[Anti-IL-5 in severe asthma associated with eosinophilic granulomatosis with polyangiitis. Real-life study]. / Anti-IL-5 dans l'asthme sévère associé à une granulomatose éosinophilique avec polyangéite. Étude en vie réelle.

INTRODUCTION: Eosinophilic granulomatosis with polyangiitis (EGPA) is a form of necrotizing vasculitis affecting small vessels and typically characterized by severe glucocorticoid (GC)-dependent eosinophilic asthma. While mepolizumab, which is indicated at a dose of 100mg/4weeks in severe eosinophilic asthma, has been shown to be an effective treatment for EGPA-related asthma at a dose of 300mg/4weeks, it was only recently approved at this dose. METHODS: This retrospective, single-center, observational study was conducted to investigate over a 5-year period (2014-2019) the effect of mepolizumab 100mg/4weeks at 12months in patients with EGPA and glucocorticoid-dependant severe asthma. Response to treatment was defined as reduction in daily dose of oral corticosteroids to at most 5mg/day or reduction in annual exacerbation by at least 50%. RESULTS: Thirty patients were included, of whom twenty-three were treated (two were not fully evaluable). Among the 21 evaluable treated patients, 13 (62%) had responded at 12months. At baseline, non-responders had lower FEV1 levels and lower blood eosinophil levels than responders. CONCLUSIONS: Mepolizumab at a "severe asthma" dose (100mg/4weeks) is effective in treatment of GC-dependent severe asthma in most patients with EGPA.

[Updated indications and contraindications in 2022 for lung transplantation in France]. / Transplantation pulmonaire en France : actualisation des indications et contre-indications en 2022.

Lung transplantation (LTx) is the last-resort treatment for end-stage respiratory insufficiency, whatever its origin, and represents a steadily expanding field of endeavor. Major developments have been impelled over the years by painstaking efforts at LTx centers to improve donor and recipient selection, and multifaceted attempts have been made to meet the challenges raised by surgical management, perioperative care, and long-term medical complications. The number of procedures has increased, leading to improved post-LTx prognosis. One consequence of these multiple developments has been a pruning away of contraindications over time, which has, in some ways, complicated the patient selection process. With these considerations in mind, the Francophone Pulmonology Society (Société de Pneumology de Langue Française [SPLF]) has set up a task force to produce up-to-date working guidelines designed to assist pulmonologists in managing end-stage respiratory insufficiency, determining which patients may be eligible for LTx, and appropriately timing LTx-center referral. The task force has examined the most recent literature and evaluated the risk factors that continue to limit patient survival after LTx. Ideally, the objectives of LTx are to prolong life while improving quality of life. The guidelines developed by the task force apply to a limited resource and are consistent with the ethical principles described below.

[Take-home messages from the COPD 2021 biennial of the French Society of Respiratory Diseases. Understanding to so as to better innovate]. / Principaux messages de la première Biennale BPCO 2021 de la SPLF. Mieux comprendre pour innover.

INTRODUCTION: The first COPD biennial organized by the French Society of Respiratory Diseases (SPLF) took place on 17 December 2021. STATE OF THE ART: The objective of the biennial was to discuss current knowledge regarding COPD pathophysiology, current treatments, research development, and future therapeutic approaches. PERSPECTIVES: The different lecturers laid emphasis on the complexity of pathophysiologic mechanisms including bronchial, bronchiolar and parenchymal alterations, and also dwelt on the role of microbiota composition in COPD pathenogenesis. They pointed out that addition to inhaled treatments, ventilatory support and endoscopic approaches have been increasingly optimized. The development of new therapeutic pathways such as biotherapy and cell therapy (stem cells…) call for further exploration. CONCLUSIONS: The dynamism of COPD research was repeatedly underlined, and needs to be further reinforced, the objective being to "understand so as to better innovate" so as to develop effective new strategies for treatment and management of COPD.

Patient perspectives following initiation of elexacaftor-tezacaftor-ivacaftor in people with cystic fibrosis and advanced lung disease.

BACKGOUND: Elexacaftor-tezacaftor-ivacaftor partially restores cystic fibrosis transmembrane conductance regulator function, and has been shown to induce significant clinical improvement in patients with at least one Phe508del allele. Yet little data exist on patient perspectives following elexacaftor-tezacaftor-ivacaftor initiation. METHODS: A mixed methods study was conducted using an online 13-item questionnaire (including 9 closed questions and 4 open questions), submitted from July 10th to August 21th 2020 to French patients aged 12 years and older with advanced CF who were treated with elexacaftor-tezacaftor-ivacaftor. Their responses were summarized as numbers (%), and free-text items were analysed using a grounded theory approach. RESULTS: Of 245 patients who started elexacaftor-tezacaftor-ivacaftor in France, 101 (41%) participated. Median [IQR] age was 35 [28-41] years and duration of elexacaftor-tezacaftor-ivacaftor treatment was 4.3 [3.0-5.6] months. Patients generally reported a rapid impact on respiratory symptoms, sleep quality, general well-being and physical self-esteem, and a reduction in overall treatment burden. The majority of patients contrasted treatment burden, symptom severity, depression and a closed future marked by death or transplantation before elexacaftor-tezacaftor-ivacaftor, to renewed and unexpected physical strength, leading to greater self-confidence, autonomy and long-term planning, after treatment initiation. A small number of patients expressed concerns, mainly regarding changes in body representation and/or the fear of becoming dependent on the treatment. CONCLUSION: After initiation of elexacaftor-tezacaftor-ivacaftor, CF patients with advanced disease reported rapid and positive physical, psychological and social effects, which translated into improved quality of life and the formulation of new life goals.

[Allergic Broncho-Pulmonary Aspergillosis (ABPA) in cystic fibrosis: Mechanisms, diagnosis and therapeutic options]. / Aspergillose bronchopulmonaire allergique (ABPA) et mucoviscidose : mécanismes, diagnostic et alternatives thérapeutiques.

INTRODUCTION: Fungal aspergillosis colonization and allergic bronchopulmonary aspergillosis (ABPA) can have a strong impact on the prognosis in cystic fibrosis (CF). We conducted round table discussions involving French experts from pediatric and adult centers caring for patients with CF, microbiologists, radiologists and pharmacists. The aim was to explore the current state of knowledge on: the pathophysiological mechanisms of Aspergillus and other micromycetes infections in CF (such as Scedosporium sp.), and on the clinico-biological diagnosis of ABPA. In perspective, the experts explored the role of imaging in the diagnosis of APBA, specifically CT and MRI; as well as the role of bronchoscopy in the management. We also reviewed the therapeutic management, including different corticosteroid regimens, antifungals and anti-IgE antibodies. CONCLUSION: The diagnosis of ABPA in CF should be based on more standardized biological assays and imaging to optimize treatment and follow-up.

[Aspergillus-related respiratory conditions and COPD: Diagnostic challenges]. / Affections aspergillaires respiratoires et BPCO : difficultés diagnostiques.

INTRODUCTION: The relations between chronic obstructive pulmonary disease (COPD) and respiratory diseases due to Aspergillus spp. are not well understood. METHODS: We analysed a retrospective series of patients hospitalized with a diagnosis of COPD and respiratory disease due to Aspergillus. Patients were identified between 2010 and 2015 from the medico-administrative database of Cochin hospital, Paris. Historical, clinical, biological, microbiological and imaging data were collected and described. Diagnoses were reclassified based on reference definitions and classifications from the literature. Patients were classified according to the type of Aspergillus-related diseases and risk factors were described. RESULTS: Forty patients were identified. Classifiable Aspergillus-related respiratory conditions were confirmed in 26 of them including 12 allergic bronchopulmonary aspergillosis (ABPA), 8 chronic pulmonary aspergillosis (CPA), 1 invasive pulmonary aspergillosis (IPA) and 3 diagnostic associations ABPA/CPA. Other respiratory comorbidities were present in all cases of CPA and immunodepression was recorded for semi-invasive and invasive forms. Finally, 16 patients could not be classified, among whom Aspergillus related lung disease was considered as likely in one-half. CONCLUSION: The complexity of the diagnosis of pulmonary aspergillosis is related to its multiple types with sometimes unclear distinctions. Any type of pulmonary aspergillosis can be observed in patients with COPD, depending on associated risks factors. It would be helpful to establish specific classifications adapted to patients with COPD. This will require larger, prospective, multicentre studies.

Genetic diagnosis in practice: From cystic fibrosis to CFTR-related disorders.

Cystic fibrosis (CF) is a channelopathy caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) protein. Diagnosis of CF has long relied on a combination of clinical (including gastrointestinal and/or respiratory) symptoms and elevated sweat chloride concentration. After cloning of the CFTR gene in 1989, genetic analysis progressively became an important aspect of diagnosis. Although combination of sweat test and genetic analysis have simplified the diagnosis of CF in most cases, difficult situations remain, especially in cases that do not fulfill all diagnostic criteria. Such situations are most frequently encountered in patients presenting with a single-organ disease (e.g., congenital absence of the vas deferens, pancreatitis, bronchiectasis) leading to a diagnosis of CFTR-related disorder, or when the presence/ absence of CF is not resolved after newborn screening. This article reviews the diagnostic criteria of CF, with special emphasis on genetic testing. © 2020 French Society of Pediatrics. Published by Elsevier Masson SAS. All rights reserved.

Prevalence and management of chronic breathlessness in COPD in a tertiary care center.

BACKGROUND: Breathlessness is the prominent symptom of chronic obstructive pulmonary disease (COPD). Despite optimal therapeutic management including pharmacological and non-pharmacological interventions, many COPD patients exhibit significant breathlessness. Chronic breathlessness is defined as breathlessness that persists despite optimal treatment of the underlying disease. Because of the major disability related to chronic breathlessness, symptomatic treatments including opioids have been recommended by several authors. The prevalence of chronic breathlessness in COPD and its management in routine clinical practice have been poorly investigated. Our aim was to examine prevalence, associated characteristics and management of chronic breathlessness in patients with COPD recruited in a real-life tertiary hospital-based cohort. METHODS: A prospective study was conducted among 120 consecutive COPD patients recruited, in stable condition, at Nancy University Hospital, France. In parallel, 88 pulmonologists of the same geographical region were asked to respond to an on-line questionnaire on breathlessness management. RESULTS: Sixty four (53%) patients had severe breathlessness (modified Medical Research Council scale≥3), despite optimal inhaled medications for 94% of them; 40% had undergone pulmonary rehabilitation within the past 2 years. The severity of breathlessness increased with increasing airflow limitation. Breathlessness was associated with increased symptoms of anxiety, depression and with osteoporosis. No relation was found with other symptoms, exacerbation rate, or cardiovascular comorbidities. Among the patients with chronic breathlessness and Hospitalized Anxiety and/or Depression score > 10, only 25% were treated with antidepressant or anxiolytic. Among the pulmonologists 46 (52%) answered to the questionnaire and expressed a high willingness to prescribe opioids forchronic breathlessness, which contrasted with the finding that none of these patients received such treatments against breathlessness. CONCLUSION: Treatment approaches to breathlessness and associated psychological distress are insufficient in COPD. This study highlights underuse of pulmonary rehabilitation and symptomatic treatment for breathlessness.

Cumulative radiation dose after lung transplantation in patients with cystic fibrosis.

PURPOSE: The purpose of this study was first to evaluate the imaging-related cumulative post-transplantation radiation dose in cystic fibrosis (CF) lung transplantation (LT) recipients and second, to identify the occurrence and type of malignancies observed after LT. MATERIALS AND METHODS: A total of 52 patients with CF who underwent LT at our institution between January 2001 and December 2006 with at least 3 years of survival were retrospectively included. There were 27 men and 25 women with a mean age of 24.4±9.2 (SD) years (range: 7.6-52.9 years) at the time of LT. Calculation of cumulative effective and organ doses after LT were based on dosimetry information and acquisition parameters of each examination. Cumulative radiation doses were calculated until June 2016, but stopped at the time of de novomalignancy diagnosis, for patients developing the condition. RESULTS: Patients received a mean cumulative effective dose of 110.0±51.6 (SD) mSv (range: 13-261.3 mSv) over a mean follow-up of 8.1±3.6 (SD) years (range: 0.5-13.5 years), with more than 100mSv in 5 years in 19/52 patients (37%). Chest CT accounted for 73% of the cumulative effective dose. Mean doses to the lung, breast and thyroid were 152.8±61.1 (SD) mGy (range: 21.2-331.6 mGy), 106.5±43.2 (SD) mGy (range: 11.9-221.4 mGy) and 72.7±31.8 (SD) mGy (range: 9.5-165.0 mGy), respectively. Nine out of 52 patients (17%) developed a total of 10 de novo malignancies, all but one attributable to immunosuppression after a mean post-transplantation follow-up period of 11.1±3.5 (SD) years (range: 3.7-16.3 years). Six-month cumulative effective dose was not greater in patients with de novomalignancies than in those without de novomalignancies (28.9±14.5 (SD) mGy (range: 13.0-53.4) vs 25.6±15.3 (range: 5.0-69.7), respectively, P>0.05). CONCLUSION: The cumulative effective dose exceeded 100 mSv in 5 years in 37% of LT recipients, the reason why continuous efforts should be made to optimize chest CT acquisitions accounting for 73% of the radiation dose.

[Acute pulmonary and non-pulmonary complications in adults with cystic fibrosis]. / Complications aiguës respiratoires et non respiratoires chez l'adulte mucoviscidosique.

INTRODUCTION: Cystic fibrosis (CF) is a genetic disease primarily affecting the lungs, which could lead to chronic respiratory failure and premature death. CF patients are usually followed in specialized centers, but may present outside of these centers when they seek care for acute pulmonary and/or non-pulmonary complications. The aim of this paper is to provide appropriate knowledge necessary for managing respiratory and non-respiratory emergencies in CF adults. METHODS: The review is based on international guidelines, extensive search of the available literature using Pubmed, and experience of the CF reference center at Cochin hospital (Paris, France). Complications occurring after solid organ transplantation (e.g., lung and/or liver) are excluded from this review. RESULTS: Main acute respiratory complications are pulmonary exacerbations, hemoptysis, pneumothorax and allergic bronchopulmonary aspergillosis. Acute non-respiratory complications include hyponatremic dehydration, acute pancreatitis, acute complications of gallstones, distal intestinal obstruction syndrome, symptomatic nephrolithiasis, acute kidney injury, drug intolerances and catheter-related acute complications. CONCLUSION: This review summarizes acute pulmonary and non-pulmonary complications occurring in adults with CF, focusing on diagnosis and principles of treatment, with the aim of providing a reference that can be used in clinical practice.

[Bronchiectasis in adults: Etiological diagnosis]. / Diagnostic étiologique d'une dilatation des bronches.

Bronchiectasis is defined by a permanent and irreversible increase in airway caliber. Computed tomography (CT) scan is required for diagnosis and allows differentiating localized (affecting only one lobe) from diffuse (affecting two or more lobes) bronchiectasis. Localized bronchiectasis is usually related to a local cause (e.g., tumor, compression by lymph nodes, foreign body) whereas there are multiple causes of diffuse bronchiectasis. Main causes of diffuse bronchiectasis can be grouped into 5 categories: (1) immune deficiencies; (2) genetic disorders responsible for abnormal mucociliairy clearance (e.g., cystic fibrosis and primary ciliary dyskinesia); (3) autoinflammatory and connective tissue diseases (e.g., rheumatoid arthritis, Sjogren syndrome); (4) chronic airway inflammatory disorders (e.g., allergic broncho-pulmonary aspergillosis) or chronic infections (e.g., by nontuberculous mycobacteria) and; (5) sequelae of pulmonary insults (e.g., infection, radiotherapy). In the absence of a specific cause, bronchiectasis are called idiopathic. Bronchoscopy is the cornerstone for etiological diagnosis in localized bronchiectasis. Investigation of diffuse bronchiectasis includes standardized biological tests, eventually completed by specialized explorations (e.g., analysis of epithelial ion transport and/or ciliary beating). After this systematic approach, an etiological diagnosis is obtained in approximately 60% of cases, often resulting in therapeutic consequences and in some cases in genetic counselling.

[Personalised COPD care: Where are we going?] / Prise en charge personnalisée de la BPCO, quelles sont les tendances ?

The concept of personalised medicine is recent but the underlying notions are not new: knowing how to adapt care to patients' characteristics is one of the components of the "art of medicine". The advances of science allow to refine considerably the applications of the concept in many fields of medicine including COPD: research has identified phenotypes, endotypes and treatable traits. Personalisation can be applied to all components of care. For instance, the decision to perform screening spirometry relies not only on risk factors (age, smoking, other exposures) but also on symptoms. Assessment of comorbidities often associated with COPD is based on risk factors and their combinations, variable between individuals. Rehabilitation and its components are in essence highly individualised, which a major condition for their success. Last but not least, personalisation of pharmacological therapy, which has long been rather poor, could not benefit from biomarkers of interest (predictive of response), such as blood eosinophil count. Practical strategies using these still need to be established, and new biomarkers may usefully enrich the collection!

[Ageing with cystic fibrosis: Classical and emerging comorbidities in adults with cystic fibrosis]. / Vieillir avec la mucoviscidose : comorbidités classiques et émergentes chez l'adulte mucoviscidosique.

Cystic fibrosis (CF) is a genetic disease with pulmonary involvement being predominant and often leading to respiratory failure and premature death. Non-pulmonary complications related to CF transmembrane conductance regulator (CFTR) defect are numerous and account for significant morbidity (exocrine pancreatic insufficiency, diabetes, CF-related liver disease, chronic sinusitis, osteoporosis). Improvement in patients' care led to a continuous increase in life expectancy, with a subsequent increase in the number of adult CF patients worldwide. Increased life expectancy comes with increased prevalence of CF-related comorbidities, but also with new emerging complications directly related to ageing (chronic kidney disease, cardiovascular risk factors, cancers). CFTR modulators might also contribute to modify the face of CF epidemiology and prognosis. Ageing with CF has become a challenge for CF patients and caregivers. This review summarizes classic and emerging comorbidities in the context of current growth and ageing of the CF population. It also addresses potential roles of CFTR modulators.