P. Bonniaud

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 the meticulous exclusion of all other possible causes. Drug dechallenge produces measurable improvement in symptoms and imaging in the majority of patients, whereas corticosteroid therapy is indicated if symptoms are present or drug dechallenge is without an effect. Rechallenge is justified in a minority of patients, and is discouraged for diagnostic purposes only. Pneumotox® (www.pneumotox.com) provides updated information on drug-induced respiratory disease.

Monitorización de las fugas en ventilación no invasiva

La ventilacion por mascarilla nasal ha dado sobradas pruebas de su eficacia. Sin embargo, en ciertos casos los resultados no son los esperados. Tres mecanismos pueden explicar estos fallos: apertura bucal, desincronizacion paciente-respirador y disminucion de la permeabilidad de la via respiratoria superior. Estos pueden detectarse por su manifestacion ultima: las fugas en el circuito, que reducen la eficacia de la ventilacion (fallo de presurizacion, disfuncion del trigger inspiratorio y prolongacion del tiempo inspiratorio), alteran la calidad del sueno y producen efectos adversos e intolerancia al tratamiento. Proponemos aqui varias tecnicas de deteccion de fugas y sus consecuencias practicas. Se sometio a 177 pacientes, con resultados de la ventilacion inferiores a los esperados (clinicos, gasometricos o poligraficos), a 310 procedimientos de deteccion de fugas, con montajes que variaron segun la modalidad ventilatoria y el mecanismo fisiopatologico juzgado como responsable. Se detectaron fugas significativas en 132 pacientes (76%), lo cual impuso modificaciones terapeuticas para optimizar los resultados. Presentamos un metodo de aplicacion practica en casos en que se asista a resultados insuficientes de la ventilacion. La deteccion de fugas bajo tratamiento ofrece la posibilidad de establecer la causa probable del fracaso, comprender el mecanismo fisiopatologico potencialmente responsable e intervenir en consecuencia.

Revisiting the systemic vasculitis in eosinophilic granulomatosis with polyangiitis (Churg-Strauss) ☆: A study of 157 patients by the Groupe d'Etudes et de Recherche sur les Maladies Orphelines Pulmonaires and the European Respiratory Society Taskforce on eosinophilic granulomatosis with polyangiitis (Churg-Strauss)

OBJECTIVE To guide nosology and classification of patients with eosinophilic granulomatosis with polyangiitis (EGPA) based on phenotype and presence or absence of ANCA. METHODS Organ manifestations and ANCA status were retrospectively analyzed based on the presence or not of predefined definite vasculitis features or surrogates of vasculitis in patients asthma, eosinophilia, and at least one systemic organ manifestation attributable to systemic disease. RESULTS The study population included 157 patients (mean age 49.4±14.1), with a follow-up of 7.4±6.4years. Patients with ANCA (31%) more frequently had weight loss, myalgias, arthralgias, biopsy-proven vasculitis, glomerulonephritis on biopsy, hematuria, leukocytoclastic capillaritis and/or eosinophilic infiltration of arterial wall on biopsy, and other renal disease. A total of 41% of patients had definite vasculitis manifestations (37%) or strong surrogates of vasculitis (4%), of whom only 53% had ANCA. Mononeuritis multiplex was associated with systemic vasculitis (p=0.005) and with the presence of ANCA (p<0.001). Overall, 59% of patients had polyangiitis as defined by definite vasculitis, strong surrogate of vasculitis, mononeuritis multiplex, and/or ANCA with at least one systemic manifestation other than ENT or respiratory. Patients with polyangiitis had more systemic manifestations including arthralgias (p=0.02) and renal disease (p=0.024), had higher peripheral eosinophilia (p=0.027), and a trend towards less myocarditis (p=0.057). Using predefined criteria of vasculitis and surrogates of vasculitis, ANCA alone were found to be insufficient to categorise patients with vasculitis features. CONCLUSION We suggest a revised nomenclature and definition for EGPA and a new proposed entity referred to as hypereosinophilic asthma with systemic (non vasculitic) manifestations.

Bleomycin induces pleural and subpleural fibrosis in the presence of carbon particles

The pathological changes in idiopathic pulmonary fibrosis (IPF) typically start in subpleural lung regions, a feature that is currently not explained. IPF, as well as bleomycin-induced lung fibrosis, are more common in smokers. We hypothesised that carbon particles, which are major components of cigarette smoke that are transported to alveoli and pleural surface, might be involved in the development of subpleural fibrosis through interaction with pleural mesothelial cells. Carbon particles were administered to mice in combination with bleomycin through intratracheal and/or intrapleural injection and fibrosis was assessed using histomorphometry. Carbon administered to the chest cavity caused severe pleural fibrosis in the presence of bleomycin, whereas bleomycin alone had no fibrogenic effect. The pleural response was associated with progressive fibrosis in subpleural regions, similar to IPF in humans. Matrix accumulation within this area evolved through mesothelial-fibroblastoid transformation, where mesothelial cells acquire myofibroblast characteristics. In contrast, carbon did not exaggerate bleomycin-induced pulmonary fibrosis after combined intratracheal administration. This represents a novel approach to induce a robust experimental model of pleural fibrosis. It also suggests that carbon particles might be involved as a cofactor in the initiation and/or progression of (subpleural) pulmonary and pleural fibrosis. Mesothelial cells appear to be critical contributors to this fibrotic process.

Usefulness of transcutaneous PCO2 to assess nocturnal hypoventilation in restrictive lung disorders.

Nocturnal 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 hypoventilation in a cohort of patients with chronic restrictive respiratory dysfunction.

Respiratory manifestations of eosinophilic granulomatosis with polyangiitis (Churg-Strauss).

The respiratory manifestations of eosinophilic granulomatosis with polyangiitis (EGPA) have not been studied in detail. In this retrospective multicentre study, EGPA was defined by asthma, eosinophilia and at least one new onset extra-bronchopulmonary organ manifestation of disease. The study population included 157 patients (mean±sd age 49.4±14.1 years), with a mean±sd blood eosinophil count of 7.4±6.4×109 L−1 at diagnosis. There was a mean±sd of 11.8±18.2 years from the onset of asthma to the diagnosis of EGPA, of 1.4±8.4 years from the first onset of peripheral eosinophilia to the diagnosis of EGPA, and of 7.4±6.4 years from EGPA diagnosis to the final visit. Despite inhaled and oral corticosteroid treatment, the severity of asthma increased 3–6 months before the onset of the systemic manifestations. Asthma was severe in 57%, 48%, and 56% of patients at diagnosis, at 3 years, and at the final visit, respectively. Persistent airflow obstruction was present in 38%, 30%, and 46% at diagnosis, at 3 years, and at the final visit, respectively. In EGPA, asthma is severe, antedates systemic manifestations by a mean of 12 years, and progresses to long-term persistent airflow obstruction despite corticosteroids in a large proportion of patients, which affects long-term management and morbidity. In EGPA, asthma is severe and progresses to persistent airflow obstruction despite corticosteroids in many patients http://ow.ly/8uf8301KSoT

Syndrome d’hypersensibilité médicamenteuse avec manifestations systémiques sévères après traitement par minocycline

Resume Introduction L’atteinte pulmonaire du syndrome d’hypersensibilite medicamenteuse (SHM) ou Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) est rare. Nous rapportons un cas survenu apres prise de minocycline. Observation Un patient de 19 ans, d’origine reunionnaise, au seul antecedent d’acne traitee depuis 28 jours par minocycline 100 mg/j, etait admis en reanimation pneumologique pour detresse respiratoire aigue febrile (40 C) associee a des adenopathies peripheriques, une hepato-splenomegalie, une eosinophilie sanguine (1 640/mm3) et sur la radiographie thoracique, des opacites alveolaires bilaterales peripheriques. L’hypoxemie severe (47 mmHg) et l’apparition brutale d’une agitation majeure avaient impose une sedation et une ventilation invasive. Des defaillances hepatique et renale severes etaient apparues rapidement. Le diagnostic de SHM a la minocycline pose, une corticotherapie intraveineuse (2 mg/kg) etait debutee a J1. L’erythrodermie n’etait survenue qu’a J3. L’evolution etait inquietante pendant 6 semaines avec des poussees successives d’atteintes viscerales. La serologie pour Human Herpes Virus 6 (HHV6) initialement negative etait devenue positive. A un an, apres arret progressif de la corticotherapie, le patient allait bien, sans sequelle. Conclusions Cette observation est remarquable par l’extreme gravite des defaillances multiviscerales. Le SHM doit etre reconnu par le Pneumologue car l’atteinte pulmonaire peut etre inaugurale et preceder les signes cutanes.

Updated guidelines (2015) for management and monitoring of adult and adolescent asthmatic patients (from 12 years and older) of the Société de Pneumologie de Langue Française (SPLF) (Full length text)

Revue des Maladies Respiratoires - In Press.Proof corrected by the author Available online since samedi 16 avril 2016

Embolie pulmonaire de cyanoacrylate après embolisation d’une malformation artérioveineuse

Introduction Les traitements des malformations vasculaires par embolisation utilisent frequemment les colles a interaction biologique en association avec du lipiodol en radiologie interventionnelle. Les difficultes techniques de ces pratiques sont parfois liees a des complications pulmonaires emboliques. Observation Nous rapportons le cas d’une patiente qui, trois jours apres l’embolisation d’une malformation arterioveineuse pelvienne par du N-butyl-2 cyanoacrylate associe a du lipiodol, a presente une douleur thoracique brutale. Seules la radiographie puis la tomodensitometrie sans injection de produit de contraste, montrant des opacites micronodulaires denses, diffuses et centrees sur les axes arteriels pulmonaires, ont permis de poser le diagnostic d’embolies pulmonaires multiples de fragments de colle biologique lipiodolee. En une heure la patiente est spontanement redevenue asymptomatique alors que, six mois apres l’embolisation, les signes radiologiques persistaient. Conclusion Des complications pulmonaires emboliques de colle biologique peuvent survenir au decours du traitement des malformations vasculaires. Associees a du lipiodol, ces emboles ne peuvent etre diagnostiques en tomodensitometrie qu’en l’absence d’injection de produit de contraste. Souvent asymptomatiques mais parfois fatales, ces complications emboliques doivent etre connues des radiologues.

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

INTRODUCTION Pulmonary localized forms of Waldenströms macroglobulinemia are rare. CASE REPORT We report the observation of a 71-year-old woman with chronic cough and persisting alveolar opacities after several courses of antibiotics. Physical examination was unremarkable. Protein electrophoresis identified a monoclonal IgM in the serum. The lymphocyte immunophenotyping from the bronchoalveolar lavage was consistent with a B-cell lymphoma and Waldenströms macroglobulinemia was confirmed by the bone marrow biopsy. Chemotherapy with a combination of rituximab, fludarabine and cyclophosphamide improved the patients symptoms and caused the pulmonary opacities to resolve. We discuss the various clinical and radiological pulmonary manifestations of this slowly progressive hematological condition. CONCLUSION Pulmonary manifestations of Waldenströms macroglobulinemia result in various clinical and radiological patterns. A serum protein electrophoresis should be performed in cases of pleuropulmonary opacities persisting despite antibiotics.