Amiodarone Pneumonitis

Amiodarone (Am) pneumonitis is currently a common and potentially severe adverse reaction, the accurate diagnosis of which remains difficult to establish. Objectives: To determine the contribution of bronchoalveolar lavage (BAL) in the diagnostic workup of patients suspected of having Am pneumonitis. Methods: Diagnosis of Am pneumonitis was established on the basis of (1) development of recent symptoms and pulmonary opacities while receiving the drug, (2) exclusion of other possible causes, and (3) improvement following cessation of Am and/or steroid therapy. (4) Confirmatory changes were obtained by histopathologic examination in eight cases. BAL was performed in each patient at the time o…

Le site de pathologie iatrogène pneumotox : données métriques sur les tableaux et médicaments, intéressant potentiellement l’allergologue

Introduction En aout 2018 a ete installee une fonctionnalite de mesure de l’activite sur Pneumotox evaluant le taux de consultation des differents medicaments, tableaux cliniques, ainsi que l’imagerie et l’histologie, de meme que les pays utilisateurs et villes d’origine des utilisateurs, en conformite avec la RGPD. Resultats Au 8 janvier 2019, sur 5 mois, 35 720 connexions ont ete recensees, 9740 (33,6 %) en provenance des Etats-Unis, 3760 de France, 1830 d’Allemagne, 1412 du Canada, 1340 du Bresil, 1320 des Pays-Bas, 1160 du Royaume-Uni, 1090 d’Espagne, 821 de Suisse, 611 d’Italie, 576 de Turquie et 430 de Belgique. Ces chiffres sont a relativiser en fonction de la population du pays, du …

Atteinte trachéobronchique isolée de la polychondrite atrophiante : intérêt du TEP-scanner

Resume Introduction La polychondrite atrophiante est une maladie rare et grave caracterisee par une atteinte inflammatoire et multifocale des cartilages. Le diagnostic bien qu’urgent est difficile lorsque l’atteinte tracheobronchique est isolee. Observation Nous rapportons le cas d’une femme de 55 ans aux antecedents recents d’episodes febriles non infectieux accompagnes d’un syndrome inflammatoire biologique et corticosensibles. L’auscultation, les explorations fonctionnelles respiratoires et le scanner thoracique evoquaient la presence d’une tracheobronchomalacie. Une polychondrite atrophiante etait suspectee sans pouvoir etre confirmee sur le plan histologique et biologique, ce d’autant …

The small heat-shock protein α B-crystallin is essential for the nuclear localization of Smad4: impact on pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by the proliferation of myofibroblasts and the accumulation of extracellular matrix (ECM) in the lungs. TGF-β1 is the major profibrotic cytokine involved in IPF and is responsible for myofibroblast proliferation and differentiation and ECM synthesis. αB-crystallin is constitutively expressed in the lungs and is inducible by stress, acts as a chaperone and is known to play a role in cell cytoskeleton architecture homeostasis. The role of αB-crystallin in fibrogenesis remains unknown. The principal signalling pathway involved in this process is the Smad-dependent pathway. We demonstrate here that αB-crystallin is stron…

The lung in inflammatory bowel disease.

Pulmonary hypertension associated with ponatinib therapy

IF 8.332; International audience; A case of pulmonary hypertension associated with ponatinib therapy in a chronic myelogenous leukaemia patient.

Pneumotox : données métriques sur les médicaments, tableaux, et pays utilisateurs. À la recherche de zones silencieuses

Introduction En aout 2018 a ete installee une mesure des medicaments, tableaux cliniques, d’imagerie ou d’histologie ainsi que les pays utilisateurs et villes d’origine, apres accord de l’utilisateur en conformite avec la RGPD. Resultats Au 5 septembre 2018, soit sur 26 jours, 4320 connexions ont ete recensees, 1645 (38,1 %) des Etats-Unis, 450 de France, 272 d’Allemagne, 242 du Canada, 201 des Pays-Bas, 201 du Bresil, 178 du Royaume-Uni, 148 d’Espagne, 120 de Suisse, 72 de Belgique et 59 d’Italie. Chiffres a interpreter au regard d’un taux de rebond de 18 %, et en fonction de la population, du nombre de medecins du pays, et de la periode estivale (Chiffres seront actualises pour le CPLF 20…

Metabolism of nilutamide in rat lung.

Nilutamide is a non-steroidal anti-androgen drug proposed in the treatment of metastatic prostatic carcinoma. Its therapeutic effects are overshadowed by the occurrence of adverse reactions, mediated by mechanisms that remain elusive. To elucidate possible mechanisms for nilutamide toxicity, we investigated the metabolism of nilutamide in rat lung homogenates, in subcellular fractions and in freshly isolated cells. In whole lung homogenates, the nitro group of nilutamide was reduced to the amine and hydroxylamine moieties. These conversions occurred exclusively in the absence of dioxygen, were increased by the addition of FMN, FAD, or NADPH. Reductive metabolism of nilutamide to the amine a…

Iatrogenic pulmonary lesions.

Treatment of patients often includes the administration of medications and sometimes radiation. While the intent is to treat an underlying condition, in some cases, adverse effects occur due to these agents. Most of these adverse effects are mild, however, some can be severe and life-threatening. Furthermore, while these effects are often reversible upon cessation of exposure, especially if the inciting agent is recognized and withdrawn early, others might be permanent or even progressing. Most common histopathologic findings in drug-induced interstitial lung disease include nonspecific interstitial pneumonia (cellular and/or fibrotic), organizing pneumonia with or without bronchiolitis, eo…

Pleuropulmonary Changes Induced by Drugs in Patients with Hematologic Diseases

Patients with hematologic diseases who are being treated with therapy drugs, or receive radiation therapy or blood transfusions may develop a host of potentially fatal infectious and noninfectious pulmonary complications [1]. The increased complexity of multimodality and high-dose treatment regimens with the intended benefit of augmented antineoplastic efficacy and prolonged disease-free survival, the use of a panel of novel drugs to treat malignant and nonmalignant hematologic conditions (e.g., azacytidine, bortezomib, cladribine, dasatinib, fludarabine, imatinib, lenalidomide, rituximab, and thalidomide), total body irradiation (TBI) and hematopietic stem cell transplantation (HSCT) have …

The Lung in Inflammatory Bowel Disease†

Respiratory involvement in patients with inflammatory bowel disease (IBD) has been reported mainly since 1976. This form of involvement should clearly be separated from interstitial lung disease due to sulfasalazine or mesalamine, although the distinction may be difficult in some cases. We report the data of an ongoing Registry containing 33 cases (23 cases receiving no drug therapy) with ulcerative colitis or, less often, Crohn's disease, who developed varied bronchopulmonary problems. In several cases, the exact diagnosis and the relation of the bronchopulmonary disease to IBD had not been established for many years, thus delaying effective treatment with steroids. In most cases (28/33), …

Une cause rare d’opacités alvéolaires : maladie de Waldenström à localisation pulmonaire

Resume Introduction Les localisations pulmonaires de la maladie de Waldenstrom sont rares. Observation Nous rapportons le cas d’une femme de 71 ans presentant une toux chronique, associee a des opacites alveolaires disseminees persistantes apres plusieurs antibiotherapies. L’examen clinique etait normal. Le diagnostic de maladie de Waldenstrom etait suspecte devant un pic monoclonal de type IgM (immunoglobuline M) a l’electrophorese des proteines plasmatiques avec immunofixation et la presence d’une population B monoclonale a l’immunophenotypage du lavage broncho-alveolaire. Ce diagnostic etait confirme par le resultat de la biopsie osteomedullaire. La patiente etait traitee par chimiothera…

Haemoptysis: a frequent diagnostic challenge

We appreciate and agree with the comments of M. Mondoni and colleagues, that the results of the ongoing prospective Italian multicentre trial ([www.ClinicalTrial.gov][1] identifier [NCT02045394][2]) will be of considerable interest for the management of haemoptysis, a frequent and severe symptom, especially since there is no clear consensus concerning aetiology and treatment. Interestingly, beyond determining the prevalence of diseases that may present with haemoptysis, their epidemiological results will be analysed according to the severity of the symptom. More importantly, their trial will hopefully make it possible to analyse the sensitivity and specificity of complementary tests, such a…

Distribution of nitroreductive activity toward nilutamide in rat.

Abstract Nilutamide is a pneumotoxic and hepatotoxic nitroaromatic (R-NO 2 ) antiandrogen used in the treatment of prostate carcinoma in man. Previously, we established that in the rat lung, the drug is metabolized into the corresponding hydroxylamine (R-NHOH) and amine (R-NH 2 ) derivatives. These results evidenced a cytosolic oxygen-sensitive (type II) nitroreductase activity in lung. In the present studies, we extended the characterization of nilutamide metabolism in liver, brain, kidney, heart, blood, intestine (small, cecum, and large, and their respective luminal contents) of male Sprague–Dawley rats. Subcellular fractions for all tissues (except blood) examined (postmitochondrial, cy…

Transient Pulmonary Infiltrates during Treatment with Anti-Thymocyte Globulin

We report the case of a 54-year-old woman with aplastic anemia, who developed transient pulmonary infiltrates following intravenous infusion of rabbit antithymocyte globulin (ATG) for 3 days. There was no other explanation than the infusion of ATG for the infiltrates. Rechallenge with ATG induced the recurrence of opacities on the chest radiograph. Although rarely involved with only 4 previous reports, ATG should be included in the list of drugs capable of inducing pulmonary infiltrates.

Knowledge Gaps and Research Priorities in Immune Checkpoint Inhibitor–related Pneumonitis. An Official American Thoracic Society Research Statement

Rationale: Immune checkpoint inhibitors (ICIs) have revolutionized cancer care but are associated with unique adverse events, including potentially life-threatening pneumonitis. The diagnosis of ICI-pneumonitis is increasing; however, the biological mechanisms, clinical and radiologic features, and the diagnosis and management have not been well defined. Objectives: To summarize evidence, identify knowledge and research gaps, and prioritize topics and propose methods for future research on ICI-pneumonitis. Methods: A multidisciplinary group of international clinical researchers reviewed available data on ICI-pneumonitis to develop and refine research questions pertaining to ICI-pneumonitis.…

Usefulness of transcutaneous PCO2to assess nocturnal hypoventilation in restrictive lung disorders

Background and objectiveNocturnal hypoventilation is now an accepted indication for the initiation of non-invasive ventilation. Nocturnal hypoventilation may be an under diagnosed condition in chronic respiratory failure. The most appropriate strategy to identify sleep hypoventilation is not yet clearly defined. In clinical practice, it is indirectly assessed using nocturnal pulse oximetry (NPO) and morning arterial blood gases (mABG). Even though continuous transcutaneous carbon dioxide partial pressure (TcPCO2) monitoring is theoretically superior to NPO plus mABG, it is not routinely used. We aimed to prospectively compare NPO plus mABG with nocturnal TcPCO2 for the detection of alveolar…

Amiodarone pulmonary toxicity

The amount of literature on amiodarone pulmonary toxicity (APT) peaked in 1983-1984 with several hundred cases reported cumulatively, and declined thereafter. Since the mid-1990s, publications have increased, which suggests that APT remains a current problem in clinical practice. Amiodarone remains difficult to diagnose noninvasively, and although the outcome is good in the majority of patients, not all cases of APT can be controlled satisfactorily.

Activité du conseil médical en environnement intérieur (CMEI) en Bourgogne : évaluation auprès des médecins et des patients

Resume Depuis decembre 2009, les pneumologues et allergologues bourguignons peuvent faire appel a un conseiller medical en environnement interieur (CMEI). Les interventions, gratuites pour le patient, sont realisees sur recommandation medicale apres tests cutanes systematiques. Objectifs Decrire les indications et la repartition des prescriptions et mesurer l’impact de la visite a six mois sur les 100 premiers patients et a 18 mois aupres des medecins. Methode Entretien telephonique des 67 medecins (prescripteurs ou non) sur leurs motivations et/ou leurs attentes et des 100 premiers patients sur le suivi des recommandations. Resultats Soixante-dix pour cent des medecins ont repondu ( n  = 4…

094 Transition épithélio-mésenchymateuse (TEM) lors de la fibrose pleurale induite par Transforming Growth Factor (TGF)-1

017 Fibrose pleurale progressive induite par le transfert du gène de Transforming Growth Factor (TGF)-β1 à la plèvre

Introduction De nombreux agents ou toxines (medicaments, radiation, amiante, maladies infectieuses) sont responsables de fibrose pleurale, pathologie invalidante entrainant un syndrome restrictif parfois severe. Les mecanismes conduisant a cette fibrose pleurale ont ete jusqu’ici peu explores. TGF-β est un facteur cle de l’initiation et de la progression de la fibrose dans de nombreux organes. Le transfert transitoire du gene de TGF-β1 actif (AdTGF-β1) aux poumons de rat, a l’aide d’adenovirus induit une fibrose pulmonaire severe et progressive ( J Clin Invest 1997; 100: 768-76). Nous avons developpe un modele de fibrose pleurale par transfert du gene de TGF-β1 au mesothelium pleural afin d…

Pleuroparenchymal fibroelastosis: one more walk on the wild side of drugs?

In this issue of the European Respiratory Journal , Beynat-Mouterde et al. [1] report on six young adults (three of whom were female) who developed a clinical imaging pattern of predominant upper lobe fibrosis with apical pneumothoraces (fig. 1). Presentation in all six patients was similar with cough, dyspnoea, occasional chest pain and weight loss. Imaging was distinctive and showed a cephalad, irregular, pleural-based thickening that encroached on the lung bilaterally. Five patients presented with “platythorax” (fig. 2), a preferential reduction in the anterio-posterior diameter of the chest wall. In all patients, severe restrictive or restrictive-obstructive lung dysfunction progressed …

Interstitial lung disease induced by drugs and radiation.

An ever-increasing number of drugs can reproduce variegated patterns of naturally occurring interstitial lung disease (ILD), including most forms of interstitial pneumonias, alveolar involvement and, rarely, vasculitis. Drugs in one therapeutic class may collectively produce the same pattern of involvement. A few drugs can produce more than one pattern of ILD. The diagnosis of drug-induced ILD (DI-ILD) essentially rests on the temporal association between exposure to the drug and the development of pulmonary infiltrates. The histopathological features of DI-ILD are generally consistent, rather than suggestive or specific to the drug etiology. Thus, the diagnosis of DI-ILD is mainly made by …

Haemoptysis in adults: a 5-year study using the French nationwide hospital administrative database.

Haemoptysis is a serious symptom with various aetiologies. Our aim was to define the aetiologies, outcomes and associations with lung cancer in the entire population of a high-income country.This retrospective multicentre study was based on the French nationwide hospital medical information database collected over 5 years (2008–2012). We analysed haemoptysis incidence, aetiologies, geographical and seasonal distribution and mortality. We studied recurrence, association with lung cancer and mortality in a 3-year follow-up analysis.Each year, ∼15 000 adult patients (mean age 62 years, male/female ratio 2/1) were admitted for haemoptysis or had haemoptysis as a complication of their hospital s…

Iatrogenic lung disease

Inhibition of HSP27 blocks fibrosis development and EMT features by promoting Snail degradation

Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by myofibroblast proliferation. Transition of epithelial/mesothelial cells into myofibroblasts [epithelial-to-mesenchymal transition (EMT)] occurs under the influence of transforming growth factor (TGF)-β1, with Snail being a major transcription factor. We study here the role of the heat-shock protein HSP27 in fibrogenesis and EMT. In vitro, we have up- and down-modulated HSP27 expression in mesothelial and epithelial cell lines and studied the expression of different EMT markers induced by TGF-β1. In vivo, we inhibited HSP27 with the antisense oligonucleotide OGX-427 (in phase II clinical trials as anticancer agent)…

Drug-Induced Respiratory Disease in Connective Tissue Diseases

Publisher Summary This chapter discusses drug-induced respiratory disease in connective tissue diseases. Drug-induced lung diseases (DILDs) vary in severity from mild to life threatening. Generally, DILDs subside upon drug discontinuance, and leave permanent sequelae in a minority of patients. Less frequently, DILDs persist unabated, or progress despite drug withdrawal, requiring specific management. Drugs used in connective tissue diseases (CTDs) can produce a constellation of pulmonary and systemic reactions. These can mimic pulmonary involvement from CTD, a systemic disease, or an infection, and are difficult to prevent, predict, and diagnose. Maintaining a high index of suspicion enable…

Drug-induced and iatrogenic infiltrative lung disease.

At present more than 350 drugs are known to cause injury of the lung parenchyma,upper and lower airways, pulmonary circulation, pleura, mediastinum, lymph nodes,and neuromuscular system. Infiltrative lung disease (ILD) is the most common pattern of drug-induced injury. This article, which is clinically oriented rather than drug oriented, reviews the patterns of ILD produced by therapeutic drugs and radiation therapy.