H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.

[Bronchoscopic COPD treatments]. / Traitements endoscopiques de la BPCO.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is associated with disabling respiratory symptoms including dyspnea, frequent exacerbations and chronic bronchitis. The currently available pharmacological and non-pharmacological therapies have limited efficacy, necessitating the development of interventional strategies, many of them endoscopic. STATE OF THE ART: Endoscopic lung volume reduction has markedly increased over recent years, principally as regards the endobronchial valves currently used in routine care. Indeed, multiple randomized trials have demonstrated a significant clinical benefit in a selected population identifiable due to the absence of interlobar collateral ventilation. Other endoscopic volume reduction techniques (polymers, thermal vapor, spirals) shall require additional studies before being considered as options in routine care. Targeted lung denervation (TLD) has aroused interest as a means of reducing exacerbations in the early phases of relevant studies. Endobronchial techniques (bronchoscopic cryospray, bronchial rheoplasty) are still at a very early stage of development, which is aimed at reducing the symptoms of chronic bronchitis. OUTLOOK: Aside from endobronchial valves, which are currently employed in routine care, all the above-mentioned endoscopic techniques require additional studies in order to determine their benefit/risk balance and to identify the population that would benefit the most. CONCLUSIONS: Endoscopic treatments constitute a major avenue of research and innovation in the therapeutic management of COPD. Inclusion of patients in disease registries and clinical trials remains essential, the objective being to gauge the interest of these treatments and their future role in everyday COPD management.

[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.

[Non-invasive home ventilation in patients with severe hypercapnic chronic obstructive pulmonary disease: The SOMNOVENT' study]. / Ventilation non invasive à domicile chez des patients BPCO sévères hypercapniques (étude SOMNOVENT').

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality, especially in cases of chronic hypercapnic respiratory failure. Following a prolonged debate, the indication and benefits of noninvasive ventilation (NIV) have been recently established. Although improved ventilation and reduction in hyperinflation appear to underlie the positive effect on NIV in COPD, only a few studies have focused on specific ventilatory algorithms for improving PaCO2. METHODS: The main objective of this study is to analyze the impact of Löwenstein's ventilatory algorithms, supposed to allow a better management of hyperinflation and its consequences on alveolar ventilation and blood gas parameters. This is an interventional study in routine care, prospective, single blind, randomized with cross over. The primary endpoint will be the transcutaneous partial pressure of nocturnal carbon dioxide. Secondary endpoints will be: abnormal respiratory events occurring during nocturnal NIV; the objective quality of sleep via polysomnography; the tolerance of ventilation and the subjective quality of sleep evaluated by auto questionnaires. EXPECTED RESULTS: The results of this study will clarify whether is it necessary to explore more the impact of the ventilatory modes developed by Löwenstein, dedicated to hypercapnic COPD patients, requiring a long-term NIV.

[Management of pulmonary arteriovenous malformation with pulmonary hypertension]. / Prise en charge d'une malformation artério-veineuse pulmonaire avec hypertension pulmonaire.

INTRODUCTION: Pulmonary arteriovenous malformations (PAVM) are abnormal communications between arteries and pulmonary veins without interposition of capillaries. Embolization is effective both in reducing lifetime complications associated with PAVM and in improving arterial oxygenation. Embolization is however not recommended in patients with pulmonary hypertension (PH) as it abolishes low resistance pathways for pulmonary blood flow and therefore might be expected to elevate pulmonary arterial pressure (PAP). CASE REPORT: We report the case of a 70-year-old patient with a large PAVM as well as group 3 PH [mean PAP=21mmHg, pulmonary vascular resistance (PVR) at 3.4 Wood units] secondary to stage 2 chronic obstructive pulmonary disease (COPD) with emphysema. According to the measured shunt flow (26% of cardiac output), predicted post-embolization PVR was estimated at 4.6 Wood units. These values were considered compatible with embolization of the PAVM. Dyspnea and gas exchange improved after PAVM embolization, without worsening PH. CONCLUSION: Embolization of a PAVM can be considered in patients with stable PH but requires careful prior hemodynamic assessment. The estimation of the shunt flow and predicted post-embolization PVR may guide the therapeutic decision.

Quantitative and qualitative evaluation of spirometry for COPD screening in general practice.

INTRODUCTION: Proper diagnosis of COPD remains a challenge. Spirometry testing in primary care may help to reduce misdiagnosis, but its reliability as a diagnostic instrument needs to be assessed. OBJECTIVES: To investigate (1) the validity of spirometry testing performed in primary care and (2) the accuracy of the diagnostic of airflow limitation obtained by these tests. METHODS: Subjects attending a COPD screening programme had screening spirometry performed either by general practitioners (GPs) or by trained nurses or technicians, who had all received two 3-hour training sessions. Subjects with airflow limitation and a subset of subjects with normal spirometry at screening were invited to undergo confirmatory spirometry performed by trained nurses in a pulmonary function laboratory. RESULTS: Of the 4610 subjects who attended the screening sessions, 96.5% had a valid screening spirometry test. A total of 392 subjects attended the confirmatory sessions. Values measured by screening spirometry were satisfactory compared with those of confirmatory spirometry (rc=0.83). Taking confirmatory spirometry as reference, the positive predictive value of screening spirometry for the diagnosis of persistent airflow limitation was 93% with a specificity of 95%. Agreement for the diagnosis of persistent airflow limitation was substantial (k=0.80). CONCLUSION: Spirometry performed in primary care by trained personnel reliably identifies persistent airflow limitation. This may encourage pulmonologists to collaborate with primary care providers with the aim of improving appropriate diagnosis of COPD.

[The new reference equations of the Global Lung function Initiative (GLI) for pulmonary function tests]. / Les nouvelles équations de référence du Global Lung Function Initiative (GLI) pour les explorations fonctionnelles respiratoires.

Until recently, the reference equations available for pulmonary function tests (PFTs) have had several weaknesses: they have often been based on relatively weak samples of normal subjects; they used mathematical models that are not very efficient in describing the evolution of PFTs over age; there were different equations for children/adolescents and for adults; the expression of the results solely as a percentage of the predicted value did not provide a good indication of the statistical significance of any difference that may exist between a measured value and its reference value. The Global Lung Initiative (GLI) aimed to establish new reference equations for PFTs that do not have these disadvantages. Based on large, representative, reference populations and allowing individualization of homogeneous ethnic groups over a wide age range, the GLI uses a statistical model that does not have any a priori hypothesis regarding the evolution of PFTs as a function of age (these models therefore make it possible to describe, in a very precise manner, the PFTs over all age ranges). For a given PFT, the equation is the same regardless of age (no discontinuity on transition to adulthood). The GLI equations are used to define a reference value, a threshold value (lower limit of the normal) and a z-score that take into account age, sex, size and, for some PFTs, ethnicity. The reference equations of the GLI were established in 2012 for spirometry, in 2017 for the TLCO and will soon be established for lung volumes. Already the representation of ethnic groups not identified by the GLI and of subjects with extreme values of age and size is being questioned.

[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.

Intermittent versus constant aerobic exercise in middle-aged males: acute effects on arterial stiffness and factors influencing the changes.

PURPOSE: Both constant and intermittent acute aerobic exercises have been found to decrease arterial stiffness. However, direct comparisons of these two types of exercise are sparse. It is not known which type of exercise has the greatest effect. METHODS: We evaluated the haemodynamic responses in 15 males (age 48.5 ± 1.3 years; BMI 27.5 ± 0.8 kg m-2) following acute constant (CE) and intermittent cycling exercise (IE). Duration and heart rate were matched during both exercises (131.8 ± 3.2 bpm for CE and 132.0 ± 3.1 bpm for IE). Central and peripheral arterial stiffness was assessed through pulse wave velocity (PWV). Plasma concentrations of nitric oxide (NO), atrial natriuretic peptide (ANP), blood lactate, noradrenaline, and adrenaline were measured before and after each exercise. RESULTS: Central (+ 1.8 ± 7.4 and - 6.5 ± 6.8% for CE and IE) and upper limb PWV (+ 2.7 ± 6.2 and - 8 ± 4.6% for CE and IE) were not significantly altered although a small decrease (small effect size) was observed after IE. However, lower limb PWV significantly decreased after exercises (- 7.3 ± 5.7 and - 15.9 ± 4% after CE and IE), with a larger effect after IE. CONCLUSIONS: Greater decrease in lower limb PWV occurred after IE despite greater heart rate. This may be due to the higher blood levels of lactate during IE, while NO, ANP, noradrenaline, and adrenaline levels remained not statistically different from CE. These results underlined the importance of lactate in triggering the post-exercise vascular response to exercise, as well as its regional characteristic.

[Pneumothorax in young cannabis smokers: A propos of three cases]. / Prise en charge des pneumothorax chez les fumeurs de cannabis : à propos de trois cas.

INTRODUCTION: Cannabis consumption is common among adolescents and young adults in France. In addition to its neurological effect, cannabis smoking can induce severe pulmonary emphysema, even in young patients. When a spontaneous pneumothorax occurs in a cannabis smoker, the possibility of a secondary spontaneous pneumothorax should be considered. This may be of importance as management of secondary spontaneous pneumothorax may differ from the well-codified handling of primary spontaneous pneumothorax. OBSERVATION: Clinical and radiological data from three young cannabis-using patients with spontaneous pneumothorax were collected. Given the presence of emphysema, they were all considered secondary spontaneous pneumothorax. Two patients underwent surgical treatment, with simple postoperative follow-up in one case and prolonged air leak in the other case. The management of the third patient, exclusively medical, was prolonged and complicated. CONCLUSION: The presence of emphysema in young cannabis smokers complicates the management of spontaneous pneumothorax. In this context, a first-line surgical intervention may be an option to be considered.

Severe dyspnea in a patient with neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a genetic disease in which pulmonary complications are rare, but severe, especially pulmonary hypertension (PH). The mechanisms underlying the onset of PH in patients with NF1 are unclear and might be multifactorial. In particular, the frequent presence of pulmonary parenchymal lesions makes etiological diagnosis of PH difficult. We describe here the case of a patient with NF1 admitted to our clinic with dyspnea and right heart failure revealing severe pre-capillary PH. Parenchymal lesions were mild and PH was attributed to pulmonary vascular involvement. Clinical and hemodynamic conditions of the patient improved under pulmonary arterial hypertension-specific combination therapy. This case suggests that treatment of PH due to pulmonary vascular involvement in NF1 may be aligned with recommendations for PAH treatment.

[Differences and similarities between occupational and tobacco induced COPD]. / BPCO professionnelles et BPCO post-tabagique : similarités et différences.

Chronic obstructive pulmonary disease (COPD) most often results from the inhalation of toxic agents. Cigarette smoking still remains the principal cause but the pertinence of occupational COPD is now clearly established. After a brief overview of the epidemiology of this "other COPD", the clinical and functional characteristics are summarized, taking into account recent advances in this field. The combined effects of occupational exposure and tobacco are also considered, providing evidence of the need to continuously reinforce campaigns of education and prevention in occupational COPD.

[Chronic Farmer's lung disease with emphysema]. / Forme emphysémateuse de la maladie du poumon de fermier.

INTRODUCTION: Farmer's lung (FL) is the most common type of hypersensitivity pneumonitis (HP), with an estimated prevalence of between 0.5 and 1.5% in dairy farmers. In chronic FL, fibrotic sequelae are widely described in the literature although our experience and occasional epidemiological studies emphasize an increased risk of developing emphysema in these patients. CASE REPORT: We report a case of FL in a 37-year-old patient with typical clinical features (exertional dyspnoea, lymphocytic alveolitis and computed tomography appearances) together with proven allergen exposure. This patient developed early pulmonary emphysema probably due to intermittent massive exposure to antigens and to bacterial and fungal micro-organisms. CONCLUSION: The current classification of HP differentiates acute, subacute and chronic forms but does not take account of the role of the mode of exposure and the evolution of the disease. The prognosis and evolution of HP seem to be dependent on the type and pattern of exposure. A new classification with two clusters has been suggested: in type 1, massive and intermittent exposure, as in FL, may lead to emphysema with chronic airflow obstruction and, in type 2, chronic exposure to a low level, as in bird fanciers, may lead to fibrosis with a restrictive pattern.

Contribution of exhaled nitric oxide measurement in airway inflammation assessment in asthma. A position paper from the French Speaking Respiratory Society.

Nitric oxide (NO) is both a gas and a ubiquitous inter- and intracellular messenger with numerous physiological functions. As its synthesis is markedly increased during inflammatory processes, NO can be used as a surrogate marker of acute and/or chronic inflammation. It is possible to quantify fractional concentration of NO in exhaled breath (FENO) to detect airway inflammation, and thus improve the diagnosis of asthma by better characterizing asthmatic patients with eosinophilic bronchial inflammation, and eventually improve the management of targeted asthmatic patients. FENO measurement can therefore be viewed as a new, reproducible and easy to perform pulmonary function test. Measuring FENO is the only non-invasive pulmonary function test allowing (1) detecting, (2) quantifying and (3) monitoring changes in inflammatory processes during the course of various respiratory disorders, including corticosensitive asthma.

Effects of three postexercice recovery treatments on femoral artery blood flow kinetics.

AIM: This study aimed to compare the kinetics of muscle leg blood flow during three recovery treatments following a prolonged exercise: contrast water therapy (CWT), compression stockings (CS) or passive recovery (PR). METHODS: Fifteen men came to the laboratory three times to perform a 45-min exercise followed 5 min after by a standardized 12-min recovery treatment in upright position, alternating between two vats every 2 min: CWT (cold: ~12 °C to warm: 36 °C), CS (~20 mmHg) or PR. The order of treatments was randomized. Blood flow was measured using Doppler ultrasound during the recovery treatments (i.e., min 3, 5, 7 and 9) in the superficial femoral artery distally to the common bifurcation (~3 cm) (above the water and stocking). RESULTS: Blood flow was significantly higher during CWT (P<0.01; +22.91%) and CS (P<0.05; +15.26%) than during PR. Although no statistical difference between CWT and CS was observed, effect sizes were larger during CWT (large) than during CS (moderate). No changes in blood flow occurred in the femoral artery between hot and cold transitions of CWT. CONCLUSION: During immediate recovery of a high intensity exercise, CWT and CS trigger higher femoral artery blood flow than PR. Moreover, effect sizes were greater during CWT than during CS.

[Pulmonary CO/NO transfer: physiological basis, technical aspects and clinical impact]. / Le double transfert pulmonaire CO/NO : bases physiologiques, aspects techniques et intérêt pratique.

Diseases affecting the alveolar-capillary membrane or the capillary blood vessels can impair pulmonary gas exchanges and lung diffusion. The single-breath transfer factor of the lung for carbon monoxide (TL,CO) is the classical technique for measuring gas transfer from the alveolus to the pulmonary capillary blood. Pulmonary gas exchanges can also be explored by the transfer factor of the lung for nitric oxide (TL,NO). TL,NO represents a better index for the diffusing capacity of the alveolar-capillary membrane whereas TL,CO is more influenced by red blood cell resistance. Membrane diffusing capacity (DM) and pulmonary capillary blood volume (Vc) derivated from TL,CO and TL,NO by the Roughton-Forster equation can give additional insights into pulmonary pathologies. The clinical impact of the CO/NO transfer has still to be precised even if this measurement seems to provide an alternative way of investigating the alveolar membrane and the blood reacting with the gas.

[COPD in dairy farmers: screening, characterization and constitution of a cohort. The BALISTIC study]. / BPCO des producteurs laitiers : dépistage, caractérisation et constitution d'une cohorte. Étude BALISTIC.

BACKGROUND: A pilot study from our group suggests that the prevalence of chronic obstructive pulmonary disease (COPD) among dairy farmers is higher than in the general population although dairy workers are less frequently smokers. OBJECTIVES AND METHODS: The study presented here aims at (i) determining the prevalence of COPD in a large and representative population of dairy farmers; (ii) characterizing these patients in terms of smoking habits, dyspnoea, quality of life, lung function, bronchial exhaled nitric oxide, systemic inflammation, arterial stiffness and exercise capacity; (iii) comparing characteristics of dairy farmers' COPD with the characteristics of COPD in patients without any occupational exposure; (iv) identifying the etiological factors of COPD in dairy farmers; and (v) constituting a cohort of COPD patients and control subjects for further longitudinal studies. Two groups of COPD patients (dairy farmers or not) and two groups of controls subjects will be selected among a representative panel of 2000 dairy workers and 2000 subjects without any occupational exposure, all aged 40 to 75 years. EXPECTED RESULTS: A better knowledge of the epidemiology and pathophysiology of COPD in dairy farmers should guide a specific strategy of prevention. The knowledge of the characteristics of COPD occurring in dairy farmers will help to define the therapeutic modalities that might be different compared with the therapeutic recommendations for COPD secondary to tobacco smoking.