ABSTRACT
In this review of new developments in pulmonology for the year 2023, we look at two contributions in the diagnostic field: the optimal way of comparing a spirometry measurement with the expected normal values, and a new tool for identifying dysfunctional breathing. On the therapeutic front, a new molecule, ensifentrine, has been shown to be effective in a phase 3 study involving COPD patients. Finally, and still for patients with severe COPD, volume reduction, either surgically or endoscopically, can lead to an improvement in function and severity scores.
Dans cet article des nouveautés en pneumologie pour l'année 2023, nous abordons deux apports dans le domaine diagnostique : la manière optimale de comparer une mesure de spirométrie aux valeurs normales attendues, ainsi qu'un nouvel outil pour identifier la respiration dysfonctionnelle. Au niveau thérapeutique, une nouvelle molécule, l'ensifentrine, s'est révélée probante dans une étude de phase 3 pour les patients atteints de BPCO. Enfin, et toujours pour les patients atteints de BPCO sévère, une réduction de volume, soit chirurgicale, soit par voie endoscopique, peut amener une amélioration fonctionnelle et des scores de sévérité.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Pulmonary Medicine , Humans , Pulmonary Disease, Chronic Obstructive/diagnosis , Pulmonary Disease, Chronic Obstructive/therapy , Spirometry , Clinical Trials, Phase III as TopicABSTRACT
Pulmonary hypertension (PH) is a frequent finding. PH secondary to left heart diseases is the most prevalent form of PH. PH caused by lung diseases and/or hypoxia is the second most frequent cause. The patient should be addressed to an expert center if the PH does not seem to be secondary to a left heart disease or a lung disease, if the PH seems too severe for the underlying cardiac or pulmonary diseases or in the presence of risk factors for PH caused by rare etiologies (group 1, 4 and 5).
L'hypertension pulmonaire (HTP) est une manifestation clinique fréquente. L'HTP secondaire aux cardiopathies gauches est la forme la plus prévalente. La deuxième forme la plus fréquente est l'HTP associée à une pneumopathie et/ou à une hypoxie chronique. Le patient devrait être adressé à un centre expert si l'HTP n'est pas facilement attribuable à une cardiopathie gauche ou à une pneumopathie, si l'HTP semble trop sévère pour la cardiopathie ou la pneumopathie sous-jacente ou en cas de présence de facteurs de risque pour une HTP causée par une étiologie rare (groupes 1, 4 et 5).
Subject(s)
Heart Diseases , Hypertension, Pulmonary , Lung Diseases , Humans , Hypertension, Pulmonary/etiology , Hypertension, Pulmonary/complications , Heart Diseases/complications , Risk Factors , Hypoxia/complications , Hypoxia/diagnosisABSTRACT
Background: High bacterial burden in the lung microbiota predicts progression of idiopathic pulmonary fibrosis (IPF). Azithromycin (AZT) is a macrolide antibiotic known to alter the lung microbiota in several chronic pulmonary diseases, and observational studies have shown a positive effect of AZT on mortality and hospitalisation rate in IPF. However, the effect of AZT on the lung microbiota in IPF remains unknown. Methods: We sought to determine the impact of a 3-month course of AZT on the lung microbiota in IPF. We assessed sputum and oropharyngeal swab specimens from 24 adults with IPF included in a randomised controlled crossover trial of oral AZT 500â mg 3 times per week. 16S rRNA gene amplicon sequencing and quantitative PCR (qPCR) were performed to assess bacterial communities. Antibiotic resistance genes (ARGs) were assessed using real-time qPCR. Results: AZT significantly decreased community diversity with a stronger and more persistent effect in the lower airways (sputum). AZT treatment altered the temporal kinetics of the upper (oropharyngeal swab) and lower airway microbiota, increasing community similarity between the two sites for 1â month after macrolide cessation. Patients with an increase in ARG carriage had lower bacterial density and enrichment of the genus Streptococcus. In contrast, patients with more stable ARG carriage had higher bacterial density and enrichment in Prevotella. Conclusions: AZT caused sustained changes in the diversity and composition of the upper and lower airway microbiota in IPF, with effects on the temporal and spatial dynamics between the two sites.
ABSTRACT
The crisis of antibiotic resistance represents a global public health challenge, affecting particularly patients with respiratory infections. The use of (bacterio)phages for the treatment of bacterial infections (phage therapy) seems safe but its effectiveness has not yet been proven by controlled clinical trials. Nevertheless, phage therapy is regaining interest, encouraged by published cases treated successfully with personalized phage combinations as well as significant advances at a preclinical level. Standardized approaches in phage production and treatment administration, as well as future translational studies, are needed to improve our understanding and explore the potential of phage therapy.
La crise de l'antibiorésistance représente un enjeu considérable en santé publique, touchant particulièrement les patients avec des infections respiratoires. L'utilisation des (bactério)phages pour le traitement des infections bactériennes semble sécuritaire mais son efficacité n'a pas encore été formellement démontrée dans des essais cliniques contrôlés. La phagothérapie regagne de l'intérêt comme traitement personnalisé pour les patients qui ne répondent pas aux traitements standards, comme en témoignent les multiples cas publiés ainsi que des découvertes significatives au niveau préclinique. Des approches standardisées concernant la production et l'administration des phages ainsi que des études translationnelles sont nécessaires afin d'améliorer notre compréhension et d'explorer le potentiel de la phagothérapie.
Subject(s)
Bacterial Infections , Bacteriophages , Phage Therapy , Respiratory Tract Infections , Humans , Bacterial Infections/therapy , Bacterial Infections/microbiology , Respiratory Tract Infections/therapy , Drug Resistance, Microbial , Anti-Bacterial Agents/therapeutic use , Anti-Bacterial Agents/pharmacologyABSTRACT
BACKGROUND: AIDS-related primary central nervous system lymphoma (AR-PCNSL) is an AIDS-defining disease that usually occurs when the CD4 count is less than 50 cells/µl. The frequency of the disease has substantially decreased in the era of highly active antiretroviral therapy (HAART). Prognosis is poor with rapid progression leading to death within 2-3 months if left untreated. CASE DESCRIPTION: A 65 years old male presented to medical attention with gait disturbance, weight loss and slight left-sided hemiparesis. Human immunodeficiency virus infection was diagnosed with an initial CD4 count of 116 cells/µl and a viral load of 260,000 copies/ml. Magnetic resonance imaging of the brain revealed three brain lesions involving the right frontal lobe and the left parietal lobe, which on biopsy led to a diagnosis of AR-PCNSL. HAART was initiated with whole-brain radiotherapy (WBRT), and the patient declined systemic chemotherapy. Due to poor performance status, he was transferred to palliative care. Under HAART, he slowly recovered with normalization of CD4 count and undetectable viral load. Medical imaging showed complete remission (CR) of the brain lesions. At 3-year follow-up, the patient remains in CR, but presented mild neurocognitive dysfunction possibly secondary to WBRT. CONCLUSION: Nowadays, treatment paradigm parallels that of primary central nervous system lymphoma in the immunocompetent population based on systemic chemotherapy (primarily high-dose intravenous methotrexate and steroids) in association with HAART. The role of WBRT is questionable because of late neurotoxic effects.
Subject(s)
Acquired Immunodeficiency Syndrome , Central Nervous System Neoplasms , HIV Infections , Lymphoma, AIDS-Related , Aged , Antiretroviral Therapy, Highly Active , Central Nervous System , Central Nervous System Neoplasms/drug therapy , HIV Infections/drug therapy , Humans , Lymphoma, AIDS-Related/drug therapy , MaleABSTRACT
Adult neurogenesis is tightly regulated by the neurogenic niche. Cellular contacts between niche cells and neural stem cells are hypothesized to regulate stem cell proliferation or lineage choice. However, the structure of adult neural stem cells and the contact they form with niche cells are poorly described. Here, we characterized the morphology of radial glia-like (RGL) cells, their molecular identity, proliferative activity, and fate determination in the adult mouse hippocampus. We found the coexistence of two morphotypes of cells with prototypical morphological characteristics of RGL stem cells: Type α cells, which represented 76% of all RGL cells, displayed a long primary process modestly branching into the molecular layer and type ß cells, which represented 24% of all RGL cells, with a shorter radial process highly branching into the outer granule cell layer-inner molecular layer border. Stem cell markers were expressed in type α cells and coexpressed with astrocytic markers in type ß cells. Consistently, in vivo lineage tracing indicated that type α cells can give rise to neurons, astrocytes, and type ß cells, whereas type ß cells do not proliferate. Our results reveal that the adult subgranular zone of the dentate gyrus harbors two functionally different RGL cells, which can be distinguished by simple morphological criteria, supporting a morphofunctional role of their thin cellular processes. Type ß cells may represent an intermediate state in the transformation of type α, RGL stem cells, into astrocytes.
