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Various reports have demonstrated the importance of small airway inflammation in the development of airflow limitation and progression of COPD. This hypothesis proposes that the pathogenesis of COPD mirrors a chronic inhalational dust-induced disease. The putative inorganic dust in cigarette smoke is aluminum silicate or kaolinite, a common component of clay soils. Kaolinite has been recovered in the alveolar macrophages of smokers and has been reported as a constituent of tobacco products. The origin of kaolinite in tobacco products remains unknown, and possible potential sources are proposed. On inhalation, kaolinite deposition in the distal lung may promote macrophage accumulation within the terminal airways leading to a respiratory bronchiolitis. In the susceptible smoker, important genetic, environmental, immunologic, and mechanical factors interact and modulate this small airway inflammation, ultimately leading to the pathologic lesion of emphysema. Further studies into the effects of kaolinite on macrophage function and the subsequent development of respiratory bronchiolitis could lead to prevention of COPD at its precursor lesion. [ABSTRACT FROM AUTHOR]

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a devastating disease, yet validated, reliable criteria for evaluating patient response to therapies in clinical trials are lacking. METHODS: To optimize selection of end point criteria for the study of interferon (IFN)-gamma1b in patients with IPF, we retrospectively analyzed the components of the primary efficacy end point used in a large, controlled study of 330 patients for reliability, validity, and sensitivity to treatment effect. The primary end point components were death, disease progression defined as a > or = 5 mm Hg increase in resting alveolar-arterial oxygen pressure gradient (P[A-a]O2), and disease progression defined as a > or = 10% decrease in percentage of predicted FVC. RESULTS: We found that the P(A-a)O2 criterion was not reliable and was not associated with mortality. In contrast, the FVC criterion was reliable and was associated with a 2.4-fold increase in the risk of death. Of the three measures, only mortality was sensitive to a treatment effect of IFN-gamma1b. Additionally, the tendency for mortality benefit was observed in nearly all patient subgroups defined by baseline physiology. The effect of IFN-gamma1b on mortality was strongest in patients with baseline percentage of predicted FVC > or = 55% (p = 0.004) or percentage of predicted diffusing capacity of the lung for carbon monoxide > or = 30% (p = 0.008). CONCLUSION: We conclude that mortality is the most inclusive end point for future trials of IFN- gamma1b in patients with IPF, and that a > 10% decrement in the percentage of predicted FVC represents a valid measure of disease progression. [ABSTRACT FROM AUTHOR]

Background: The chronic granulomatous inflammation of sarcoidosis has been hypothesized to depend on the CD4+ T-helper lymphocyte. HIV infection, which depletes these cells, has been reported to attenuate the manifestations of sarcoidosis.Study Objectives: We asked whether the development of symptomatic sarcoidosis in the context of preexisting HIV infection was dependent on the CD4+ lymphocyte count.Design: We performed a retrospective standardized chart review of all patients who developed granulomatous inflammation following HIV infection at an urban academic referral center.Measurements: We identified seven patients with sarcoidosis within this cohort and compared their CD4+ lymphocyte count to that in a cohort of 16 patients in whom similar granulomatous inflammation was found but who did not have sarcoidosis. We then compared our cases to all reported cases using a systematic literature review.Results: The CD4+ lymphocyte count was > 200 cells/ microL in all of our patients with HIV infection when they developed subsequent sarcoidosis. In contrast, specific etiologies for granulomatous inflammation were found in all 10 HIV-infected patients who presented with granulomatous inflammation and a CD4+ lymphocyte count of < 200 cells/ microL, with infectious etiologies found in 8 patients. Similarly, there was relative preservation of the CD4+ lymphocyte count in previously reported cases, with 14 of 19 patients (74%) having an absolute CD4+ lymphocyte count of > 200 cells/ microL.Conclusions: We conclude that the development of the chronic granulomatous inflammation of sarcoidosis appears to depend on the preservation or restoration of the peripheral CD4+ lymphocyte count and that in most cases the CD4+ lymphocyte count exceeds 200 cells/ microL. Furthermore, alternative specific etiologies of granulomatous inflammation are generally identifiable in HIV-infected patients with peripheral CD4+ lymphocyte counts of < 200 cells/ microL. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) is an important cause of morbidity and mortality in patients with scleroderma (Scl). Risk prediction and prognostication in patients with Scl-ILD are challenging because of heterogeneity in the disease course., Methods: We aimed to develop a clinical mortality risk prediction model for Scl-ILD. Patients with Scl-ILD were identified from two ongoing longitudinal cohorts: 135 patients at the University of California, San Francisco (derivation cohort) and 90 patients at the Mayo Clinic (validation cohort). Using these two separate cohorts, a mortality risk prediction model was developed and validated by testing every potential candidate Cox model, each including three or four variables of a possible 19 clinical predictors, for time to death. Model discrimination was assessed using the C-index., Results: Three variables were included in the final risk prediction model (SADL): ever smoking history, age, and diffusing capacity of the lung for carbon monoxide (% predicted). This continuous model had similar performance in the derivation (C-index, 0.88) and validation (C-index, 0.84) cohorts. We created a point scoring system using the combined cohort (C-index, 0.82) and used it to identify a classification with low, moderate, and high mortality risk at 3 years., Conclusions: The SADL model uses simple, readily accessible clinical variables to predict all-cause mortality in Scl-ILD., (Copyright © 2017 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: FVC outcomes in clinical trials on idiopathic pulmonary fibrosis (IPF) can be substantially influenced by the analytic methodology and the handling of missing data. We conducted a series of sensitivity analyses to assess the robustness of the statistical finding and the stability of the estimate of the magnitude of treatment effect on the primary end point of FVC change in a phase 3 trial evaluating pirfenidone in adults with IPF., Methods: Source data included all 555 study participants randomized to treatment with pirfenidone or placebo in the Assessment of Pirfenidone to Confirm Efficacy and Safety in Idiopathic Pulmonary Fibrosis (ASCEND) study. Sensitivity analyses were conducted to assess whether alternative statistical tests and methods for handling missing data influenced the observed magnitude of treatment effect on the primary end point of change from baseline to week 52 in FVC., Results: The distribution of FVC change at week 52 was systematically different between the two treatment groups and favored pirfenidone in each analysis. The method used to impute missing data due to death had a marked effect on the magnitude of change in FVC in both treatment groups; however, the magnitude of treatment benefit was generally consistent on a relative basis, with an approximate 50% reduction in FVC decline observed in the pirfenidone group in each analysis., Conclusions: Our results confirm the robustness of the statistical finding on the primary end point of change in FVC in the ASCEND trial and corroborate the estimated magnitude of the pirfenidone treatment effect in patients with IPF., Trial Registry: ClinicalTrials.gov; No.: NCT01366209; URL: www.clinicaltrials.gov.

Background: Risk prediction is challenging in chronic interstitial lung disease (ILD) because of heterogeneity in disease-specific and patient-specific variables. Our objective was to determine whether mortality is accurately predicted in patients with chronic ILD using the GAP model, a clinical prediction model based on sex, age, and lung physiology, that was previously validated in patients with idiopathic pulmonary fibrosis., Methods: Patients with idiopathic pulmonary fibrosis (n=307), chronic hypersensitivity pneumonitis (n=206), connective tissue disease-associated ILD (n=281), idiopathic nonspecific interstitial pneumonia (n=45), or unclassifiable ILD (n=173) were selected from an ongoing database (N=1,012). Performance of the previously validated GAP model was compared with novel prediction models in each ILD subtype and the combined cohort. Patients with follow-up pulmonary function data were used for longitudinal model validation., Results: The GAP model had good performance in all ILD subtypes (c-index, 74.6 in the combined cohort), which was maintained at all stages of disease severity and during follow-up evaluation. The GAP model had similar performance compared with alternative prediction models. A modified ILD-GAP Index was developed for application across all ILD subtypes to provide disease-specific survival estimates using a single risk prediction model. This was done by adding a disease subtype variable that accounted for better adjusted survival in connective tissue disease-associated ILD, chronic hypersensitivity pneumonitis, and idiopathic nonspecific interstitial pneumonia., Conclusion: The GAP model accurately predicts risk of death in chronic ILD. The ILD-GAP model accurately predicts mortality in major chronic ILD subtypes and at all stages of disease.

Background: It is unknown if the radiographic fibrosis score predicts mortality in persistent hypersensitivity pneumonitis (HP) and if survival is similar to that observed in idiopathic pulmonary fibrosis (IPF) when adjusting for the extent of radiographic fibrosis., Methods: We reviewed records from 177 patients with HP and 224 patients with IPF whose diagnoses were established by multidisciplinary consensus. Two thoracic radiologists scored high-resolution CT (HRCT) scan lung images. Independent predictors of transplant-free survival were determined using a Cox proportional hazards analysis. Kaplan-Meier survival curves were constructed, stratified by disease as well as fibrosis score., Results: HRCT scan fibrosis score and radiographic reticulation independently predicted time to death or lung transplantation. Clinical predictors included a history of cigarette smoking, auscultatory crackles on lung examination, baseline FVC, and FEV1/FVC ratio. The majority of HP deaths occurred in patients with both radiographic reticulation and auscultatory crackles on examination, compared with patients with only one of these manifestations (P &lt; .0001). Patients with IPF had worse survival than those with HP at any given degree of radiographic fibrosis (hazard ratio 2.31; P &lt; .01)., Conclusions: Survival in patients with HP was superior to that of those with IPF with similar degrees of radiographic fibrosis. The combination of auscultatory crackles and radiographic reticulation identified patients with HP who had a particularly poor outcome.

Background: Combined pulmonary fibrosis and emphysema (CPFE) is increasingly recognized, but its prevalence and prognosis remain unclear. We sought to determine the prevalence, clinical features, and prognosis of CPFE in idiopathic pulmonary fibrosis (IPF), using a standardized and reproducible definition., Methods: Patients with IPF were identified from two ongoing cohorts. Two radiologists scored emphysema and fibrosis severity on high-resolution CT (HRCT) scans. CPFE was defined as ≥10% emphysema on HRCT scan. Clinical characteristics and outcomes of patients with CPFE and IPF and those with non-CPFE IPF were compared with unadjusted analysis and then analysis after adjustment for HRCT fibrosis score. Mortality was compared using competing risks regression to handle lung transplantation. Sensitivity analyses were performed using Cox proportional hazards, including time to death (transplantation censored) and time to death or transplant., Results: CPFE criteria were met in 29 of 365 patients with IPF (8%), with high agreement between radiologists (κ=0.74). Patients with CPFE had less fibrosis on HRCT scans and higher FVC, but greater oxygen requirements (P≤.01 for all comparisons). Findings were maintained with adjustment for fibrosis severity. Inhaled therapies for COPD were used by 53% of patients with CPFE. There was no significant difference in mortality comparing patients with CPFE and IPF to those with non-CPFE IPF (hazard ratio, 1.14; 95% CI, 0.61-2.13; P=.69)., Conclusions: CPFE was identified in 8% of patients with IPF and is a distinct, clinical phenotype with potential therapies that remain underutilized. Patients with CPFE and IPF and those with non-CPFE IPF have similar mortality.

Idiopathic pulmonary fibrosis (IPF), a heterogeneous disease with respect to clinical presentation and rates of progression, disproportionately affects older adults. The diagnosis of IPF is descriptive, based on clinical, radiologic, and histopathologic examination, and definitive diagnosis is hampered by poor interobserver agreement and lack of a consensus definition. There are no effective treatments. Cellular, molecular, genetic, and environmental risk factors have been identified for IPF, but the initiating event and the characteristics of preclinical stages are not known. IPF is predominantly a disease of older adults, and the processes underlying normal aging might significantly influence the development of IPF. Yet, the biology of aging and the principles of medical care for this population have been typically ignored in basic, translational, or clinical IPF research. In August 2009, the Association of Specialty Professors, in collaboration with the American College of Chest Physicians, the American Geriatrics Society, the National Institute on Aging, and the National Heart, Lung, and Blood Institute, held a workshop, summarized herein, to review what is known, to identify research gaps at the interface of aging and IPF, and to suggest priority areas for future research. Efforts to answer the questions identified will require the integration of geriatrics, gerontology, and pulmonary research, but these efforts have great potential to improve care for patients with IPF.

Interstitial lung disease (ILD) is a frequent extraarticular manifestation of rheumatoid arthritis (RA). While the nonspecific interstitial pneumonia pattern predominates in most forms of connective tissue-associated ILD, studies in patients with RA-associated ILD (RA-ILD) suggest that the usual interstitial pneumonia (UIP) pattern is more common in this patient population. High-resolution CT (HRCT) scans appear accurate in identifying UIP pattern in many patients with RA-ILD. Although the data are limited, UIP pattern appears to predict worse survival in RA-ILD patients. Larger, prospective, multicenter studies are needed to confirm this finding. We propose that the evaluation of patients with RA-ILD should focus on identifying those with UIP pattern on HRCT scans, as these patients are likely to carry a worse prognosis. In patients in whom the underlying pattern cannot be determined by HRCT scanning, surgical lung biopsy should be considered.

Background: Serum surfactant protein (SP) A and SP-D had prognostic value for mortality in patients with idiopathic pulmonary fibrosis (IPF) in prior studies before the reclassification of the idiopathic interstitial pneumonias. We hypothesized that baseline serum SP-A and SP-D concentrations would be independently associated with mortality among patients with biopsy-proven IPF and would improve a prediction model for mortality., Methods: We evaluated the association between serum SP-A and SP-D concentrations and mortality in 82 patients with surgical lung biopsy-proven IPF. Regression models with clinical predictors alone and clinical and biomarker predictors were used to predict mortality at 1 year., Results: After controlling for known clinical predictors of mortality, we found that each increase of 49 ng/mL (1 SD) in baseline SP-A level was associated with a 3.3-fold increased risk of mortality (adjusted hazard ratio, 3.27; 95% confidence interval, 1.49 to 7.17; adjusted p = 0.003) in the first year after presentation. We did not observe a statistically significant association between serum SP-D and mortality (adjusted hazard ratio, 2.04; p = 0.053). Regression models demonstrated a significant improvement in the 1-year mortality prediction model when serum SP-A and SP-D (area under the receiving operator curve [AROC], 0.89) were added to the clinical predictors alone (AROC, 0.79; p = 0.03)., Conclusions: Increased serum SP-A level is a strong and independent predictor of early mortality among patients with IPF. A prediction model containing SP-A and SP-D was substantially superior to a model with clinical predictors alone.

Background: The prognostic value of BAL fluid cell count differential in patients with idiopathic pulmonary fibrosis (IPF) is unknown. We hypothesized that baseline BAL fluid cell count differential (ie, elevated levels of neutrophils and eosinophils, or reduced levels of lymphocytes) would predict higher mortality among persons with IPF., Methods: We evaluated the association of BAL fluid cell count differential and mortality among 156 persons with surgical lung biopsy-proven IPF who underwent bronchoscopy with BAL and cell count differential measurements at presentation. Vital status was obtained among all participants. Cox regression analysis evaluated the association of BAL fluid cell count differential and mortality., Results: After controlling for known clinical predictors of mortality, we found that each doubling of baseline BAL fluid neutrophil percentage was associated with a 30% increased risk of mortality (adjusted hazard ratio [HR], 1.28; 95% confidence interval [CI], 1.01 to 1.62; adjusted p = 0.04) in the first year after presentation. We observed no association with BAL fluid lymphocyte percentage and mortality (adjusted HR per doubling, 0.99; 95% CI, 0.76 to 1.29; p = 0.93) or eosinophil percentage and mortality (adjusted HR per doubling, 0.99; 95% CI, 0.69 to 1.40; p = 0.95)., Conclusions: Increased BAL fluid neutrophil percentage is an independent predictor of early mortality among persons with IPF. Alternatively, BAL fluid lymphocyte and eosinophil percentages were not associated with mortality. The clinical utility of BAL at the time of diagnosis of IPF should be reconsidered.

Background: The clinical and physiologic features of respiratory bronchiolitis (RB)-interstitial lung disease (ILD) have been previously described; however, the natural history and outcome have not been systematically evaluated. The majority of published reports consider RB-ILD to be a nonprogressive ILD that clinically improves with smoking cessation and antiinflammatory treatment. In this study, we sought to determine the outcome of RB-ILD patients with and without smoking cessation and with and without corticosteroid therapy., Methods: Thirty-two RB-ILD cases confirmed by surgical lung biopsy were identified from a prospectively enrolled cohort of subjects with ILD. Initial and follow-up data on symptoms, physiology, treatment, and outcome were collected and analyzed., Results: Kaplan-Meier analysis revealed that at least 75% of RB-ILD patients survived > 7 years after diagnosis. Clinical improvement occurred in only 28% of cases, and physiologic improvement occurred in 10.5% of cases. One patient died of progressive ILD, and two patients died of non-small cell lung cancer. While physiologic improvement was limited to those who had ceased smoking, corticosteroids and/or other immunosuppressive therapy had little effect on symptoms or physiology., Conclusions: This study shows that prolonged survival is common in RB-ILD. However, symptomatic and physiologic improvement occurs in only a minority of patients, and neither smoking cessation nor immunosuppressive therapy is regularly associated with clinically significant benefit.

Study Objectives: Treatment of patients with idiopathic pulmonary fibrosis (IPF) conventionally includes corticosteroids and cytotoxic agents. No study to date has adequately evaluated the benefits of this approach. This study retrospectively compared combination corticosteroid and cyclophosphamide therapy in a large population of patients who meet the current consensus definition of IPF., Design: Patients were identified retrospectively and treatment addressed on an intention-to-treat basis. Treated and untreated patients were matched by age and percentage of predicted FVC (FVC%) at the time of the initial visit., Setting: Two academic tertiary referral centers., Patients or Participants: The diagnosis of IPF was based on current consensus criteria. A total of 164 patients (82 treated and 82 untreated) were included., Interventions: Treatment consisted of combined corticosteroid and cyclophosphamide therapy using a standardized protocol., Measurements and Results: There was no difference in age, FVC%, gender, or smoking status between groups. No survival difference was found between patients who were treated (median survival, 1,431 days) or untreated (median survival, 1,665 days) [p = 0.58]. The lack of treatment effect persisted when only those patients with a diagnosis by surgical biopsy (n = 24) or FVC% >/= 60 (n = 107) were analyzed., Conclusions: Our data suggest that combined corticosteroid and cyclophosphamide therapy has no impact on survival in patients with IPF. This finding supports the evolving concept that chronic inflammation plays a minimal role in the progression of IPF and reinforces the importance of careful consideration of the risks and benefits of such therapies prior to their institution.

Purpose: To determine which clinical and radiologic findings are independently associated with a pathologic diagnosis of usual interstitial pneumonia (UIP)., Methods: We recently reported, using a prospective, multicenter study of patients suspected of having idiopathic interstitial pneumonia (IIP), that a confident diagnosis of UIP made by experienced radiologists was correct in 95% of cases. In the current article, we further analyzed data from this study. Ninety-one patients were entered into the study. Clinical, physiologic, chest radiographic, and CT features were prospectively recorded, and analyzed using univariate and multivariate logistic regression analysis to compare the patients with a histologic diagnosis of UIP with those who received other pathologic diagnoses., Results: Fifty-four of 91 patients (59%) received a pathologic diagnosis of UIP. The following features recorded at the referring clinical centers were associated with a pathologic diagnosis of UIP on multivariate analysis: lower-lobe honeycombing on high-resolution CT (HRCT) [odds ratio, 11.45], radiographic findings consistent with UIP (odds ratio, 5.73), elevated ratio of FEV(1) to FVC (odds ratio, 4.8), and absence of smoking history (odds ratio, 0.19). On multivariate analysis of specific HRCT features recorded by four experienced chest radiologists, lower-lung honeycombing (odds ratio, 5.36) and upper-lung irregular lines (odds ratio, 6.28) were the only independent predictors of UIP. Using only these two factors, a diagnosis of UIP could be established with a sensitivity of 74%, a specificity of 81%, and a positive predictive value of 85%., Conclusion: In patients presenting with a clinical syndrome suggestive of IIP, CT findings of lower-lung honeycombing and upper-lung irregular lines are most closely associated with a pathologic diagnosis of UIP.

Purpose: To assess quantitative high-resolution CT (quantitative CT) as a diagnostic and prognostic tool in pulmonary lymphangioleiomyomatosis., Methods: Spirometry, lung volumes, diffusing capacity, exercise physiology, and expiratory high-resolution CT (HRCT) examinations were performed on a cohort of ten patients with the diagnosis of lymphangioleiomyomatosis (LAM) referred to a tertiary care center. HRCT examinations were also done on ten normal control subjects. A thresholding technique was used to quantitatively assess the amount of abnormal cystic parenchyma present on each of the two images obtained for each subject with LAM and for each normal control subject. This numeric index of cystic parenchyma, the quantitative CT index, was then examined (1) as a diagnostic measure to distinguish the subjects with LAM from the normal control subjects and (2) as a prognostic measure to assess disease severity in the subjects with LAM. Linear regression of the quantitative CT index against physiologic indexes of pulmonary function and exercise performance was analyzed to determine the relationship between this radiologic assessment of disease severity and functional impairment., Results: The quantitative CT index was significantly greater for the LAM patients, 37.2 +/- 6.9 (SEM), compared with the control group, 0.8 +/- 0.2 (p = 0.0001). Linear regression analysis demonstrated significant linear correlation between the quantitative CT index and measures of airflow (FEV1, r = -0.90, p = 0.0005), air trapping (residual volume, r = 0.70, p = 0.02), diffusing capacity (diffusing capacity for carbon monoxide, r = -0.76, p = 0.01), gas exchange (alveolar to arterial oxygen gradient) at rest, r = 0.69, p = 0.007, and at maximum exercise, r = 0.79, p = 0.007) and exercise performance (maximum workload, r = -0.84, p = 0.002), and oxygen utilization (oxygen utilization at maximum exercise, r = -0.76, p = 0.01)., Conclusion: Quantitative CT techniques can distinguish subjects with LAM from normal controls. Further, the quantitative CT index correlates well with physiologic measurements of airflow, lung volumes, diffusing capacity, and exercise performance and, thus, may provide a useful measure of disease severity.

Cryptogenic organizing pneumonitis is a clinical and pathologic syndrome characterized by a "pneumonia-like" illness with excessive proliferation of granulation tissue within small airways and alveolar ducts associated with chronic inflammation in the surrounding alveoli. The duration of illness prior to lung biopsy is short, usually less than 2 months, and it is markedly different from that of IPF. Interestingly, unlike in IPF where the patient has difficulty remembering the exact onset of symptoms, patients with COP are frequently very specific about the timing of their disease onset. This is because the disease onset is recent and is often dramatic with the development of a severe flulike illness, ie, cough, fever, malaise, fatigue, and weight loss. Inspiratory crackles are frequently present on chest examination. Pulmonary function is usually impaired with a restrictive defect being most common. Gas exchange abnormalities are extremely common with a reduction in Dco and resting hypoxemia being almost universal findings. The roentgenographic manifestations are quite distinctive with a pattern of bilateral, diffuse but inhomogeneous, ground-glass or alveolar opacities being present in the majority of the cases. Bronchoalveolar lavage findings are nonspecific but usually reveal a lymphocytosis. The response to corticosteroid treatment is quite favorable and death from progressive disease is uncommon in COP, especially if treatment is instituted early in the course of the disease. In our experience, the cases with the worse prognosis are those associated with another disease process, in particular, connective tissue disorders like rheumatoid arthritis. In fact, these patients are prone to develop a rapidly progressive form of BOOP with a clinical course similar to the "Hamman-Rich syndrome." Recurrences are relatively frequent, consequently, withdrawal of treatment should be done with extreme caution. Corticosteroids have been the conventional initial treatment of COP, although to our knowledge, there are no controlled clinical trials to support it use. Antibiotics are not effective in treating this syndrome. Thus, based solely on our experience and that of others, we believe that high-dose corticosteroid therapy should be used to treat COP, usually initiated with 1 to 1.5 mg/kg/day (using ideal body weight) not to exceed 100 mg/day. Prednisone is given as a single oral dose in the morning. We recommended maintaining this dose for 4 to 8 weeks. If the patient's condition is stable or improved, the prednisone dosage is gradually tapered to 0.5 to 1 mg/kg/day (using ideal body weight) for the ensuing 4 to 6 weeks.(ABSTRACT TRUNCATED AT 400 WORDS)

Tablets and capsules containing the essential amino acid L-tryptophan are currently being investigated as a cause of the newly recognized eosinophilia/myalgia syndrome. In the five histologically documented cases reported herein, L-tryptophan ingestion was associated with prominent pulmonary complications. All patients were women ranging from 34 to 65 years, and all presented with respiratory symptoms that began after one to nine months of L-tryptophan therapy. Peripheral eosinophilia was present in four patients as were bilateral interstitial infiltrates on chest roentgenograms. One patient had a normal chest roentgenogram. Lung biopsies were done in all patients and biopsy specimens showed a vasculitis and perivasculitis associated with a mild chronic interstitial pneumonitis and eosinophilia. Three patients had clinical and/or histologic evidence of pulmonary hypertension, and one had a follicular bronchiolitis. Four patients recovered promptly with steroid therapy and discontinuation of L-tryptophan therapy, and one patient has had minimal symptomatic improvement.

Eighteen patients with lupus erythematosus (LE) and pleural effusions were evaluated. Fourteen patients had lupus pleuritis and four had pleural effusions of other etiologies. All patients were symptomatic, and the presenting signs and symptoms did not help distinguish between lupus pleuritis and pleural effusions of other causes. The presence of LE cells confirmed the diagnosis of lupus pleuritis in seven of eight patients. In 11 of 13 patients with lupus pleuritis, the pleural fluid antinuclear antibody (ANA) titer was greater than or equal to 1:160, and in nine of 13 patients with lupus pleuritis, the pleural fluid to serum (PF/S) ANA ratio was greater than or equal to 1. In the four patients with LE and a pleural effusion of another etiology, the pleural fluid ANA titer was negative in two and low titer in two (1:40, 1:80); the pleural fluid to serum ANA titer was always less than one. Of 67 patients with pleural effusions of other etiologies, the pleural fluid ANA was negative. The signs and symptoms of lupus pleuritis are nonspecific, however; the findings of LE cells in pleural fluid confirms the diagnosis and a high pleural fluid ANA titer (greater than or equal to 1:160) and a PF/S ANA ratio of greater than or equal to 1 strongly supports the diagnosis.

A 48-year-old woman with profound, rapidly progressive dyspnea requested a second opinion regarding the diagnosis and management of an undiagnosed interstitial process. One year prior to this evaluation, she had been placed on therapy with exogenous estrogens for the treatment of osteoporosis. During this therapy, she had a marked deterioration of her pulmonary status. Review of her open lung biopsy, which was obtained five years previously, revealed lymphangioleiomyomatosis. Discontinuation of estrogen therapy and treatment with tamoxifen were successful in stopping the progressive course. This patient's clinical course suggested an association between estrogen therapy and clinical deterioration during the menopause.

This study was designed to investigate the frequency and diagnostic importance of the pleuropulmonary manifestations of the postcardiac injury syndrome. A retrospective study of 35 patients (2 to 76 years old) with clearly defined postcardiac injury syndrome is presented. Twenty-one cases followed cardiac surgery, and 14 appeared after myocardial infarction. The onset of the syndrome was an average of 20 days following injury. The major clinical findings were pleurisy (91 percent; 32/35), fever (66 percent; 23/35), pericardial rub (63 percent; 22/35), dyspnea (57 percent; 20/35), rales (51 percent; 18/35), pleural rub (46 percent; 16/35), elevated erythrocyte sedimentation rate (96 percent; 25/26), and leukocytosis (49 percent; 17/35). The chest roentgenogram was abnormal in 94 percent (33/35). Pleural effusion was present in 83 percent (29/35), parenchymal infiltrates in 74 percent (26/35), and an enlarged cardiac silhouette in 49 percent (17/35). Analysis of pleural fluid was performed on 16 samples from 12 patients and revealed a bloody exudate with a pH greater than 7.40. The data presented document that pleuropulmonary involvement is a common manifestation of postcardiac injury syndrome. In addition, we discuss how these findings can be used to differentiate this syndrome from other clinical entities that may appear following cardiac injury, ie, parapneumonic effusions, congestive heart failure, and pulmonary embolism.

Cardiac tamponade is a rare complication of the postpericardiotomy syndrome in the absence of anticoagulation therapy. Three cases are presented where cardiac tamponade developed as a result of the postpericardiotomy syndrome with normal coagulation parameters. The pericardial effusions were serous in two and serosanguinous in the third case. Pericardial fluid studies were consistent with an exudate. The effusion resolved following a single pericardial tap and short-term corticosteroid therapy in one case. Repeated pericardiocentesis and drainage via an indwelling catheter were required in the other two cases.