Prevalence of cocaine use and its impact on asthma exacerbation in an urban population.

OBJECTIVES: To assess the prevalence of cocaine use, and its impact on severity of presentation, among adults presenting to the emergency department (ED) with asthma. A secondary aim was to assess the use of various asthma treatment modalities, with reference to the 1997 National Asthma Education and Prevention Program (NAEPP) guidelines. METHODS: All adults aged 18 to 55 years who presented to the ED of this institution with an asthma attack, were approached about participating in the study, which required giving informed consent, answering a facilitated questionnaire, and giving a urine sample for drug screening. RESULTS: Patients were enrolled during a 7-month period. A total of 163 patients were approached to enter the study; 116 patients consented to participate in the study, with 103 submitting complete urine samples. Thirty-seven patients refused to participate, and 10 were excluded. Sixty-eight percent of the patients were women, with a mean age of 33 years. African-Americans made up 89% of the total group. Thirty-five percent were cigarette smokers. Urine cocaine tests were positive in 13 of 103 (13%); 6 of 103 (5.8%) were positive for opiates. In the cocaine-positive group, 5 of 13 patients (38%) were admitted to the hospital, including two patients requiring intubation and mechanical ventilation. Of the total group, 23 of 103 patients (22%) were admitted, and 5 of those 23 admitted patients (22%) were cocaine-positive. Length of stay was significantly longer (5 vs 2.5 days, p < 0.05) in the cocaine-positive admitted patients. Forty-six percent of all patients reported using inhaled corticosteroids (ICS), with 39% of admitted patients using them. Thirty-two percent of all patients had obtained three or more refills of their beta(2)-agonist inhaler in the previous month. CONCLUSIONS: The prevalence of cocaine use may be much higher than the 13% shown in this study, because of patients' refusal to participate in the study. Second, the severity of exacerbation appears to be worse in the cocaine-positive group. Finally, the majority of patients presenting did not use ICS in accordance with the NAEPP guidelines.

Susceptibility to amiodarone-induced pulmonary toxicity: relationship to the uptake of amiodarone by isolated lung cells.

In previous studies, we showed that Fischer rats fed 175 mg/kg of amiodarone accumulated large amounts of drug and metabolite in the lung and developed pulmonary toxicity, whereas Wistar rats fed the same drug dose had significantly less amiodarone in the lung and did not develop pulmonary inflammation. The present study was designed to determine whether this difference in susceptibility between the strains was related to differences in uptake of amiodarone by lung cells. We found that isolated mixed lung cells of Fischer rats sequester significantly more drug than cells from Wistar rats. This difference in uptake cannot be due to drug metabolism because the lung is not capable of metabolizing amiodarone. We also found that the alveolar macrophage is one of the cell types in the mixed cell population that is partially responsible for the difference in drug uptake and that fibroblasts and type II pneumocytes are not involved. In addition, despite the fact that there was no difference in drug uptake, we found that fibroblasts isolated from Fischer rats were more susceptible to amiodarone-induced cytotoxicity than were Wistar fibroblasts. We conclude that genetic differences in lung drug sequestration and possibly the sensitivity to cytotoxicity may explain differences in susceptibility to amiodarone-induced pulmonary toxicity.

Bacteremic pneumococcal pneumonia. A community hospital experience.

We reviewed our experience with bacteremic pneumococcal pneumonia (BPP) over a 1-year period at a 600-bed community teaching hospital; 26 cases were identified. The mean age was 57.5 years and there were 12 male and 14 female subjects. Cough, sputum production, fever, and mental status changes were the most frequent symptoms. Risk factors included drug abuse in 10, HIV in 4, current smoking in 7, diabetes in 3, and cancer in 3. The mean PaO2/FIo2 ratio was 274. Radiographic features included a consolidation pattern in 7, bronchopneumonia in 15, combined in 1, and an initial normal film in 3. Average length of stay (LOS) was 11 days with an overall mortality of 11.5%. Four patients required mechanical ventilation, two meeting the criteria for ARDS (if this group were eliminated, LOS would be 8.4 days). Three of these survived. Four patients had organisms resistant to penicillin and all survived. We conclude that (1) BPP remains a serious but treatable infection particularly when utilizing full supportive care; (2) the bronchopneumonia x-ray film pattern was associated with all the mortality; and (3) the occurrence of penicillin resistance did not contribute to the mortality, since early recognition and the use of appropriate antibiotics saved all of these patients.

Amiodarone pulmonary toxicity in the rat is associated with increased lavage immunoglobulin and alveolar macrophages primed for increased interleukin-1 secretion.

To determine whether a hypersensitivity reaction played a role in amiodarone-induced pulmonary inflammation and affected humoral immunity, we examined pulmonary immunoglobulin (Ig) levels, alveolar macrophage release of interleukin-1 (IL-1)-like activity, and the ability to generate both systemic and pulmonary humoral immune responses after immunization. Levels of IgG, IgM, and albumin in lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA) in control rats and rats fed drug for 3, 8, 11, and 30 wk. Control rats showed no change in lavage Ig levels at any time point. However, drug-fed rats had a significant increase in IgG/albumin at 11 and 30 wk and IgM/albumin at 30 wk. To determine whether alveolar macrophages were in an activated state, the amount of IL-1-like activity released by cells from control rats was compared with drug-fed rats, using the standard C3H/HeJ thymocyte proliferation assay. We found no difference in the spontaneous release of IL-1 activity, but lipopolysaccharide-stimulated macrophages from the drug-fed rats produced significantly more IL-1 than did control macrophages. Finally, to examine antibody responses, control and drug-fed rats were immunized and boosted with 1 mg/ml of ovalbumin (OA) in adjuvant followed by an intratracheal immunization of OA. There was no difference in antibody titers measured by ELISA. In conclusion, although there is some suggestion of an immune-mediated component in amiodarone-induced pulmonary inflammation, the increase in lymphocytes and lavage Ig appears too late to be the sole cause.

Amiodarone causes decreased cell-mediated immune responses and inhibits the phospholipase C signaling pathway.

Amiodarone can cause pulmonary toxicity along with an increase in phospholipid in macrophages, lymphocytes, and other cell types. Phospholipid accumulates because amiodarone inhibits the lysosomal phospholipases A1 and A2. Since a wide array of cells are affected by amiodarone and because amiodarone might inhibit other phospholipases, we postulated that cellular functions might be affected. Therefore, the major focus of this study was to determine whether amiodarone inhibited cellular functions. We found that alveolar macrophages isolated from drug-fed rats were significantly less phagocytic, and that the rats had significantly depressed delayed-type hypersensitivity responses. Spleen cells isolated from the drug-fed rats also had severely depressed mitogen responses. Since the spleen cell proliferative response could be partially restored by stimulating the cells with ionomycin and phorbol myristate acetate, we postulated that amiodarone was inhibiting phospholipase C. To substantiate this hypothesis, we found that amiodarone could directly inhibit phospholipase C in vitro. We conclude that amiodarone affects both phagocytic responses and the development of cell-mediated immunity and that the lack of these normal responses could exacerbate amiodarone toxicity. One possible mechanism for decreased cellular functions may be the inhibition of phospholipase C. However, further studies are necessary to confirm this finding.

Pleural effusions in right-sided endocarditis: characteristics and pathophysiology.

The incidence, characteristics, and pathogenesis of pleural effusions in patients with right-sided endocarditis (RSE) are poorly defined. We have recently observed four patients with a history of intravenous drug abuse and bacteremia due to Staphylococcus aureus who had pleural effusions during an episode of RSE. We report the pleural fluid characteristics of five effusions in these four patients and attempt to define the pathogenesis of each. We found that (1) an exudative, sterile, serosanguineous, or bloody effusion is common in RSE, (2) empyema occurred in only one patient, and (3) transudative effusions due to CHF were not observed. Possible mechanisms of pleural fluid formation in RSE include parapneumonic effusion, septic pulmonary emboli with or without infarction, and empyema. Congestive heart failure does not appear to be a common cause of pleural effusion in pure right-sided endocarditis.

Amiodarone-induced pulmonary inflammation. Correlation with drug dose and lung levels of drug, metabolite, and phospholipid.

To investigate the hypotheses that amiodarone-induced pulmonary inflammation may be related to direct drug toxicity, groups of 10 or more Wistar rats were fed amiodarone by gavage at concentrations of 175, 300, 400, and 500 mg/kg/day, or vehicle alone. After 6 wk of drug feeding, the rats were examined for histologic and cellular evidence of pulmonary inflammation. In addition, the amounts of amiodarone, the major metabolite of amiodarone N-desethylamiodarone (N-des), and phospholipid in the lungs were determined. We found that rats fed 175 mg/kg of amiodarone were essentially no different from control animals. The 175 mg/kg group had normal lung histologies, no change in lavage cell counts or differential counts, and very little amiodarone, N-des, or phospholipid in the lungs. In contrast, the three high-dose groups had abnormal lung histologies along with increases in lavage cell counts and change in differential counts. There were also significant increases in the amounts of amiodarone, N-des, and phospholipid in the lung. We conclude that the development of amiodarone-induced pulmonary inflammation is dose dependent, and that there is a direct correlation between the amount of amiodarone, N-des, and phospholipid in the lung with the development of inflammation. It therefore appears that the drug is directly toxic to lung tissue.

Pulmonary accumulation of amiodarone and N-desethylamiodarone. Relationship to the development of pulmonary toxicity.

To investigate the relationship between the amount of amiodarone and the major metabolite N-desethylamiodarone found in the lung with the development of toxicity, Fischer 344 and Wistar rats were given 175 mg/kg/day of drug by gavage. After 1, 3, 6, and 12 wk of drug feeding, both stains were examined for histologic evidence of pulmonary inflammation and for changes in lavage cell counts and differentials. The amounts of amiodarone and N-desethylamiodarone in the lungs were determined using high performance liquid chromatography. We found that in drug-fed Wistar rats the lavage differentials were unchanged, lavage cell counts were decreased compared with those in control rats, and the lungs appeared normal except for some foamy macrophages. Wistar rats also had low levels of amiodarone and metabolite in both lung tissue and cells. In contrast, Fischer rats had an increase in lavage lymphocytes, neutrophils, and macrophages compared with that in control rats and abnormal lung histologies. Also, there was much more drug and metabolite in the lungs than the amounts found in Wistar rats. Because Fischer rats had more metabolite than amiodarone in the lung and the reverse was true in Wistar rats, the in vitro cytotoxicity of amiodarone and N-desethylamiodarone were compared. We found that N-desethylamiodarone was significantly more cytotoxic than amiodarone to both fibroblasts and endothelial cells. We conclude that there is a relationship between the amounts of drug and metabolite in the lung and the development of pulmonary inflammation, and that N-desethylamiodarone may be more cytotoxic than amiodarone.

Amiodarone-induced pulmonary toxicity in the rat.

A rat model of amiodarone-induced pulmonary toxicity is described. The rats were fed, by gavage, 175 mg/kg/day of amiodarone hydrochloride suspended in methyl cellulose. Controls received methyl cellulose alone. Groups of rats were examined after 1, 3, 6, 9, and 12 weeks of feeding. We found that drug-fed rats had significantly more macrophages, neutrophils, and lymphocytes in the bronchoalveolar lavage (BAL). The early increase in cellularity was due to an increase in macrophages, and the macrophage count peaked after 6 weeks of drug treatment. The number of neutrophils in the experimental animals remained high throughout the course of the experiment. An increasing number of lymphocytes was seen in the BAL between 6 and 12 weeks of drug treatment. Protein in the lavage fluid was significantly elevated after 12 weeks of amiodarone exposure. Histologic sections were abnormal after 3 weeks of drug treatment, characterized by interstitial thickening with accumulation of mononuclear cells and alveoli packed with large foamy macrophages. There was only minimal evidence of fibrosis. This model appears to be very similar to human amiodarone-induced pulmonary toxicity and should be useful for the study of the pathogenesis of amiodarone-induced toxicity.

Utility of immediate postlobectomy fiberoptic bronchoscopy in preventing atelectasis.

In a prospective randomized trial, we examined the value of routine postlobectomy fiberoptic bronchoscopy (FOB) in preventing postoperative atelectasis. Twenty patients who underwent lobectomy were randomly assigned to either chest physical therapy alone (group 1) or immediate bronchoscopy (group 2). Both group 1 and group 2 were placed on a standard physical therapy regimen consisting of aerosol bronchodilator therapy, chest percussion, and incentive spirometry. It was concluded that routine postlobectomy bronchoscopy offers no advantage over the usual physical therapy measures in preventing the development of postoperative atelectasis.

Usefulness of tumor markers in serum and bronchoalveolar lavage of patients undergoing fiberoptic bronchoscopy.

To evaluate the diagnostic usefulness of simultaneous determinations of 4 tumor markers (carcinoembryonic antigen, calcitonin, creatinine kinase-BB, and DNA), we studied 31 patients with lung cancer, 22 with benign lung disease, and 15 normal volunteers as control subjects. The measurements were made by radioimmunoassay in bronchoalveolar lavage (BAL) and in serum obtained on the same day. The results showed that in serum, only CEA levels were significantly higher in malignancy; in lavage fluids, all 4 markers were abnormally high in cancer patients when compared with control subjects (p less than 0.05); there was no correlation between the levels in lavage and those in the bloodstream. When the mean levels in lavage of the normal control subjects were designated as the limits for a positive test, significant association was found between malignancy and abnormally elevated marker concentration (p less than 0.01). The particular combination of CEA-BAL greater than 35 ng/mg, CEA-serum greater than 4 ng/ml, and calcitonin-BAL greater than 120 pg/mg taken together with the results of bronchoscopy (histologic and cytologic) showed the highest discriminating power between malignant and benign lung disease. The sensitivity of the bronchoscopy procedure increased from 50 to 89%, with at least 2 positive markers, and had a specificity of 71%. When both bronchoscopy and all 3 markers were negative, the results showed a negative predictive value of 100%. We conclude that tumor marker levels in lavage are a useful aid in the diagnosis of malignancy in patients undergoing bronchoscopy.

Clinical diagnosis of massive hemoptysis using the fiberoptic bronchoscope.

Pulmonary resection, when possible, is the conventional treatment of massive hemoptysis. Alternatives include bronchial artery embolization, Fogarty catheter balloon tamponade, and pharmacologic approaches. We used endotracheal intubation and flexible bronchoscopy to locate the bleeding site in three of four patients with massive hemoptysis. These cases are used to review the etiology of massive hemoptysis and the usefulness of flexible bronchoscopy to localize the source of hemorrhage.

Endobronchial lymphocytic infiltration. Unusual manifestation of chronic lymphocytic leukemia.

This report describes a patient with chronic lymphocytic leukemia followed over a 15-year period. The distinctive feature of her course was the infiltration of the bronchial wall by malignant lymphocytes, which produced endobronchial obstruction, atelectasis, and infection. Symptomatic improvement occurred following local irradiation and steroid therapy. A review of the literature establishes that the development of endobronchial infiltration during the course of chronic lymphocytic leukemia and other lymphoproliferative disorders is distinctly uncommon.

Hypercapnia complicating massive pulmonary embolism.

An elevated PaCO2 is distinctly unusual in pulmonary embolic disease. We report 2 patients with massive pulmonary emboli complicated by hypercapnia in the absence of underlying chronic obstructive lung disease. Profound alterations in ventilation/perfusion matching and reduced cardiac output are probable mechanisms of this gas-exchange problem.

Is pulmonary artery catheterization necessary for the diagnosis of pulmonary edema?

The ability to differentiate cardiac from permeability edema on the basis of clinical and radiographic criteria was studied in 70 ICU patients in whom subsequent pulmonary artery catheterization (PAC) was performed. Our study demonstrated that the clinical assessment of permeability pulmonary edema was correct in 17 of 20 patients (85%). In contrast, of the 50 patients initially suspected of having cardiac edema, only 31 (62%) were predicted correctly (p less than 0.05). Complications relating to catheterization occurred in 25% of patients, with 3 deaths. We conclude that the diagnosis of cardiogenic pulmonary edema, based on clinical criteria alone, is often inaccurate in the intensive care setting. The failure of patients to respond to initial therapy should mandate pulmonary artery catheterization, despite the attendant risks. Furthermore, even though the clinical diagnosis is correct in 85% of patients with permeability pulmonary edema, PAC data may be necessary for optimal management.

Cardiopulmonary effects of acute thallium poisoning.

Gastrointestinal distress and alopecia are the most commonly reported symptoms of acute thallium intoxication; however, cardiac and pulmonary disease may dominate the acute stages of the disease. We report four cases which illustrate the importance of cardiac and respiratory disease in this syndrome.