Cell-based therapy for bronchopulmonary dysplasia in preterm infants 1.

Bronchopulmonary dysplasia (BPD) is the most common complication of extreme prematurity. Currently, there is no specific treatment available. Preclinical studies support cell therapy as a promising therapy for BPD in preterm infants. A successful translation to a safe and effective clinical intervention depends on multiple factors including the perspective of neonatal health care providers. A 2-hour workshop with 40 Canadian neonatologists was held to enhance the design of a phase II trial of stem cells for babies at risk for BPD, with a focus on the population to target and the outcomes to measure in such a trial. The consensus was that infants recruited in an early trial of stem cells should be the ones with the highest risk of developing severe BPD. This risk should be established based on known antenatal, perinatal, and postnatal risk factors. The primary outcome in a phase II trial will be focussed on a non-clinical outcome (e.g., a dose-finding study or a safety study). With other aspects of a translational study discussed, this workshop contributed to accelerate the design of a first Canadian clinical cell-therapy study for BPD in preterm infants.

Somatic growth and the risks of bronchopulmonary dysplasia and pulmonary hypertension: connecting epidemiology and physiology 1.

In the premature infant, poor growth in utero (fetal growth restriction) and in the first weeks of life (postnatal growth restriction) are associated with increased risk for bronchopulmonary dysplasia and pulmonary hypertension. In this review, we summarize the epidemiologic data supporting these associations, present a novel rodent model of postnatal growth restriction, and review 5 promising mechanisms by which poor nutrition may affect the developing lung. These observations support the hypothesis that nutritional and (or) pharmacologic interventions early in life may be able to decrease risk of the pulmonary complications of extreme prematurity.

[The age of artificial intelligence in lung cancer pathology: Between hope, gloom and perspectives]. / La pathologie cancéreuse pulmonaire à l'heure de l'intelligence artificielle : entre espoir, désespoir et perspectives.

Histopathology is the fundamental tool of pathology used for more than a century to establish the final diagnosis of lung cancer. In addition, the phenotypic data contained in the histological images reflects the overall effect of molecular alterations on the behavior of cancer cells and provides a practical visual reading of the aggressiveness of the disease. However, the human evaluation of the histological images is sometimes subjective and may lack reproducibility. Therefore, computational analysis of histological imaging using so-called "artificial intelligence" (AI) approaches has recently received considerable attention to improve this diagnostic accuracy. Thus, computational analysis of lung cancer images has recently been evaluated for the optimization of histological or cytological classification, prognostic prediction or genomic profile of patients with lung cancer. This rapidly growing field constantly demonstrates great power in the field of computing medical imaging by producing highly accurate detection, segmentation or recognition tasks. However, there are still several challenges or issues to be addressed in order to successfully succeed the actual transfer into clinical routine. The objective of this review is to emphasize recent applications of AI in pulmonary cancer pathology, but also to clarify the advantages and limitations of this approach, as well as the perspectives to be implemented for a potential transfer into clinical routine.

Cost estimation of medical care management of lung cancer in Tunisia.

BACKGROUND: Lung cancer management is very expensive for the Tunisian healthcare system. AIM: The aim of this study was to evaluate the direct costs of treating lung cancer in Tunisia, and to identify the main treatment of high expenditure. METHODS: A retrospective study was conducted in 2012 including all patients admitted between 2008 and 2010 for lung cancer management. The hospital payment system was used to estimate the direct costs of the medical care management of lung cancer. RESULTS: We collected 549 patients and the majority of patients were diagnosed with advanced stages of the disease: 60 % in stage T4 and 59 % in stage M1. 26 % of patients underwent surgery and 44.1 % chemotherapy. The total direct costs of lung cancer management were estimated to be TND 3900 (US$ 1980) per patient. CONCLUSIONS: Chemotherapy accounted for the largest percentage of direct costs (46 %) followed by the cost of the hospital stay. Primary prevention, based on the application of policies to control tobacco, is the best strategy to reduce this morbidity.

Perinatal oxygen in the developing lung.

Lung diseases, such as bronchopulmonary dysplasia (BPD), wheezing, and asthma, remain significant causes of morbidity and mortality in the pediatric population, particularly in the setting of premature birth. Pulmonary outcomes in these infants are highly influenced by perinatal exposures including prenatal inflammation, postnatal intensive care unit interventions, and environmental agents. Here, there is strong evidence that perinatal supplemental oxygen administration has significant effects on pulmonary development and health. This is of particular importance in the preterm lung, where premature exposure to room air represents a hyperoxic insult that may cause harm to a lung primed to develop in a hypoxic environment. Preterm infants are also subject to increased episodes of hypoxia, which may also result in pulmonary damage and disease. Here, we summarize the current understanding of the effects of oxygen on the developing lung and how low vs. high oxygen may predispose to pulmonary disease that may extend even into adulthood. Better understanding of the underlying mechanisms will help lead to improved care and outcomes in this vulnerable population.

[Physical activity and lung cancer: A synthesis of the literature]. / Activité physique et cancer broncho-pulmonaire : Synthèse de la littérature.

INTRODUCTION: Physical activity (PA) has its place in the continuum of care, the objective being to limit alterations associated with cancer and its treatments. This review of the literature collates the evidence and current data relating to PA carried out at different periods of treatment for lung cancer. STATE OF THE ART: PA is safe and feasible in patients with lung cancer throughout their oncologic treatment. The efficacy of multimodal programs is demonstrated regarding symptoms, exercise capacity, functional capacity, postoperative complications, length of hospital stay and quality of life. Nevertheless, this result remains to be confirmed with more robust upcoming trial, notably in the long term. PERSPECTIVES: Utilization of activity and energy expenditure sensors or PA questionnaires could help to increase the PA level of lung cancer patients during their continuum of care. For those not at ease with conventional training modalities, it may be judicious to offer intermittent high-intensity training or respiratory muscle strength training. Telerehabilitation could also be implemented. The targeting of populations at high risk should be investigated. CONCLUSION: Teams caring for patients with lung cancer during or after their oncologic treatment should develop innovative strategies designed to overcome difficulties of access or adherence to exercise programs, so that the PA be an integral part of the care of these patients. Physical therapists play an important role in supporting these patients during their assessment or treatment.

[D-CBP study: Evaluation of lung cancer management times]. / Étude D-CBP : Évaluation des délais de prise en charge du cancer broncho- pulmonaire au sein du service de Pneumologie et d'Oncologie Thoracique du CHU de Caen.

INTRODUCTION: Lung cancer is the leading cause of cancer-related death. Delays may have an impact on patient survival. The objective of this study was to evaluate the diagnostic and therapeutic management times for patients admitted for lung cancer treatment in the Respiratory Department of CHU de Caen Normandie. MATERIALS AND METHODS: This is a retrospective, single-center and observational study, conducted on all patients treated for lung cancer from June 2017 to January 2018 in our department of pneumology in the Caen Normandie CHU. The main median times were investigated were: Global Time (abnormal imaging-treatment), Diagnosis time (abnormal imaging-diagnosis) and Treatment Time (diagnosis-treatment). RESULTS: One hundred and twenty-seven (127) patients were included. Median global time was 55.5 days [31,25; 393], median diagnosis time was 22 days [13; 49], and median treatment time was 24.5 days [12,25; 45]. DISCUSSION: Our treatment times are consistent with those previously published. Areas for improvement are being developed in accordance with the 2014-2019 cancer plan, in particularly the creation in our institution of a specific care pathway for patients with lung cancer.

[Implication of bronchopulmonary cancer patients in thoracic oncology]. / Implication des patients atteints d'un cancer broncho-pulmonaire en oncologie thoracique.

Changed relationships between patient and health care provider have given patients a greater role in their care. Nowadays, they have the opportunity to be involved in decision-making regarding any diagnostic, therapeutic or monitoring intervention related to their disease. Access to international scientific data through the web, the activity of different patient associations, and the information given by their referring physician can enrich their knowledge about their disease and its possible treatments. In addition to the objective criteria usually assessed, the role currently assumed by patient associations in clinical research helps to identify their expectations. In addition, a number of new tools allow the thoracic oncologist to better understand patients' wishes. Health authorities' use of patient-reported outcomes and patients' use of digital applications contribute to improved survival without any deleterious impact on quality of life. Web applications designed to monitor a patient's toxicities during treatment are now commercially available. To meet our patients' expectations, we are called upon to incorporate these different digital tools into our daily practice.

[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.

[Emergency room management of patients with lung cancer and organ failure]. / Prise en charge aux urgences de patients avec cancer thoracique et défaillance d'organe.

BACKGROUND: When patients with lung cancer present to the emergency department with organ failure the question of admission to intensive care has to be considered. Our aim is to describe the process leading to the proposed management. METHODS: Retrospectively, all patients admitted to the emergency room between December 2010 and January 2015 with a diagnosis of ICD-10 C34.9 (lung cancer) were reviewed. Those with at least one organ failure were included. RESULTS: The records of 561 patients were reviewed, 79 (14%) had at least one organ failure. The majority of these patients received maximal medical care (59%), 25% exclusive palliative care, and 15% intensive care. Performance status, metastatic status and efficacy of anti-tumor treatment were recorded in the emergency medical record in 20%, 66% and 74% of cases, respectively. An opinion was obtained from the oncologist in 44% of cases and from the intensivist in 41% of cases. No external advice was provided in 27% of cases. CONCLUSION: In the majority of cases, the decision on the intensity of care to be provided to patients with lung cancer and organ failure was made in a collective manner.

[Biomarkers predictive of PD1/PD-L1 immunotherapy in non-small cell lung cancer]. / Biomarqueurs prédictifs de l'immunothérapie anti-PD1/PD-L1 dans le cancer broncho-pulmonaire non à petites cellules.

Immune checkpoint inhibitors (ICI), targeting the PD1/PD-L1 axis has shown their efficacy in lung cancer but only in a restricted population of patients, thus it is mandatory to identify biomarkers predicting the clinical benefit. In this article we will describe and analyzed biomarkers already published, from protein, to RNA and at last DNA markers, discussing each markers feasibility and interest. In the future, combined analysis of several markers will probably be proposed, particularly with the increasing complexity of therapy schema with molecules association.

[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.

[Allergic bronchopulmonary aspergillosis: Evaluation of a maintenance therapy with nebulized Ambisome®]. / Aspergillose bronchopulmonaire allergique : évaluation d'un traitement d'entretien par Ambisome® nébulisé.

BACKGROUND: Allergic bronchopulmonary aspergillosis (ABPA) affects 3-13% of patients with asthma. Its natural history includes possibly life-threatening exacerbations and evolution towards fixed obstructive ventilatory disorders or even irreversible lung fibrosis lesions. ABPA prognosis is directly associated with exacerbation control and the main objective of the treatment is to decrease their frequency and duration. Recommendations regarding dosage and duration of treatment are not very precise. The currently used combination of itraconazole and corticosteroid therapy has many limitations. The interests of a therapeutic strategy using nebulized liposomal amphotericin B (LAmB) are to heighten antifungal lung tissue concentration, to circumvent drug interactions and decrease the potential toxicity of systemic antifungal treatments. Finally, this association leads to improved eradication of Aspergillus, thereby limiting the risk of side effects and the emergence of treatment-resistant Aspergillus strains. METHODS: This is a phase II, multicentre, randomized, single blind, controlled therapeutic study, with the objective of comparing the potential benefit on exacerbation control of a maintenance therapy by LAmB nebulization. The main objective of the study is to compare the incidence of severe clinical exacerbations in ABPA treatment, between a maintenance treatment strategy with nebulized LAmB and a conventional strategy without antifungal maintenance therapy. EXPECTED RESULTS: The results will guide practitioners in the management of ABPA treatments and help to define the place of aerosols of LAmB on "evidence base medicine" criteria.

[Free circulating DNA as a tool for lung cancer patients management]. / Intérêts de l'ADN circulant pour la prise en charge du cancer broncho-pulmonaire.

Free circulating DNA (cfDNA) has been known for several decades. These small DNA fragments are released into the circulation from nucleated cells through necrosis, apoptosis and/or active secretion. These genomic fragments are mainly constitutional (nucleated blood cell DNA), but in patients with cancer, a fraction comes from tumor cells. Although poorly known in the field of thoracic oncology, quantitative and qualitative analysis of the cDNA is nevertheless of great interest. Total cfDNA concentration appears to be an independent prognostic factor in lung cancer. Although changes in total cfDNA concentration is not informative to assess the effectiveness of chemotherapy, following-up the fraction of mutated genes such as EGFR during therapy with tyrosine kinase inhibitors appears to be particularly promising for the early detection of disease progression. The use of cfDNA as liquid biopsy is also very promising for the non-invasive somatic molecular profile either at baseline either for sampling at follow-up. Thus, cfDNA is a very promising tool in thoracic oncology and its translation into practice should be developed quickly.

[Patient's beliefs about oral targeted therapies and impact on drug adherence in lung cancer: A pilot prospective study]. / Croyances des patients envers les thérapies ciblées orales et leur influence sur l'observance dans le cancer broncho-pulmonaire : une étude pilote prospective.

INTRODUCTION: Oral targeted therapies are a new option for lung cancer treatment. However, patient's belief about these drugs - which may interact with adherence - is poorly known in this setting. METHOD: Our study is a pilot prospective unicentric study. Inclusion criteria were: to have been diagnosed with a lung cancer; and to be prescribed with an oral targeted therapy in second line or more. The main objective was to assess patient's specific (SB) and general beliefs (GB) about these drugs according to the Beliefs about Medicines Questionnaire (BMQ). The declared adherence was assessed with the Morisky's test. All included patients underwent a semi-structured interview with a psychologist. RESULTS: Fifthteen patients were included: 12 underwent erlotinib treatment and 3 a crizotinib treatment. The mean score (±standard deviation) at BMQ was 54/85 (±6) overall; 34/50 (±5) for specific belief and 19/35 (±3) for general belief about drugs. During interview, 47% believed in efficacy of targeted oral therapy; 93% reported concerns about their drug; 80% considered that the information given by the physician about the drug was comprehensive; but 40% still required additional information about it. The mean score at Morisky's test was 3/4 (±2) and 53% reported to have forgotten at least once their antineoplastic drug. No correlation was found between belief and adherence. CONCLUSION: Belief about t anti-cancer targeted oral therapy is relatively fair but adherence is moderate in this pilot study. Interview shows the need for additional information about the prescribed drug.

[Experiences of main caregivers helping patients suffering from lung cancer and position assigned to general practitioners]. / Vécu des aidants principaux de patients traités pour cancer broncho-pulmonaire et place attribuée au médecin généraliste.

INTRODUCTION: Cancer turns into a chronic disease. Its impact on patient's daily life may require the assistance of caregiver. AIMS: To explore the experiences of main caregivers (MCs) helping patients suffering from lung cancer (LC), and to explore the role and the position assigned to general practitioners (GPs). METHOD: Qualitative study using semi-directive interviews with 13 PCs, recruited in Roanne's hospital and the Cancer Institute Lucien-Neuwirth (Rhône-Alpes), conducted from February to May 2014. RESULTS: MCs' life was affected on a social, family, and professional level. Despite a need of listening and support, they remained behind, by devotion. GPs' were care managers, and were found out empathic, compassionate and reassuring. Present at the cancer announcement and viewed as an actor at the end of life, their functions were variable, following MCs during the treatment phase. During this phase, some of them perceived that lack of time, expertise and/or information seemed to be an obstacle to their solicitations. CONCLUSION: GPs' regular care could improve MCs' quality of life. Telemedicine could facilitate communication between GPs and hospital staff asked by the MCs.

[Paucisymptomatic presentation of an allergic bronchopulmonary aspergillosis]. / Une aspergillose broncho-pulmonaire allergique de présentation pauci-symptomatique.

Clinical atypical presentations of rare lung disease can cause a diagnostic issue. In this case report, allergic bronchopulmonary aspergillosis is not like in the traditional form of severe asthma but is revealed by a persistent cough. CT scan and biological examinations should be prescribed when there is doubt in confirming the diagnosis. Diagnostic and therapeutic management should be done early in this disease to avoid complications such as bronchiectasis.

[Lung cancer surgery in solid organ transplanted patients]. / Chirurgie du cancer du poumon chez les greffés d'organe solide.

BACKGROUND: The incidence of lung cancer is reputed to be higher and prognosis worse in solid organ transplant recipients than in the general population. Our purpose was to review the results of surgery in this group of patients. METHODS: We retrospectively reviewed 49 male and 6 female patients; mean aged 60.6 years (38-85). Transplanted organ was heart (n = 37), kidney (n=12), liver (n = 5) and both-lungs (n = 1); 48 patients had smoking habits and 42 heavy comorbidities (76.4%). Lung cancer was diagnosed during surveillance (78.2%, n = 43) or because of symptoms (21.8%, n = 12). We reviewed TNM and other main characteristics, among them histology (squamous-cell-carcinoma n = 23, adenocarcinomas n = 24, others n = 8). RESULTS: Surgery consisted of: exploratory thoracotomy (n = 2), wedge resections (n = 6), segmentectomy (n = 1), lobectomy (n = 42), pneumonectomy (n = 4). Postoperative mortality was 7.4% (n = 4) and complication rate 34.5% (n = 19). Five-year survival rate was 46.4% (65.4% for stage I patients, n = 25). Among the 35 dead patients during follow-up, 14 died of their lung cancer (40%). Two had been re-operated from another lung cancer: one after 3 and 8 years who survived 16 years, and the other after 2 years who survived 70 months. CONCLUSIONS: Surgery results are good and postoperative events acceptable despite theoretically increased risks. This also supports performing a close follow-up of transplanted patients and particularly those with smoking history in view of detecting lung cancer appearing at an early stage.