Use of FeNO to predict anti-IL-5 and IL-5R biologics efficacy in a real-world cohort of adults with severe eosinophilic asthma.

INTRODUCTION: Severe eosinophilic asthma (SEA) is associated with multiple exacerbations. Fractional exhaled nitric oxide (FeNO), a biomarker of airway T2 inflammation, is known to be correlated with the risk of exacerbations. While the use of FeNO is well established to predict the therapeutic response to dupilumab (anti-IL-4/IL-13), it remains uncertain for biologics targeting the IL-5 pathway. METHODS: We conducted an observational, retrospective, monocentric analysis of adults with SEA who started mepolizumab (anti-IL-5) or benralizumab (anti-IL-5R) between January 1, 2016 and December 31, 2020. RESULTS: Data were collected for 109 patients. All participants reported uncontrolled asthma with a median of 3 annual exacerbations and a median Asthma Control Test score of 12. They all had an initial blood eosinophilia >300/mm3, with a median at 610/mm3 (IQR 420-856). Patients with a baseline FeNO ≥50 ppb reported more exacerbations in the previous year than those with a FeNO <50 ppb (p = 0.02). After initiation of treatment, change in FeNO was not associated with therapeutic response. However, decrease in the annual number of exacerbations was significantly greater in patients with a baseline FeNO ≥50 ppb than in those with a baseline FeNO <50 ppb (-3.3 ± 2.7 vs -0.9 ± 2.4, respectively; p = 0.01). There was no association between baseline FeNO values and subsequent lung function, asthma control or reduction of oral corticosteroids use. CONCLUSION: In this real-world cohort, adults with SEA who had a baseline FeNO ≥50 ppb experienced a greater decrease in exacerbations after 12 months of anti-IL-5 or IL-5R biologics than those with a FeNO <50 ppb.

[Respiratory telerehabilitation in cases of COPD]. / Mise au point sur la téléréadaptation respiratoire dans la BPCO.

Telerehabilitation brings together a set of rehabilitation practices applied remotely by means of information and communication technologies. Even though it has been taking on increasing importance in many health fields over 10 years, telerehabilitation had yet to find its place in pulmonary rehabilitation before 2020, when the pandemic situation impelled numerous teams to put it to work. Pilot studies on respiratory diseases, primarily COPD, along with recent data from randomized or non-randomized studies, have enhanced our understanding of "remote" practice. In this review of the literature, we will show that pulmonary telerehabilitation is feasible, safe and likely to yield short-term (and possibly longer term) effects generally similar to those achieved in the pulmonary rehabilitation programs of specialized centers, especially as regards some indicators of exercise tolerance, dyspnea or patient quality of life. However, the number of studies and patients included in these programs remains too limited in terms of modalities, duration, long-term effects, or adaptations in case of exacerbation to be the subject of recommendations. The potential of respiratory telerehabilitation justifies continuing clinical trials and experiments, which need to be coordinated with the interventions characterizing a conventional program.

[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.

Does training respiratory physicians in clinical respiratory physiology and interpretation of pulmonary function tests improve core knowledge?

Lung function tests have a major role in respiratory medicine. Training in lung function tests is variable within the European Union. In this study, we have shown that an internship in a lung function tests laboratory significantly improved the technical and diagnostic skills of French respiratory trainees.

Normal values of offline exhaled and nasal nitric oxide in healthy children and teens using chemiluminescence.

Nitric oxide (NO) can be used to detect respiratory or ciliary diseases. Fractional exhaled nitric oxide (FeNO) measurement can reflect ongoing eosinophilic airway inflammation and has a diagnostic utility as a test for asthma screening and follow-up while nasal nitric oxide (nNO) is a valuable screening tool for the diagnosis of primary ciliary dyskinesia. The possibility of collecting airway gas samples in an offline manner offers the advantage to extend these measures and improve the screening and management of these diseases, but normal values from healthy children and teens remain sparse. METHODS: Samples were consecutively collected using the offline method for eNO and nNO chemiluminescence measurement in 88 and 31 healthy children and teens, respectively. Offline eNO measurement was also performed in 30 consecutive children with naïve asthma and/or respiratory allergy. RESULTS: The normal offline eNO value was determined by the following regression equation -8.206 + 0.176 × height. The upper limit of the norm for the offline eNO value was 27.4 parts per billion (ppb). A separate analysis was performed in children, pre-teens and teens, for which offline eNO was 13.6 ± 4.7 ppb, 16.3 ± 13.7 ppb and 20.0 ± 7.2 ppb, respectively. The optimal cut-off value of the offline eNO to predict asthma or respiratory allergies was 23.3 ppb, with a sensitivity and specificity of 77% and 91%, respectively. Mean offline nNO was determined at 660 ppb with the lower limit of the norm at 197 ppb. CONCLUSION: The use of offline eNO and nNO normal values should favour the widespread screening of respiratory diseases in children of school age in their usual environment.

[Importance of comorbidities in the anemia of COPD: Economic implications and 3-year survival analysis]. / Importance des comorbidités dans l'anémie de la BPCO : impact médico-économique et survie à 3 ans.

INTRODUCTION: Anemia occurs commonly in COPD and is associated with a poor prognosis. The role of comorbidities in this is suspected but poorly characterized and the economic implications of anemia combined with COPD in France have not been studied. The healthcare resource utilization and cost impact of anemia remain to be investigated. METHODS: One hundred and fifty-one COPD patients attending a pulmonology outpatient department during a 6 months period were retrospectively selected if they had undergone a pulmonary function test, a blood gas analysis or a blood count. The Charlson comorbidity index, resource utilization and economic data from the year before the diagnosis of anemia were compared between anemic and non-anemic patients as well as 3-year survival analysis. RESULTS: The prevalence of anemia was 18.5% and was not influenced by GOLD stage. The identification of anemia was similar from blood gas results and full blood count analysis. Comorbidities - mainly cardiovascular - were found in 86% of the anemic patients. The Charlson index was 5.4±2 in the anemic group compared to 4.1±1.5 in the non-anemic group (P<0.01). The Charlson index was the only predictive factor of anemia using logistic regression analysis. The 3-year mortality was 36% in the anemic versus 7% in the non-anemic group (P<0.05). The main factor identified which predicted 3-year mortality was the presence of anemia using logistic regression. Healthcare costs the year prior to the diagnosis of anemia were not significantly different between groups, but there was a tendency to an increase in the cost of the hospitalizations in the anemic group. CONCLUSIONS: Anemia is easy to diagnose in COPD from the blood gas analysis. It is frequently linked to the presence of comorbidities - mainly cardiovascular diseases - and is the more important predictive factor of the 3-year mortality. There was a tendency towards an increase in the costs of hospitalizations in anemic patients but this remains to be confirmed in a larger economic study.

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.

Partial versus maximal forced exhalations in COPD: enhanced signal detection for novel therapies.

BACKGROUND: Evaluation of novel compounds for COPD often relies on FEV1 for signal detection. Partial forced exhalations from end-tidal inspiration (PEFV) might complement FEV1 in identifying such a signal. We examined the prevalence of bronchodilator response (BDR) using PEFV and FEV1 in patients with COPD. METHODS: 110 consecutive COPD patients were tested prospectively with PEFV and maximal expiratory flow before and after inhalation of a short-acting ß2 agonist (salbutamol, 400 µg). Partial flow at 800 ml above residual volume was derived from the PEFV (PF800). Significant changes in PF800 and/or FEV1 were set at the upper 95% confidence interval after placebo (n = 28). RESULTS: Four groups were identified by the presence (+) or absence (-) of a BDR: Group 1 [PF800 (-)FEV1(-)] when no change was observed (n = 31), Group 2 [PF800(+)FEV1(-)] when PF800 alone improved (n = 31), Group 3 [PF800(-)FEV1(+)] when FEV1 alone improved (n = 26), and Group 4 [PF800(+)FEV1(+)] when both variables improved (n = 18). There were 35 non-responders in any parameter, and 75/110 subjects who showed a response in at least one parameter. The changes in PF800 and FEV1 were not correlated suggesting these assess different airway generations. CONCLUSIONS: The use of PF800 increased detection of a BDR in COPD compared to FEV1 alone and may reflect small airway responses. The PEFV maneuver is simple, repeatable and may avoid some of the theoretical disadvantages of FEV1. The role of PF800 for evaluating novel anti-inflammatory agents remains to be determined.

Stable long-term pulmonary function after fludarabine, antithymocyte globulin and i.v. BU for reduced-intensity conditioning allogeneic SCT.

Lung function decline is a well-recognized complication following allogeneic SCT (allo-SCT). Reduced-intensity conditioning (RIC) and in vivo T-cell depletion by administration of antithymocyte globulin (ATG) may have a protective role in the occurrence of late pulmonary complications. This retrospective study reported the evolution of lung function parameters within the first 2 years after allo-SCT in a population receiving the same RIC regimen that included fludarabine and i.v. BU in combination with low-dose ATG. The median follow-up was 35.2 months. With a median age of 59 years at the time of transplant, at 2 years, the cumulative incidences of non-relapse mortality was as low as 9.7%. The cumulative incidence of relapse was 33%. At 2 years, the cumulative incidences of extensive chronic GVHD (cGVHD) and of pulmonary cGVHD were 23.1% and 1.9%, respectively. The cumulative incidences of airflow obstruction and restrictive pattern were 3.8% and 9.6%, respectively. Moreover, forced expiratory volume (FEV1), forced vital capacity (FVC) and FEV1/FVC ratio remained stable from baseline up to 2 years post transplantation (P=0.26, P=0.27 and P=0.07, respectively). These results correspond favorably with the results obtained with other RIC regimens not incorporating ATG, and suggest that ATG may have a protective pulmonary role after allo-SCT.

[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 and erythropoiesis: interactions and consequences]. / BPCO et érythropoïèse : interactions et conséquences.

Erythropoiesis is modified in chronic obstructive pulmonary disease (COPD). Tobacco smoke, hypoxaemia, systemic inflammation, and infectious exacerbations are the main factors involved. Polymorphisms in genes involved in the regulation of erythropoiesis probably explain the individual susceptibility and variability in the response. The roles of comorbidities related to COPD and the impact of treatment on erythropoiesis are important confounding factors. While polycythaemia is often related to tobacco smoke and hypoxaemia, it has become less common due to the improvement of COPD follow-up and especially the initiation of long-term oxygen therapy. The control of the main causes is often sufficient, but in cases of severe polycythaemia an erythrapheresis is indicated. Anaemia has recently been reported as a more common and serious complication. It increases dyspnoea and reduces physical activity and quality of life. Its impact on survival and the requirements for healthcare has recently been confirmed. The main approach to the management of anaemia remains exclusion of any curable causes, reducing exacerbations and systemic inflammation, and controlling the comorbidities. Though erythropoietin has some benefits in the so-called "anaemia of chronic disease", this still remains to be confirmed in patients with COPD.

[A survey on the performance of the six-minute walk test]. / Enquête sur la réalisation du test de marche de six minutes.

OBJECTIVE: To ascertain, through a national survey, whether the performance of the six-minute walk test (MW6) is in accordance with the recommendations of the American thoracic society (ATS). METHODS: An anonymous questionnaire was sent electronically to 206 departments of respiratory medicine (39 teaching hospitals and 167 general hospitals) and to respiratory rehabilitation departments provided by the Alveolar group of the SLPF (French language respiratory society), and then distributed on a discussion site specialising in respiratory physiotherapy and a professional information site for physiotherapists. RESULTS: One hundred and eleven questionnaires were returned between October 2009 and April 2010, 105 from France. The response rate from hospitals was 30%. The MW6 was performed mainly by physiotherapists and nurses. In 48% there was no precise time for its performance. The site used was a corridor longer than 30 metres in 52% of cases. In 60% the patient was accompanied by the observer. In 35% a familiarisation test was performed, with a delay of 30 minutes or less between the two tests in 62% of these. In 40% encouragement was given. SpO(2) was monitored during the MW6 in 95%. CONCLUSION: For many items the recommendations of the ATS are not followed. The differences found were mainly due to constraints on the services (availability of operators and/or patients).

Beyond corticosteroids: future prospects in the management of inflammation in COPD.

Inflammation plays a central role in the pathophysiology of chronic obstructive pulmonary disease (COPD). Exposure to cigarette smoke induces the recruitment of inflammatory cells in the airways and stimulates innate and adaptive immune mechanisms. Airway inflammation is involved in increased bronchial wall thickness, increased bronchial smooth muscle tone, mucus hypersecretion and loss of parenchymal elastic structures. Oxidative stress impairs tissue integrity, accelerates lung ageing and reduces the efficacy of corticosteroids by decreasing levels of histone deacetylase-2. Protease-antiprotease imbalance impairs tissues and is involved in inflammatory processes. Inflammation is also present in the pulmonary artery wall and at the systemic level in COPD patients, and may be involved in COPD-associated comorbidities. Proximal airways inflammation contributes to symptoms of chronic bronchitis while distal and parenchymal inflammation relates to airflow obstruction, emphysema and hyperinflation. Basal levels of airways and systemic inflammation are increased in frequent exacerbators. Inhaled corticosteroids are much less effective in COPD than in asthma, which relates to the intrinsically poor reversibility of COPD-related airflow obstruction and to molecular mechanisms of resistance relating to oxidative stress. Ongoing research aims at developing new drugs targeting more intimately COPD-specific mechanisms of inflammation, hypersecretion and tissue destruction and repair. Among new anti-inflammatory agents, phosphodiesterase-4 inhibitors have been the first to emerge.