Evolution of bone metastases in patients receiving at least three months of checkpoint inhibitors.

BACKGROUND: To investigate the evolution of bone metastases in patients receiving immune checkpoint inhibitors (ICI). METHODS: A single-center retrospective study included cancer patients with bone metastases treated with ICI at our institution between January 2014 and September 2019. Clinical and biological data were collected from medical records and independent expert review of imaging was performed. Target and non-target lesions were identified and followed up to 1 year. Patients were then classified as bone responder or non-responder. Comparisons between groups were performed with Student's t test or Mann-Whitney test. RESULTS: Among 1108 patients screened, 192 patients had bone metastases and 48 patients were included in the final analysis, with lung cancer, renal carcinoma and melanoma as most represented cancer type. Half of the patients experienced stability, condensation or peripheral sclerosis of bone lesions. Initial progression before stabilization with or without sclerosis of bone lesion occurred for 19% of patients (pseudoprogression). There was an association between bone response and global oncological outcomes. Bone responder patients had a significant decrease in morphine and co-analgesic prescription as well as a significant decrease in alkaline phosphatases compared to non-responder patients. CONCLUSION: Bone response was observed in half of patients with available imaging and follow-up after 3 months of ICI treatment, with sclerosis observed in one-third of bone lesions at month 3, in all tumor types. Up to 20% of patients experienced a pseudoprogression of bone lesions such as previously described in primary tumor and other metastatic sites. Bone response was associated with improvement of pain and survival.

COPD burden on sexual well-being.

BACKGROUND: Sexual function is often affected in patients suffering from chronic diseases especially chronic obstructive pulmonary disease (COPD). However, the effect of COPD on sexual satisfaction is underappreciated in clinical practice. The aim of this study is to evaluate the impact of COPD on patient's sexuality and the explanatory variables of sexual dissatisfaction. METHODS: Questionnaires were emailed to participants and they submitted their responses on the Santé Respiratoire France website. Data about sexual well-being (Arizona Sexual Experience Scale, ASEX), Quality of life (VQ11), anxiety, depression (Hospitalized anxiety and depression, HAD) and self-declared COPD grade were collected. RESULTS: Seven hundred and fifty one subjects were included and were characterized as follows: women-51%, mean age-61 years, in a couple-62% and 70%-retired. Every grade of COPD was represented. Out of 751 participants, 301 participants (40%) had no sexual activity and 450 (60%) had sexual activity. From the 450 participants, 60% needed to change their sexual life because of their disease (rhythm, frequency and position). Subjects often used medications to improve sexual performance (43% used short-acting bronchodilator and 13% -specific erectile dysfunction drugs). ASEX questionnaire confirmed patients' dissatisfaction (diminution of sexual appetite for 68% and sexual desire for 60%) because of breathlessness and fatigue. Eighty one percent of the responders had an altered quality of life (VQ11 mean score 35) and frequent suspected anxiety or depression (HAD mean score 10.8). Ninety percent declared that sexual dysfunction had never been discussed by their doctors, while 36% of patients would have preferred to undergo a specialized consultation. CONCLUSION: Sexual dysfunction is frequent among COPD patients and leads to an altered well-being, however being a cultural taboo, it remains frequently neglected. Sexual guidance should be a part of patient's consultations improve quality of sexual life.

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.

[Biologic agents in COPD management]. / Place des biothérapies dans la BPCO.

Chronic obstructive pulmonary disease (COPD) is a frequently occurring disease entailing high morbidity and mortality, and relevant therapeutic resources are limited. As is the case with asthma, the current trend consists in the phenotyping of COPD patients so as to develop personalized medicine tailored to a given individual's inflammatory profile. The aim of this review is to summarize the role of biologic agents in the management of COPD, taking into consideration not only COPD pathophysiology, but also the previously published studies and the relatively encouraging prospects for the future.

[Take-home messages from the 2nd COPD 2023 Biennial of the French Society of Respiratory Diseases. Placing the patient at the center of the care pathway]. / Principaux messages de la deuxième Biennale BPCO 2023 de la SPLF. Le patient au cœur du parcours de soins.

INTRODUCTION: The second COPD Biennial organized by the COPD working group of the French Society of Respiratory Diseases took place in Paris (Cochin) on 13th December 2023. STATE OF THE ART: Major trends in 2023 were discussed; they encompassed concepts, definitions, biologics, care pathways, pulmonary rehabilitation and complex situations entailed by respiratory infections, cardiovascular comorbidities and pulmonary hypertension, and modalities of oxygen therapy and ventilation. PERSPECTIVES: The different talks underlined major changes in COPD including the concepts of pre-COPD, etiotypes, health trajectories and new definitions of exacerbation. Recent results in biologics for COPD open the door to new pharmacological options. Assessment of current care pathways in France highlighted some causes for concern. For example, pulmonary rehabilitation is a key but insufficiently practiced element. Respiratory infections require careful assessment and treatments. Diagnosis and treatment of cardiovascular comorbidities and pulmonary hypertension are of paramount importance. As of late, oxygen therapy and ventilation modalities have evolved, and are beginning to afford more personalized options. CONCLUSIONS: As regards COPD, a personalized approach is crucial, placing the patient at the center of the care pathway and facilitating coordination between healthcare providers.

[COPD and eosinophils]. / BPCO et éosinophiles.

COPD is a major cause of morbidity and mortality worldwide. As research progresses, new patient phenotypes are being defined, providing hope for more personalized management of the disease. A significant proportion of patients present with an increased level of blood eosinophils, which may reflect bronchial eosinophilic inflammation. The aims of this article are to characterize the role of eosinophils in COPD in terms of pathophysiology, associated respiratory symptoms, impact on treatment and, finally, to consider different future treatment options.

[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.

[The impact of exposure to cigarette smoke on the haemodynamic response during exercise of patients under specific treatment for pulmonary arterial hypertension]. / Impact de l'exposition à la fumée de cigarette sur la réponse hémodynamique à l'exercice de patients sous traitement spécifique de l'HTAP.

INTRODUCTION: Pulmonary hypertension (PH) is a life-threatening haemodynamic condition associated with many disorders. In pulmonary arterial hypertension (PAH) and chronic thrombo-embolic pulmonary hypertension, several treatments acting against pulmonary endothelial dysfunction have been shown to be effective. Exposure to cigarette smoke leads to endothelial dysfunction which is comparable to that observed in patients with PAH. The main objective was to investigate the difference in the haemodynamic changes during exercise in patients under specific treatment, from diagnosis (T0) to the first reassessment visit with a right heart catheterisation (T1), between those exposed or not exposed to cigarette smoke. MATERIALS AND METHODS: Between January 2002 and December 2018, all patients under specific treatment for PAH or chronic thromboembolic PH who underwent supine submaximal exercise assessment at T0 and T1 in our institution were asked specific questions about tobacco smoking. RESULTS: Overall (n=109), difference in mean isoflow mPAP was 19.0±15.4mmHg in patients exposed to tobacco smoke versus 21.3±16.6mmHg in unexposed patients (P=0.59). Median survival in exposed group was 83 months while in the unexposed group, median survival was 100 months (P=0.099). DISCUSSION: Our study did not show any significant difference in terms of haemodynamic changes during exercise between a group of patients under specific PH treatment exposed to cigarette smoke and a group unexposed. Endothelial dysfunction induced by smoke exposure does not appear to have a major impact on the response to the specific PH treatment.

[Woman's asthma throughout life: Towards a personalized management?] / Asthme de la femme au fil du temps : vers une prise en charge personnalisée ?

In a woman's life, asthma can affect her in a variety of ways, with the onset of premenstrual asthma currently under-diagnosed. It is estimated that about 20% of women with asthma have premenstrual asthma, which is more common in patients with severe asthma. Women with asthma are at high risk of exacerbations and of severe asthma. Asthma is the most common chronic disease during pregnancy with potential maternal and foetal complications. Asthma medications are safe for the foetus and it is essential to continue pre-existing treatment and adapt it to the progress of asthma during the pregnancy. Sex steroids modulate the structure and function of bronchial and immune cells. Understanding their role in asthma pathogenesis is complicated by the ambivalent effects of bronchodilating and pro-inflammatory oestrogens as well as the diversity of response to their association with progesterone. Menopausal asthma is a clinical entity and is part of one of the phenotypes of severe non-allergic and low steroid-sensitive asthma. Targeted assessment of the domestic and professional environment allows optimization of asthma management.

[Guide for follow-up of patients with SARS-CoV-2 pneumonia. Management proposals developed by the French-language Respiratory Medicine Society. Version of 10 May 2020]. / Guide pour le suivi respiratoire des patients ayant présenté une pneumonie à SARS-CoV-2. Propositions de prise en charge élaborées par la Société de pneumologie de langue française. Version du 10 mai 2020.

The French-language Respiratory Medicine Society (SPLF) proposes a guide for the follow-up of patients who have presented with SARS-CoV-2 pneumonia. The proposals are based on known data from previous epidemics, on acute lesions observed in SARS-CoV-2 patients and on expert opinion. This guide proposes a follow-up based on three categories of patients: (1) patients managed outside hospital for possible or proven SARS-CoV-2 infection, referred by their physician for persistent dyspnoea; (2) patients hospitalized for SARS-CoV-2 pneumonia in a medical unit; (3) patients hospitalized for SARS-CoV-2 pneumonia in an intensive care unit. The subsequent follow-up will have to be adapted to the initial assessment. This guide emphasises the possibility of others causes of dyspnoea (cardiac, thromboembolic, hyperventilation syndrome…). These proposals may evolve over time as more knowledge becomes available.

[Early determinants of chronic obstructive pulmonary disease: Lung regeneration, a new therapeutic target?] / Déterminants précoces de la bronchopneumopathie chronique obstructive : la régénération pulmonaire, une nouvelle piste thérapeutique ?

Chronic obstructive pulmonary disease, a disease of increasing incidence, is related mainly to smoking. Although symptoms only appear at adulthood, the disease can develop from early life events. For example, bronchopulmonary dysplasia, which occurs in preterm infants, is characterized by airspace enlargement and could lead to late lung consequences. Once the lesions are established, no curative treatment is available. Stimulating lung regeneration from endogenous stem cells is therefore an exciting research domain, particularly through the activation of the mesenchymal contingent located in the lung stem cell niche.

[Evaluation of cardiac MRI in the follow up assessment of patients with pulmonary arterial hypertension]. / Évaluation de l'IRM cardiaque dans le suivi des patients ayant une hypertension artérielle pulmonaire (EVITA). IRM cardiaque dans le suivi de l'hypertension artérielle pulmonaire.

Haemodynamic follow up in pulmonary arterial hypertension (PAH) is currently based on right heart catheterisation (RHC). The primary objective of the EVITA study is to compare the use of cardiac magnetic resonance imaging (cMRI) with RHC in the identification of an unfavourable hemodynamic status. The secondary objectives are to determine the role of cMRI in the follow up process. Patients will undergo at diagnosis and at follow up visits both RHC and cMRI. Patients will be followed and treated according to the current guidelines. The primary endpoint will be an unfavourable haemodynamic status defined by cardiac index<2.5L/min/m2 or a right atrial pressure≥8mm Hg measured with RHC compared with a cardiac index<2.5L/min/m2 or right ventricle ejection fraction<35% or an absolute decrease of 10% from the previous measurement with cMRI. Exact values of sensitivity, specificity and 95% confidence intervals will be computed. A population of 180 subjects will have a power of 90% with an α risk of 5%. Univariate and multivariate Cox analysis will allow answering to the secondary objectives. We expect to demonstrate that cMRI could be partly used instead of RHC in the follow up of patients with PAH.

[Complementary and alternative medicine use by lung cancer patients]. / Le recours aux médecines « complémentaires et alternatives ¼ par les patients atteints d'un cancer bronchique.

INTRODUCTION: Complementary and alternative medicine (CMA) use is frequent among cancer patients. Only few results are available about lung cancer patients. The aim of this study was to evaluate how often the CMA were used by lung cancer patients and to define the type of CMA used. METHODS: Every lung cancer patients with an ongoing chemotherapy in the respiratory department of the University Hospital of Nancy were approached between November 2014 to July 2015. A detailed and anonymous survey was conducted and the socioeconomic characteristics were collected from medical records. RESULTS: Ninety-one patients were questioned. On 82 patients having answered, 19.5 % had used at least a CMA. The main CMA used was the physical exercise in 50 % of the patients. CMA users were significantly younger with a mean age of 56.4 years versus 65.4 years (P=0.0007). More than half patients did not indicate to their specialist that they used a CMA. The main information source was the circle of acquaintances. CONCLUSIONS: CMA use is frequent among lung cancer patients. The physical exercise is quoted most of the time among the various CMA. There is a real lack of communication on the subject between the physician and the patient. It is thus imperative that the pulmonologists give much interest to these practices in order to give better advices and to reinforce the patient-physician relationship.

[Malignant rhabdoid tumor of the lung]. / Tumeur pulmonaire maligne de type rhabdoïde.

INTRODUCTION: Rhabdoid tumours usually develop in brain and spinal cord or kidney; they are highly malignant neoplasms that typically arise in infancy and early childhood. However, rare cases of pulmonary localization have been described, particularly among young adults. CASE REPORT: A 26-year-old man, smoker, had a right apical lung mass associated with a Pancoast syndrome leading to haemoptysis. There was also a tumour of the left thigh and scalp. Histological samples taken at these three locations were in favour of an undifferentiated carcinoma. The lack of nuclear integrase interactor 1 expression, and immunohistochemical appearance supported the diagnosis of rhabdoid tumour. Despite treatment, unfavourable progression confirmed this hypothesis, doubling time was less than six weeks with development of multiple metastases resulted in death within only three months after diagnosis. CONCLUSION: The lack of expression of integrase interactor 1 should suggest the diagnosis of rhabdoid tumour, especially when there is quick progression. The prognosis of these tumours remains poor and therapeutic options are limited.

Pharmacological treatment optimization for stable chronic obstructive pulmonary disease. Proposals from the Société de Pneumologie de Langue Française.

The Société de Pneumologie de Langue Française proposes a decision algorithm on long-term pharmacological COPD treatment. A working group reviewed the literature published between January 2009 and May 2016. This document lays out proposals and not guidelines. It only focuses on pharmacological treatments except vaccinations, smoking cessation treatments and oxygen therapy. Any COPD diagnosis, based on pulmonary function tests, should lead to recommend smoking cessation, vaccinations, physical activity, pulmonary rehabilitation in case of activity limitation, and short-acting bronchodilators. Symptoms like dyspnea and exacerbations determine the therapeutic choices. In case of daily dyspnea and/or exacerbations, a long-acting bronchodilator should be suggested (beta-2 agonist, LABA or anticholinergics, LAMA). A clinical and lung function reevaluation is suggested 1 to 3 months after any treatment modification and every 3-12 months according to the severity of the disease. In case of persisting dyspnea, a fixed dose LABA+LAMA combination improves pulmonary function (FEV1), quality of life, dyspnea and decreases exacerbations without increasing side effects. In case of frequent exacerbations and a FEV1≤70%, a fixed dose long-acting bronchodilator combination or a LABA+ inhaled corticosteroids (ICS) combination can be proposed. A triple combination (LABA+LAMA+ICS) is indicated when exacerbations persist despite one of these combinations. Dyspnea in spite of a bronchodilator combination or exacerbations in spite of a triple combination should lead to consider other pharmacological treatments (theophylline if dyspnea, macrolides if exacerbations, low-dose opioids if refractory dyspnea).