Laboratory studies in cross-species lung transplantation.

The lack of sufficient suitable human donor lungs for the many patients requiring pulmonary transplantation as life-saving therapy for end-stage lung diseases has generated extensive interest in cross-species lung transplantation. Ethical concerns and those of animal rights advocates have prompted studies of nonprimate species as potential solid organ donors for humans. This paper provides an overview of some of the laboratory studies of cross-species pulmonary transplantation performed over the past 20 years and focuses, in particular, on more recent work (from our laboratory and others) in the area of porcine-to-primate pulmonary xenotransplantation.

Resurgence of tuberculosis: the perspective a dozen years later.

More than a dozen years ago, case rates of tuberculosis (TB) began to increase in the United States, as well as in other industrialized and Third World countries. Our US urban centers were the epicenter of the "new" TB epidemic, with New York City accounting for more than 15% of all TB cases in the United States. Numerous factors were responsible for this dramatic, unexpected explosion in mankind's most prevalent and lethal disease, including (1) an increasing pool of susceptible individuals who, by virtue of human immunodeficiency virus (HIV) infection, were much more likely to rapidly progress to active (contagious) TB after becoming infected with Mycobacterium tuberculosis; (2) a reduction in the resources and sites available for the identification, treatment, and surveillance of patients with tuberculous infection and disease; and (3) the importation of TB cases via immigration. Coupled with the resurgence of tuberculosis, new strains of difficult-to-treat, multiple-drug-resistant M tuberculosis (MDRTB) were isolated with increasing frequency, with New York City again the focal point. More than 60% of the nation's MDRTB cases occurred in New York City, reaching a peak of 441 cases in 1992. Over the past 2 years, epidemiologic data suggest that the epidemic has come under control, with a 38% decrease in new cases (1995) compared with the peak year (1992). A number of factors have been important in regaining control of TB, including enhanced diagnostic modalities, such as the use of some molecular biologic strategies; active case and contact finding by public health workers; tailored therapeutic approaches, such as four-drug initial therapy for non-MDRTB, advanced multidrug management for MDRTB, and expanded use of directly observed therapy; and use of personnel-protective devices and environmental controls to decrease nosocomial transmission of TB. These factors are highlighted in this overview article.

Fiberoptic bronchoscopy in the presence of space-occupying intracranial lesions.

The performance of flexible fiberoptic bronchoscopy (FFB) has anecdotally been considered to carry a high risk of neurologic complications in patients with raised intracranial pressure (ICP). There is no evidence in the literature to support this concern. We evaluated this risk by reviewing hospital records of 132 patients who underwent FFB and computer tomography of the central nervous system (CNS-CT) during the same hospitalization. Twenty-nine patients had CT evidence of increased ICP. For the purpose of analysis, patients were divided into two groups: 17 patients had evidence of raised ICP prior to the performance of FFB and had received treatment with an intent to lower the ICP, and 12 patients in whom increased ICP was not suspected at the time of FFB and therefore did not receive any form of pretreatment. There was no evidence of neurologic complications in either group during the first postbronchoscopy week. We conclude that FFB carries a low risk in patients with elevated ICP.

Cardiopulmonary responses to continuous positive airway pressure in acute asthma.

The effects of nasal continuous positive airway pressure (CPAP) on expiratory flow, arterial blood gas tensions, cardiovascular status, and dyspnea were studied in 21 patients with acute asthma. Therapy consisted of the following CPAP sequence: 30 minutes at 5 cm H2O, 20 minutes at 0 cm H2O, 30 minutes at 7.5 cm H2O, and 20 minutes at 0 cm H2O. Six control patients were fitted with a CPAP mask but given no positive-pressure therapy. Significant reductions in respiratory rate occurred from a baseline of 22.0 +/- 1.0 to 19.8 +/- 3.8 breaths/min at CPAP 5 cm H2O and to 19.4 +/- 4.3 breaths/min at CPAP 7.5 cm H2O (P < .05). No significant change occurred in forced expiratory volume in 1 second (FEV1), heart rate, mean arterial blood pressure, or arterial blood gas tension with either level of CPAP. Dyspnea, as assessed by a breathlessness score, improved during CPAP therapy (P < .05). These levels of CPAP were tolerated without deleterious side effects. In comparison, the control group showed no change in heart rate, respiratory rate, or breathlessness score during the study period. These data show that application of CPAP in acute asthma reduces respiratory rate and dyspnea with no untoward effects on gas exchange, expiratory airflow, or hemodynamics.

Drug-resistant tuberculosis in an urban population including patients at risk for human immunodeficiency virus infection.

In the past 5 yr, an increased incidence of tuberculosis has been noted in the United States. Simultaneously, the population infected with human immunodeficiency virus-type I (HIV-I) and the number of cases of acquired immunodeficiency syndrome (AIDS) have increased. Selected areas of the United States have also reported increases in the frequency of drug-resistant isolates of Mycobacterium tuberculosis. Because our institution serves a population in which tuberculosis, AIDS, and drug resistant isolates of M. tuberculosis are frequently encountered, we sought to better define interrelationships among these factors by retrospectively reviewing the demographic, clinical, bacteriologic, and radiologic data for all adult patients in whom M. tuberculosis was isolated from a culture of respiratory-tract secretions during a 1-year period (June 1, 1988 to May 31, 1989). Two hundred forty-six patients were thus identified; 66.5% were U.S. born blacks, and 62.6% were 17 to 40 yr of age. Risk factors for HIV infection were present in 106 patients. The overall resistance rate (one or more drugs) = 30.9%, with primary resistance = 22.6% (35 of 155) and secondary resistance = 49.2% (29 of 59). In addition, 12 resistant isolates were found in 32 patients whose prior treatment status was indeterminate. Of the resistant isolates, 56.6% (43 of 76) were multiply resistant. Isoniazid resistance was noted in 90.7% (69 of 76) and rifampin resistance was noted in 50% (38 of 76) of the resistant isolates. No significant differences in the overall frequency of resistance were noted in patients at risk for HIV infection compared with those without these risks.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchitis mimicking opportunistic lung infection in patients with human immunodeficiency virus infection/AIDS.

Purulent bronchitis was identified in 19 of 422 patients undergoing fiberoptic bronchoscopy during a 32-month period because of suspicion of an opportunistic lung infection complicating acquired immunodeficiency syndrome or human immunodeficiency virus infection. Five patients had Pneumocystis carinii pneumonia, but other opportunistic lung infections were excluded in the remaining 14 patients. Characteristics of these 14 patients included fever (greater than 38.3 degrees C), cough, and dyspnea in 14 of 14 patients; purulence of expectorated sputum (11/14); and widened alveolar-arterial oxygen gradient (13/14). Rapid (2 +/- 1.4 days) clinical response (defervescence and resolution of pulmonary symptoms) occurred with antibiotic therapy in 10 of 14 patients. In three patients, there was no improvement, and adult respiratory distress syndrome developed. Bacterial isolates from bronchoalveolar lavage included Streptococcus viridans (n = 12), Haemophilus influenzae (n = 7), Staphylococcus aureus (n = 3). Roentgenographic features of bronchiectasis were present in seven patients. Differential cell counts revealed greater than 50% neutrophils in the bronchial washings of all patients with purulent bronchitis. Neutrophil percentages in bronchoalveolar lavage were as follows: patient with purulent bronchitis without P carinii pneumonia (n = 14), 54.53% +/- 29.18%; patients with purulent bronchitis and concomitant P carinii pneumonia (n = 5), 62% +/- 31.9%. In a control group of 17 patients with P carinii pneumonia who did not have purulent bronchitis, the neutrophil percentage was 6.8% +/- 6.17% (p = less than 0.00001, t-test). Purulent bronchitis appears to be a distinct, treatable entity in patients with HIV infection and may accompany bacterial pneumonia, bronchiectasis, and P carinii pneumonia.

The role of fiberoptic bronchoscopy for diagnosis of pulmonary tuberculosis in patients at risk for AIDS.

In patients with acquired immunodeficiency syndrome (AIDS)-associated pulmonary Mycobacterium tuberculosis (MTB) (group 1), we analyzed whether the addition of transbronchial biopsy (TBB) and bronchial brushings augmented the diagnostic MTB yield over nonbiopsy sampling. Positive acid-fast bacilli (AFB) smears from combined sputum, bronchoalveolar lavage (BAL), and washings were 30 percent compared with 37 percent when brushings and TBB were added (p = NS). The addition of TBB increased culture yield from 96 percent to 100 percent (p = NS). Similar results were seen in patients with pulmonary MTB without human immunodeficiency virus (HIV) risk factors (group 2). Group 1 patients most commonly had a nonspecific inflammation on TBB histopathology and had a lower incidence of granuloma formation than group 2 (p less than 0.05). Our results suggest that more invasive sampling with bronchial brushings and TBB does not contribute to the microscopic, bacteriologic, or histopathologic diagnosis of pulmonary MTB, independent of AIDS risk factors.

Optimal therapy of cryptococcosis in patients with the acquired immunodeficiency syndrome.

Although amphotericin B (AB) is the primary therapeutic agent for cryptococcosis complicating the acquired immunodeficiency syndrome (AIDS), the total dose administered is extremely variable, and the end point of therapy has not been well defined. Since these patients require life-long suppressive therapy following the primary therapy, the definition of treatment "end point" becomes crucial. To delineate more effective treatment approaches, we reviewed the medical records of 48 patients with cryptococcosis complicating AIDS. Fever (81%) and headache (77%) were the predominant symptoms. A clinical response to AB (defervescence and resolution of symptoms) was noted in 46% of the febrile patients. The cumulative AB dose administered to the time of clinical response was variable (0.1-1.76 g), but was noted early in the majority of the patients (less than 0.4 g). Repeat fungal cultures from the initial positive site for Cryptococcus neoformans (CN), obtained after observation of the clinical response, were negative in 7/7 patients. Nosocomial bacterial infections were quite common and often complicated intravenous AB therapy. Bacteremias were documented in 10/14 febrile episodes occurring during AB therapy in the 22 patients with an initial clinical response. Bacteremias were identified in 6/21 patients who failed to defervesce with AB therapy. Staphylococcus aureus (N = 9) and Salmonella species (N = 2) were the most common pathogens causing bacteremia. An algorithm for the treatment of cryptococcosis complicating AIDS may shorten the duration of primary intravenous AB therapy. This might reduce secondary infectious complications and the costs of hospitalization.

Utility of bronchoscopic sampling techniques for cryptococcal disease in AIDS.

Although cryptococcal pneumonia is a well recognized complication of the acquired immunodeficiency syndrome, optimal diagnostic approaches remain to be defined. During a 32-month period (October 1984 to June 1987), 11 patients were diagnosed with CP at our institution. The diagnosis was established in all 11 patients from specimens obtained via fiberoptic bronchoscopy (ten) and/or double-lumen catheter lavage (one). Direct stains of sedimented bronchoalveolar lavage were positive for organisms characteristic of Cryptococcus neoformans in nine of 11 patients. Transbronchial biopsies were positive (special histologic stains) in six of eight patients; bronchial washings were positive (direct smear) in seven of ten patients, the bronchial brushings were positive on stain in six of nine patients, and in one patient, a Wang transbronchial needle aspirate was positive on stain. Fungal cultures were positive on the BAL in seven of 11 patients, and on the bronchial washings in four of ten patients; the TBBx culture samples were all negative (zero of three). The serum cryptococcal antigen titer was elevated (median = 1:1024) in all eight patients in which it was assayed. Our data suggest that BAL and bronchial washings have a combined sensitivity on smear equal to that of TBBx and superior to that of TBBx fungal culture. The TBBx does not appear to be necessary in this setting. In addition, an elevated serum cryptococcal antigen titer appears to be an important adjunct in the evaluation of pulmonary infiltrates in AIDS.

Necrotizing tracheobronchitis: complication of mechanical ventilation in an adult.

A 51-year-old woman had localized interstitial pneumonia that rapidly progressed to involve all lung fields. After 9 days of conventional mechanical ventilation, pneumothorax developed in the presence of an obstruction of the right main bronchus. Bronchoscopy and endobronchial biopsies revealed NTB involving the tracheobronchial tree distal to the tip of the endotracheal tube, with complete obstruction of the right main bronchus by hard, eschar-like material. Tracheal mucosa proximal to the tip of the endotracheal tube was normal. Subsequent bronchoscopy, 20 days later, showed marked resolution of NTB. Though a frequent complication of mechanical ventilation in the neonate, NTB as a complication of conventional mechanical ventilation has not previously been recognized in an adult. Necrotizing tracheobronchitis should be suspected in adults who have had mechanical ventilation and who are experiencing ventilatory difficulties, after routine problems have been treated or excluded.

Pneumocystis carinii pneumonia in patients with AIDS: evaluation of lavage and staining techniques in diagnosis.

The diagnostic yield of unilateral vs. bilateral bronchoalveolar lavage (BAL) was prospectively evaluated in 65 consecutive patients suspected of having Pneumocystis carinii pneumonia (PCP) complicating acquired immune deficiency syndrome (AIDS). Gram-Weigert (GW), Papanicolaou (PAP), and Gomori's methenamine silver (GMS) stains were used for identification of P. carinii in all cases. Forty-eight patients had PCP that was identified by GW staining of BAL in 47/48 patients followed by PAP/GMS staining of BAL in 44/48 patients and PAP/GMS staining of bronchial washings in 40/48 patients. In patients with bilateral interstitial infiltrates, unilateral lavage was sufficient for diagnosis of PCP when GW stain was utilized. In patients with PCP complicating AIDS, the diagnostic yield of BAL may be increased by use of both GW and GMS stains.

Pulmonary manifestations of disseminated cryptococcosis in patients with AIDS.

Forty-eight patients with disseminated cryptococcosis and AIDS were retrospectively studied to define the pulmonary manifestations. Cryptococcus neoformans (CN) was first isolated from a pulmonary site in 12 patients. Disseminated disease was subsequently documented in all these patients. Symptoms and roentgenographic manifestations (normal, nodular/circumscribed infiltrates, pleural effusions, lobar consolidation) were diverse. Interstitial infiltrates predicted the presence of another opportunistic lung infection besides cryptococcosis in five patients (three untreated and two treated patients). Infectious causes other than cryptococcosis were established by culture and clinical course in five of the ten patients who developed chest roentgenographic abnormalities during amphotericin B therapy. Endobronchial abnormalities were identified in four patients at bronchoscopy. Bronchoalveolar lavage (9/9) and pleural fluid (3/3) cultures were sensitive tests for detection of pulmonary involvement with CN.

Pulmonary non-Hodgkin's lymphoma mimicking infection.

Progressive pulmonary shadows prompted investigations which provided the diagnosis of pulmonary non-Hodgkin's lymphoma in three patients (two with the acquired immunodeficiency syndrome). Rapid progression of radiographic abnormalities seen in these three patients is unusual for pulmonary non-Hodgkin's lymphoma and mimics disease evolution commonly associated with pulmonary infections.