Biomedical subjects
Publications and source records attributed to R H Winterbauer.
Oral corticosteroids remain the cornerstone therapy for sarcoidosis. Critical clinical decisions include selecting the patient who should be treated, dose and duration of therapy, and accurate analysis of the anticipated benefits and potential side effects for the individual patient. The treatment of pulmonary and cardiac sarcoidosis is emphasized and the role of inhaled corticosteroids in the treatment of pulmonary sarcoidosis is reviewed.
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STUDY OBJECTIVE: To evaluate histologic, microbiological, and clinical criteria in the recognition of ventilator-associated pneumonia (VAP) in patients who died while mechanically ventilated. METHODS: The study group consisted of 39 patients who died after a mean of 14 days of mechanical ventilation. Postmortem fiberoptic bronchoscopy (FOB) and open lung biopsy were performed with collection of specimens initiated <1 h after death. The microbiological specimens included suction catheter aspirate of tracheal secretions, FOB-guided protected specimen brush (PSB) of tracheal secretions, blindly placed PSB in a distal airway, FOB-guided PSB in a distal airway, and FOB-guided BAL fluid (BALF) in a distal airway. Qualitative bacteriologic study was performed on all specimens, and quantitative bacteriologic study was performed on all but the suction catheter aspirate of the trachea. A biopsy specimen of peripheral lung parenchyma from the same region sampled by FOB was sent for quantitative culture and histologic analysis. The BALF was analyzed for cell population and percent of neutrophils containing intracellular organisms. The clinical criteria selected for comparison with histologic and microbiological results included a temperature > or =38.5 degrees C during the 48 h prior to death, a WBC count > or =15,000/mm3 in the 48 h prior to death, presence of a bacterial or fungal pathogen on the last sputum culture, radiographic worsening in the week prior to death, and worsening gas exchange defined as a 15% decrease in the PaO2/fraction of inspired oxygen ratio in the 72 h prior to death. RESULTS: None of the quantitative cultures had a reliable positive predictive value for histologic pneumonia. None of the five clinical criteria tested showed agreement with the presence or absence of histologic pneumonia. There was a significant correlation between qualitative and quantitative microbiological results from the distal airway/FOB-guided PSB, distal airway/BALF, and quantitative culture of the lung parenchyma. Also, suction catheter aspirate of the trachea had a sensitivity of 87% in recognizing the bacterial species simultaneously present in lung parenchyma. None of the patients with histologic pneumonia had <50% neutrophils in the BALF. CONCLUSIONS: Neither the bacterial, density from the four airway quantitative cultures, nor the bacterial density from quantitative culture of lung parenchyma accurately separated the histologic pneumonia and nonpneumonia groups. No clinical criteria or combination of clinical criteria correlated with the presence or absence of histologic pneumonia. A BALF with <50% neutrophils had a 100% negative predictive value for histologic pneumonia. A BALF quantitative culture had a sensitivity of 63%, specificity of 96%, and positive predictive value of 91% in recognizing sterile lung parenchyma. Thus, BALF may have a role in excluding pneumonia/infection in the ventilated patient. Antibiotic choice for the empiric therapy of VAP can be accurately guided by the microbial population recognized through culture of a tracheal suction catheter aspirate.
STUDY OBJECTIVE: To establish a histologic diagnosis of pneumonia by consensus of a panel of pathologists, to test the interobserver and intraobserver variation in the histologic diagnosis of pneumonia, to compare the diagnostic accuracy of diagnosing pneumonia with and without preselected histologic criteria, and to establish more specific histologic criteria for the diagnosis of pneumonia. METHODS: The study group consisted of 39 patients who died after a mean of 14 days of mechanical ventilation. A postmortem open lung biopsy was performed on all patients. The tissue was reviewed independently by four pathologists who categorized the slides from each patient as showing or not showing pneumonia. Interobserver variation was calculated using the kappa statistic. Six months following the initial evaluation, the same slides were resubmitted to one of the pathologists for reevaluation to look for intraobserver error. Finally, the slides were reviewed and categorized by the criteria of Johanson et al into no pneumonia, mild, moderate, or severe bronchopneumonia. A comparison was made of the patients selected as demonstrating histologic pneumonia by each of the examinations. RESULTS: The reliability coefficient (kappa) measuring agreement among the four pathologists was good at 0.916. However, the prevalence of pneumonia as determined by each of the four pathologists varied; pathologist A, 15 of 39 (38%); pathologist B, 12 of 39 (31%); pathologist C, 9 of 39 (23%); and pathologist D, 7 of 39 (18%). Resubmitting the same slides to the same pathologist 6 months later resulted in reclassification of 2 of 39 patients. Using the histologic criteria of Johanson and colleagues, 14 patients were selected as having pneumonia compared with only nine patients selected by consensus of three of four pathologists. CONCLUSIONS: Recognition of histologic pneumonia varies among pathologists. The preselected criteria of Johanson and colleagues detected histologic pneumonia in eight of nine patients picked by consensus of pathologists, but six additional patients classified as "no histologic pneumonia" by the consensus of pathologists were judged to have histologic pneumonia by these criteria. The results established the necessity for standardization of histologic criteria for studies using biopsy as the gold standard for bacterial pneumonia. An atlas showing the criteria used in our selection was developed.
The study group consisted of 58 patients with idiopathic pulmonary fibrosis (IPF) recognized between 1970 and 1991 who were treated for their pulmonary disease, survived for at least 1 year from the time of initiation of treatment, and had forced vital capacity (FVC) measurements at the time of diagnosis and 9 to 15 months later. Forty-four of the patients also had a single-breath diffusing capacity (Dsb) measured initially and after 9 to 15 months of treatment and 33 patients had an arterial blood gas, breathing room air at the time of diagnosis and 9 to 15 months into therapy. Patients' conditions were classified as improved, unchanged, or worse after the year of treatment based on each of the three pulmonary function tests. A > or = 10% increase in FVC, > or = 20% increase in Dsb, and > or = 5 mm Hg decrease in alveolar-arterial difference in oxygen partial pressure [P(A-a)O2] defined improved function. A > or = 10% decrease in FVC, > or = 20% decrease in Dsb, and > or = 5 mm Hg increase in P(A-a)O2 defined worse function. Patients with < 10% change in FVC, < 20% change in Dsb, and < 5 mm Hg change in P(A-a)O2 were regarded as having unchanged conditions. Kaplan-Meier survival plots and the Cox proportional hazard regression model were used to analyze survival time in relation to change in pulmonary function after 1 year of therapy. Patients with an improved or unchanged FVC at 1 year had no difference in survival (p = 0.75), but both showed enhanced survival compared with patients with a > or = 10% reduction in FVC with 1 year of treatment (p < 0.001). Patients with an improved or unchanged Dsb at 1 year also had no difference in survival (p = 0.21) but again, both showed enhanced survival compared with patients with > or = 20% decrease in Dsb with 1 year of treatment (p < 0.001). Changes in gas exchange after 1 year of treatment did not correlate with survival in the three groups. There was a trend for longer survival in improved patients compared with those with worsening gas exchange, but the p value was not significant at 0.17. We conclude that changes in the FVC and Dsb after 1 year of treatment are strongly predictive of duration of survival in patients with IPF.
The onset of fever and pulmonary infiltrates in patients who have been treated with thoracic irradiation is a relatively common occurrence. Radiation pneumonitis and infectious pneumonitis share many clinical features. The major objective of the clinician in evaluating patients who present with a febrile pneumonitis syndrome is to establish the correct diagnosis with as much certainty as possible. This article will review the pathogenesis, histopathology, and clinical features of radiation pneumonitis. Certain clinical and radiographic aspects of radiation pneumonitis will help the clinician arrive at the correct diagnosis. The patient with radiation pneumonitis will present with an insidious onset of dyspnea, fever, and nonproductive cough. Review of the chest radiograph at presentation and all chest radiographs since the completion of radiation therapy will provide the key to the clinical diagnosis of radiation pneumonitis. The infiltrate characteristically has a sharp margin that conforms to the port of irradiation. If the chest radiograph is not characteristic, it will be necessary to rule out infection. If noninvasive studies are nondiagnostic, then bronchoscopy may be necessary to exclude potential infectious agents.
Systemic lupus erythematosus, polymyositis/dermatomyositis, connective tissue disease, and polyarteritis nodosa are the collagen vascular diseases (CVDs) most likely to mimic pneumonia. All can be associated with an acute illness characterized by fever, cough, dyspnea, pleural symptoms, and an abnormal chest roentgenogram. Recognition of the CVD-associated pulmonary process requires sophisticated serological testing and chemical pleural fluid analysis coupled with the exclusion of pulmonary infection and pulmonary embolization. This review emphasizes the clinical characteristics of these CVDs, the diagnostic tests most helpful in recognizing them, and the differential diagnosis of pleuroparenchymal disorders that occur in these patients.
A disturbing increase in mortality from asthma has occurred over the past decade. Asthmatic patients who are over age 55 and have coexisting cardiac or pulmonary disease, those who have a history of mechanical ventilation, and those who require continuous outpatient use of corticosteroids to control symptoms have an increased risk of severe or fatal exacerbations of their disease. Patients hospitalized for severe asthma should receive inhaled beta 2-adrenergic agonists for bronchodilation and intravenous corticosteroids. Patients requiring mechanical ventilation have about a 20% incidence of pneumothorax and an enhanced risk of nosocomial pneumonia, and their mortality rate approaches 20%. Once severe asthma improves, patients must have their outpatient regimen strengthened by the use of oral corticosteroids, inhaled corticosteroids, and/or inhaled cromolyn sodium (Intal).
Activity in interstitial lung disease is indicated by the progression of illness, but is neither an estimate of total disease nor can it be equated with the outcome or need for therapy. There is no unifying concept of activity or progression of disease that will fit the decision processes for all of interstitial lung disease. Great effort has been directed to identifying clinical indices, serum markers, bronchoalveolar lavage findings, and imaging techniques that predict activity or progression from single observations at the time of diagnosis, and thus allowing early recognition of patients who have differing natural history of disease. The past year has seen special emphasis on patient symptoms, initial results of pulmonary function tests, and especially high-resolution computed tomography imaging at the time of diagnosis and the relation these factors have to disease progression, response to therapy, and survival.
OBJECTIVE: To review the clinical presentation, radiology, microbiology, and response to therapy of patients with chronic bacterial pneumonia. DESIGN: A retrospective analysis. SETTING: An urban tertiary care medical center. PARTICIPANTS: One hundred fifteen patients with pulmonary and/or constitutional symptoms of at least 1 month's duration with 4,000 or more colony-forming units (CFUs) of a single bacterial species identified by quantitative culture obtained via fiberoptic bronchoscopy. MEASUREMENTS: Charts were analyzed for presence or absence of any predisposing illness, symptoms at presentation, roentgenographic abnormalities, microbiologic results, findings at fiberoptic bronchoscopy, and results of therapeutic intervention. RESULTS: Sixty-five percent of patients with chronic bacterial pneumonia had a predisposing disease, 35 percent were "normal." Cough, fatigue, dyspnea, and weight loss were predominant symptoms in both groups. Bronchogenic carcinoma was newly diagnosed in 16 patients (14 percent). Haemophilus influenzae or alpha-hemolytic streptococcus was isolated in 68 percent of patients. Risk of recurrence of infection was inversely associated with duration of therapy in both groups. CONCLUSIONS: Chronic bacterial pneumonia is more common than previously recognized. It occurs in patients with and without a predisposing illness. Clinical presentation, roentgenographic appearance, and bacteriology are similar between the two groups. Cure requires prolonged antibiotic therapy.
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STUDY DESIGN: Bronchoalveolar lavage with seven 20-ml aliquots was performed on 9 patients with sarcoidosis and 11 patients with idiopathic pulmonary fibrosis (IPF). The returns from the first 20-ml aliquot (volume 1), the next 100 ml of bronchoalveolar lavage fluid (volume 2), and the last 20 ml of lavage fluid (volume 3) were analyzed separately for cell content and differential cell counts. The cell content was calculated four different ways, including absolute number of cells per milliliter of return and as a differential cell count using three different denominators. The denominators used were (1) neutrophils, lymphocytes, eosinophils, macrophages, and epithelial cells; (2) neutrophils, lymphocytes, eosinophils, and macrophages; and (3) neutrophils, lymphocytes and eosinophils. The data were analyzed to see what volume and arithmetic expression of cell content provided the best means of distinguishing sarcoidosis from IPF. RESULTS: The results confirmed a proximal distribution of the first 20-ml aliquot with more bronchial epithelial cells and neutrophils than volumes 2 and 3. There were more macrophages and lymphocytes in volumes 2 and 3 than in volume 1. Volumes 2 and 3 had similar cell content. Sequential fractional analysis showed that the cells in volume 2 and 3 more clearly distinguished sarcoidosis from IPF than the cell content of volume 1. CONCLUSION: The presence of lymphocytes, and especially a predominance of lymphocytes with the relative absence of neutrophils, correlated best with sarcoidosis. The percentages of differential cell counts proved superior to both the absolute number of neutrophils and of lymphocytes per milliliter of return in distinguishing sarcoidosis from IPF. A percentage differential cell count with a denominator of neutrophils+lymphocytes+eosinophils provided the best means of distinguishing between sarcoidosis and IPF.
STUDY DESIGN: Between February 1, 1984, and February 1, 1989, fiberoptic bronchoscopy was performed on 2,692 patients, 592 of whom had bronchoalveolar lavage (BAL). One hundred twenty-eight patients with 16 percent or more lymphocytes in BAL fluid (BALF) were selected for further study. The group included 27 patients with sarcoidosis, 28 with nonsarcoidosis interstitial lung disease (ILD), 22 with lung infection (organism isolated), 31 with inflammation (presumed infection, no organism isolated), 14 with neoplasm, and 6 with bronchial hyperreactivity. METHODS: The percentages of lymphocytes, B lymphocytes, and T lymphocytes, the CD4/CD8 ratio and the percentages of neutrophils and eosinophils were analyzed individually and in combination for discrimination between the sarcoidosis and nonsarcoidosis patients and compared with the diagnostic accuracy of multiple noncaseating granuloma (MNG) on a simultaneous transbronchial biopsy (Tbbx). RESULTS: Neither the percentages of lymphocytes, T lymphocytes, or B lymphocytes discriminated sarcoidosis from nonsarcoidosis patients. Sarcoidosis patients had higher CD4/CD8 ratios, fewer neutrophils, and 1 percent or less eosinophils in the BAL cell populations. An analysis of CD4/CD8 ratios, and percentages of neutrophils and eosinophils individually revealed that a CD4/CD8 ratio of 4:1 or greater had a positive predictive value of 94 percent in distinguishing sarcoidosis from other ILD but a sensitivity of only 59 percent. The positive predictive value of CD4/CD8 ratio of 4:1 or greater fell to 50 percent in separating sarcoidosis from all other diseases. A CD4/CD8 ratio of less than 1:1 has a 100 percent negative predictive value to exclude the diagnosis of sarcoidosis. Finding 1 percent or less neutrophils in BAL had an 80 percent positive predictive value in distinguishing sarcoidosis from nonsarcoidosis ILD and 51 percent for distinguishing sarcoidosis from all other disease groups. The CD4/CD8 ratio and the percentages of neutrophils and eosinophils also were combined and analyzed for the diagnosis of sarcoidosis. CONCLUSIONS: Results showed a BALF with a CD4/CD8 ratio of 2:1 or greater, 1 percent or less neutrophils, and 1 percent or less eosinophils has essentially the same specificity and positive predictive value as MNG on Tbbx in distinguishing sarcoidosis from nonsarcoidosis disease. The combination of finding MNG in a Tbbx specimen plus a BALF CD4/CD8 ratio of 4:1 or greater had a 100 percent positive predictive value in separating sarcoidosis from other ILD and an 81 percent value in separating sarcoidosis from all other disease. Finding MNG in a Tbbx specimen plus a BALF with a CD4/CD8 ratio of 2:1 or greater, 1 percent or less neutrophils, and 1 percent or less eosinophils had a 93 percent positive predictive value in distinguishing sarcoidosis from both nonsarcoidosis ILD and all other diseases.
Familiarity with the natural history of common pneumonias is obligatory for the clinician to determine whether a specific case of pneumonia is resolving at the expected rate. To many clinicians, the term slowly resolving pneumonia conjures an association with underlying neoplasm and/or less common pathogens. In reality, host factors or common pathogens such as Streptococcus pneumoniae and Legionella pneumophila are more likely responsible for delayed resolution. Familiarity with the pattern of resolution of pneumonias caused by these organisms should allow the clinician to follow such patients and avoid premature invasive evaluation. In contrast, Mycoplasma pneumoniae and Chlamydia species rarely result in slowly resolving pneumonia. Chronic bacterial pneumonia is an infectious syndrome that may present in the absence of systemic symptoms. The presentation is varied and may mimic neoplasm, interstitial lung disease, or chronic fungal or mycobacterial infection. Bacteria most commonly associated with chronic pneumonia include Haemophilus influenzae, Staphylococcus aureus, alpha-hemolytic streptococci (not S pneumoniae), and Pseudomonas aeruginosa.
Twenty-seven newly diagnosed patients with idiopathic pulmonary fibrosis (IPF) who were previously untreated for IPF were enrolled in a prospective, double-blind, randomized, placebo-controlled study to compare the therapeutic effect of combined prednisone/azathioprine (n = 14) with prednisone plus placebo (n = 13). Prednisone was started at 1.5 mg/kg/day (not to exceed 100 mg/day) for the first 2 wk followed by a biweekly taper to a maintenance dose of 20 mg/day. Azathioprine was administered at a daily dose of 3 mg/kg (not to exceed 200 mg/day). The patients tolerated the use of azathioprine well with few associated side effects. Changes in lung function at 1 yr, as measured by resting alveolar-arterial oxygen difference P[A-a]O2, FVC, and single breath diffusing capacity for carbon monoxide (DLCOSB), were all somewhat better in the azathioprine/prednisone group compared with the prednisone alone group, although none of these comparisons were statistically significant. Six of 14 (43%) patients randomized to prednisone plus azathioprine died during the 9-yr follow-up period, compared with 10 of 13 (77%) patients randomized to prednisone plus placebo. A Cox model survival analysis shows a nonsignificant but potentially large survival advantage for azathioprine/prednisone (hazard ratio 0.48, with 95% confidence interval increasing from 0.17 to 1.38). When adjusted for age, the survival advantage of azathioprine/prednisone becomes marginally significant (hazard ratio 0.26, with 95% confidence interval increasing from 0.08 to 0.88; p = 0.02 by large sample approximation, p = 0.05 by randomization test). We conclude that combined prednisone and azathioprine is a safe and possibly effective regimen for the treatment of IPF.(ABSTRACT TRUNCATED AT 250 WORDS)
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The purpose of this article is to describe the spectrum and frequency of diseases presenting as unexplained dyspnea and to develop a logical diagnostic approach to such patients. Seventy-two consecutive physician-referred patients had dyspnea greater than one-month duration unexplained by the initial history, physical examination, chest roentgenogram, and spirometry. Patients underwent a standard diagnostic evaluation. A definite cause for dyspnea was recognized in 58 patients, and no answer was found in 14. Twenty-two diseases were recognized in the patient group. Dyspnea was due to pulmonary disease in 26 (36 percent) patients, cardiac disease in ten (14 percent) patients, hyperventilation in 14 (19 percent) patients, and only 3 patients had extrathoracic disease causing dyspnea. Age younger than 40 years, intermittent dyspnea, and normal alveolar-arterial oxygen pressure difference (P[A-a]O2) at rest breathing room air was strongly predictive of bronchial hyperreactivity or hyperventilation. No patient diagnosed as having disease of the lung parenchyma or vasculature had a P(A-a)O2 less than or equal to 20 mm Hg. The differential diagnosis to explain dyspnea in patients with nondirective histories, normal findings from physical examinations, normal chest roentgenograms, and normal spirograms is extensive. The patient's age and measurement of gas exchange at rest help to formulate a diagnostic approach.