Characterization of reactive oxygen species in diaphragm.

Reactive oxygen species (ROS) exist as natural mediators of metabolism to maintain cellular homeostasis. However, ROS production may significantly increase in response to environmental stressors, resulting in extensive cellular damage. Although several potential sources of increased ROS have been proposed, exact mechanisms of their generation have not been completely elucidated. This is particularly true for diaphragmatic skeletal muscle, the key muscle used for respiration. Several experimental models have focused on detection of ROS generation in rodent diaphragm tissue under stressful conditions, including hypoxia, exercise, and heat, as well as ROS formation in single myofibres. Identification methods include direct detection of ROS with confocal or fluorescent microscopy and indirect detection of ROS through end product analysis. This article explores implications of ROS generation and oxidative stress, and also evaluates potential mechanisms of cellular ROS formation in diaphragmatic skeletal muscle.

Acute effects of exercise on cognition in patients with chronic obstructive pulmonary disease.

Prior data indicate positive effects of long-term exercise interventions for cognitive functioning among patients with chronic obstructive pulmonary disease (COPD), but no prior studies have examined acute effects of individual bouts of exercise among patients with COPD. This study evaluated acute effects of exercise on cognitive performance in a community-based sample of patients with COPD and a healthy control group, matched by age, sex, and education. Twenty-nine older adults with COPD (mean age = 67.8 yr [+/- 7.4]; range: 56-85; 17 women) and 29 matched healthy control subjects (mean age = 68.7 yr [+/- 6.0] ) were recruited from the community. All participants completed a 20-min exercise session in which they exercised to a peak level and a video control condition in which they were provided information about exercise and cholesterol. Conditions were separated by a 1-wk interval, and order of participation in conditions was randomly assigned. Assessments of cognitive performance (Trail Making Test, Digit Symbol, Verbal Fluency, Digit Span, Finger Tapping) were administered before and after each condition (exercise and video). Among patients with COPD, acute exercise was associated with improved performance on the Verbal Fluency test, a measure of verbal processing, suggesting that acute exercise may benefit aspects of cognitive performance among patients with COPD.

BAL and serum IgG levels in healthy asymptomatic HIV-infected patients.

OBJECTIVES: To determine if the increased susceptibility to bacterial infection in asymptomatic HIV-infected patients is associated with decreased total IgG or IgG2 levels in lung epithelial lining fluid. BACKGROUND: A decrease in lung IgG levels or subtypes has been proposed as contributing to the increased risk of bacterial lung infections in HIV-infected patients. Previous studies measuring lung lavage IgG concentrations have been inconsistent. METHODS: Twenty-three HIV patients and 25 control subjects underwent BAL. Both patient groups were of similar age, and had similar pulmonary function studies and body mass index. Smokers were equally represented in both groups, and the majority of subjects in both groups were male. Total IgG and IgG2 levels in lavage fluid were assayed in both cohorts and compared using a two-tailed Student's t test. RESULTS: The lung lining fluid IgG level in HIV-infected patients was 0.19 +/- 0.13 microg/microg of protein (mean +/- SD) vs 0.11 +/- 0.09 microg/microg of protein in control subjects (p < 0.05). The IgG(2) level in HIV patients was 0.034 +/- 0.038 microg/microg of protein and 0.014 +/- 0.01 microg/microg of protein in control subjects (p = 0.054). Lavage IgG levels reflected serum IgG values (correlation coefficient, 0.56; p < 0.001) but did not correlate with lung immunoglobulin-producing cells. CONCLUSIONS: The increased susceptibility to bacterial pneumonia in asymptomatic HIV-infected individuals is neither explained by depressed total IgG levels nor a deficiency in IgG(2) levels in the lungs. The strong correlation between serum and lavage IgG levels suggests that lavage IgG derives from serum.

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.

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.

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.

Cigarette smoking in HIV infection induces a suppressive inflammatory environment in the lung.

Lung lymphocyte numbers are frequently increased in human immunodeficiency virus (HIV)-infected individuals in the absence of lung infection, and may play a critical role in viral surveillance and protection against new infections. In this context, cigarette smoking by HIV-infected individuals has been associated with a relative increase in the peripheral blood CD4(+) T-lymphocyte count as compared with that of nonsmokers. Because lung defense is local, the aim of the present study was to determine whether cigarette smoking had a significant impact on local lung defenses in HIV-infected individuals. The numbers and subtypes of bronchoalveolar lymphocytes and the ability of lung lavage cells to produce proinflammatory cytokines were compared in 58 smokers and 34 nonsmokers. In contrast to a trend toward an increase in peripheral blood CD4(+) cell counts among nonsmokers, smokers had significant depressions in both the percentage and absolute numbers of CD4(+) and CD8(+) cells in their bronchoalveolar lavage fluid (BALF). A decrease in CD4(+)/CD8(+) cell ratios was also seen with smoking. In addition, production of both interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) was suppressed with cigarette smoking. These observations show that cigarette smoking is associated with suppression in localized lung defenses, and suggest that smoking cessation may have a positive impact on lung defenses in HIV-infected smokers.

Dithiothreitol improves recovery from in vitro diaphragm fatigue.

There is increasing evidence that reactive oxygen species are produced during strenuous skeletal muscle work and that they contribute to the development of muscle fatigue. Although the precise cellular mechanisms underlying such a phenomenon remain obscure, it has been hypothesized that endogenously produced reactive oxygen species may down-regulate force production during fatigue by oxidizing critical sulfhydryl groups on important contractile proteins. To test this hypothesis, we fatigued rat diaphragm strips in vitro for 4 min at 20 Hz stimulation and a duty cycle of 0.33. Following fatigue, the tissue baths were drained and randomly replaced with either physiologic saline or physiologic saline containing the disulfide reducing agent, dithiothreitol (DTT) at varying doses (0.1-5.0 mM). Force-frequency characteristics were then measured over a 90-min recovery period. At the 0.5 and 1.0 mM doses, DTT treatment was associated with significantly greater force production in the recovery period. DTT's effects were observed at most frequencies tested, but appeared more prominent at the higher frequencies. The beneficial effects of DTT were not evident at the 0.1 or 5.0 mM doses and appeared to be specific for fatigued muscle. These recovery-enhancing effects of a potent disulfide reducing agent suggest that important contractile proteins may be oxidized during fatigue; such changes may be readily reversible.

Respiratory failure from metastatic choriocarcinoma: a survivor of mechanical ventilation.

A patient with respiratory failure from metastatic choriocarcinoma was treated with mechanical ventilation while receiving chemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine. The patient recovered from respiratory failure with the assistance of standard mechanical ventilation using low tidal volumes. The patient has sustained clinical remission with normal respiratory function. Mechanical ventilation with low tidal volumes and a pressure-targeted approach should be considered in the patient who develops early respiratory failure from metastatic choriocarcinoma.

Biological reactions of peroxynitrite: evidence for an alternative pathway of salicylate hydroxylation.

Salicylate hydroxylation has often been used as an assay of hydroxyl radical production in vivo. We have examined here if hydroxylation of salicylate might also occur by its reaction with peroxynitrite. To test this hypothesis, we exposed salicylate to various concentrations of peroxynitrite, in vitro. We observed the hydroxylation of salicylate at 37 degrees C by peroxynitrite at pH 6, 7 and 7.5, where the primary products had similar retention times on HPLC to 2,3- and 2,5-dihydroxybenzoic acid. The product yields were pH dependent with maximal amounts formed at pH 6. Furthermore, the relative concentration of 2,3- to 2,5-dihydroxybenzoic acid increased with decreasing pH. Nitration of salicylate was also observed and both nitration and hydroxylation reaction products were confirmed independently by mass spectrometry. The spin trap N-t-butyl-alpha-phenylnitrone (PBN), with or without dimethyl sulfoxide (DMSO), was incapable of trapping the peroxynitrite decomposition intermediates. Moreover, free radical adducts of the type PBN/.CH3 and PBN/.OH were susceptible to destruction by peroxynitrite (pH 7, 0.1 M phosphate buffer). These results suggest direct peroxynitrite hydroxylation of salicylate and that the presence of hydroxyl radicals is not a prerequisite for hydroxylation reactions.

Bronchial dilatation in patients with HIV infection: CT assessment and correlation with pulmonary function tests and findings at bronchoalveolar lavage.

OBJECTIVE: Symptoms of airway disease occur in patients infected with HIV, and bronchiectasis has been reported in patients with AIDS. We evaluated thin-section thoracic CT scans in HIV-positive individuals for bronchial dilatation and correlated imaging findings with pulmonary function abnormalities and findings at bronchoalveolar lavage (BAL). SUBJECTS AND METHODS: Sixty-one subjects, 50 of whom were HIV-positive and 11 of whom were HIV-negative, underwent thin-section CT, BAL, and pulmonary function tests. Two radiologists evaluated the CT scans on two separate occasions for bronchial dilatation in each lobe. BAL and pulmonary function test data in the subjects with bronchial dilatation were compared with such data in subjects with normal bronchi seen on CT scans. RESULTS: Eighteen of the 50 HIV-positive subjects and none of the HIV-negative subjects had bronchial dilatation revealed by CT. Subjects with bronchial dilatation revealed by CT had significantly higher BAL neutrophil counts (p = .014) and significantly lower diffusing capacity (p = .003) than did subjects with normal bronchi revealed by CT. CONCLUSION: Bronchial dilatation is commonly revealed by CT scans of HIV-positive individuals. The association of elevated levels of BAL neutrophils and decreased diffusing capacity with bronchial dilatation that we found in this study suggests that the neutrophil may be associated with airway damage and lung destruction in patients who are infected with HIV.

Respiratory muscle dysfunction associated with human immunodeficiency virus infection.

Although skeletal muscle abnormalities have been described in association with human immunodeficiency virus (HIV), the effects of HIV infection on respiratory muscle function have not been well characterized. We hypothesized that HIV+ individuals may develop respiratory muscle weakness and that respiratory muscle dysfunction may contribute to the unexplained dyspnea that occurs in the setting of HIV. To test this hypothesis we studied maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), inspiratory muscle endurance, and respiratory symptoms in 23 HIV+ male outpatients who had no history of acquired immune deficiency syndrome (AIDS)-related pulmonary complications, with a CD4+ T-lymphocyte count of 331.6 +/- 62.1 (mean +/- SEM). Respiratory muscle endurance was measured with an incremental threshold loading (ITL) protocol. We compared these results to those for 14 HIV- males matched for age and weight. Compared with the controls, HIV+ subjects had a significantly lower mean MIP (98.7 +/- 7.4 versus 121.4 +/- 9.3 cm H2O, p < 0.05) and MEP (115.0 +/- 9.3 versus 152.1 +/- 14.8 cm H2O, p < 0.05). Furthermore, during ITL, the mean load at task failure in the HIV+ group was 295.7 +/- 36.2 g, versus 405.8 +/- 52.2 g in the control group (p < 0.05). In the HIV+ subjects there was no relationship between muscle performance and CD4+ count or azidothymidine (AZT) use. There was, however, a highly significant relationship between respiratory muscle dysfunction and symptoms of dyspnea. We conclude that HIV seropositivity is associated with a decline in respiratory muscle performance. This impairment in respiratory muscle function may contribute to the feeling of breathlessness that has been well described in this patient population.

Alpha 1-antitrypsin deficiency: evaluation of bronchiectasis with CT.

PURPOSE: To assess bronchiectasis depicted with computed tomography (CT) in patients with alpha 1-antitrypsin deficiency and to examine associated clinical correlates. MATERIALS AND METHODS: CT scans in 14 patients with alpha 1-antitrypsin deficiency were evaluated by two thoracic radiologists for the presence and extent of bronchiectasis and emphysema. The findings were correlated with numeric infection scores on the basis of symptoms of sputum production and respiratory infection and with a history of conditions that may predispose to development of bronchiectasis. RESULTS: Six (43%) of 14 patients had CT evidence of bronchiectasis. Patients with bronchiectasis had significantly higher infection scores than did patients without bronchiectasis (P < .005). Two patients had diffuse cystic bronchiectasis, and neither reported a history of illness that may have predisposed them to this condition. CONCLUSION: Bronchiectasis may be more common in patients with alpha 1-antitrypsin deficiency than has been previously recognized. The diagnosis of alpha 1-antitrypsin deficiency should be considered in patients with emphysema and diffuse cystic bronchiectasis.

N-tert-butyl-alpha-phenylnitrone: a free radical trap with unanticipated effects on diaphragm function.

The spin trap N-tert-butyl-alpha-phenylnitrone (PBN) has a high avidity for free radical species and hence functions as an antioxidant in many biological systems. As such, we hypothesized that PBN would have powerful antioxidant effects on muscle function. We examined the effects of PBN on directly stimulated in vitro (37 degrees C) rat diaphragm. First, a dose-response curve for the effects of PBN on force frequency (n = 8) was established by comparing PBN-treated muscle strips (0.01-10 mM) with time- and stimulus-matched control strips. Second, the effect of 1.0 mM PBN on muscle endurance (n = 8) was established. Our findings were as follows. 1) Compared with baseline, peak twitch and low-frequency muscle tensions increased in a dose-dependent fashion, with peak effects at 1.0 mM PBN. 2) Muscle function at all stimulation frequencies was depressed at doses above 1.0 mM PBN. 3) Complete inhibition at 10 mM PBN was reversed with caffeine administration or washout. 4) During early fatigue, 1.0 mM PBN facilitated force. However, endurance time decreased in the PBN-treated group. We conclude that PBN has direct reversible dose-dependent effects on diaphragm function. However, facilitation of low-frequency forces and the lack of fatigue-attenuating properties suggest that PBN has atypical antioxidant effects on muscle function.

Clinical assessment of the respiratory muscles.

This review examines approaches to evaluation of the respiratory muscles and describes new techniques that may be more quantitative, less effort dependent, and less invasive than conventional methods. To evaluate strength of the respiratory muscles, maximum inspiratory and expiratory pressures remain useful measures. Potential methodologic errors, however, necessitate careful technique. Evaluation of the twitch response to direct phrenic nerve stimulation may ultimately prove more quantitative and less effort dependent than measurements of maximum pressure. Many techniques are also available to measure endurance of respiratory muscles, but most are less than satisfactory outside the research environment because of poor reproducibility and other procedural difficulties. The maximum incremental resistive loading test, however, has proven to be practical and well tolerated. There is little substitute for careful clinical observation of respiratory muscle coordination and movement, particularly in the patient with suspected respiratory muscle weakness or chest wall distortion. In conclusion, though the respiratory muscles are difficult to evaluate, techniques are available that can be quite helpful for assessment, particularly in response to interventions such as rehabilitation.

Effects of N-acetylcysteine on in vitro diaphragm function are temperature dependent.

Recent evidence has shown that systemic administration of N-acetylcysteine (NAC), a compound structurally similar to the intracellular antioxidant glutathione, inhibits skeletal muscle fatigue. To further elucidate the actions of NAC, we studied its effects on in vitro rat diaphragm contractile function. Rat diaphragm strips were incubated in tissue baths containing physiological salt solution (n = 29) or physiological salt solution containing 4 mg/ml of NAC (n = 29). Strips were stimulated by either indirect or direct means. After determination of baseline contractile characteristics, strips were fatigued for 4 min at 20 Hz (1 train/s, 0.33 ms train duration). Force-frequency relationships were then studied over a 60-min recovery period. We found that 1) NAC had significant effects on the baseline force-frequency relationship; treated strips had increased peak tension but diminished twitch tension and accelerated twitch kinetics; 2) NAC had significant fatigue-sparing effects that were magnified at 37 degrees C; and 3) NAC treatment did not improve postfatigue recovery. The effects of NAC were generally independent of the stimulation method. We conclude that NAC has direct temperature-dependent effects on diaphragm function. These effects are consistent with the properties of NAC as an antioxidant and suggest important but complex effects of oxidant stress on skeletal muscle.

Hydroxylation of salicylate by the in vitro diaphragm: evidence for hydroxyl radical production during fatigue.

There is increasing evidence that oxygen-derived free radicals produced during strenuous work by the diaphragm may contribute to diaphragm fatigue and/or injury. However, the precise identity of these oxygen radicals remains unknown, inasmuch as oxygen free radicals are extremely short lived and their detection in biologic systems is quite difficult. There is recent evidence that the salicylate-trapping method may be a useful means of monitoring tissue production of hydroxyl radical (.OH). This method is predicated on the fact that salicylate's phenolic ring can be attacked by .OH at the 3 or 5 position to yield 2,3- or 2,5-dihydroxybenzoic acid (DHB). These metabolites are stable and can be identified by high-performance liquid chromatography (HPLC) coupled with electrochemical or ultraviolet detection. To test the hypothesis that hydroxylated salicylates are produced during diaphragm fatigue, we exposed in vitro rat diaphragm strips to a physiological saline solution containing 2.0 mM sodium salicylate for approximately 15 min. The solution was then removed, and the strips were fatigued (20 Hz, 200-ms train duration, 1 train/s) via phrenic nerve stimulation for 30 s-10 min. The diaphragm strips were subsequently homogenized, and the homogenate was analyzed by HPLC coupled with ultraviolet detection. Levels of 2,3-DHB were significantly higher in fatigued than in control nonfatigued strips. There was also a significant correlation between the amount of 2,3-DHB in the fatigued muscle and the accumulated tension-time product developed during fatigue. 2,5-DHB was not consistently identified in control or experimental strips.(ABSTRACT TRUNCATED AT 250 WORDS)

Tumor necrosis factor and endotoxin do not directly affect in vitro diaphragm function.

Ventilatory pump failure can occur in the setting of severe infection. Recent in vivo studies have shown a significant decrease in diaphragm force production in rats with pneumococcal sepsis and sepsis secondary to Escherichia coli endotoxin. We hypothesized that diaphragm impairment during sepsis may be mediated by a direct effect of tumor necrosis factor-alpha (TNF) or endotoxin. To test this hypothesis we studied the mechanical characteristics of isolated rat diaphragm strips in tissue baths containing rTNF-alpha or endotoxin and compared the results with control strips. The strips were stimulated to contract isometrically in the tissue baths that were aerated with 95% O2-5% CO2. Baseline force-frequency determinations were made at 60 min. Following this, the strips were fatigued over a 4-min period (20 Hz, 0.33-s trains, 1 train/s) and force-frequency relationships determined 30 s, 10 min, and 60 min post-fatigue. There were no significant differences found between control and experimental strips in any aspect of contractile function tested, including force-frequency characteristics, fatiguability, and recovery from fatigue. Using an isolated cell line assay (L929), we found evidence of attenuated cytotoxicity of TNF at 26 degrees C compared with 37 degrees C. Therefore, we repeated the experiments studying the effects of TNF on in vitro muscle at 37 degrees C. We once again found no effect of TNF on contractile function. We conclude that the impairment of diaphragm function during sepsis is not mediated by a direct effect of TNF or endotoxin.

Marked pulmonary function abnormalities in a case of HIV-associated pulmonary hypertension.

Recent reports have suggested an association between primary pulmonary hypertension and human immunodeficiency virus (HIV) infection. This appears to be an accelerated syndrome, associated with a relatively brief duration of symptoms, yet prominent right ventricular failure and severe pulmonary hypertension on presentation. We present a case of a primary pulmonary hypertension in a 35-year-old HIV-seropositive hemophiliac. His accelerated clinical course is consistent with previously reported cases of HIV-related pulmonary hypertension. However, this patient's pulmonary function tests revealed marked hyperinflation, a decreased diffusing capacity, and no airflow obstruction. To our knowledge, this very usual constellation of pulmonary function changes has not been described previously in this syndrome.

Emphysema-like pulmonary disease associated with human immunodeficiency virus infection.

OBJECTIVE: To describe a possible association between prolonged infection with human immunodeficiency virus (HIV) and a pathophysiologic process suggestive of pulmonary emphysema. DESIGN: Case series. SETTING: The Ohio State University Hospital, Columbus, Ohio. MEASUREMENTS AND MAIN RESULTS: We describe four HIV-seropositive individuals ranging in age from 32 to 55 years who presented with dyspnea. Radiographic examination of the chest showed no infiltrates. All patients were presumed to have had prolonged HIV infection (mean CD4 count, 99.8 +/- 43 cells/mm3), but none had a previous history of pneumonia or opportunistic infections. Comprehensive examination of bronchoalveolar lavage fluid showed no pathogens or other complications of HIV infection. All patients had markedly abnormal pulmonary function tests that were suggestive of emphysema with air-trapping, hyperinflation, and a markedly decreased diffusing capacity. However, only minimal evidence of airflow obstruction was noted. Three patients subsequently had high-resolution computed tomographic scans of the chest that revealed emphysema-like bullous changes. Known causes of emphysema were not present in these patients. CONCLUSIONS: Our findings support an association between prolonged HIV infection and an emphysema-like process. This syndrome may occur in the absence of previous pulmonary infections or apparent pulmonary complications and is characterized by unusual pulmonary function test abnormalities.