Increased susceptibility to pulmonary emphysema among HIV-seropositive smokers.

BACKGROUND: Previous uncontrolled reports have suggested that HIV-seropositive persons develop an accelerated form of emphysema. OBJECTIVE: To characterize the risk for emphysema in a stable HIV-seropositive outpatient population. DESIGN: Controlled, cross-sectional analysis. SETTING: Midwestern urban community. PARTICIPANTS: HIV-seropositive persons (n = 114) without AIDS-related pulmonary complications and HIV-seronegative controls (n = 44), matched for age and smoking history. MEASUREMENTS: Measurement of pulmonary function, bronchoalveolar lavage, and high-resolution computed tomography of the chest. RESULTS: The incidence of emphysema was 15% (17 of 114) in the HIV-seropositive group compared with 2% (1 of 44) in the HIV-seronegative group (P = 0.025). The incidence of emphysema in participants with a smoking history of 12 pack-years or greater was 37% (14 of 38 persons) in the HIV-seropositive group compared with 0% (0 of 14 persons) in the HIV-seronegative group (P = 0.011). The percentage of cytotoxic lymphocytes in lavage fluid was much higher in HIV-seropositive smokers with emphysema. CONCLUSIONS: Infection with HIV accelerates the onset of smoking-induced emphysema. The results of this study support the emerging concept that cytotoxic lymphocytes may have an important role in emphysema pathogenesis.

Herpes simplex type 2 causing fulminant hepatic failure.

Although exceedingly rare, fulminant hepatic failure (FHF) in immunocompetent patients can develop with primary or recurrent infection due to herpes simplex virus (HSV). The diagnosis is frequently obscured by the absence of mucocutaneous involvement. Elevated transaminase values with leukopenia and a relatively low bilirubin level may provide clues to the diagnosis. We describe an immunocompetent woman who died of FHF before a definitive diagnosis of HSV type 2 hepatitis was established. Herpes simplex virus hepatitis is one of the few causes of FHF for which potentially effective therapy is available. Thus, early diagnosis is paramount and usually requires liver biopsy. Recent studies suggest that transjugular liver biopsy is safe and effective in establishing the cause of FHF. Since the diagnosis and management of FHF are frequently influenced by the results of transjugular liver biopsy, it may become a standard diagnostic tool for managing FHF in centers where such expertise exists.

Focal air trapping in patients with HIV infection: CT evaluation and correlation with pulmonary function test results.

OBJECTIVE: HIV-positive individuals commonly have symptoms of airway disease. We evaluated thin-section CT scans of HIV-infected individuals during inspiration and expiration for evidence of focal air trapping. We also correlated imaging findings with pulmonary function test results. SUBJECTS AND METHODS: Fifty-nine subjects, 48 of whom were HIV-positive and 11 of whom were HIV-negative, underwent thin-section CT of the thorax during inspiration and expiration. All subjects also underwent pulmonary function tests. Two radiologists, who were unaware of the subjects' HIV status and smoking history and of the results of pulmonary function tests, evaluated the CT scans for the presence and severity of focal air trapping. RESULTS: Expiratory CT revealed focal air trapping in 33 subjects: 30 were HIV-positive and three were HIV-negative (p = .0338). The mean values of forced expiratory volume in 1 sec (FEV1), forced mid expiratory flow, and diffusion capacity (DL(CO)) were significantly lower for subjects with focal air trapping (mean = 88.85, 84.52, and 80.80, respectively) than for those with normal findings on CT (mean = 100.84, 99.24, and 95.82, respectively; p = .001, p = .021, and p = .003, respectively). We found no significant differences in smoking history between HIV-positive and HIV-negative subjects. Severe air trapping on expiratory CT scans was seen in three subjects: All three had HIV infection, low CD4 counts, and abnormally decreased FEV1 and DL(CO) values. CONCLUSION: Focal air trapping was a common finding on thoracic CT scans obtained during expiration in HIV-positive subjects. In addition, focal air trapping was associated with significantly lower FEV1, forced mid expiratory flow, and DL(CO) values than those found for subjects in whom CT revealed no focal air trapping. These results suggest that small airways disease may accompany a decline in pulmonary function in HIV-positive individuals.

Effect of enteral feeding with eicosapentaenoic acid, gamma-linolenic acid, and antioxidants in patients with acute respiratory distress syndrome. Enteral Nutrition in ARDS Study Group.

OBJECTIVES: Recent studies in animal models of sepsis-induced acute respiratory distress syndrome (ARDS) have shown that a low-carbohydrate, high-fat diet combining the anti-inflammatory and vasodilatory properties of eicosapentaenoic acid (EPA; fish oil), gamma-linolenic acid (GLA; borage oil) (EPA+GLA), and antioxidants improves lung microvascular permeability, oxygenation, and cardiopulmonary function and reduces proinflammatory eicosanoid synthesis and lung inflammation. These findings suggest that enteral nutrition with EPA+GLA and antioxidants may reduce pulmonary inflammation and may improve oxygenation and clinical outcomes in patients with ARDS. DESIGN: Prospective, multicentered, double-blind, randomized controlled trial. SETTING: Intensive care units of five academic and teaching hospitals in the United States. PATIENTS: We enrolled 146 patients with ARDS (as defined by the American-European Consensus Conference) caused by sepsis/pneumonia, trauma, or aspiration injury in the study. INTERVENTIONS: Patients meeting entry criteria were randomized and continuously tube-fed either EPA+GLA or an isonitrogenous, isocaloric standard diet at a minimum caloric delivery of 75% of basal energy expenditure x 1.3 for at least 4-7 days. MEASUREMENTS AND MAIN RESULTS: Arterial blood gases were measured, and ventilator settings were recorded at baseline and study days 4 and 7 to enable calculation of PaO2/FIO2, a measure of gas exchange. Pulmonary neutrophil recruitment was assessed by measuring the number of neutrophils and the total cell count in bronchoalveolar lavage fluid at the same time points. Clinical outcomes were recorded. Baseline characteristics of 98 evaluable patients revealed that key demographic, physiologic, and ventilatory variables were similar at entry between both groups. Multiple bronchoalveolar lavages revealed significant decreases (approximately 2.5-fold) in the number of total cells and neutrophils per mL of recovered lavage fluid during the study with EPA+GLA compared with patients fed the control diet. Significant improvements in oxygenation (PaO2/FIO2) from baseline to study days 4 and 7 with lower ventilation variables (FIO2, positive end-expiratory pressure, and minute ventilation) occurred in patients fed EPA+GLA compared with controls. Patients fed EPA+GLA required significantly fewer days of ventilatory support (11 vs. 16.3 days; p = .011), and had a decreased length of stay in the intensive care unit (12.8 vs. 17.5 days; p = .016) compared with controls. Only four of 51 (8%) patients fed EPA+GLA vs. 13 of 47 (28%) control patients developed a new organ failure during the study (p = .015). CONCLUSIONS: The beneficial effects of the EPA+GLA diet on pulmonary neutrophil recruitment, gas exchange, requirement for mechanical ventilation, length of intensive care unit stay, and the reduction of new organ failures suggest that this enteral nutrition formula would be a useful adjuvant therapy in the clinical management of patients with or at risk of developing ARDS.

The pathophysiology of pulmonary diffusion impairment in human immunodeficiency virus infection.

Numerous reports have demonstrated that prior to the development of acquired immunodeficiency syndrome (AIDS)-related pulmonary complications, human immunodeficiency virus-positive (HIV+) individuals commonly develop unexplained reductions in pulmonary diffusing capacity (DLCO). The potential relevance of this observation is underscored by recent data demonstrating that reductions in DLCO independently predict the subsequent development of opportunistic pneumonia. To delineate the alterations in gas exchange associated with HIV, we investigated a group of HIV+ subjects with unexplained reductions in DLCO, using high-resolution computed tomography (HRCT) of the chest and a separation of diffusing capacity into its membrane (Dm) and capillary blood volume (Vc) components. We compared this abnormal group with HIV+ subjects with more normal gas exchange and also with a group of HIV- volunteers matched for age and smoking history. Compared with other groups, the HIV+ group with diffusion impairment demonstrated prominent reductions in Vc, despite a well-preserved total lung capacity (TLC). HRCT demonstrated virtually no evidence of interstitial fibrosis in any HIV+ subject, but evidence of early emphysema that significantly correlated with DLCO. Our results suggest that the previously reported impairment in pulmonary gas exchange in the HIV+ population involves loss of Vc and likely represents the development of early emphysema.

Pulmonary infections in hospitalized patients with cirrhosis.

We have further characterized pulmonary infections by bronchoalveolar lavage in hospitalized patients with cirrhosis. Sixty-seven consecutive patients admitted to the Ohio State University Medical Center from 1992 to 1995 with liver disease who underwent bronchoscopy with bronchoalveolar lavage were identified. Twenty-one patients with cirrhosis and pneumonia were further analyzed. During the same period, we consecutively identified 23 patients without liver disease or immunosuppression, 19 patients with HIV infections, and 30 patients with cancer or pharmacologic immunosuppression who had bronchoscopy with bronchoalveolar lavage for pneumonia. These groups were included in these analyses as a control and immunosuppressed controls, respectively. Bronchoscopy isolated respiratory pathogens in 16 patients (76.2%) with cirrhosis and 6 patients (26.1%) in the control group (p = 0.002). Fungal organisms were most commonly found in patients with cirrhosis although several patients had more than one organism identified. The control group had mostly bacterial pathogens; the immunosuppressed controls were commonly infected with opportunistic organisms. Six (85.7%) of 7 patients with cirrhosis and fungal pneumonia died of their respiratory illness. Hospitalized patients with cirrhosis commonly have opportunistic pulmonary infections; diagnostic bronchoscopy and empiric antifungal therapy should be considered in those who do not respond to antibiotics.

Effectiveness of telemedicine in the outpatient pulmonary clinic.

BACKGROUND: Over the past several years, there has been a resurgence of interest in telemedicine. Despite this renewed interest, some health care providers remain skeptical regarding the effectiveness of telemedicine for the delivery of health care. OBJECTIVE: The objective of this prospective, crossover study was to determine if there was any difference between care delivered using video conferencing-based telemedicine technology and that given by a traditional face-to-face encounter in a pulmonary medicine clinic. METHODS: Two pulmonologists sequentially examined 40 individuals via video conferencing-based telemedicine technology and by the traditional face-to-face method. Two additional pulmonologists, in a blinded fashion, compared the results for consistency in the history, examination with focus on auscultation of the lungs, diagnostic impression, and evaluation and treatment plans. RESULTS: Evaluation of patients by telemedicine was as effective as the traditional mode. The telemedicine physician and the physician examining the patient in the traditional manner were able to elicit the same key complaints and hear the same adventitious sounds on auscultation of the lungs. CONCLUSION: Telemedicine can enable the provision of high-quality care in a pulmonary clinic setting.

Serum vitamin E decreases in HIV-seropositive subjects over time.

Vitamin E is an important lipid soluble antioxidant that has a number of crucial functions including protecting lipids from oxidative damage. It also may play an important role in enhancing the immune response in subjects with Human Immunodeficiency Virus (HIV) infection. The current study measured the serum level of vitamin E in 121 HIV seropositive subjects with no prior pulmonary complications. Although the mean level was normal at 9.0 +/- 0.5 microg/ml, 22.3% of the subjects had a deficient level of less than 5 microg/ml. In addition, 42 subjects were studied longitudinally and serum vitamin E levels were determined at baseline and 12 months later. The mean serum vitamin E level in this group significantly decreased after 12 months compared with baseline levels (5.9 +/- 0.5 microg/ml compared with 9.6 +/- 0.9 microg/ml, p = 0.001). The CD4 counts also were significantly decreased after 12 months (460.6 +/- 36.0 cells/mm3 versus 390.5 +/- 37.7 cells/mm3, p = 0.032). No significant correlations were observed between the decrease in serum vitamin E and the change in CD4 count, body mass index (BMI), or serum albumin levels over the 12-month period. In conclusion, a significant portion of HIV-seropositive subjects have a deficiency in serum vitamin E early in the course of their disease. Furthermore, there is a significant decrease in serum vitamin E levels in these subjects over 12 months.

Alveolar fluid glutathione decreases in asymptomatic HIV-seropositive subjects over time.

BACKGROUND: Initial investigations demonstrated a deficiency of glutathione (GSH) in the epithelial lining fluid (ELF) of HIV-seropositive patients. In a recent study, our laboratory was unable to document such a deficiency. The current study was performed in an attempt to reconcile those disparate findings. STUDY OBJECTIVES: To determine if ELF GSH decreases over time in asymptomatic HIV-seropositive subjects. DESIGN: Prospective, longitudinal study. SETTING: Major university medical center. PATIENTS OR PARTICIPANTS: Thirty-three asymptomatic HIV-seropositive volunteers. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: BAL was performed on 33 asymptomatic HIV-seropositive subjects at baseline, 6 months later, and 12 months later. The volume of ELF and the concentration of GSH and oxidized GSH were determined. The concentration of total GSH in ELF was 689.0+/-100.4 microM. This significantly decreased when measured 6 and 12 months later (355.9+/-41.7 microM, and 397.9+/-52.7 microM, respectively, p=0.01, compared with baseline, both comparisons). Significant decreases were also noted in the HIV-seropositive subjects who smoked cigarettes (baseline--762.6+/-142.4 microM; 6 months--373.7+/-45.9 microM; 12 months--459.3+/-73.8 microM, p<0.03, for baseline vs 6 months, and baseline vs 12 months). In nonsmoking HIV-seropositive subjects, there was a decrease in ELF GSH over time, but it did not reach statistical significance (baseline--589.1+/-138.2 microM; 6 months--335.3+/-74.1 microM; 12 months--345.8+/-74.0 microM, p>0.1, all comparisons). The percentage of total GSH in the oxidized form was similar at all three time points (baseline--3.8+/-0.5%; 6 months--3.1+/-0.5%; 12 months--3.9+/-0.9%, p>0.1, all comparisons). CONCLUSIONS: The current study demonstrates that the GSH level in ELF is significantly decreased in HIV-seropositive subjects 6 and 12 months after the initial determination.

Alveolar fluid glutathione is not reduced in asymptomatic HIV-seropositive subjects.

Glutathione is an important antioxidant tripeptide that is found in high concentrations in the epithelial lining fluid (ELF) of the lung. Previous investigators demonstrated a deficiency of glutathione (GSH) in the epithelial lining fluid of human immunodeficiency virus (HIV)-seropositive patients. The current investigation performed bronchoalveolar lavage (BAL) on 59 asymptomatic HIV-seropositive subjects (mean CD4: 365.9 +/- 31.2 cells/mm3) and 12 normal control subjects. The volume of ELF and the concentration of glutathione and oxidized glutathione were determined. The concentration of total GSH in ELF was not significantly different in HIV-seropositive individuals compared with normal subjects (628.1 +/- 63.9 microM versus 499.9 +/- 86.0 microM, p = 0.38). However, there was a significantly higher concentration of ELF GSH in HIV-seropositive cigarette smokers (n = 30) compared with nonsmokers (n = 29) (800.3 +/- 107.7 microM versus 443.6 +/- 45.3 microM, p = 0.004). The percentage of total GSH in the oxidized form (GSSG) was similar in both the HIV-seropositive and the normal subject groups (3.4 +/- 0.3% versus 3.0 +/- 0.4%, p = 0.559). There were no significant correlations between ELF GSH or GSSG concentrations and age, CD4 count, or pulmonary function. There was, however, a significant negative correlation between BAL lymphocyte percentage and GSH. The current study suggests that for those patients whose HIV infection is at a relatively early phase, the levels of GSH in the lung ELF are normal.

The interdependence of lung antioxidants and antiprotease defense in ARDS.

As in hereditary alpha 1-antitrypsin deficiency, protease-antiprotease and oxidant-antioxidant balances play a significant role in the pathogenesis of ARDS. However, the disease processes and possibilities for therapeutic intervention differ markedly.

Emergent bullectomy in a patient with severe bullous emphysema receiving mechanical ventilatory assistance.

This case report concerns a 29-year-old man with severe bullous disease who was admitted to the hospital with pneumonia and respiratory failure requiring mechanical ventilation. The patient underwent emergency bullectomy and was subsequently successfully weaned from the ventilator. He continues to do well 38 months after the surgery. This case demonstrates that bullectomy, even in a patient receiving mechanical ventilatory assistance, can be a lifesaving operation.

Prevention of intracellular adenosine triphosphate depletion after sublethal oxidant injury to rat type II alveolar epithelial cells with exogenous glutathione and N-acetylcysteine.

The alveolar epithelial cells of the lower respiratory tract are exposed continuously to injurious agents, including oxygen radicals. The type II alveolar epithelial cell is critically important to the normal function of the lung, because it is responsible for synthesis of surfactant and other essential duties. In the current investigation, the authors documented the loss of intracellular adenosine triphosphate (ATP) after exposure of the cells to sublethal concentrations of hydrogen peroxide (H2O2) and hypochlorous acid. Subsequent experiments attempted to alleviate or prevent this oxidant mediated loss of ATP by preincubating the cells with either glutathione or N-acetylcysteine (NAC). Initially, it was determined that exposure of the type II cells to 250 microM hypochlorous acid or 250 microM H2O2 for 1 hour each would cause significant loss of type II cell ATP. However, preincubation with glutathione (1,000 microM) inhibited the loss of ATP after both exposure to 250 microM H2O2 (24 +/- 3% loss of ATP without glutathione compared with 13 +/- 2% loss with glutathione, P < 0.05), and 250 microM hypochlorous acid (12 +/- 2% loss of ATP without glutathione compared with 1 +/- 1% increase of ATP with glutathione). Similar results were obtained using NAC (2 mg/mL) after exposure to 250 microM H2O2 (23 +/- 2% loss of ATP without NAC compared with a 4 +/- 3% loss of ATP with NAC). This study demonstrates that exogenous glutathione and NAC are able to protect type II cells from oxidant mediated sublethal injury and loss of intracellular ATP stores.

Normal arterial blood gas in a patient with saddle pulmonary artery embolus: diagnosis by transesophageal echocardiography.

This article describes a patient with a large, main pulmonary artery thromboembolus with normal arterial blood gas results, including normal alveolar-arterial oxygen gradient. The diagnosis was established using transesophageal echocardiography and confirmed with pulmonary angiography. The patient subsequently underwent anticoagulation and eventually was discharged without complications.

Alteration of adenosine triphosphate and other nucleotides after sublethal oxidant injury to rat type II alveolar epithelial cells.

The alveolar epithelial cells of the lower respiratory tract are continuously exposed to injurious agents, including oxygen radicals. The type II alveolar epithelial cell is critically important to the normal function of the lung, because it is responsible for synthesis of surfactant and other essential duties. The present investigation measured the level of intracellular nucleotides and adenosine over time after exposure of type II cells to sublethal concentrations of physiologically relevant oxidants, hydrogen peroxide and hypochlorous acid (HOCl). Initially, it was determined that 250 microM HOCl or 250 microM hydrogen peroxide could each cause sublethal injury to the type II cells after exposure of up to 1 and 2 hours, respectively. After exposure to 250 microM hydrogen peroxide, the intracellular levels of adenosine, adenosine diphosphate, and adenosine triphosphate all initially increased in the first 1 to 15 minutes, but subsequently decreased significantly, ultimately reaching close to 40% below control levels. The level of adenosine monophosphate remained significantly elevated throughout the exposure until returning to control levels after 2 hours. Similar results occurred after the type II cells were exposed to 250 microM HOCl. This study demonstrates that adenosine triphosphate and other cellular nucleotides and nucleosides were decreased in type II cells before lethal injury and subsequent cell death.

Complications of fiberoptic bronchoscopy at a university hospital.

STUDY OBJECTIVE: To retrospectively review the indications and complications associated with flexible fiberoptic bronchoscopy (FFB) in a university teaching hospital. DESIGN: retrospective review from April 1, 1988 to March 30, 1993. SETTING: Large tertiary care university hospital. PATIENTS OR PARTICIPANTS: We reviewed 4,273 consecutive FFBs, including 2,493 bronchoalveolar lavages and 173 transbronchial biopsy procedures. INTERVENTIONS: None. RESULTS: Most (52%) FFBs were performed for obtaining lower respiratory tract samples for evaluation of suspected infection. An additional 17% were performed to evaluate an abnormality seen on chest radiograph. The most common therapeutic indication was removal of retained secretions in 8% of FFBs. The mortality rate was 0%, and the frequency of major and minor complications was 0.5% and 0.8%, respectively. The incidence of major complications secondary to transbronchial biopsy was 6.8%. CONCLUSIONS: Flexible fiberoptic bronchoscopy can be performed safely in a teaching hospital with appropriate preparation, supervision, and adherence to protocol.

Clinical features, management, and outcome of patients with severe asthma admitted to the intensive care unit.

The objective of this study was to retrospectively review the medical records of 38 consecutive admissions to the medical intensive care unit of a tertiary-care university hospital of patients with severe asthma, and to determine the clinical characteristics of these patients, treatment regimens, and ultimate outcome. The 38 patients presented with severe asthma accompanied by hypoxemia, hypercapnia (mean pCO2 of 54.3 +/- 4.5 mm Hg), and decreased peak flow rates (125.5 +/- 12.4 L/min). The patients spent a mean of 60.1 +/- 9.7 hr in the medical intensive care unit. Seventeen of the 38 patients required intubation and mechanical ventilation. Overall, there were no deaths or significant complications. All 38 patients were discharged from the hospital. We conclude that severe, life-threatening asthma can be appropriately managed in the medical intensive care unit with a low incidence of complications and death. Prolonged mechanical ventilation is rarely required and most patients respond while the relatively simple management strategies.