Bronchoscopic techniques for the diagnosis of pulmonary complications of HIV infection

Bronchoscopy has played the central role in defining the spectrum of pulmonary disorders that occur in patients with HIV infection. Transbronchial biopsy (TBB) and bronchoalveolar lavage (BAL) both have high yields in the diagnosis of Pneumocystis carinii pneumonia (PCP) and other infections. Paradoxically, despite our knowledge and experience using bronchoscopy, controversy still exists regarding whether to attempt to make a bronchoscopic diagnosis in most patients with suspected PCP who have negative sputum studies or whether to administer initial empiric therapy and reserve invasive diagnostic techniques for patients who have a response. I prefer establishing a diagnosis as soon as possible because bronchoscopy is safe and because the patient may not have PCP and may become too ill to have bronchoscopy after a few days of ineffective therapy. A second controversy relates to the necessity of including routine TBB in addition to BAL during bronchoscopy. Although biopsies increase the risk of pneumothorax and hemorrhage, they add to the diagnostic yield in PCP and other infections. They are also necessary to provide tissue specimens for diagnosing noninfectious pulmonary disorders such as Kaposi's sarcoma and lymphocytic and nonspecific pneumonitis.     

Limited asymptomatic carriage of Pneumocystis jiroveci in human immunodeficiency virus-infected patients

Forty-seven bronchoalveolar lavage fluid samples from 16 human immunodeficiency virus (HIV)-infected patients were used to test the latency model of Pneumocystis infection in the human host. Identification of DNA sequence polymorphisms at 4 independent loci were used to genotype Pneumocystis jiroveci from the 35 samples that contained detectable P. jiroveci DNA. Eighteen of those 35 samples came from patients who did not have Pneumocystis pneumonia (PCP) and had confirmed alternative diagnoses. Seven patients had asymptomatic carriage of P. jiroveci over periods of < or = 9.5 months after an episode of PCP, and in all 7 cases, a change in genotype from that in the original episode of PCP was observed. The absence of P. jiroveci DNA in one-fourth of the 47 samples and the observed changes in genotype during asymptomatic carriage do not support the latency model of infection. Asymptomatic carriage in HIV-infected patients may play a role in transmission of P. jiroveci and may even supply a reservoir for future infections.     

Role of CD8 lymphocytes and neutrophilic alveolitis in Pneumocystis jiroveci pneumonia

We described the characteristics of bronchoalveolar inflammatory cells and their correlation with lung injury in patients with Pneumocystis jiroveci pneumonia.We reviewed all cases of patients with Pneumocystis jiroveci pneumonia in newly diagnosed HIV infected patients admitted to a large metropolitan referral hospital during June 2003 to December 2004. Nine patients (5M, 4F) with Pneumocystis jiroveci pneumonia diagnosed with bronchoscopy and cytological examination of bronchoalveolar lavage (BAL) were identified. There was a positive correlation between peripheral CD8 count and BAL neutrophilia and negative correlation with hypoxemia. Although the number patients in this case series is small, our findings suggest that CD8 cells and alveolar neutrophilic inflammation have a role in lung injury in Pneumocystis jiroveci pneumonia. These findings are consistent with data from animal studies.     

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.     

Diagnosis of Pneumocystis pneumonia by bronchoalveolar lavage cytology: experience at a tertiary care centre in India

BACKGROUND: Diagnosis of Pneumocystis pneumonia requires morphological demostration of P. carinii (now re-named as P. jiroveci). Although bronchoalveolar lavage (BAL) fluid cytology constitutes a formidable tool for detecting this infection, few studies on the utility of BAL cytology in diagnosing PCP are available from India. The present study reports the clinical spectrum, cytomorphological features and the utility of BAL cytology in diagnosing Pneumocystis infection from a tertiary care centre in India. METHODS: Retrospective study of 13 patients with PCP, diagnosed on examination of BAL fluid. RESULTS: The mean age of the patients was 41.2 years. One patient had human immunodeficiency virus (HIV) infection, while the other 10 were renal transplant receipients on immunosuppressive therapy. The immune status of two patients was unknown. Fever, cough and shortness of breath were the main presenting symptoms. Radiological diagnosis of Pneumocystis pneumonia was offered in only one case. Foamy alveolar casts were present in all cases. Silver methanamine stain enhanced the rounded, helmet or cleft forms of sporozoites. Inflammatory infiltrate was mainly polymorphonuclear. CONCLUSIONS: BAL cytology, thus, constitutes a useful diagnostic modality for morphological documentation and reliable diagnosis of Pneumocystis pneumonia in an immunocompromised host. Pneumocystis pneumonia appears to be a common opportunistic infection in renal transplant receipients in India.     

Multi-skeletal Pneumocystis jiroveci (carinii) in an HIV-seropositive patient

We present our experience with skeletal involvement of Pneumocystis jiroveci (ex P. carinii) infection in an HIV-seropositive patient. The objective of this study was to alert clinicians to the possibility that extrapulmonary P. jiroveci could affect the skeletal system in HIV-infected patients with extremely rapid progression. P. jiroveci infection of skeletal system has been rarely described elsewhere. A 51-year-old man complained of fever for six weeks, cough, anorexia, fatigue, and chest pain. He was found to be HIV seropositive. Repetitive (six samples) sputum and bronchoalveolar lavage fluid microbiologic tests were negative. High-resolution chest computed tomography (CT) scan revealed a small pulmonary mass. Abdominal CT scan revealed lesions in liver, spleen, kidneys, adrenal glands, lumbar vertebrae, and sacrum. Brain and skull CT scan was normal. A fine-needle biopsy of the lung mass was unrevealing. Cytological examination of sputum specimens showed findings consistent with non-small-cell lung carcinoma. Nineteen weeks post-presentation, the patient reported low-back pain. Within 24 hours after the onset of low-back pain, he developed focal neurological deficits, and a magnetic resonance imaging (MRI) of the skull and spine showed osteolytic lesions of the temporal bones bilaterally, multiple vertebral lesions, and lesions of sacrum and iliac bones. Radiotherapy of the lumbar spine and pelvis was given. Sternal aspiration was performed. Cytological examination revealed P. jiroveci. In conclusion, we describe a rare case of disseminated P. jiroveci infection in an HIV-seropositive patient, with multiple skeletal lesions, especially in the skull and in vertebrae region, and concomitant non-small-cell lung cancer, with a very poor prognosis.     

Bilateral upper-lobe cavitary Pneumocystis carinii pneumonia in a patient on dapsone prophylaxis

Pneumocystis carinii pneumonia (PCP) presenting as bilateral upper-lobe cavitary disease is rare. Isolated upper-lobe involvement has traditionally been associated with aerosolized pentamidine prophylaxis. Dapsone is a cheap and effective prophylactic agent against P carinii in patients who cannot tolerate trimethoprim-sulfamethoxazole. This is a case of a man who presented with bilateral upper-lobe cavitary P carinii pneumonia despite being on dapsone prophylaxis. Bronchoalveolar lavage was negative for P carinii. Transbronchial biopsy was positive for P carinii. The patient improved significantly with radiological resolution on specific treatment for P carinii. PCP should be included in the differential diagnosis of upper-lobe cavitary lung disease, and a transbronchial biopsy should be performed when the diagnosis is suspected.     

The place of lung 99mTc DTPA aerosol transfer in the investigation of lung infections in HIV positive patients

Pneumocystis carinii pneumonia (PCP) is the most common cause of pneumonia in HIV antibody positive patients, but other pneumonias remain important, i.e. streptococcal and mycobacterial infections. A definitive diagnosis relies on obtaining samples from the lung either noninvasively (induced sputum), or invasively (bronchoalveolar lavage, transbronchial or open lung biopsy). We have used the noninvasive technique of nebulized 99mTc DTPA transfer, to assess patients with PCP (n = 30) and other lung infections (n = 20) to see whether this test will distinguish between the various infections. The presence of a biphasic, rapid transfer curve indicates severe extensive alveolar damage and is seen in PCP or legionella pneumonia. The mean transfer time (T50 +/- SEM) for patients with PCP (whether smokers or nonsmokers) was 2.1 +/- 0.2 min, and for two of the patients with legionella 3.2 min. In PCP effective treatment causes the transfer to slow (mean T50 22.7 +/- 3.3 min, n = 24) and become monoexponential. Other causes of these changes in transfer are discussed. The other pneumonias (streptococcal, mycobacterial, and staphylococcal) did not result in biphasic curves or very rapid times, their T50 values are indistinguishable from cigarette smokers. In this patient group the DTPA transfer is a useful noninvasive investigation with a very rapid, biphasic curve indicating a high probability of PCP.     

Risk factors analysis for Pneumocystis jiroveci pneumonia (PCP) in patients with haematological malignancies and pneumonia

A retrospective matched case-control investigation was conducted to assess risk factors suggesting Pneumocystis jiroveci pneumonia (PCP) when pneumonia occurs in adult patients with haematological malignancies. Cases and controls included were HIV-negative, presented with pneumonia and had benefited from a bronchoalveolar lavage (BAL). The presence of Pneumocystis jiroveci cysts was systematically investigated by cytochemical staining and/or immunofluorescence. Cases were patients with Pneumocystis jiroveci cysts isolated on BAL fluid (n = 31, mean age 51+/-14 y; range 20-73 y). Controls were patients without Pneumocystis jiroveci cysts (n = 62, mean age 54+/-13 y; range 25-75 y) and were matched to case patients by age and y of pneumonia diagnosis. Statistical analysis indicated that the following factors were associated with PCP: vincristine (p = 0.009, odds ratio (OR) =2.11, 95% confidence interval (CI): 1.19-3.72), a daily corticosteroid therapy for more than 1 month (p = 0.05) during the past y, and a lymphocyte count less than 0.5 x 10(9)/l on the d of pneumonia diagnosis (p = 0.04). Clinicians should be aware, in order to evoke this diagnosis when pneumonia occurs in patients with these risk factors. The goal of this exploratory study was to identify risk factors that could eventually be further investigated by a larger prospective multicentre study.     

Granulomatous Pneumocystis jiroveci Pneumonia in a patient with chronic lymphocytic leukemia: a literature review and hypothesis on pathogenesis

BACKGROUND: Pneumocystis jiroveci pneumonia occurs frequently in patients with immunodeficiency syndromes, especially AIDS. Approximately 5% of AIDS patients have atypical granulomatous histology. CASE REPORT/METHODS: A 75-year-old woman with chronic lymphocytic leukemia was treated with alemtuzumab (campath-1H) 3 times weekly for 12 weeks. After completion of therapy she presented with dyspnea, hypoxemia, and bilateral infiltrates. Bronchoscopy with biopsy revealed Pneumocystis organisms with granulomatous history. She responded well to trimethoprim-sulfamethoxazole. RESULTS/LITERATURE REVIEW: Our literature review identified 19 patients without AIDS who had granulomatous Pneumocystis infection. These patients often had nodular infiltrates on x-rays and negative bronchoalveolar lavage study findings. Most patients required open lung biopsies. Histologic specimens frequently revealed necrosis. These patients responded well to therapy. CONCLUSION: The limited information available from these studies suggests that these patients have immune reconstitution-like syndrome related to either increasing numbers of CD4+ lymphocytes following therapeutic suppression or impaired modulation of CD4+ function. This unusual clinical presentation may delay diagnosis and effective therapy.     

Organizing pneumonia as a manifestation of Pneumocystis jiroveci immune reconstitution syndrome in HIV-positive patients: report of 2 cases

Organizing pneumonia (OP) is a nonspecific response to various forms of lung injury. Although patients with human immunodeficiency virus (HIV) infection tend to develop several respiratory disorders, especially infections and malignances, the association of HIV infection and OP is unusual. Pneumocystis jiroveci infection is also rarely associated with OP. We describe the radiologic findings in 2 HIV-positive patients who shortly after introduction of highly active antiretroviral therapy, presented with clinical and radiologic deterioration, despite elevation of the CD4 cell count and viral load decrease. In both patients, clinical and radiologic features were consistent with OP and lung biopsy revealed OP associated with P. jiroveci infection. These findings are consistent with immune reconstitution syndrome due to P. jiroveci.     

Pneumocystis pneumonia

Pneumocystis (carinii) jiroveci pneumonia can occur in immunocompromised individuals, especially hematopoietic stem and solid organ transplant recipients and those receiving immunosuppressive agents, and is the most common opportunistic infection in persons with advanced human immunodeficiency virus (HIV) infection. The Pneumocystis genus was initially mistaken as a trypanosome and later as a protozoan. Genetic analysis identified the organism as a unicellular fungus. Pneumocystis jiroveci is the species responsible for human infections. A slow indolent time course with symptoms of pneumonia progressing over weeks to months is characteristic in HIV-infected patients. Fulminant respiratory failure associated with fever and dry cough is typical in non-HIV-infected patients. Definitive diagnosis relies on histopathological testing of sputum, induced or sampled by fiberoptic bronchoscopy with bronchoalveolar lavage. The first-line drug for treatment and prevention is trimethoprim-sulfamethoxazole.     

Acute fibrinous and organizing pneumonia in a patient with HIV infection and Pneumocystis jiroveci pneumonia

Acute fibrinous and organizing pneumonia (AFOP) is a disease of the small airways that is characterized by deposition of fibrin within the alveolar spaces. The histological pattern is described as a variant of cryptogenic organizing pneumonia (COP). Although COP has been occasionally described in patients with HIV infection, the variant form, AFOP, has not been previously reported in such patients. This report describes an intriguing case of AFOP in a patient with HIV infection and Pneumocystis jiroveci pneumonia. AFOP was diagnosed after tapering of corticosteroid therapy. This case illustrates that non-infectious pulmonary infiltrates should be considered in the differential diagnosis of lung disease in patients with HIV infection.     

Adenoviral bronchopneumonia in an immunocompetent adult: computed tomography and pathologic correlations

Acute febrile lung disease associated with "patchy ground-glass pattern" on high-resolution computed tomography (HRCT) of the lung in an immunocompromised patient is suggestive of Pneumocystis carinii pneumonia; however, in an immunocompetent young person, it is suggestive of an atypical pneumonia, including viral bronchopneumonia. We studied a 31-year-old man who presented with fever, cough and hypoxemia. HRCT showed bilateral patchy ground-glass opacification. HIV test was negative and lung biopsy specimen grew adenovirus on viral culture. Histopathology of the lung was compatible with bronchopneumonia. In patients without HIV who present with acute lower respiratory infections and patchy ground-glass opacification on HRCT, adenoviral bronchopneumonia should be included in the differential diagnosis.     

Prognostic implications of bronchoalveolar lavage neutrophilia in patients with Pneumocystis carinii pneumonia and AIDS

The clinical records and bronchoalveolar lavage (BAL) cell differential counts were analyzed in 96 patients at risk for Pneumocystis carinii pneumonia (PCP) from human immunodeficiency virus (HIV) infection to determine if this information may be prognostically useful and to identify possible mechanisms of BAL neutrophilia. In 60 patients with PCP, 15 fatalities or episodes of respiratory failure occurred, and 14 of these patients had greater than 5% BAL neutrophils. Only one of 33 patients with PCP and less than 5% BAL neutrophils died. In contrast, there was no correlation between survival and BAL neutrophil percentages in 33 patients who did not have PCP. Three patients with HIV infection without lung disease had normal BAL cell differentials. Intra-alveolar and interstitial leukocytes found in 17 transbronchial lung biopsies in patients with PCP indicate that the alveolar and interstitial compartments of the lung may be the source of BAL neutrophils. Pathologic evidence of increased severity of diffuse alveolar damage to explain BAL neutrophilia was not found. As BAL neutrophil percentages in PCP had both positive and negative predictive value, this information may be useful to stratify therapeutic trials or to identify the patient with PCP who is at high risk of a complicated or fatal outcome.     

Postoperative respiratory failure secondary to Pneumocystis carinii pneumonia.

Pneumocystis carinii pneumonia (PCP) occurs frequently in individuals infected with the HIV virus. Malignancy, immunosuppressive drugs, and congenital immune deficiency may be associated with PCP. We describe a patient with stage 1 testicular carcinoma who developed hypoxemic respiratory failure two days after retroperitoneal lymph node dissection. Pneumocystis carinii organisms were demonstrated by catheter lavage samples and confirmed on bronchoalveolar lavage. Testing for HIV antibody by ELISA and the Western blot test were negative; HIV viral culture and polymerase chain reaction were also negative. Pneumocystis carinii pneumonia is unusual in localized surgically cured malignancies without obvious immunodeficiency and, to our knowledge, has not been described as a cause of postoperative respiratory failure.     

A case of acute progressive pulmonary cystic disease associated with Pneumocystis carinii pneumonia in a non-HIV-infected patient]

We report a case of Pneumocystis carinii pneumonia (PCP) in which acute lung tissue destruction progressed within a few days to form multiple bullae in a patient with no HIV-1 infection. A 59-year-old man with mild pulmonary emphysema had been followed for two years. He had smoked 40 cigarettes per day for forty years. Six months before, bronchogenic carcinoma had been diagnosed in the lower right lung. After chemotherapy and radiotherapy, he had a sudden onset of high fever with respiratory failure. PCP was diagnosed by examination of the bronchoalveolar lavage fluid (BALF), and the patient was treated with intravenously administered trimethoprim-sulphamethoxazole (TMP-SMX) and methylprednisolone. His chest radiograph was not typical for PCP, and showed no diffuse ground-grass or fine granular opacities. A high-resolution CT of the chest revealed a low attenuation area consistent with severe emphysematous alterations and progressively enlarging bullae. A few cases have been reported of progressive pulmonary cystic disease associated with PCP pneumonia in patients with AIDS, in which the cause of bulla formation was thought to be lung parenchyma destruction induced by HIV itself, or increased elastase release from HIV-infected macrophages. The present case demonstrated that HIV infection was not an essential factor in the development of bullous changes. In a patient with a long history of smoking and emphysema, PCP may trigger-macrophage activation and an excessive release of leukocyte elastase, leading to elastin destruction in the alveoli.     

Granulomatous Pneumocystis carinii pneumonia in Wegener's granulomatosis.

This study reports on a first case of granulomatous Pneumocystis carinii pneumonia (PCP) in a human immunodeficiency virus-negative patient with antineutrophil cytoplasmic antibody-positive Wegener's granulomatosis whilst receiving immunosuppressive treatment. The patient presented with diffuse alveolar haemorrhage, pauci-immune rapid progressive glomerulonephritis and leukocytoclastic vasculitis of the skin. Granulomatous Pneumocystis carinii pneumonia developed under immunosuppressive treatment with cyclophosphamide and prednisone. At the time Pneumocystis carinii pneumonia developed, there was a marked lymphopenia with a very low CD8+ cell count in the blood. Grocott staining in bronchoalveolar lavage fluid revealed no Pneumocystis carinii. The diagnosis was made via a video-assisted thoracoscopic lung biopsy which showed granulomas containing high numbers of Pneumocystis carinii cysts.     

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.     

Outcome of Pneumocystis jirovecii pneumonia diagnosed by polymerase chain reaction in patients without human immunodeficiency virus infection

Background and objective: Pneumonia caused by Pneumocystis jirovecii (PCP) in patients without human immunodeficiency virus (HIV) infection is associated with high mortality. The diagnosis of PCP at our institution is based on detection of DNA using a polymerase chain reaction (PCR) assay. The aim of this study was to describe the clinical manifestations, outcomes and factors associated with mortality due to PCP, as diagnosed by PCR, in patients without HIV infection. Methods: Over a 6‐year period, all HIV‐negative immunocompromised patients suspected of having an opportunistic pulmonary infection underwent diagnostic bronchoscopy. A multigene PCR assay that detects Pneumocystis jirovecii DNA was used for the diagnosis of PCP. Patients were considered to have PCP if they had underlying immunodeficiency, compatible signs and symptoms, abnormal radiological findings, and Pneumocystis jirovecii DNA was detected in a bronchoalveolar lavage fluid sample. Data was collected retrospectively. Results: PCP was diagnosed in 58 patients. The underlying conditions included haematological malignancies (60.3%), solid tumours (17.2%) and immunosuppressive treatment (22.4%). The most common clinical features in patients with PCP were fever (94.6%), dyspnoea (67.2%) and cough (36.2%). The overall in‐hospital mortality was 17.2% (10/58). Mortality was associated with co‐infections, high lactate dehydrogenase levels, female gender, and higher pneumonia severity index and acute physiology and chronic health evaluation III scores. Conclusions: In this study, the mortality of HIV‐negative patients with PCP was low compared with previous reports. We hypothesize that this finding resulted from the increased sensitivity of a PCR‐based assay, as compared with traditional methods, for the diagnosis of PCP in HIV‐negative patients.