The use of exhaled air analysis in discriminating interstitial lung diseases: a pilot study.

BACKGROUND: Fibrotic Interstitial lung diseases (ILD) are a heterogeneous group of chronic lung diseases characterized by diverse degrees of lung inflammation and remodeling. They include idiopathic ILD such as idiopathic pulmonary fibrosis (IPF), and ILD secondary to chronic inflammatory diseases such as connective tissue disease (CTD). Precise differential diagnosis of ILD is critical since anti-inflammatory and immunosuppressive drugs, which are beneficial in inflammatory ILD, are detrimental in IPF. However, differential diagnosis of ILD is still difficult and often requires an invasive lung biopsy. The primary aim of this study is to identify volatile organic compounds (VOCs) patterns in exhaled air to non-invasively discriminate IPF and CTD-ILD. As secondary aim, the association between the IPF and CTD-ILD discriminating VOC patterns and functional impairment is investigated. METHODS: Fifty-three IPF patients, 53 CTD-ILD patients and 51 controls donated exhaled air, which was analyzed for its VOC content using gas chromatograph- time of flight- mass spectrometry. RESULTS: By applying multivariate analysis, a discriminative profile of 34 VOCs was observed to discriminate between IPF patients and healthy controls whereas 11 VOCs were able to distinguish between CTD-ILD patients and healthy controls. The separation between IPF and CTD-ILD could be made using 16 discriminating VOCs, that also displayed a significant correlation with total lung capacity and the 6 min' walk distance. CONCLUSIONS: This study reports for the first time that specific VOC profiles can be found to differentiate IPF and CTD-ILD from both healthy controls and each other. Moreover, an ILD-specific VOC profile was strongly correlated with functional parameters. Future research applying larger cohorts of patients suffering from a larger variety of ILDs should confirm the potential use of breathomics to facilitate fast, non-invasive and proper differential diagnosis of specific ILDs in the future as first step towards personalized medicine for these complex diseases.

[Survey on hygiene practices after the COVID-19 pandemic in EFR departments]. / Mesures d'hygiène pour les explorations fonctionnelles respiratoires (EFR) après la pandémie de COVID-19 ­ Résultats d'une enquête nationale auprès de 28 centres hospitaliers en 2023.

During the COVID-19 pandemic, airborne transmission of lung disease was a cause for major concern, and scientific societies published strict hygiene guidelines for pulmonary function tests (PFT) and cardiopulmonary exercise testing (CPET). These guidelines led to a major decrease in patient access to PFT and CPET, and their relevance in the 2023 post-pandemic context may be called into question. Under the hypothesis that PFT/CPET expert centers have modified their practices in accordance with the applicable guidelines, a survey was conducted from the 8th through the 23rd of February 2023 in 28 French PFT/CPET hospital departments. An overwhelming majority of the centers (96%) did not limit indications for PFT/CPET, and requested neither a vaccination or recovery certificate (93%) nor a negative diagnostic test (89%). While the use by patients and caregivers of surgical masks and antimicrobial filters was unanimously adopted, only 36% of centers declared that FFP2/N95-filtering face masks were worn. Disinfection of caregivers' hands was carried out by 96%, and a majority of centers reported break time (75%) and disinfection of equipment surfaces (89%) between the testing of two patients. In conclusion: aside from a few modifications, the practices reported by PFT/CPET French expert centers in 2023 were close to those in force prior to the COVID-19 epidemic.

[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.

The specific metabolome profiling of patients infected by SARS-COV-2 supports the key role of tryptophan-nicotinamide pathway and cytosine metabolism.

The biological mechanisms involved in SARS-CoV-2 infection are only partially understood. Thus we explored the plasma metabolome of patients infected with SARS-CoV-2 to search for diagnostic and/or prognostic biomarkers and to improve the knowledge of metabolic disturbance in this infection. We analyzed the plasma metabolome of 55 patients infected with SARS-CoV-2 and 45 controls by LC-HRMS at the time of viral diagnosis (D0). We first evaluated the ability to predict the diagnosis from the metabotype at D0 in an independent population. Next, we assessed the feasibility of predicting the disease evolution at the 7th and 15th day. Plasma metabolome allowed us to generate a discriminant multivariate model to predict the diagnosis of SARS-CoV-2 in an independent population (accuracy > 74%, sensitivity, specificity > 75%). We identified the role of the cytosine and tryptophan-nicotinamide pathways in this discrimination. However, metabolomic exploration modestly explained the disease evolution. Here, we present the first metabolomic study in SARS-CoV-2 patients which showed a high reliable prediction of early diagnosis. We have highlighted the role of the tryptophan-nicotinamide pathway clearly linked to inflammatory signals and microbiota, and the involvement of cytosine, previously described as a coordinator of cell metabolism in SARS-CoV-2. These findings could open new therapeutic perspectives as indirect targets.

Dysregulation of elastin expression by fibroblasts in pulmonary emphysema: role of cellular retinoic acid binding protein 2.

BACKGROUND: All-trans retinoic acid (ATRA) stimulates elastin synthesis by lung fibroblasts and induces alveolar regeneration in animal models of pulmonary emphysema. However, ATRA treatment has had disappointing results in human emphysema. It was hypothesised that a defect in the ATRA signalling pathway contributes to the defect of alveolar repair in the human emphysematous lung. METHODS: Fibroblasts were cultured from the lung of 10 control subjects and eight patients with emphysema. Elastin and retinoic acid receptor (RAR)-beta mRNAs were measured in those cells in the presence of incremental concentrations of ATRA. RARs, retinoic X receptors (RXRs) and cellular retinoic acid binding protein (CRABP) 1 and 2 mRNAs were measured as well as CRABP2 protein content. The effect of CRABP2 silencing on elastin and RAR-beta expression in response to ATRA was measured in MRC5 lung fibroblasts. RESULTS: ATRA at 10(-9) M and 10(-8) M increased median elastin mRNA expression by 182% and 126% in control but not in emphysema fibroblasts. RAR-beta mRNA expression was induced by ATRA in control as well as emphysema fibroblasts. RARs, RXRs and CRABP1 mRNAs were similarly expressed in control and emphysema fibroblasts while CRABP2 mRNA and protein were lower in emphysema fibroblasts. CRABP2 silencing abrogated the induction of elastin but not RAR-beta expression by ATRA in MRC5 fibroblasts. CONCLUSION: Pulmonary emphysema fibroblasts fail to express elastin under ATRA stimulation. CRABP2, which is necessary for elastin induction by ATRA in MRC-5 cells, is expressed at low levels in emphysema fibroblasts. This alteration in the retinoic acid signalling pathway in lung fibroblasts may contribute to the defect of alveolar repair in human pulmonary emphysema. These results are the first demonstration of the involvement of CRABP2 in elastin expression.

[Study of the feasibility of spirometry in general practice]. / Étude de faisabilité de la spirométrie en médecine générale.

COPD is common but is under-diagnosed by general practitioners (GP). GP have a major role in the early diagnosis of this disease. GP could have access to spirometry. The aim of this study was to evaluate the quality and interpretation of spirometry performed by primary care residents following a short education session. Three residents were trained in spirometry for half a day. They then performed spirometry on all smokers over the age of 35 visiting five general practices. The results were reviewed blindly by an independent specialist pulmonologist to assess their quality and interpretation. Among 184 eligible patients, 89% agreed to participate and 66% (n=107) came for the second appointment. The pulmonologist evaluated the quality of spirometry as good in 72% of cases, of suboptimal but acceptable quality in 20% and of poor quality in 8%. Interpretation was accurate in 91% of tests. The Kappa concordance coefficient between GPs and the expert was 0.93. Airflow obstruction was detected in 17.5% of the screened subjects. The average time for a consultation with spirometry was 19minutes. The consultation dedicated to spirometry was well accepted by patients. A short training has to be structured to allow GPs to perform and interpret spirometry properly. This work needs to be extended to better assess reproducibility in cases of abnormal spirometry.

[The pentoxifylline, a corticosteroid sparing in the treatment of sarcoidosis: A case report]. / La pentoxifylline, un épargneur de corticoïdes dans le traitement de la sarcoïdose : à propos d'une observation.

INTRODUCTION: The pentoxifylline seems to have some effects on immune cells by inhibiting tumor necrosis factor alpha (TNFα). Its role as a sparing corticosteroids in the treatment of sarcoidosis remains to be defined. CLINICAL CASE: We present the case of a patient with sarcoidosis corticodependent despite the use of azathioprine. It was finally improved clinically, functionally and by a thoracic computed tomography with addition of pentoxifylline. CONCLUSION: When the tolerance of the pentoxifylline is good and there is not a bleeding risk, the benefit-risk in the long term might be interesting in some patients with sarcoidosis corticodependent.

Therapeutic antibodies: A new era in the treatment of respiratory diseases?

Respiratory diseases affect millions of people worldwide, and account for significant levels of disability and mortality. The treatment of lung cancer and asthma with therapeutic antibodies (Abs) is a breakthrough that opens up new paradigms for the management of respiratory diseases. Antibodies are becoming increasingly important in respiratory medicine; dozens of Abs have received marketing approval, and many more are currently in clinical development. Most of these Abs target asthma, lung cancer and respiratory infections, while very few target chronic obstructive pulmonary disease - one of the most common non-communicable causes of death - and idiopathic pulmonary fibrosis. Here, we review Abs approved for or in clinical development for the treatment of respiratory diseases. We notably highlight their molecular mechanisms, strengths, and likely future trends.

[Guidelines for methacholine provocation testing]. / Recommandations pour le test de provocation bronchique à la méthacholine en pratique clinique, à partir de l'âge scolaire.

Bronchial challenge with the direct bronchoconstrictor agent methacholine is commonly used for the diagnosis of asthma. The "Lung Function" thematic group of the French Pulmonology Society (SPLF) elaborated a series of guidelines for the performance and the interpretation of methacholine challenge testing, based on French clinical guideline methodology. Specifically, guidelines are provided with regard to the choice of judgment criteria, the management of deep inspirations, and the role of methacholine bronchial challenge in the care of asthma, exercise-induced asthma, and professional asthma.

[Mechanisms of non-specific airway hyperresponsiveness: Methacholine-induced alterations in airway architecture]. / Mécanismes de l'hyperréactivité bronchique non spécifique : modifications de l'architecture des voies aériennes induites par la méthacholine.

Multiple mechanisms drive non-specific airway hyperresponsiveness in asthma. At the organ level, methacholine inhalation induces a complex bronchomotor response involving both bronchoconstriction and, to some extent, paradoxical bronchodilatation. This response is heterogeneous both serially, along a single bronchial axis, and in parallel, among lung regions. The bronchomotor response to methacholine induces contraction of distal airways as well as focal airway closure in select lung territories, leading to anatomically defined ventilation defects and decreased vital capacity. In addition, loss of the bronchoprotector and bronchodilator effects of deep inspirations is a key contributor to airway hyperresponsiveness in asthma.

Pulmonary manifestations revealing Rosai-Dorfman disease.

Rosai-Dorfman disease is a rare non-Langerhans cell histiocytosis, mainly involving cervical nodes. We present the case of a patient with a pulmonary form of Rosai-Dorfman disease without peripheral or intra-thoracic lymph nodes, characterized by the presence of pulmonary nodules and cysts associated with bilateral pleural effusions.

[Moderately abundant hemoptysis revealing endobronchial hamartochondroma]. / Une hémoptysie de moyenne abondance révélant un hamartochondrome endobronchique.

Hemoptysis is rarely the inaugural sign of endobronchial hamartoma. Abundance may range from moderate to massive, and may be life-threatening. We report the case of a 44-year-old woman who was referred to our center with moderate and persistent hemoptysis. A left upper lobe lobectomy was performed. We discuss the therapeutic options in such cases.