Nonspecific interstitial pneumonitis without evidence of Pneumocystis carinii in asymptomatic patients infected with human immunodeficiency virus (HIV)

STUDY OBJECTIVE: To assess how often Pneumocystis carinii organisms, P. carinii pneumonia, or other pulmonary pathologic processes were present in persons infected with human immunodeficiency virus (HIV) without pulmonary symptoms or previous history of P. carinii, and with a normal chest roentgenogram. DESIGN: Serial, prospective assessment of eligible HIV-seropositive patients over 21 months. PATIENTS: Twenty-four HIV-seropositive patients with either a nonpulmonary manifestation of the acquired immunodeficiency syndrome (AIDS) (n = 12) or an absolute CD4 lymphocyte count of 0.200 X 10(9) cells/L or less (n = 12), no pulmonary symptoms, a normal chest roentgenogram, no history of P. carinii pneumonia, and no history of treatment with antipneumocystis prophylaxis. INTERVENTIONS: Pulmonary assessment with arterial blood gases, pulmonary function tests, gallium-67 citrate scans, and bronchoscopy with bronchoalveolar lavage and transbronchial biopsies. MEASUREMENTS AND MAIN RESULTS: Mean alveolar-arterial gradient was 11.1 mm Hg +/- 8.5 and mean diffusion capacity was 73.0% +/- 20.0% of predicted. None of the 24 patients showed P. carinii or other pathogens on stains of bronchoalveolar lavage fluid. No patient had histologic evidence of P. carinii pneumonia. Transbronchial biopsy specimens showed chronic, nonspecific interstitial pneumonitis (11 of 23) and no pathologic abnormality (12 of 23). Six patients have developed P. carinii pneumonia during 2 to 18 months of follow-up. CONCLUSIONS: HIV-infected patients without pulmonary symptoms did not have detectable Pneumocystis organisms in bronchoalveolar lavage fluid or transbronchial biopsy specimens; but 11 of 23 had evidence of chronic, nonspecific interstitial pneumonitis. Pneumocystis organisms in a pulmonary specimen from a symptomatic patient probably indicate the cause of the pulmonary dysfunction even if only a few are detected.     

Bilateral bronchoalveolar lavage in the diagnosis of opportunistic pulmonary infections.

To further improve the diagnostic value of bronchoscopy in the immunosuppressed population presenting with diffuse pulmonary infiltrates, we prospectively investigated the utility of bilateral bronchoalveolar lavage (BAL). We performed 62 bronchoscopies on 52 immunosuppressed patients. Of the 52 patients, 33 had pulmonary infections. The yield for Pneumocystis carinii pneumonia on bilateral BAL was 94 percent (31/33), compared to the 84 percent (51/61) previously obtained with unilateral BAL in our institution. The recovery of P carinii was unilateral in four of five patients without AIDS and in four of 26 patients with AIDS. Transbronchial biopsy gave a yield of 85 percent (11/13). In ten patients with definitive cytomegalovirus (CMV) pneumonia, recovery of CMV by combined culture and cytology was 100 percent. Of nine bronchoscopies with positive cytology for CMV, five showed cytopathologic changes in the BAL from both sides and four in the BAL from one side only. No complications were seen in the 14 patients with thrombocytopenia or the five patients receiving mechanical ventilation. Our findings indicate that bilateral BAL significantly increases the yield for recovery of P carinii (p less than 0.02) and CMV (p less than 0.001) in immunosuppressed patients.     

Utility of gallium67 scintigraphy and bronchial washings in the diagnosis and treatment of Pneumocystis carinii pneumonia in patients with the acquired immune deficiency syndrome

Twenty patients with the acquired immune deficiency syndrome (AIDS) and suspected Pneumocystis carinii pneumonia were evaluated by gallium67 (Ga67 scintigraphy and fiberoptic bronchoscopy for initial diagnosis and response to therapy. Lung uptake of Ga67 was demonstrated in 100% of AIDS patients with P. carinii pneumonia, including those with subclinical infection. Fiberoptic bronchoscopy identified P. carinii in the bronchial washings of 100% of cases (19 patients), whereas only 13 of 16 (81%) patients had P. carinii in lung tissue obtained by transbronchial biopsy. Repeat fiberoptic bronchoscopy was performed in 16 of 20 patients. After 2 to 4 wk of therapy, P. carinii was identified in bronchial washings in 8 of 16 (50%) patients and in transbronchial biopsy in 1 of 10 (10%) patients examined. Bronchial washing has a higher yield than transbronchial biopsy in demonstrating P. carinii in patients with AIDS and may evolve as the procedure of choice in such patients. Based on the clinical course and results of Ga67 scintigraphy and fiberoptic bronchoscopy in AIDS patients with P. carinii pneumonia, optimal therapy may require at least 3 wk of treatment.     

Lack of utility of bronchial brush biopsy in patients infected with the human immunodeficiency virus.

While bronchoalveolar lavage has been shown to be more sensitive than brush biopsy (BB) for the diagnosis of Pneumocystis carinii pneumonia in AIDS patients, some have reported that BB occasionally is positive in spite of a negative BAL. Many bronchoscopists, therefore, continue to perform routine BB when doing bronchoscopy on AIDS patients. We performed a retrospective study of all fiberoptic bronchoscopies done on human immunodeficiency virus-infected patients over a one-year period at our institution to determine if the use of BB added to the diagnostic yield of bronchoscopy over that of BAL alone. Of 84 bronchoscopies in which BB was performed in addition to BAL, BB yielded no diagnoses that were not obtained by BAL. Brush biopsy added approximately $400 to the cost of bronchoscopy. We conclude that BB should not be routinely done when performing bronchoscopy on HIV-infected patients.     

Bronchoalveolar lavage and transbronchial biopsy for the diagnosis of pulmonary infections in the acquired immunodeficiency syndrome

The efficacy of bronchoalveolar lavage and transbronchial biopsy in diagnosing lung infection was determined in 276 fiberoptic bronchoscopic examinations done on 171 patients with known or suspected acquired immunodeficiency syndrome. Of 173 pathogens (Pneumocystis carinii, cytomegalovirus, Mycobacterium avium-intracellulare, Cryptococcus neoformans, M. tuberculosis, Coccidioides immitis, and Histoplasma capsulatum) identified during the initial evaluation or in the subsequent month, the initial bronchoscopic examination detected 166 (96%). Bronchoalveolar lavage and transbronchial biopsy had sensitivities of 86% and 87%, respectively. When bronchoscopy included both bronchoalveolar lavage and transbronchial biopsy, the yield for all pathogens was 98% and the sensitivity for P. carinii infections was 100%. Follow-up for at least 3 weeks after examination failed to detect any additional false-negative results. Fiberoptic bronchoscopy is extremely accurate for the detection of pathogens in patients with the acquired immunodeficiency syndrome, especially when bronchoalveolar lavage and transbronchial biopsy are combined. In patients at high risk of complications from transbronchial biopsy, bronchoalveolar lavage is sufficiently accurate to be used alone.     

Diagnosis of Pneumocystis carinii pneumonia. Roentgenographic-pathologic correlates based on fiberoptic bronchoscopy specimens from patients with the acquired immunodeficiency syndrome

We analyzed the diagnosis of Pneumocystis carinii pneumonia by fiberoptic bronchoscopy in a large series of patients with the acquired immunodeficiency syndrome (AIDS). Transbronchial biopsy fragments, as opposed to endobronchial specimens, were found to have high diagnostic value. Their optimal number for diagnosis was determined by a simple statistical principle. It varied from a minimum of two in cases of severe pneumonia to a maximum of four when roentgenographic manifestations were altogether absent. The diagnostic yield of the transbronchial biopsy alone was 97 percent and that of "touch" preparations of the biopsies 88 percent; when both techniques were combined, the accuracy rose to 98 percent. By comparison, bronchial "washings" and "brushings" had a much lower yield, 59 percent and 57 percent, respectively. Because their diagnostic contribution was negligible, we conclude that the latter two procedures represent an unnecessary expense and waste of technical and professional effort.     

Fiberoptic bronchoscopy and sputum examination for diagnosis of pulmonary disease in AIDS patients in Stockholm

For diagnosing pulmonary disease on 82 occasions in 68 patients (64 males) aged 39 (23-73) years infected with HIV-1 we used flexible fiberoptic bronchoscopy (FFB) with bronchoalveolar lavage (BAL) or washing with or without transbronchial lung biopsy (TBB) and brushing. A clinical diagnosis of lower respiratory tract disease was obtained in 68/82 episodes (83%). An etiological diagnosis was reached by FFB in 59/82 episodes (72%). Pneumocystis carinii (PC), the dominating pathogen causing pneumonia in 54/82 episodes (66%), was detected by FFB in 51/54 (94%). In spite of being isolated in bronchoscopy material in 36/82 episodes (44%) cytomegalovirus (CMV) seemed to be the cause of pneumonia only in 2/36 (5%) episodes. Except PC and CMV, only bacteria (including mycobacteria) were found as infectious etiological agents. Kaposi's sarcoma and pulmonary edema were diagnosed in one patient each. For detection of PC in 37 episodes we compared staining of BAL fluid with indirect immunofluorescence (IF) using monoclonal antibodies (MoAB) with staining of BAL material by silver methenamine (Grocott). Staining with IF MoAB alone of BAL fluid only seemed to be even more sensitive than silver methenamine staining of BAL, TBB and brushing material. When using IF MoAB staining of BAL fluid, TBB and brushing added nothing to the result, except in the patient with Kaposi's sarcoma, diagnosed by TBB. Sputum investigation using IF MoAB for detection was increasingly adopted during the study time. It was very useful (sensitivity approximately 74%) and reduced the number of required FFBs.     

Pneumocystis carinii pneumonia in HIV-infected patients: diagnostic yield of induced sputum and immunofluorescent stain with monoclonal antibodies.

The purpose of this study was to evaluate the diagnostic yield of induced sputum (IS), assessing the reliability of indirect immunofluorescent stain with monoclonal antibodies (IFMoAb) and methenamine silver (Met-Ag) and analysing factors likely to influence the sensitivity of these techniques. An analysis was prospectively carried out on IS specimens collected from 61 human immunodeficiency virus (HIV)-infected patients during 69 episodes of suspected Pneumocystis carinii pneumonia. Ultrasonic nebulizers with hypertonic 2% saline were used. IFMoAb to P. carinii and Met-Ag were performed after cytocentrifugation of the specimen. Results were compared with those of bronchoalveolar lavage (BAL) with/without transbronchial biopsy (TBB), performed not more than seven days after induction of sputum. P. carinii pneumonia was confirmed in 32 episodes, of which IS was diagnostic in 23. The sensitivity of the staining procedures was 69% for IFMoAb, and 28% for Met-Ag. The three episodes of P. carinii pneumonia in patients on oral chemoprophylaxis yielded negative IS results; in contrast, IS was negative in only 6 of the 29 cases not receiving chemoprophylaxis. IS is a non-aggressive procedure that diagnosed P. carinii pneumonia in 72% of our cases. The yield increased significantly when IFMoAb was used in patients not receiving oral chemoprophylaxis.     

Pneumocystis carinii pneumonia in patients with AIDS in Central Africa.

Over a period of 11 months, 37 patients infected with the Human Immunodeficiency Virus (HIV) presenting with symptoms of bronchopulmonary disease were investigated. Patients presented with cough, weight loss, fever and dyspnoea. Investigations included fibreoptic bronchoscopy with bronchoalveolar lavage and transbronchial biopsy. In eight patients (22%) Pneumocystis carinii was found. Pulmonary infiltrates were found on chest radiographs of six patients, while in the remaining two patients chest radiographs showed clear lung fields. P. carinii was found in two patients with pulmonary Kaposi's sarcoma. Infection with P. carinii often occurred with other pathogens: Streptococcus pneumoniae was found in four patients, Staphylococcus aureus in two and tuberculosis in two. P. carinii pneumonia does occur in patients with HIV infection in Africa and the diagnosis is relatively simple to make provided that transbronchial biopsy and bronchoalveolar lavage are carried out through a fibreoptic bronchoscope and specimens examined after appropriate staining. However, the prevalence of P. carinii in patients with HIV infection in Africa appears to be lower than that found in patients with HIV infection in Europe and North America.     

Aerosolized pentamidine: effect on diagnosis and presentation of Pneumocystis carinii pneumonia

STUDY OBJECTIVE: To determine the effect of previous aerosolized pentamidine therapy on diagnosis and presentation of Pneumocystis carinii pneumonia. DESIGN: A retrospective study. SETTING: A tertiary care hospital. PATIENTS: Fifty-two consecutive patients with P. carinii pneumonia and underlying infection with the human immunodeficiency virus (HIV) who had bronchoscopy. Twenty-one patients who were on aerosolized pentamidine therapy served as the study group. Thirty-one patients who had not received the drug served as the control group. MEASUREMENTS AND MAIN RESULTS: The yield of bronchoalveolar lavage for P. carinii pneumonia was 62% for the study group and 100% for the control group (P less than 0.05). This lower yield was significant for the subset of patients having their first episode of P. carinii pneumonia. The yield of transbronchial biopsy was similar for both groups of patients (81% compared with 84%). The yield of bronchoscopy was not influenced by use of zidovudine. Review of lavage specimen slides suggested that there may be fewer organisms present in patients receiving aerosolized pentamidine. An atypical roentgenographic presentation of upper lobe predominant infiltrates was seen in 38% of the study patients and 7% of the control patients. In addition, pneumothoraces and cystic changes were also frequently seen in the study patients. Gallium scans, when done, were also atypical in the study group. Markers of the severity of disease, however, were similar in both groups. CONCLUSION: The yield of bronchoalveolar lavage for P. carinii pneumonia in HIV-infected patients is lower in patients receiving aerosolized pentamidine. Unusual roentgenographic presentations and atypical gallium scans are also found in this setting.     

Sputum examination for the diagnosis of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome

The diagnostic utility of sputum examination in patients with Pneumocystis carinii pneumonia secondary to the acquired immunodeficiency syndrome (AIDS) has so far not been determined. Sputum was induced in 43 patients with AIDS or suspected AIDS just prior to fiberoptic bronchoscopy, scheduled because of an unexplained pulmonary infiltrate on a chest radiograph. Pneumocystis carinii pneumonia was diagnosed by sputum examination and/or by a bronchoscopic procedure in 20 patients. Of these, sputum samples were positive for Pneumocystis organisms in 11 (55%) of 20 patients tested, bronchial washings were positive in 11 (79%) of 14 patients tested, brush biopsies were positive in 9 (53%) of 17 patients tested, and transbronchial lung biopsies were positive in 18 (90%) of 20 patients tested. The presence of P. carinii cysts in sputum did not correlate with the presence of alveolar macrophages in sputum nor with the volume of sputum. Sputum examination for P. carinii organisms, employed as a first diagnostic step in patients with AIDS with pulmonary infiltrates, may frequently obviate the need for bronchoscopy.     

Cytomegalovirus the predominant cause of pneumonia in renal transplant patients. A two-year study of pneumonia in renal transplant recipients with evaluation of fiberoptic bronchoscopy

The microbiological etiology of pneumonia in 34 renal transplant patients with clinical and X-ray evidence of pulmonary parenchymal disease was studied. Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB) and brushing was performed on 18 patients. Laboratory evaluation included histological and cytological methods, cultures for bacteria, fungus and virus and immunofluorescence techniques for the detection of Pneumocystis carinii, cytomegalovirus (CMV) and legionella. Serum samples were obtained concomitantly for antibody studies. CMV, the most common etiology, was considered to be the cause of disease in 18/34 patients. All but one of these patients had positive CMV isolates in culture on leucocytes. Pulmonary edema was found in 7 patients, bacterial pneumonia in 11 patients, P. carinii in 4 patients and Candida albicans in 1 patient. Multifactorial etiology was found in 12/34 cases. The overall mortality was 32%. Bronchoscopy gave correct diagnosis in 13/14 patients with infectious pulmonary diseases (93%). Bronchoscopy procedures were well tolerated and should be considered in transplant patients with evidence of pulmonary parenchymal disease.     

THE ROLE OF BRONCHOALVEOLAR LAVAGE IN THE DIAGNOSIS OF SUSPECTED OPPORTUNISTIC PNEUMONIA

Abstract We report 50 immunocompromised patients with pulmonary infiltrates who underwent fibreoptic bronchoscopy, including bronchoalveolar lavage, on 56 occasions. The underlying diseases were mostly lymphoma, leukemia, other malignancies and renal failure. The commonest immunodeficiency factors were chemotherapy, steroids and neutropenia. A positive diagnosis could be made from analysis of the bronchoalveolar lavage on 59% (33/56) occasions. This was a comparable yield to transbronchial lung biopsy 57% (16/27), and superior to proximal airways wash 24% (13/55), or bronchial brushings 29% (10/34). Open lung biopsy added additional diagnostic information in three of the four cases in which it was performed. The most common final diagnoses were bacterial, viral or Pneumocystis carinii pneumonia and recurrent malignancy. We conclude that bronchoalveolar lavage is a safe procedure with a high diagnostic yield in the immunocompromised host with suspected opportunistic pneumonia.     

Fiberoptic bronchoscopy for diagnosis of opportunistic pulmonary infections after bone marrow transplantation

As a part of the diagnostic procedure for 16 suspected pulmonary infections in 15 marrow transplant recipients fiberoptic bronchoscopy with bronchoalveolar lavage (BAL), transbronchial lung biopsy (TBB) and brushing were performed. Cytomegalovirus (CMV) was the most common microorganism and CMV pneumonia was diagnosed in 8/16 (50%) episodes of pulmonary disease studied. Pneumonias were diagnosed as caused by Candida or Aspergillus species in 6 episodes and by gram-positive cocci in 2 cases. Adenovirus and Pneumocystis carinii was also isolated in 1 patient each. Three noninfectious diseases (pulmonary oedema, idiopathic pneumonia and pulmonary embolism) were diagnosed by methods other than bronchoscopy. The use of fiberoptic bronchoscopy with BAL and TBB allowed correct identification of 14/18 microorganisms involved. Brushing was less useful. Four patients' pneumonias had a multiple etiology. The bronchoscopy methods used were well tolerated even by patients whose condition was poor.     

Retrospective utility of bronchoscopy after hematopoietic stem cell transplant

Fiberoptic bronchoscopy with bronchoalveolar lavage (BAL) is thought to be the procedure of choice to evaluate pulmonary infiltrates in hematopoietic stem cell transplant (HSCT) recipients. We retrospectively reviewed 91 bronchoscopies performed on 190 in-patient HSCT recipients admitted or treated for pneumonia from January 1994 to December 2004. These yielded a diagnosis 49% of the time with an overall survival of 35 days post-bronchoscopy. We were unable to detect any survival benefit from an addition to the treatment regimen after a positive result from analysis of the BAL fluid or transbronchial biopsy. The most common bacteria isolated was Pseudomonas that was often resistant to the patient's current antibiotics, suggesting that in lieu of this diagnostic procedure, changes to better cover resistant Gram-negative bacteria are reasonable. Although transbronchial biopsies provided an additional diagnosis in one out of 21 biopsies performed, six of the seven complications in our series were directly related to the transbronchial biopsy. With approximately a 50% yield from a bronchoscopy, additional treatment given after only 20% of all bronchoscopies, and no detectable survival benefit with a bronchoscopy that yielded a diagnosis, the utility of a bronchoscopy in this patient population is questioned by these data.     

Persistence of Pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. Evaluation of therapy by follow-up transbronchial lung biopsy

The effectiveness of therapy with trimethoprim-sulfamethoxazole and/or pentamidine has not been fully evaluated in AIDS patients with Pneumocystis carinii pneumonia (PCP). Since recurrence of PCP is common, follow-up lung biopsy (15 transbronchial, one open) was performed as part of the clinical evaluation of 16 episodes of PCP. All patients had shown evidence of clinical improvement during treatment and had received a mean duration of therapy of 17.6 days. In six of 16 episodes (38 percent), however, a repeat biopsy remained positive for PCP an average of 25.2 days after initial diagnosis. Retrospective comparison of standard clinical parameters (fever response, arterial blood gas results, roentgenographic characteristics) could not adequately distinguish episodes with positive follow-up biopsies from those with negative biopsies. Persistence of PCP after conventional treatment may be an important factor in recurrences of this infection in AIDS patients.     

Bronchoalveolar lavage as the exclusive diagnostic modality for Pneumocystis carinii pneumonia. A prospective study among patients with acquired immunodeficiency syndrome

Pneumocystis carinii pneumonia (PCP) is the most common life-threatening opportunistic infection among patients with the acquired immunodeficiency syndrome (AIDS). Because retrospective studies suggested that bronchoalveolar lavage (BAL) compared favorably to lung biopsy in the diagnosis of PCP, we prospectively evaluated the utility of BAL in 40 consecutive patients with AIDS or risk of AIDS who presented with respiratory complaints. The BAL revealed P carinii in 36 of 42 episodes of pneumonia (86 percent) among 40 patients. Clinical follow-up of the six patients whose BAL was negative for PCP suggested only one possible false negative BAL for PCP. Therefore, BAL detected PCP in 36 of 37 patients for a sensitivity of 97 percent. BAL detected cytomegalovirus in 15 of 38 patients, as well as Mycobacterium avium-intracellulare and Cryptococcus (each in one patient). By virtue of accuracy and lack of morbidity demonstrated in our study, BAL should supplant lung biopsy techniques in the evaluation of AIDS patients with pulmonary symptoms.     

Pneumocystis carinii pneumonia. Cytologic manifestations and rapid diagnosis in routinely prepared Papanicolaou-stained preparations

In this study of 28 immunocompromised patients, it was found that Pneumocystis carinii pneumonia could be easily and reliably diagnosed by examination of routinely prepared, Papanicolaou-stained cellular samples obtained by bronchoalveolar lavage, bronchial brushing, and bronchial washing. The distinctive intra-alveolar exudate of pneumocystosis observed in lung biopsy specimens was readily discernible in all of the cellular samples that demonstrated P. carinii by special stains. The exudate was not present in any of the P. carinii-negative samples. Routinely prepared, Papanicolaou-stained cellular samples can be relied upon for the rapid diagnosis of P. carinii pneumonia.     

Coccidioidomycosis in acquired immune deficiency syndrome. Depressed humoral as well as cellular immunity

Progressive pulmonary coccidioidomycosis has not been previously reported in the setting of acquired immune deficiency syndrome (AIDS). A patient with AIDS, progressive pulmonary coccidioidomycosis, Pneumocystis carinii pneumonia, and disseminated cytomegalovirus is described. Diagnosis of these opportunistic pathogens was made by bronchoalveolar lavage and transbronchial lung biopsy. Results of traditional complement fixation serologic testing for cytomegalovirus were negative; however, the more sensitive enzyme-linked immunosorbent assay did indicate infection. Coccidioidal complement fixation tests, precipitin tests, counter-immunoelectrophoresis, and immunodiffusion tests demonstrated negative findings. These results provide additional evidence that some patients with AIDS have defects in humoral as well as cellular immunity.     

Bronchoalveolar lavage in the diagnosis of diffuse pulmonary infiltrates in the immunosuppressed host

The usefulness of bronchoalveolar lavage in the diagnosis of pulmonary infiltrates in the immunosuppressed patient was studied in 97 patients. In immunosuppressed patients, the available diagnostic procedures are often invasive and have variable yield and a potential for serious complications. Bronchoalveolar lavage had an overall diagnostic yield of 66% (61 of 92 diseases). It was most effective in the diagnosis of opportunistic infections, including infection with Pneumocystis carinii (18 of 22 cases), cytomegalovirus pneumonia (10 of 12 cases), fungal pneumonia (5 of 6 cases), and mycobacterial disease (4 of 5 cases). The technique was also helpful in suspected pulmonary hemorrhage (7 of 9 cases) but was less useful for diagnosing malignancy (10 of 22 cases) and drug-induced toxicity (6 of 15 cases). Findings of bronchoalveolar lavage could be combined with those of transbronchial biopsies, brushings, and washings in the diagnosis of most of the diseases. The procedure was safe, even in thrombocytopenic patients and those requiring mechanical ventilatory support. Bronchoalveolar lavage is a valuable procedure for evaluation of pulmonary disease in the immunosuppressed host.