Diagnosis of pulmonary disease in human immunodeficiency virus infection: role of transbronchial biopsy and bronchoalveolar lavage.

The value of transbronchial biopsy and bronchoalveolar lavage was assessed in the diagnosis of pulmonary disease in patients infected with the human immunodeficiency virus (HIV). Seventy four transbronchial biopsy and 66 bronchoalveolar lavage specimens (60 paired specimens) from 80 examinations in 64 patients were reviewed. Pneumocystis carinii was the most common pathogen isolated (43 patients). Bronchoalveolar lavage was superior to transbronchial biopsy for the diagnosis of this pathogen, the sensitivities being 90% and 56%. Cytomegalovirus was identified three times by lavage and once by transbronchial biopsy. Neither method detected Kaposi's sarcoma in the one patient shown to have it by open lung biopsy. The complication rate in a concurrent study of bronchoscopy with transbronchial biopsy in 74 consecutive HIV positive patients was 22%. This study does not support the use of transbronchial biopsy in these patients.     

Diagnosis for interstitial lung disease in patients with acquired immunodeficiency syndrome (AIDS): a prospective comparison of bronchial washing, alveolar lavage, transbronchial lung biopsy, and open-lung biopsy

This study was undertaken to compare prospectively the diagnostic yield of the various bronchoscopic techniques with that of open-lung biopsy for interstitial lung disease in patients with acquired immunodeficiency syndrome (AIDS). Under general anesthesia, 15 patients sequentially underwent bronchial washing, transbronchial lung biopsy, alveolar lavage, and open-lung biopsy in the same segment of lung. Of nine patients with Pneumocystis carinii, seven were diagnosed by means of the transbronchial lung biopsy, eight by the open-lung biopsy, and all nine by alveolar lavage. Of the six patients with cytomegalovirus, five were diagnosed by the open-lung biopsy, five by the transbronchial lung biopsy, and three by alveolar lavage. The sensitivities of the procedures for identifying infection were washings (15%), transbronchial lung biopsy (50%), alveolar lavage (73%), and open-lung biopsy (88%). Combined, transbronchial lung biopsy and alveolar lavage showed a diagnostic yield (85%) for infections comparable to that of open-lung biopsy (88%), thereby obviating the need for open-lung biopsy for such diagnoses. However, open-lung biopsy was the only procedure that diagnosed Kaposi's sarcoma in lung.     

Retrospective analysis of the efficacy of open lung biopsy in acquired immunodeficiency syndrome

Open lung biopsy (OLB) was performed on 66 patients with acquired immunodeficiency syndrome from November 1981 through December 1987. Twenty-two patients with severe respiratory failure died within a month, 3 during operation. Fourteen patients with negative transbronchial biopsy and 19 with failure of treatment based on transbronchial biopsy died within a year. Six were alive and 5 were lost to follow-up. The most common organism found in patients with severe respiratory failure was Pneumocystis carinii alone or with other pathogens. Successful therapeutic change based on OLB findings was possible in only 1 (1.5%) of the 66 patients. Open lung biopsy has limited application in the management of acquired immunodeficiency syndrome. In patients with overt pulmonary failure, OLB is invariably fatal. Those seen with suspicious lung infiltrates without risk factors or with known risk factors and negative transbronchial biopsy results might benefit from OLB. In our institution, 18 of 64 acquired immunodeficiency syndrome admissions underwent OLB in 1983, whereas in 1987, only 2 of 302 patients admitted with acquired immunodeficiency syndrome had OLB.     

Bronchiolitis obliterans organizing pneumonia associated with Pneumocystis carinii infection in a liver transplant patient receiving tacrolimus

We report on a case of bronchiolitis obliterans organizing pneumonia (BOOP) associated with Pneumocystis carinii pneumonia (PCP) after liver transplantation and tacrolimus based immunosuppression. Radiologically, bilateral diffuse interstitial shadowing and patchy alveolar infiltrates developed after switching the patient from cyclosporin A to tacrolimus for persistent rejection. Bronchoalveolar lavage (BAL) fluid showed inflammatory cells but no pathogenic organisms. Open lung biopsy revealed BOOP with granulomatous PCP. Thus, even in the case of negative BAL the possibility of an atypical P. carinii infection has to be considered for differential diagnosis of pneumonia in immunocompromised patients after organ transplantation. The combination of BOOP with PCP after liver transplantation and tacrolimus medication has not been reported previously.     

Bronchoscopy of symptom free patients infected with human immunodeficiency virus for detection of pneumocystosis.

No evidence of Pneumocystis carinii infection was found in eight symptom free patients who were positive for the human immunodeficiency virus and who underwent bronchoscopy, bronchoalveolar lavage, and brush biopsy. This suggests that the presence of Pneumocystis carinii in bronchoscopy material is likely to indicate pneumocystis infection.     

Diagnostic fibreoptic bronchoscopy in the immunocompromised host with pulmonary infiltrates.

Nineteen immunocompromised patients with pulmonary infiltrates underwent diagnostic fibreoptic bronchoscopy with transbronchial forceps and brush biopsy. A specific diagnosis was obtained in 21/25 procedures (10/11 focal lesions and 11/14 diffuse legions). The most common diagnosis was infection, and organisms isolated included bacteria, fungi, Pneumocystis carinii, and herpes simplex. A pneumothroax requiring tube drainage occurred in two cases and mild lung parenchymal bleeding was noted in two others. It is concluded that fibreoptic bronchoscopy with forceps and brush biopsy can be performed safely with an excellent diagnostic yield in immunocompromised hosts with lung lesions. Supplemental oxygen should be administered during fibreoptic procedures in these patients and platelet transfusions should be given when thrombocytopenia is present.     

Comparison of biopsy-proven Pneumocystis carinii pneumonia in acquired immune deficiency syndrome patients and renal allograft recipients

Pneumonia unresponsive to antibacterial agents in patients with acquired immune deficiency syndrome (AIDS) has become a new indication for lung biopsy. In 14 patients, transbronchial or open-lung biopsy demonstrated Pneumocystis carinii. An additional 12 patients, who were immunosuppressed after renal transplantation, were seen with P. carinii pneumonia. The diagnosis was established by transbronchial biopsy in the majority of patients. All patients were treated initially with trimethoprim plus sulfamethoxazole. Pentamidine was added after diagnosis if improvement did not occur. Both groups demonstrated reversal in the T cell helper: suppressor ratio. We compared these two groups of immunocompromised patients with respect to clinical presentation, lung pathology, response to therapy, and survival. Patients with AIDS were seen with a two- to three-week prodrome of fever, lymphadenopathy, weight loss, and malaise followed by hypoxia and leukopenia within 12 hours. Transplant patients became acutely ill with fever and hypoxia within 24 to 36 hours. In both groups, chest roentgenogram showed bilateral diffuse infiltrates; sputum cultures were generally negative; and lung biopsy demonstrated Gomori-Jones periodic acid-methenamine-silver-positive P. carinii. Mortality was substantially higher in patients with AIDS (50% versus 8%). This difference may be explained by the fact that the T cell defect in AIDS has an infectious cause, while the defect in the renal allograft recipient is pharmacologically mediated.     

Diagnosis of pulmonary complications of the acquired immune deficiency syndrome.

Forty eight patients with the acquired immunedeficiency syndrome (AIDS) presented to the Mount Sinai Hospital in New York with persistent cough and dyspnoea or an abnormal chest radiograph, or both. Thirty two (67%) were found to have Pneumocystis carinii pneumonia, either alone or in combination with another pathogen. Of these patients, eight (25%) had a normal chest radiograph. Abnormalities in the single breath carbon monoxide diffusing capacity and alveolar-arterial oxygen gradient [A-a) DO2) suggested infection with Pneumocystis carinii. Fibreoptic bronchoscopy with transbronchial biopsy was 100% sensitive in the diagnosis of pneumocytis pneumonia. Fibreoptic bronchoscopy should be undertaken in patients suspected of having a pulmonary complication of AIDS, even if the chest radiograph is normal.     

Histologically atypical Pneumocystis carinii pneumonia.

BACKGROUND--Infection with Pneumocystis carinii typically results in a pneumonia which histologically is seen to consist of an eosinophilic foamy alveolar exudate associated with a mild plasma cell interstitial infiltrate. Special stains show that cysts of P carinii lie within the alveolar exudate. Atypical histological appearances may occasionally be seen, including a granulomatous pneumonia and diffuse alveolar damage. In these patients the clinical presentation may be atypical and results of investigations negative unless lung biopsies are performed and tissue obtained for histological examination. METHODS--The incidence and mode of presentation of histologically atypical pneumocystis pneumonia was studied in a cohort of HIV-I antibody positive patients. RESULTS--Over a 30 month period 138 patients had pneumocystis pneumonia, of whom eight (6%) had atypical histological appearances which were diagnosed (after negative bronchoalveolar lavage) by open lung biopsy in five, percutaneous biopsy in one, and at post mortem examination in two. Atypical appearances included granulomatous inflammation in four patients, "pneumocystoma" in two (one also had extrapulmonary pneumocystosis), bronchiolitis obliterans organising pneumonia in one patient, diffuse alveolar damage and subpleural cysts in one (who also had intrapulmonary cytomegalovirus infection), and extrapulmonary pneumocystosis in two patients. CONCLUSIONS--Various atypical histological appearances may be seen in pneumocystis pneumonia. Lung biopsy (either percutaneous or open) should be considered when bronchoalveolar lavage is repeatedly negative and evidence of P carinii should be sought, by use of special stains, in all lung biopsy material from HIV-I antibody positive patients.     

Serologic methods for the early diagnosis of Pneumocystis carinii infection in renal allograft recipients

Because of the nephrotoxic action of trimethoprimsulfamethoxazole (TMP-SMX) in cyclosporine (CsA)-treated patients, combined with the (CsA)-treated patients, combined with the possibility of selecting resistant gram-negative or Nocardia asteroides organisms, a monitoring tool to detect early Pneumocystis carinii (PC) infection permitting a selective treatment approach is highly desirable. A review of 401 consecutive renal transplants revealed 26 cases (18 suspected and 8 histologically proved) of PC infection in 21 cadaver and 5 living-related renal recipients. The diagnosis was confirmed in 8/18 patients who were invasively studied by open-lung biopsy (1/2), bronchoscopy with transbronchial biopsy (4/9), bronchoscopy with brushing (1/2), bronchoscopy with bronchoalveolar lavage (2/5), and transpleural needle biopsy (0/1)-yielding a confirmed incidence of 2% (8/401). All positive invasive studies had been performed prior to or within 24 hr of the inception of TMP-SMX therapy. Nine of ten negative invasive studies were performed after more than 24 hr of treatment. The mean time from transplantation to the onset of clinical symptoms was 2.5 +/- 1.5 months. The infection rate would be 6.5%, assuming all 18 suspected cases would be PC-positive if studied pretreatment. In order to assess the efficacy of a variety of serologic methods of PC detection, qualitative counter-immunoelectrophoresis (CIE) for P carinii antigen (PC-Ag), IgG antibody reactive with PC (enzyme-linked immunosorbent assay [ELISA]), and a latex particle agglutination test (LPA) were performed on 279 sera; 85 sera from the 26 suspected or proved cases, 100 sera from normal age-matched controls, and 94 sera from 78 asymptomatic allograft recipients followed as outpatients. In the eight histologically proven cases, CIE was positive in only 3/8 and turned positive late in the clinical course. LPA was positive in all histologically proved cases; however, it was also positive in 60% of asymptomatic renal recipients. In cases that developed clinical disease, LPA increased in titer weeks to months prior to the onset of symptoms. Additionally, LPA titers decreased or stabilized during successful TMP-SMX therapy, providing an early therapeutic index. Measurement of anti-PC IgG was not useful per se, as it was elevated in both controls and documented PC infection. The combination of very low antibody titer (less than or equal to 1:16) with a positive or increasing LPA PC-Ag titer appeared to be disease-predictive.(ABSTRACT TRUNCATED AT 400 WORDS)     

Recurrent Pneumocystis carinii colonization in a heart-lung transplant recipient on long-term trimethoprim-sulfamethoxazole prophylaxis.

INTRODUCTION: In the setting of organ transplantation, prior to prophylaxis, Pneumocystis carinii pneumonia (PCP) had been a common clinical problem, particularly in heart-lung and lung recipients who receive long-term immunosuppressive therapy to prevent allograft rejection. Continuous oral trimethoprim-sulfamethoxazole (TMP-SMX) has been highly effective in preventing PCP in these patients. REPORT: In this paper we report a case of recurrent Pneumocystis carinii infection in a chronic (> 15 years) heart-lung allograft recipient on long-term TMP-SMX prophylaxis. Twice, in 1995 and again in 1998, Pneumocystis carinii infection was diagnosed by bronchoalveolar lavage (BAL), in the same patient, despite continued oral TMP-SMX (960 mg TMP/4800 mg SMX per week) prophylaxis. The subject was not lymphopenic (his CD4 count was 569/mm3) and there was no associated deterioration in pulmonary function, nor evidence of hypoxemia. CONCLUSION: This case demonstrates that asymptomatic Pneumocystis carinii lung infections may recur in chronic heart-lung transplant recipients who take standard oral PCP prophylaxis.     

Plastic embedding evaluation of Pneumocystis carinii pneumonia in AIDS. Simultaneous demonstration of cyst and sporozoite forms

To study the possible role of plastic embedding in the surgical pathologic diagnosis of Pneumocystis carinii pneumonia, bronchial biopsy specimens from five patients with AIDS were examined using 0.9 micron thick methacrylate sections stained with silver methenamine borate and counterstained with toluidine blue. This technique was found to be superior to paraffin embedding in the demonstration of the fine structural details of both Pneumocystis and the surrounding lung tissue. This method permitted the simultaneous demonstration of both the cyst wall and intracystic sporozoites of Pneumocystis in biopsy tissue, which had been previously possible only by using electron microscopy. This technique assists in the differentiation of Pneumocystis from other opportunistic agents, and may be useful in estimating the relative numbers of cyst and sporozoite forms of the organism. We recommend that bronchoscopic and open lung biopsies from AIDS patients suspected of having Pneumocystis pneumonia be submitted for plastic embedding and high-resolution light microscopy.     

Interstitial pneumonitis in patients infected with the human immunodeficiency virus.

BACKGROUND--A study was performed to identify the clinical, radiographic, and histopathological features of interstitial pneumonitis in patients infected with the human immunodeficiency virus. METHODS--A retrospective review was made of the case notes, chest radiographs, and histopathological results of seven HIV-1 antibody positive patients with symptomatic diffuse pulmonary disease and a pathological diagnosis of non-specific interstitial pneumonitis. RESULTS--All patients had dyspnoea, with or without cough, and chest radiographs showing diffuse infiltrates. The arterial oxygen tension ranged widely from 5.9 to 13.1 kPa. The initial clinical diagnosis was Pneumocystis carinii pneumonia in most cases. The pathological diagnosis was made by transbronchial biopsy in one case and by open lung biopsy in six cases. The interstitial pneumonitis consisted of a patchy lymphocytic infiltrate composed of B cells in focal aggregates and T cells in a more diffuse distribution. The T cell population was a mixture of CD4+ and CD8+ cells. The histological findings contrast with the more extensive infiltrate of predominantly CD8+ lymphocytes seen in HIV-associated lymphocytic interstitial pneumonitis which occurs mainly in children. The condition ran a subacute course. Three patients spontaneously improved and three improved with steroid therapy. Long term survival was less than three years, the prognosis being determined by other infective or neoplastic complications. CONCLUSIONS--Non-specific interstitial pneumonitis usually presents with an illness resembling Pneumocystis carinii pneumonia but occurs when the CD4 and total lymphocyte counts are still preserved. The pneumonitis resolves spontaneously or responds to steroids, and does not itself lead directly to the patient's death. It does, however, appear to mark a downturn in the course of HIV infection.     

Indications for and Diagnostic Efficacy of Open-Lung Biopsy in the Patient with Acquired Immunodeficiency Syndrome (AIDS)

Pulmonary infiltrates in the patient with acquired immunodeficiency syndrome (AIDS) may be associated with a spectrum of unusual neoplastic and infectious process. Transbronchial biopsy frequently reveals the cause of these infiltrates; however, when transbronchial biopsy is nondiagnostic or contraindicated, or if the patient fails to improve after a diagnostic transbronchial biopsy, further investigation is warranted to direct appropriate therapy. Efficacy of 23 open-lung biopsies in 19 AIDS patients with pulmonary infiltrates was evaluated to define the indications for and the diagnostic yield of open-lung biopsy. Pulmonary infiltrates were recognized for a mean duration (± standard error) of 16 ± 2 days before open-lung biopsy and were associated with fever and cough. These patients did not have prior transbronchial biopsy, and open-lung biopsy was diagnostic in all of these. Prior transbronchial biopsy performed in the remaining 16 patients was nondiagnostic in 10. Open-lung biopsy was diagnostic in 70% of these patients (Pneumocystis carinii pneumonia, 2 patients; Kaposi's sarcoma, 3 patients; Kaposi's sarcoma and Legionella pneumophila, 1 patient; cytomegalovirus, 1 patient). The other 6 patients having a previous diagnostic transbronchial biopsy failed to improve with therapy, and open-lung biopsy resulted in a therapeutic change in 67% of these patients. Two deaths were attributable to open-lung biopsy in patients with postoperative thrombocytopenic hemorrhage. Open-lung biopsy should be performed in AIDS patients when transbronchial biopsy is nondiagnostic or contraindicated, or in patients who fail to improve with appropriate therapy after diagnostic trans-bronchial biopsy, especially in patients with Kaposi's sarcoma. The diagnostic yield will be high, and major therapeutic changes will be instituted.     

Bronchiolitis obliterans organizing pneumonia (BOOP) after renal transplantation

A 42-year-old renal transplant recipient was admitted with fever, anorexia, malaise, nonproductive cough, and dyspnea of 1-week duration. Multiple cultures of blood, sputum, and urine were negative. The possibility of bronchiolitis obliterans with organizing pneumonia (BOOP) was considered when pulmonary infiltrate did not respond to conventional antibiotic therapy. High-resolution computed tomography of the chest revealed patchy air-space consolidation and ground-glass opacities, predominantly located in the periphery of the lungs. Cultures and stains of bronchoalveolar lavage specimen and bronchoscopic biopsy of lung tissue were negative for organisms such as Pneumocystis (carinii) jiroveci, bacteria, Mycobacterium tuberculosis, cytomegalovirus, fungi, and atypical germs, and showed evidence of BOOP. The patient recovered completely after treatment with steroids.     

Pneumocystis carinii pneumonia after heart transplantation

Five patients with Pneumocystis carinii pneumonia after heart transplantation are reported. Four had severe clinical symptoms, whereas 1 was asymptomatic. Mechanical ventilatory support was necessary in 1 because of respiratory distress. Pneumocystis carinii infection developed in 4 patients within the first 4 postoperative months, and 1 patient had clinical disease 1 year after transplantation with a recurrence 9 months later. All were treated with trimethoprim-sulfamethoxazole either orally or intravenously (10 to 20 mg.kg-1.day-1 of trimethoprim). All patients recovered from infection and received the same drug prophylactically for 2 to 20 months after the infection. All patients are doing well after Pneumocystis carinii infection except 1 who died after an acute myocardial infarction 4 years after infection. We conclude that trimethoprim-sulfamethoxazole is an effective agent for the treatment of Pneumocystis carinii pneumonia after heart transplantation.     

Bronchoalveolar lavage cell analysis in patients with human immunodeficiency virus related diseases

The value of differential cell counts in bronchoalveolar lavage fluid in patients who were serologically positive for the human immunodeficiency virus (HIV) was studied in 30 patients with classified into four groups according to the severity of illness: (1) seven subjects with the AIDS related complex without clinical or radiological evidence of pulmonary infection; (2) eight patients with the AIDS related complex and pulmonary tuberculosis; (3) eight patients with AIDS and Pneumocystis carinii pneumonia; and (4) seven patients with AIDS, Pneumocystis carinii pneumonia, and severe respiratory failure. All four groups had a similar percentage of lymphocytes, significantly higher than that of a control group of 15 healthy volunteers. A significant increase in the percentage of neutrophils was observed in groups 2, 3, and 4. The lavage fluid differential cell count does not therefore appear to help in the differential diagnosis of pulmonary infections in HIV positive patients. The abnormal percentage of lymphocytes observed in some patients with the AIDS related complex without clinical evidence of pulmonary infection suggests that lung injury may exist before clinical or radiological abnormalities develop. This might be related to an immunological mechanism or might be caused by an undetected subclinical infection.     

Emergency lung biopsy: friend or foe of the immunosuppressed child?

An acute pneumonic process in an immunosuppressed child poses a diagnostic and therapeutic challenge. These patients tolerate infection poorly. An open lung biopsy may provide prompt diagnosis. Nevertheless, a beneficial change in therapy that results in survival does not necessarily follow. Fifty-six immunosuppressed children with acute respiratory symptoms and interstitial pulmonary infiltrates underwent lung biopsy from 1974 to 1985. The most common underlying diagnosis was acute lymphocytic leukemia (60%). A specific etiology was determined in 46 (82%). Operative morbidity in 52% included prolonged intubation, recurrent pneumothorax, and hemorrhage. Overall, mortality was 34%. Those patients with solid tumor and those who required postoperative ventilation had a statistically significant higher mortality than all others. We defined biopsy "patient benefit" as follows: (1) the biopsy yielded an etiology for which a change of treatment was required; and (2) the child survived this acute illness. Despite the successful diagnostic results of this procedure, only 13 (23%) of the patients derived clinical benefit. Even though a specific infectious etiology was diagnosed in 39 (69%) patients only ten (18%) of these improved and survived after an appropriate change in therapy. Eight of these had Pneumocystis carinii. One survivor benefited from the treatment of documented radiation pneumonitis. Another was successfully treated for graft v host reaction but this diagnosis also was made by skin biopsy. One half of the biopsies were performed very early in the course of the illness, specifically to exclude Pneumocystis carinii of which we saw a peak incidence in 1978 to 1979.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pneumocystis carinii pneumonia following heart transplantation

Pneumocystis carinii pneumonia represents a rare complication that is associated with a high mortality following heart transplantation. The cases of two heart transplant recipients who developed Pneumocystis pneumonia within the first 3 postoperative months are reported. Both patients had severe clinical symptoms of the disease; the diagnosis was confirmed by bronchoalveolar lavage, and the patients were treated with a combination of trimethoprim and sulfamethoxazole. Both patients recovered and are well at the time of this report.     

Pulmonary infiltration after exposure to home renovation dust: histopathology and microanalysis.

A subacute self-resolving illness associated with bilateral pulmonary infiltration developed in a patient following renovation in her home. This may have been related to exposure to silicaceous plaster dust which was found in an environmental sample as well as on microanalysis of a transbronchial lung biopsy specimen and bronchoalveolar lavage fluid.