Charles Mayaud

Rituximab-induced lung disease: a systematic literature review

The anti-CD20 antibody rituximab has been reported to induce a heterogeneous spectrum of lung disorders. The aim of the present study was to critically review data on the clinical presentations, causality assessments and management strategies of lung diseases possibly related to rituximab. A systematic literature review was performed on English-language reports in PubMed until September 2008. Cases of lung diseases ascribed to rituximab (n = 45) were identified, with three time-to-onset patterns. The most common presentation was acute/subacute hypoxaemic organising pneumonia (n = 37), starting 2 weeks after the last infusion (often around the fourth cycle) and resolving, in most cases, provided glucocorticoid therapy was given early. Acute respiratory distress syndrome occurred in five patients, within a few hours and usually after the first infusion. In the remaining three patients, macronodular organising pneumonia developed insidiously long after rituximab therapy and responded to steroids. Eight patients died. Based on time to onset, symptoms, and responses to discontinuation and rechallenge with rituximab and other drugs, 13 cases were highly compatible and 32 compatible with rituximab-induced lung disease. Knowledge of these presentations of rituximab-induced lung disease should prove helpful for diagnosis and causality assessment purposes. Time-to-onset data, suggesting different pathogenic mechanisms, support closer clinical and perhaps radiological monitoring between infusions, particularly in patients with a history of reversible respiratory symptoms.

Sarcoidosis in HIV-Infected Patients in the Era of Highly Active Antiretroviral Therapy

To analyze the impact of highly active antiretroviral therapy (HAART) on the characteristics and outcome of sarcoidosis in patients infected with human immunodeficiency virus (HIV), we identified HIV-infected patients in whom sarcoidosis was diagnosed between 1996 and 2000 from the admission registers of the pneumology departments of 12 hospitals in the Paris region (France). Sarcoidosis was diagnosed in 11 HIV-infected patients, of whom 8 were receiving HAART. HIV infection was diagnosed before sarcoidosis in 9 cases. At diagnosis of sarcoidosis, the mean CD4 cell count (+/-SD) was 390+/-213 cells/mm(3), and the mean plasma virus load was 4002+/-10,183 copies/mL. Sarcoidosis occurred several months after HAART introduction, when the CD4 cell count had increased and the plasma HIV load had decreased. Clinical and radiological characteristics, laboratory values for bronchoalveolar lavage fluid samples, and outcome after a long follow-up were similar for the patients receiving HAART and for HIV-uninfected patients.

Lung cancer in HIV infected patients: facts, questions and challenges

AIDS related mortality has fallen sharply in industrialised countries since 1996 following the introduction of highly active antiretroviral therapy. This has been accompanied by an increase in the proportion of deaths attributable to non-AIDS defining solid tumours, especially lung cancer. The risk of developing lung cancer seems to be higher in HIV infected subjects than in the general population of the same age, partly because the former tend more frequently to be smokers and, especially, intravenous drug users. The carcinogenic role of the antiretroviral nucleoside drugs and their interaction with smoking needs to be examined. Interestingly, there is no clear relationship between the degree of immunosuppression and the risk of lung cancer, so the reason for the increased risk is unknown. The mean age of HIV infected patients at the time of lung cancer diagnosis is 45 years and most are symptomatic. Lung cancer is diagnosed when locally advanced or metastatic (stage III–IV) in 75–90% of cases, similar to patients with unknown HIV status. Adenocarcinoma is the most frequent histological type. The prognosis is worse in HIV infected patients than in the general lung cancer population. Efficacy and toxicity data for chemotherapy and radiation therapy are few and imprecise. Surgery remains the treatment of choice for localised disease in patients with adequate pulmonary function and general good health, regardless of immune status. Prospective clinical trials are needed to define the optimal detection and treatment strategies for lung cancer in HIV infected patients.

A persistent challenge: the diagnosis of respiratory disease in the non-AIDS immunocompromised host

The diagnostic and therapeutic approach to respiratory disease in the immunocompromised host remains a challenge for several reasons: (1) the current increase in both the number of immunocompromised hosts and their length of survival; (2) the high frequency of lung disease in these patients,1-3 and (3) the severity of these lung diseases.3-5 A good example is given in a recent review by Paterson et al of the epidemiology of invasive aspergillosis in transplant recipients.5 The incidence of this opportunistic infection, which mainly affects the lung, varies from 1% in kidney recipients to 9% in lung recipients (with 2% in liver recipients and 7% in bone marrow recipients). In this population it has a mortality rate of 55–92% and accounts for 10–15% of deaths of all transplant recipients. In fact, the diagnostic challenge is continuously evolving in the immunocompromised host and the following three questions need to be considered: (1) What new data are available on the diagnostic and therapeutic approach? (2) What current changes are there in the diagnostic and therapeutic approach in neutropenic patients? (3) What current changes are there in the diagnostic and therapeutic approach in the immunocompromised host without neutropenia? ### IS THERE AN EVOLUTION IN THE TYPE AND SEVERITY OF THE UNDERLYING IMMUNODEFICIENCIES? The data from the literature clearly show the continuous changes both in the indications for immunosuppressive treatment and in the nature and dosages of the immunosuppressive drugs used. For example, steroids are increasingly used in patients with chronic lung disease such as lung cancer, chronic obstructive lung disease, idiopathic pulmonary fibrosis, or sarcoidosis6; the use of combined treatment for solid tumours—for example, chemotherapy and thoracic radiotherapy for lung cancer7 or intensive chemotherapy combined with total body irradiation, transplantation of autologous bone marrow, and 13-cis-retinoic acid for neuroblastoma8; and the performance of solid organ transplantations for lung, liver, cardiac or …

Massive hemoptysis due to Rasmussen aneurysm: detection with helicoidal CT angiography and successful steel coil embolization.

ObjectiveTo present the successful management of two cases of massive hemoptysis related to pulmonary aneurysms in patients with active tuberculosis.Design and settingRetrospective study in the respiratory intensive care unit (ICU) of a university hospital.PatientsBetween July 1996 and January 2002, 46 cases of hemoptysis related to active tuberculosis needed ICU admission. In two cases, pulmonary aneurysm was the source of bleeding.ResultsDiagnosis was suspected on enhanced CT scan and confirmed by pulmonary angiograms. Transcatheter occlusion of pulmonary arterial circulation was successful. Both patients were alive at 1-year follow-up.ConclusionsMassive hemoptysis occurring in patients with active tuberculosis could arise from pulmonary aneurysms. In such cases, bronchial artery embolization is ineffective. Before referring those patients for emergency surgery, an alternative strategy using angiographic study and transcatheter occlusion of pulmonary arterial circulation might be of interest.

Early Chest Computed Tomography Scan to Assist Diagnosis and Guide Treatment Decision for Suspected Community-acquired Pneumonia

RATIONALE Clinical decision making relative to community-acquired pneumonia (CAP) diagnosis is difficult. Chest radiograph is key in establishing parenchymal lung involvement. However, radiologic performance may lead to misdiagnosis, rendering questionable the use of chest computed tomography (CT) scan in patients with clinically suspected CAP. OBJECTIVES To assess whether early multidetector chest CT scan affects diagnosis and management of patients visiting the emergency department with suspected CAP. METHODS A total of 319 prospectively enrolled patients with clinically suspected CAP underwent multidetector chest CT scan within 4 hours. CAP diagnosis probability (definite, probable, possible, or excluded) and therapeutic plans (antibiotic initiation/discontinuation, hospitalization/discharge) were established by emergency physicians before and after CT scan results. The adjudication committee established the final CAP classification on Day 28. MEASUREMENTS AND MAIN RESULTS Chest radiograph revealed a parenchymal infiltrate in 188 patients. CAP was initially classified as definite in 143 patients (44.8%), probable or possible in 172 (53.8%), and excluded in 4 (1.2%). CT scan revealed a parenchymal infiltrate in 40 (33%) of the patients without infiltrate on chest radiograph and excluded CAP in 56 (29.8%) of the 188 with parenchymal infiltrate on radiograph. CT scan modified classification in 187 (58.6%; 95% confidence interval, 53.2-64.0), leading to 50.8% definite CAP and 28.8% excluded CAP, and 80% of modifications were in accordance with adjudication committee classification. Because of CT scan, antibiotics were initiated in 51 (16%) and discontinued in 29 (9%), and hospitalization was decided in 22 and discharge in 23. CONCLUSIONS In CAP-suspected patients visiting the emergency unit, early CT scan findings complementary to chest radiograph markedly affect both diagnosis and clinical management. Clinical trial registered with www.clinicaltrials.gov (NCT 01574066).

Results of chemotherapy in 30 AIDS patients with symptomatic pulmonary Kaposi's sarcoma.

BACKGROUND--The aim of this study was to report the effects of a three-drug chemotherapy regimen in patients with symptomatic AIDS-related pulmonary Kaposis sarcoma and to analyse prognostic factors for survival. METHODS--Thirty consecutive HIV seropositive patients with respiratory symptoms and proven pulmonary Kaposis sarcoma were treated with the same therapeutic regimen comprising adriamycin (30 mg/m2), bleomycin (10 mg/m2), and vincristine (2 mg) administered intravenously once every four weeks. RESULTS--Two patients died during the first course of chemotherapy. In the other 28 cases dyspnoea improved and Pao2 rose despite minimal (n = 17) or no (n = 11) improvement in the chest radiographic appearance. The median survival from the beginning of chemotherapy was 6.5 months. Poor prognostic factors for survival were: (1) absence of cutaneous Kaposis sarcoma; (2) previous opportunistic infection; (3) CD4 cell count < 100/microliters; (4) leucocytes < 3500/microliters; (5) haemoglobin < 10 g/dl; and (6) absence of radiological response. Of the 28 patients 24 experienced at least one episode of neutropenia which was associated with bacterial infection in 16 cases. CONCLUSIONS--Chemotherapy may improve respiratory impairment in patients with extensive pulmonary Kaposis sarcoma but the outcome remains poor. The efficacy of chemotherapy may be limited by neutropenia.

Improvement of Symptomatic Human Immunodeficiency Virus-Related Lymphoid Interstitial Pneumonia in Patients Receiving Highly Active Antiretroviral Therapy

To analyze the impact of highly active antiretroviral therapy on lymphoid interstitial pneumonia (LIP), we reviewed the medical files of 5 human immunodeficiency virus (HIV)-infected patients in whom LIP was diagnosed during 1996-2001 who had never previously received antiretroviral treatment. Patients were mildly immunosuppressed at the time of diagnosis of LIP but had high plasma HIV loads and marked circulating and pulmonary CD8 hyperlymphocytosis. All patients improved clinically, radiologically, and functionally; improvement was accompanied by a drastic reduction in the virus load and an increase in the CD4 lymphocyte count.

Use of bronchoalveolar lavage in the evaluation of methotrexate lung disease.

The results of bronchoalveolar lavage in three patients with a presumptive diagnosis of methotrexate induced lung disease are presented. Lavage fluid was characterised by the presence of large numbers of lymphocytes, which in two patients were predominantly lymphocytes of the T8 phenotype. These findings further support the hypothesis that immune mediated mechanisms may play a part in the pathogenesis of this disorder in some patients, and indicate that bronchoalveolar lavage may be helpful in the evaluation of patients suspected of having methotrexate induced lung disease.

Pulmonary melioidosis in Cambodia: a prospective study.

BackgroundMelioidosis is a disease caused by Burkholderia pseudomallei and considered endemic in South-East Asia but remains poorly documented in Cambodia. We report the first series of hospitalized pulmonary melioidosis cases identified in Cambodia describing clinical characteristics and outcomes.MethodsWe characterized cases of acute lower respiratory infections (ALRI) that were identified through surveillance in two provincial hospitals. Severity was defined by systolic blood pressure, cardiac frequency, respiratory rate, oxygen saturation and body temperature. B. pseudomallei was detected in sputum or blood cultures and confirmed by API20NE gallery. We followed up these cases between 6 months and 2 years after hospital discharge to assess the cost-of-illness and long-term outcome.ResultsDuring April 2007 - January 2010, 39 ALRI cases had melioidosis, of which three aged ≤2 years; the median age was 46 years and 56.4% were males. A close contact with soil and water was identified in 30 patients (76.9%). Pneumonia was the main radiological feature (82.3%). Eleven patients were severe cases. Twenty-four (61.5%) patients died including 13 who died within 61 days after discharge. Of the deceased, 23 did not receive any antibiotics effective against B. pseudomallei. Effective drugs that were available did not include ceftazidime. Mean total illness-related costs was of US