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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. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background Exposure to respiratory allergens triggers airway hyperresponsiveness and inflammation characterized by the expansion of TH2 cells and the production of allergen specific IgE. Allergic asthma is characterized by an alteration in immune regulatory mechanisms leading to an imbalance between pro- and anti-inflammatory components of the immune system. Aims Recently B cells have been described as central regulators of exacerbated inflammation, notably in the case of autoimmunity. However, to what extent these cells can regulate airway inflammation and asthma remains to be elucidated. Materials & Methods We took advantage of a allergic asthma model in mice induced by percutaneous sensitization and respiratory challenge with an extract of house dust mite. Results In this study, we showed that the induction of allergic asthma alters the homeostasis of IL-10+ Bregs and favors the production of inflammatory cytokines by B cells. Deeper transcriptomic and phenotypic analysis of Bregs revealed that they were enriched in a CD9+ B cell subset. In asthmatic mice the adoptive transfer of CD9+ B cells normalized airway inflammation and lung function by inhibiting TH2- and TH17-driven inflammation in an IL-10-dependent manner, restoring a favorable immunological balance in lung tissues. Indeed we further showed that injection of CD9+ Bregs controls the expansion of lung effector T cells allowing the establishment of a favorable regulatory T cells/effector T cells ratio in lungs. Conclusion This finding strengthens the potential for Breg-targeted therapies in allergic asthma. [ABSTRACT FROM AUTHOR]

In some cases of interstitial lung disease (ILD), clinical and biological findings associated with CT scan pattern during multidisciplinary discussion (MDD) fail to yield a confident diagnosis. In these cases, histology may be necessary. Transbronchial lung cryobiopsy (TBLC) is a bronchoscopic procedure that has been developed in recent years and currently contributes to diagnostic work-up in patients with ILD. TBLC provides tissue samples for histological analysis with an acceptable risk of complications, consisting mainly in pneumothorax or bleeding. In addition to higher diagnostic yield than conventional forceps biopsies, the procedure shows a better safety profile than surgical biopsies. The indication to perform TBLC is decided during a 1st MDD and during a 2nd MDD, results can provide a diagnostic yield approximating 80%. TBLC appears to be an attractive, minimally invasive technique to be proposed as a first-line procedure in selected patients in experienced centers, while surgical lung biopsy may be considered as a second-line solution., (Copyright © 2023 SPLF. Published by Elsevier Masson SAS. All rights reserved.)

Background: Bronchoalveolar lavage (BAL) is a major diagnostic tool in interstitial lung disease (ILD). Its use remains largely quantitative, usually focused on cell differential ratio. However, cellular morphological features provide additional valuable information. The significance of the "immune alveolitis" cytological profile, characterized by lymphocytic alveolitis with activated lymphocytes and macrophages in epithelioid transformation or foamy macrophages desquamating in cohesive clusters with lymphocytes, remains unknown in ILD. Our objective was to describe patients' characteristics and diagnoses associated with an immune alveolitis profile in undiagnosed ILD., Methods: We performed a monocentric retrospective observational study. Eligible patients were adults undergoing diagnostic exploration for ILD and whose BAL fluid displayed an immune alveolitis profile. For each patient, we collected clinical, radiological and biological findings as well as the final etiology of ILD., Results: Between January 2012 and December 2018, 249 patients were included. Mean age was 57 ± 16 years, 140 patients (56%) were men, and 65% of patients were immunocompromised. The main etiological diagnosis was Pneumocystis pneumonia (PCP) (24%), followed by drug-induced lung disease (DILD) (20%), viral pneumonia (14%) and hypersensitivity pneumonitis (HP) (10%). All PCP were diagnosed in immunocompromised patients while HP was found in only 8% of this subgroup. DILD and viral pneumonia were also commonly diagnosed in immunocompromised patients (94% and 80%, respectively)., Conclusion: Our study highlights the additional value of BAL qualitative description in ILD. We suggest incorporating the immune alveolitis profile for the diagnosis and management of ILD, especially in immunocompromised patients, since it guides towards specific diagnoses., (© 2022. The Author(s).)

Introduction: COVID-19 sequelae are numerous and multisystemic, and how to evaluate those symptomatic patients is a timely issue. Klok et al proposed the Post-COVID-19 Functional Status (PCFS) Scale as an easy tool to evaluate limitations related to persistent symptoms. Our aim was to analyse PCFS Scale ability to detect functional limitations and its correlation with quality of life in a cohort of patients, 2-9 months after hospitalisation for COVID-19 hypoxemic pneumonia., Methods: PCFS Scale was evaluated in 121 patients together with quality of life and dyspnoea questionnaires, pulmonary function tests and CT scans., Results: We observed a high correlation with multiple questionnaires (Short Form-36, Hospital Anxiety and Depression Scale, modified Medical Research Council, end Borg Six-Minute Walk Test), making the PCFS Scale a quick and global tool to evaluate functional limitations related to various persistent symptoms following COVID-19 pneumonia., Discussion: The PCFS Scale seems to be a suitable instrument to screen for patients who will require careful follow-up after COVID-19 hypoxemic pneumonia even in the absence of pulmonary sequelae., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Long-term survivors after allogeneic hematopoietic stem cell transplantation (allo-HSCT) are at high risk for treatment-related adverse events, that may worsen physical capacity and may induce fatigue and disability. The aims of this prospective study were to evaluate exercise capacity in allotransplant survivors and its relationship with fatigue and disability. Patient-reported outcomes and exercise capacity were evaluated in 71 non-relapse patients 1 year after allo-HSCT, using validated questionnaires, cardiopulmonary exercise testing (CPET) with measure of peak oxygen uptake (peakVO 2 ) and deconditioning, pulmonary function testing, echocardiography and 6-min walk test. A high proportion (75.4%) of allo-HSCT survivors showed abnormal cardiopulmonary exercise testing parameters as compared to predicted normal values, including 49.3% patients who exhibited moderate to severe impairment in exercise capacity and 37.7% patients with physical deconditioning. PeakVO 2 values were not accurately predicted by 6-min walk distances (r = 0.53). Disability and fatigue were strongly associated with decreased peakVO 2 values (p = 0.002 and p = 0.008, respectively). Exercise capacity was reduced in most allo-HSCT long-term survivors. Because reduced exercise capacity was associated with fatigue, disability and a decrease in quality of life, cardiopulmonary exercise testing should be performed in every patient who reports fatigue and disability.

Mesenchymal stem cell (MSC) immunosuppressive functions make them attractive candidates for anti-inflammatory therapy in allergic asthma. However, the mechanisms by which they ensure therapeutic effects remain to be elucidated. In an acute mouse model of house dust mite (Der f)-induced asthma, one i.v. MSC injection was sufficient to normalize and stabilize lung function in Der f-sensitized mice as compared to control mice. MSC injection decreased in vivo airway responsiveness and decreased ex vivo carbachol-induced bronchial contraction, maintaining bronchial expression of the inhibitory type 2 muscarinic receptor. To evaluate in vivo MSC survival, MSCs were labeled with PKH26 fluorescent marker prior to i.v. injection, and 1 to 10 days later total lungs were digested to obtain single-cell suspensions. 91.5 ± 2.3% and 86.6 ± 6.3% of the recovered PKH26(+) lung cells expressed specific macrophage markers in control and Der f mice, respectively, suggesting that macrophages had phagocyted in vivo the injected MSCs. Interestingly, only PKH26(+) macrophages expressed M2 phenotype, while the innate PKH26(-) macrophages expressed M1 phenotype. Finally, the remaining 0.5% PKH26(+) MSCs expressed 10- to 100-fold more COX-2 than before injection, suggesting in vivo MSC phenotype modification. Together, the results of this study indicate that MSCs attenuate asthma by being phagocyted by lung macrophages, which in turn acquire a M2 suppressive phenotype. Stem Cells 2016;34:1836-1845., (© 2016 AlphaMed Press.)