to asbestos: a light and electron microscopy study.

Fiberoptic bronchoscopy has permitted the development of lavage procedures for the collection of lung washes. In certain disease states this material may contain large numbers of phagocytic cells (macrophages and neutrophils). Since these phagocytes are the predominant "dust scavenger cells" in the lung, the assessment of their particulate burden as well as that of the overall lavage material has been suggested as a potentially important diagnostic tool. The studies to date have shown that the presence of ferruginous bodies is an indication of past occupational exposure. In the present study, a digestion procedure was carried out on bronchoalveolar lavage material collected from individuals who were occupationally exposed to asbestos and from samples obtained from the general population. The parameters used for distinguishing the source of these samples included both light microscopy assessment of the filters for the presence of ferruginous bodies and electron microscopic screening for the presence of uncoated fibers.

Adult↗
PubMed1991

Rewash bronchoalveolar lavage.

A significant limitation of standard bronchoalveolar lavage (BAL) technique is the inability to measure or calculate epithelial lining fluid (ELF) volume and, therefore, in vivo concentrations of substances in the ELF. We evaluated a new rewash BAL procedure with the radiolabeled tracer technetium pertechnetate (99mTcO4-) that theoretically should be immune to even exaggerated fluid shifts during BAL. To test this theory, we measured ELF volume in control sheep using isosmotic (280 mosm/L) hypoosmotic (140 mosm/L) and hyperosmotic (570 mosm/L) BAL solutions to induce exaggerated fluid shifts during the lavage procedure. The mean ELF volume of the lavaged lung segment was not significantly different for the three solutions (isosmotic, 1.7 +/- 0.8 ml; hypoosmotic, 1.1 +/- 1.2 ml; hyperosmotic, 2.1 +/- 1.6 ml). The slope of the 99mTcO4- disappearance curve, however, was significantly steeper for the hyperosmotic solution (-0.40 +/- 0.04%/min) compared with the other solutions (isosmotic, -0.14 +/- .01%/min; hypoosmotic, -0.12 +/- 0.07%/min). Calculation of ELF volume using sodium as an endogenous tracer gave consistently smaller values with each of the mannitol solutions (isosmotic, 0.21 +/- 0.30 ml; hypoosmotic, 0.02 +/- 0.03 ml; hyperosmotic, 0.18 +/- 0.18 ml). The failure of sodium to provide accurate estimates of the ELF volume may be due to complicated sodium movement in the lung and errors in our assumption of the initial concentration of sodium in the ELF fluid. We conclude that the rewash BAL technique with 99mTcO4- gives values of ELF volume that are not significantly affected by even exaggeration of the fluid flux that invariably accompanies BAL.

Animals↗
PubMed1991

Pneumonia in chronic obstructive lung disease.

Despite the apparent common occurrence of pneumonia in patients with chronic obstructive pulmonary disease (COPD), there are little firm data on incidence, etiology, diagnostic procedures, and therapy in these patients. It appears that traditional respiratory pathogens such as the pneumococcus are declining in importance while "new" pathogens such as Pseudomonas sp., Moraxella catarrhalis, and Legionella sp. are becoming more important. The diagnosis of a specific etiologic agent is difficult in COPD and can be aided by obtaining specimens bronchoscopically. Directed therapy is optimal; however, empiric therapy is frequently unavoidable.

Diagnosis, Differential↗
PubMed1990

Reduced diffusing capacity as an isolated finding in asbestos- and silica-exposed workers.

From a cohort of 286 patients referred to an Occupational Medicine Clinic because of exposure to asbestos and/or silica, we identified 53 patients with a reduced diffusing capacity (Dco) (less than 75 percent predicted) as their only abnormality. Specifically, their clinical evaluation, chest roentgenograms, and remaining pulmonary function test results were all normal. These patients were divided into non-smokers (n = 13) and smokers (n = 40). The significance of the isolated reduction in diffusing capacity in these patients (n = 53) was explored with graded exercise testing (n = 19) and bronchoalveolar lavage (BAL) (n = 50). The results obtained from the patients with reduced diffusion were compared with those obtained from comparable smoking (n = 35) and nonsmoking patients (n = 37) in the original cohort who had normal chest roentgenograms and normal results of pulmonary function studies, including normal Dco values (greater than or equal to 75 percent of predicted value). Patients with low diffusion demonstrated a tendency for elevated alveolar to arterial O2 differences both at rest and during exercise, and a significant reduction in exercise capacity (VO2 max) was observed in the smoking patients with reduced diffusion when compared with their smoking counterparts with normal diffusion. All other exercise testing indexes were normal in the study groups and there was no correlation between the percent predicted Dco value and any of the exercise variables. In contrast, BAL revealed significant differences between patient groups. Both the smoking and nonsmoking patient groups with low Dco values had greater numbers of total BAL cells, alveolar macrophages, neutrophils, lymphocytes, and eosinophils in their BAL fluid than did their comparable controls with normal diffusion values. These differences were statistically significant (p less than .05) for total BAL cells and total macrophages in the nonsmoking patients and for total BAL cells, total macrophages, and total lymphocytes in the smoking patients expressed as either the total cell number per BAL or total cells per milliliter of BAL. In contrast to the observed exercise testing results, there was significant and inverse correlation between Dco values and each BAL cell type for all four groups combined as well as nonsmokers alone. The Dco values from smokers were significantly and inversely correlated with total BAL cells and total macrophages. These results suggest that the finding of a reduced Dco may be related to an active inflammatory process in the lung caused by occupational dust exposure.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants, Occupational↗
PubMed1990

Asbestos exposure results in increased lung procoagulant activity in vivo and in vitro.

Enhanced fibrin deposition is a common histologic finding in fibrotic lung disorders including asbestosis and may be an important mechanism by which fibroblast proliferation is modulated. Asbestos-induced activation of lung interstitial cells may result in enhanced expression of procoagulant activity which contributes to the inflammatory response resulting in subsequent fibrin deposition. The current study examines procoagulant activity in bronchoalveolar lavage fluid from patients with clinically diagnosed asbestosis, patients with asbestos exposure without asbestosis, and normal, control subjects. Results indicated that asbestos exposure resulted in increased lung procoagulant expression in vivo, and furthermore, suggested that both endothelial cells and alveolar macrophages represented lung parenchymal cells which may contribute to this activity. This imbalance in coagulation homeostasis may be important in the regulation of fibrotic responses observed in asbestosis.

Adult↗
PubMed1989

Ofloxacin in community-acquired lower respiratory infections. A comparison with amoxicillin or erythromycin.

Ninety-one patients with community-acquired lower respiratory infections were treated orally in a comparative 10-day trial of ofloxacin versus amoxicillin or erythromycin. Approximately one-half of the patients had no major underlying disease and the other half had some form of chronic lung disease. Pneumonia was present in 31 percent of the patients and the remainder had purulent bronchitis. Bacterial pathogens were recovered from 60 percent of the patients, with Haemophilus influenzae (33 isolates) and Streptococcus pneumoniae (16 isolates) being the most common. Ofloxacin was found to be a safe, well-tolerated therapeutic agent, which was as effective clinically as amoxicillin or erythromycin and with an advantage of less frequent administration. Ofloxacin was more effective than amoxicillin (90 percent versus 75 percent; p = 0.05) in elimination of pathogenic bacteria from lower airway cultures. Caution should be exercised in the use of ofloxacin, at least in short-term treatment regimens, with anaerobic pulmonary infections; additional information is needed for S. pneumoniae given the relatively high minimal inhibitory concentrations for this species.

Adult↗
PubMed1989

Respiratory effects of outdoor air pollution.

Outdoor air pollution adversely affects human health and the quality of the environment. However, epidemiologic studies of these effects are difficult to control because of confounding variables such as age and cigarette smoking and the difficulty in estimating doses of pollutants. Drs Griffith and Levin discuss the relationship between major types of pollutants and increased morbidity and mortality from respiratory disease.

Air Pollutants↗
PubMed1989

Alveolar macrophages from patients with asbestos exposure release increased levels of leukotriene B4.

The alveolar influx and subsequent activation of inflammatory cells such as neutrophils and eosinophils are believed to be important in the pathogenesis of many interstitial lung disorders, including asbestosis. Indices of lower respiratory tract abnormalities detected by bronchoalveolar lavage (BAL) were investigated in 93 asbestos-exposed workers as well as in smoking (n = 12) and nonsmoking (n = 10) control subjects. Patients with clinical asbestosis (n = 12) exhibited increases in both BAL neutrophils and BAL eosinophils, expressed as both percentage of total cells and total numbers, when compared to asbestos-exposed workers without asbestosis (n = 81) and control subjects. Significantly greater numbers of BAL neutrophils were also found in asbestos-exposed workers without asbestosis than in either smoking or nonsmoking control subjects. These abnormalities correlated significantly with in vitro BAL alveolar macrophage production of the potent leukocyte chemotaxin, leukotriene B4 (LTB4). For example, basal, unstimulated LTB4 production was 3.1 +/- 0.8 ng/10(6) alveolar macrophages for patients with asbestosis, 1.05 +/- 0.2 ng/10(6) cells in asbestos workers without asbestosis, 0.9 +/- 0.2 ng/10(6) cells in control nonsmokers, and 0.2 +/- 0.05 ng/10(6) cells in control smokers. Stimulated LTB4 release from BAL alveolar macrophages (A23187 or arachidonate) was even more pronounced in asbestos workers with or without asbestosis, suggesting an in vivo priming effect on alveolar macrophage synthesis of LTB4. Cell-free BAL supernatants from asbestos-exposed patients with or without asbestosis also contained significantly greater amounts of LTB4 than did those from control subjects, indicating enhanced in vivo production of this inflammatory mediator.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗