Huguette Lioté

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.

Role for interferon-gamma release assays in latent tuberculosis screening before TNF-α antagonist therapy.

TNF-α antagonist therapy is associated with a risk of severe, extrapulmonary, disseminated tuberculosis, which is fatal in 10% of cases. The risk of tuberculosis is increased four-fold in patients on TNF-α antagonist therapy. The main risk factors are a history of untreated or inadequately treated primary tuberculosis, recent contact with a tuberculosis patient, and residence in or travel to a high-endemicity region. Infection surveillance agencies throughout the world have issued recommendations to ensure the detection and treatment of latent tuberculosis before TNF-α antagonist initiation. These recommendations have returned the incidence of tuberculosis to the level seen before the introduction of TNF-α antagonists. Nevertheless, there is still room for improvement. Recommendations about latent tuberculosis screening include the use of tuberculin skin tests. However, these tests are positive in individuals vaccinated with the BCG vaccine, which leads to overuse of tuberculosis chemoprophylaxis and, therefore, to unnecessary patient exposure to hepatotoxic effects. Furthermore, tuberculin skin tests may be falsely negative in immunosuppressed patients, leading to underuse of tuberculosis prophylaxis. These shortcomings of tuberculin skin tests have generated interest in interferon-gamma release assays (IGRAs). In patients with overt tuberculosis, IGRAs are more sensitive and more specific than tuberculin skin tests. However, the accuracy of IGRAs for diagnosing latent tuberculosis remains unknown, because no reference standard is available. In addition, patients taking immunosuppressant agents to treat systemic disease may exhibit anergia, which complicates the interpretation of IGRAs. Until additional data become available, caution requires that IGRAs be used only when a positive or negative result, as assessed on a case-by-case basis, will help to decide whether tuberculosis chemoprophylaxis is in order.

Formalisation de la démarche diagnostique des pneumopathies médicamenteuses : le système PneumoDoc

Resume La pneumopathie medicamenteuse (PM), souvent evoquee, reste un diagnostic difficile car les medicaments pneumotoxiques sont nombreux, la clinique est heterogene, et il n’y a pas de critere diagnostique formel. PneumoDoc est un systeme informatise qui propose une formalisation de la demarche diagnostique du pneumologue devant un tableau evocateur sur la base d’arguments chronologiques, semiologiques, d’imagerie et cytologiques (lavage broncho-alveolaire). Ces criteres dits « intrinseques » sont croises avec les criteres extrinseques tires de la litterature, en particulier Pneumotox. Ils sont renseignes sous forme de questions/reponses successives a choix ferme. Un recapitulatif final permet de visualiser l’ensemble des donnees caracterisant la situation clinique observee. Le logiciel estime la probabilite de PM selon une des cinq modalites suivantes : incompatible, douteux, compatible, suggestif, tres suggestif. La multiplicite des drogues, l’intrication a une pathologie cardiopulmonaire et l’absence de cas rapporte constituent les limites du systeme.Establishing the diagnosis of drug-related pulmonary disease (DRPD) remains a difficult task because of the large number of drug-related toxic situations and the variety of clinical presentations. PneumoDoc is a computer-based support system designed to facilitate the diagnosis of lung disease using chronological, clinical, imaging, and cytological (alveolar lavage) input. These intrinsic items are crosschecked against extrinsic items reported in the literature (Pneumotox). Data input is in the form of yes-no questions. The final output displays the characteristic features of the observed clinical situation and calculates the probability of DRPD defined in five categories: incompatible, doubtful, compatible, suggestive, and highly suggestive. Use of multiple drugs, interaction with cardiopulmonary disease, and the absence of reported cases are limitations of the system.

The Relationship Between Introduction of American Society of Clinical Oncology Guidelines and the Use of Colony-Stimulating Factors in Clinical Practice in a Paris University Hospital

BACKGROUND Clinical practice guidelines are issued periodically by professional medical societies or committees to assist practitioners in clinical decision making. However, it is unclear whether such guidelines have any lasting impact on clinical practice. OBJECTIVE The purpose of this study was to assess the impact of the American Society of Clinical Oncology (ASCO) guidelines regarding use of hematopoietic colony-stimulating factors (CSF) on cancer care in a university hospital in Paris. METHODS The study was performed at Hĵpital Tenon, an 830-bed university hospital in Paris, in 1996 and 1997, both before and after the ASCO guidelines were implemented. The guidelines were first disseminated as a continuing medical education program and then actively implemented using a CSF prescription order form summarizing the guidelines. This form had to be used during the patient consultation and was sent to the Hĵpital Tenon pharmacy for CSF dispensation. Even if CSF use did not comply with the ASCO guidelines, the pharmacy filled the prescription. Seven other university hospitals in Paris, where the ASCO guidelines were not actively implemented, comprised the control group. The main outcome measure was the proportion of prescriptions in compliance with the 1996 update of the ASCO guidelines. Secondary outcome measures were the proportions of prescriptions in compliance with ASCO guidelines regarding primary prophylactic, secondary prophylactic, and therapeutic CSF administration. RESULTS Before implementation of the ASCO guidelines, CSF use in compliance with the guidelines was 39% (41/105) at the study site and 31% (16/51) at the control sites (P > 0.05). Six months after dissemination and implementation of the guidelines, the proportion of CSF prescriptions complying with ASCO guidelines increased significantly versus baseline (P = 0.003) in the study group, to 61% (50/82). However, even after the guidelines were implemented, compliance with guidelines on primary prophylactic CSF administration did not change significantly versus before implementation in the study group (12% [5/41] before implementation vs 6% [2/33] after implementation; P > 0.05). CONCLUSIONS The results suggest an association between the active implementation strategy (continuing medical education and CSF prescription reminder form) and physician compliance with the ASCO guidelines. Implementation of the ASCO guidelines appears to have had some impact on medical practice.

Computer-Aided Assessment of Drug-Induced Lung Disease Plausibility

Drug-induced lung disease (DILD), often suspected in pneumology, is still a diagnostic challenge because of the ever increasing number of pneumotoxic drugs and the large diversity of observed clinical patterns. As a result, DILD can only be evoked as a plausible diagnosis after the exclusion of all other possible causes. PneumoDoc is a computer-based decision support that formalises the evaluation process of the drug-imputability of a lung disease. The knowledge base has been structured as a two-level decision tree. Patient-specific chronological and semiological criteria are first examined leading to the assessment of a qualitative intrinsic DILD plausibility score. Then literature-based data including the frequency of DILD with a given drug and the frequency of the observed clinical situation among the clinical patterns reported with the same drug are evaluated to compute a qualitative extrinsic DILD plausibility score. Based on a simple multimodal qualitative model, extrinsic and intrinsic scores are combined to yield an overall DILD plausibility score.