Search

BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA).METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician.FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78).INTERPRETATION: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation.FUNDING: None.

Assessment of respiratory effort (RE) is key for characterization of respiratory events. The discrimination between central and obstructive events is important because these events are caused by different physio-pathological mechanisms and require different treatment approaches. Many of the currently available options for home sleep apnea testing either do not measure RE, or RE signal recording is not always reliable. This is due to a variety of factors, including for instance wrong placement of the respiratory inductance plethysmography (RIP) sensors leading to artifacts or signal loss. Monitoring of mandibular jaw movements (MJM) provides the ability to accurately measure RE through a single point of contact sensor placed on the patient's chin. The inertial unit included in the capturing technology and overnight positional stability of the sensor provide a robust MJM bio-signal to detect sleep-disordered breathing (SDB). Many of the pharyngeal muscles are attached to the mandible directly, or indirectly via the hyoid bone. The motor trigeminal nerve impulses to contract or relax these muscles generate discrete MJM that reflect changes in RE during sleep. Indeed, the central drive utilizes the lower jaw as a fine-tuning lever to stiffen the upper airway musculature and safeguard the patency of the pharynx. Associations between the MJM bio-signal properties and both physiological and pathological breathing patterns during sleep have been extensively studied. These show a close relationship between changes in the MJM bio-signal as a function of RE that is similar to levels of RE measured simultaneously by the reference bio-signals such as esophageal pressure or crural diaphragmatic electromyography. Specific waveforms, frequencies, and amplitudes of these discrete MJM are seen across a variety of breathing disturbances that are recommended to be scored by the American Academy of Sleep Medicine. Moreover, MJM monitoring provides information about sleep/wake states and arousals, which enables total sleep time measurement for accurate calculation of conventional hourly indices. The MJM bio-signal can be interpreted and its automatic analysis using a dedicated machine learning algorithm delivers a comprehensive and clinically informative study report that provides physicians with the necessary information to aid in the diagnosis of SDB.

The added value of patient-reported outcome measures (PROMs) in addition to standard clinical outcome tools in the assessment of relapsing-remitting multiple sclerosis (RRMS) patients' status is increasingly recognized. PROMs facilitate the detection of hidden aspects of MS and help to integrate the patient's subjective experience of health-related quality of life (HRQoL) status and treatment satisfaction in a holistic way. However, the relationship between PROMs and clinical and cognitive status has been scarcely investigated up to now. To investigate the association of PROMs with physical and cognitive disability in a cohort of RRMS patients at initiation of a new disease-modifying treatment. In this cross-sectional bicenter study, 59 consecutive RRMS patients underwent neurological examination with EDSS assessment, comprehensive cognitive tests (BVMT-R, SDMT, CVLT-II) and a set of self-reported questionnaires. Lesion and brain volumes were analyzed and processed by the automated MSmetrix software (Icometrix, Leuven, Belgium). Spearman's correlation coefficient was used to evaluate the association of collected variables. A cross-sectional logistic regression analysis was performed to find baseline correlates of cognitive impairment. Of the 59 RRMS patients (mean age 39 ± 9.8 years, 79.7% female, median EDSS 2.0), 33 (56%) had cognitive impairment. While almost all dimensions of health, explored by PROMs, were impacted in the overall sample, no significant difference was observed in patients with and without cognitive impairment. All PROMs were significantly associated with EDSS (R = 0.37-0.55; p

Le 14 décembre dernier, l’Institut des Maladies Rares organisait une nouvelle réunion scientifique interdisciplinaire. Six des 11 thématiques abordées font l’objet d’une communication dans cette édition du Louvain Médical. Il s’agit des télomères, des atteintes pulmonaires de la polyarthrite rhumatoïde, de l'impact de l’inhibition de l'inflammasome sur le phénotype de la dystrophie musculaire de Duchenne et de l’évaluation de la force musculaire des patients atteints de la mucoviscidose. Citons également la prise en charge multidisciplinaire des enfants porteurs de trisomie 21 et finalement le dépistage systématique des conductrices de l’hémophilie. Ces communications et celles dont nous ne publions pas le résumé ont suscité un très grand intérêt. Elles témoignent de la très grande diversité des maladies rares prises en charge par l’institut et ses partenaires. Elles sont aussi le reflet du dynamisme des équipes de recherche et de l’originalité des multiples projets en cours.

Restin is a member of the melanoma-associated antigen (MAGE) superfamily. Its expression has been reported to be up- or downregulated in cancer. Preclinical data suggest it is a tumor suppressor. In this study, we aimed to evaluate restin expression and prognostic value in non-small cell lung cancer (NSCLC). Restin expression was analyzed by immunohistochemistry in three tissue microarrays consisting of formalin-fixed/paraffin-embedded NSCLC specimens from 113 patients, represented in triplicate. Restin staining H-score was the result of the staining intensity (0-no, 1-weak, 2-moderate, and 3-strong) multiplied by the percentage of stained tumor cells; it was defined as low if 1-100, moderate if 101-200, and strong if 201-300. Haverage-score was the average H-score in the triplicate. Restin Haverage-scores were tested for correlations with clinical and pathological characteristics and patient outcome. Restin expression was localized to the cytoplasm, with nuclear enhancement, of 112/113 (99.1%) NSCLCs. Restin Haverage-scores were 0 in 1/113 (0.88%), low in 15/113 (13.3%), moderate in 48/113 (42.5%), and strong in 49/113 (43.4%) NSCLCs. Restin Haverage-scores did not correlate with NSCLC histological subtype, disease stage, recurrence/progression-free, or overall survival. Restin is moderately to strongly expressed in the majority of NSCLC tumors but its expression has no prognostic value in patients with NSCLC.

Data de publicació electrònica: 22-11-2022 Background: The self-reporting of asthma frequently leads to patient misidentification in epidemiological studies. Strategies combining the triangulation of data sources may help to improve the identification of people with asthma. We aimed to combine information from the self-reporting of asthma, medication use and symptoms to identify asthma patterns in the users of an mHealth app. Methods: We studied MASK-air® users who reported their daily asthma symptoms (assessed by a 0-100 visual analogue scale - "VAS Asthma") at least three times (either in three different months or in any period). K-means cluster analysis methods were applied to identify asthma patterns based on: (i) whether the user self-reported asthma; (ii) whether the user reported asthma medication use and (iii) VAS asthma. Clusters were compared by the number of medications used, VAS asthma levels and Control of Asthma and Allergic Rhinitis Test (CARAT) levels. Findings: We assessed a total of 8,075 MASK-air® users. The main clustering approach resulted in the identification of seven groups. These groups were interpreted as probable: (i) severe/uncontrolled asthma despite treatment (11.9-16.1% of MASK-air® users); (ii) treated and partly-controlled asthma (6.3-9.7%); (iii) treated and controlled asthma (4.6-5.5%); (iv) untreated uncontrolled asthma (18.2-20.5%); (v) untreated partly-controlled asthma (10.1-10.7%); (vi) untreated controlled asthma (6.7-8.5%) and (vii) no evidence of asthma (33.0-40.2%). This classification was validated in a study of 192 patients enrolled by physicians. Interpretation: We identified seven profiles based on the probability of having asthma and on its level of control. mHealth tools are hypothesis-generating and complement classical epidemiological approaches in identifying patients with asthma.

Asthma is a heterogeneous disease sharing airway instability but with different biology, risk factors, and response-to-therapy patterns. Biologics have revolutionized the one-size-fits-to-all approach to personalized medicine in severe asthma (SA), which relies on the identification of biomarkers that define distinct endotypes. Thus, blood eosinophils and, to some extent, exhaled nitric oxide (FeNO) can predict the response to approved anti-type 2 (T2) biologics (anti-IgE, anti–IL-5, and anti–IL-4R alpha), whereas age at onset and comorbidities such as anxiety/depression, obesity, reflux, and upper airway disease (UAD) also influence therapeutic responses in SA. In this article, focusing on the predictive value of biomarkers for the therapeutic response to biologics in SA, we first summarize the level of prediction achieved by T2 biomarkers (blood eosinophils, FeNO) and then review whether data support the predictive value of upper airway diagnosis on such outcomes. Post hoc analysis of most studies with T2 biologics suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) and, to a lower extent, allergic rhinitis may help in predicting clinical response. Considering that T2 biologics are now also approved for the treatment of severe CRSwNP, diagnosis of upper airway disease is a key step in determining eligibility for such therapy.

La médecine respiratoire se personnalise au gré d’une meilleure compréhension des mécanismes physiopathologiques sous-jacents aux endotypes des pathologies pulmonaires, fréquentes (SAS, cancer bronchique, BPCO, asthme et allergies) ou plus rares (pathologies interstitielles diffuses, mucoviscidose), de manière complémentaire de soins plus génériques bénéficiant au plus grand nombre (tels que conseils d’éviction environnementale, exercice physique). Cet article décline ces concepts enthousiasmants dans les principales maladies respiratoires en y développant les avancées majeures en 2022.

MASK-air® , a validated mHealth app (Medical Device regulation Class IIa) has enabled large observational implementation studies in over 58,000 people with allergic rhinitis and/or asthma. It can help to address unmet patient needs in rhinitis and asthma care. MASK-air® is a Good Practice of DG Santé on digitally-enabled, patient-centred care. It is also a candidate Good Practice of OECD (Organisation for Economic Co-operation and Development). MASK-air® data has enabled novel phenotype discovery and characterisation, as well as novel insights into the management of allergic rhinitis. MASK-air® data show that most rhinitis patients (i) are not adherent and do not follow guidelines, (ii) use as-needed treatment, (iii) do not take medication when they are well, (iv) increase their treatment based on symptoms and (v) do not use the recommended treatment. The data also show that control (symptoms, work productivity, educational performance) is not always improved by medications. A combined symptom-medication score (ARIA-EAACI-CSMS) has been validated for clinical practice and trials. The implications of the novel MASK-air® results should lead to change management in rhinitis and asthma. info:eu-repo/semantics/publishedVersion

Biomarkers of systemic inflammation/nutritional status have been associated with outcomes in advanced-stage non-small-cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs). However, most of them were not tested in cohorts of patients treated with ICIs in combination with chemotherapy (CT) (ICI + CT) or with CT alone, making it impossible to discriminate a predictive from a prognostic effect. We conducted a single-center retrospective study to search for associations between various baseline biomarkers/scores that reflected the systemic inflammation/nutritional status (Lung Immune Prognostic Index, Modified Lung Immune Prognostic Index, Scottish Inflammatory Prognostic Score, Advanced Lung Cancer Inflammation Index, EPSILoN, Prognostic Nutritional Index, Systemic Immune-Inflammation Index, Gustave Roussy Immune Score, Royal Marsden Hospital Prognostic Score, Lung Immuno-oncology Prognostic Score 3, Lung Immuno-oncology Prognostic Score 4, score published by Holtzman et al., and Glasgow Prognostic Score) and outcomes in metastatic NSCLC treated in a first-line setting either with ICI in monotherapy (cohort 1; n = 75), ICI + CT (cohort 2; n = 56), or CT alone (cohort 3; n = 221). In the three cohorts, the biomarkers/scores were moderately associated with overall survival (OS) and progression-free survival (PFS). Their prognostic performance was relatively poor, with a maximum c-index of 0.66. None of them was specific to ICIs and could help to choose the best treatment modality. The systemic inflammation/nutritional status, associated with outcomes independently of the treatment, is therefore prognostic but not predictive in metastatic NSCLC.

The molecular steps leading to small cell lung cancer (SCLC) development and progression are still poorly understood, resulting in the absence of targeted therapy and an extremely poor prognosis. Activation of Focal Adhesion Kinase (FAK) plays a key role in the invasive behavior of this cancer in vitro. Our hypothesis is that FAK could be a therapeutic target in SCLC. Our work aims to describe a mouse model to study the role of FAK and the antitumoral potential of its inhibition in SCLC in vivo.

Junctional adhesion molecule-A (JAM-A), expressed on the surface of myeloid cells, is required for extravasation at sites of inflammation and may also modulate myeloid cell activation. Infiltration of myeloid cells is a common feature of tumors that drives disease progression, but the function of JAM-A in this phenomenon and its impact on tumor-infiltrating myeloid cells is little understood. Here we show that systemic cancer-associated inflammation in mice enhanced JAM-A expression selectively on circulating monocytes in an IL1β-dependent manner. Using myeloid-specific JAM-A-deficient mice, we found that JAM-A was dispensable for recruitment of monocytes and other myeloid cells to tumors, in contrast to its reported role in inflammation. Single-cell RNA sequencing revealed that loss of JAM-A did not influence the transcriptional reprogramming of myeloid cells in the tumor microenvironment. Overall, our results support the notion that cancer-associated inflammation can modulate the phenotype of circulating immune cells, and we demonstrate that tumors can bypass the requirement of JAM-A for myeloid cell recruitment and reprogramming. ispartof: FRONTIERS IN IMMUNOLOGY vol:13 ispartof: location:Switzerland status: published

Aims: Long-term survival after lung transplantation (LT) is hampered by the occurrence of chronic lung allograft dysfunction (CLAD), manifesting as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS). CLAD is triggered by several factors, e.g. recurrent infections. As immunoglobulin (Ig) A is crucial to ensure mucosal immunity and limit airway microbial load, we explored whether IgA and its epithelial receptor, the polymeric Ig receptor (pIgR) are impaired in BOS. Methods: Bronchoalveolar lavages (BAL, n=120) from LT recipients included in the Cohort for Lung Transplantation were collected at pre-defined timepoints prior to the diagnosis of functional stability (BOS-free, n=30) or BOS (pre-BOS, n=30), and assessed for secretory (S)-IgA. Bronchiolar epithelium pIgR expression was quantified in transbronchial biopsies from BOS-free (n=20), pre-BOS (n=19) and BOS LT recipients (n=12), as well as in end-stage BOS explants (n=15). Results: S-IgA levels were reduced in BAL from pre-BOS LT recipients versus BOS-free (16.1 vs 33.4 µg/ml, p

International audience; No abstract available

(1) Background: High immunosuppressive regimen in lung transplant recipients (LTRs) hampers the immune response to vaccination. We prospectively investigated the immunogenicity of heterologous ChAdOx1 nCoV-19-BNT162b2 mRNA vaccination in an LTR cohort. (2) Methods: Forty-nine COVID-19 naïve LTRs received a two-dose regimen ChAdOx1 nCoV-19 vaccine. A subset of 32 patients received a booster dose of BNT162b2 mRNA vaccine 18 weeks after the second dose. (3) Results: Two-doses of ChAdOx1 nCoV-19 induced poor immunogenicity with 7.2% seropositivity at day 180 and low neutralizing capacities. The BNT162b2 mRNA vaccine induced significant increases in IgG titers with means of 197.8 binding antibody units per milliliter (BAU/mL) (95% CI 0–491.4) and neutralizing antibodies, with means of 76.6 AU/mL (95% CI 0–159.6). At day 238, 32.2% of LTRs seroconverted after the booster dose. Seroneutralization capacities against Delta and Omicron variants were found in only 13 and 9 LTRs, respectively. Mycophenolate mofetil and high-dose corticosteroids were associated with a weak serological response. (4) Conclusions: The immunogenicity of a two-dose ChAdOx1 nCoV-19 vaccine regimen was very poor in LTRs, but was significantly enhanced after the booster dose in one-third of LTRs. In immunocompromised individuals, the administration of a fourth dose may be considered to increase the immune response against SARS-CoV-2.

Bronchoalveolar cell count at diagnosis is not linked to lung function decline and exacerbations in a large prospective cohort of idiopathic pulmonary fibrosis patients.

Funding Information: IA reports personal fees from Roxall, Menarini, UCB, Faes Farma, Sanofi, Bial, Amgen, Abbott, Bayer, Organon. SBA reports grants from TEVA, personal fees from TEVA, AstraZeneca, Boehringer Ingelheim, GSK, Sanofi, Mylan. JB reports personal fees from Chiesi, Cipla, Hikma, Menarini, Mundipharma, Mylan, Novartis, Sanofi‐Aventis, Takeda, Teva, Uriach, other from KYomed‐Innov, personal fees from Purina, other from MASK‐air. VC reports personal fees from Thermofisher. PCM reports personal fees from Abbvie, AZ, Bial, GSK, Mylan, Medinfar, Novartis, Sanofi. LC reports personal fees from Malesci, Menarini, Astra Zeneca, Novartis. AC reports grants and personal fees from Astrazeneca, GSK, Sanofi, personal fees from Boehringer‐Ingelheim, Chiesi, Glenmark, Novartis, personal fees from Mylan, Abdi‐Ibrahim. PD reports personal fees and non‐financial support from Stallergenes Greer, ALK‐Abello, Astra Zeneca, CHIESI, MYLAN/Meda Pharma, Novartis, GlaxoSmithKline, Sanofi, IQVIA personal fees from MENARINI. JAFonseca reports participation in SME that has mHealth technologies for patients with asthma. JCI reports personal fees from Abbott Ecuador, Bago Bolivia, Faes Farma, Laboratorios Casasco, Sanofi. LK reports grants and personal fees from Allergopharma, LETI Pharma,MEDA/Mylan, Sanofi, personal fees from HAL Allergie, Allergy Therapeut., Cassella med, grants from ALK Abelló, Stallergenes, Quintiles, ASIT biotech, Lofarma, AstraZeneca, GSK, Inmunotk, and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. VK reports other from Norameda, BerlinCHemie Menarini. PK reports personal fees from Adamed, AstraZeneca, Berlin Chemie Menarini, Boehringer Ingelheim, Chiesi, GSK, Novartis, Polpharma. DLL reports personal fees from Allakos, Amstrong, Astrazeneca, Chiesi, DBV Technologies, Grunenthal, GSK, Mylan/Viatris, Menarini, MSD, Novartis, Pfizer, Sanofi, Siegfried, UCB, Alakos, Gossamer, Carnot, grants from Sanofi, Astrazeneca, Novartis, Circassia, UCB, GSK, Purina institute, Abvvie, Lilly, Pfizer. BL reports grants and personal fees from Meda, personal fees from Glenamrk. RL reports grants and personal fees from GSK, AZ, Chiesi, personal fees from Novartis, Sanofi. MM reports personal fees from Novartis, Gsk, Menarini, Az, Chiesi, Sanofi, Pfizer. RM reports personal fees from Angelini Pharma ALK, Allergopharma, Allergy Therapeutics, Friulchem, Hexal, Servier, Klosterfrau, Bayer, FAES, GSK, MSD, Johnson&Johnson, Meda, Stada, UCB, Nuvo, Menarini, Mundipharma, Pohl‐Boskamp, Laboratoire de la Mer, Sidroga, Lek, PRO‐AdWise, grants and personal fees from Bencard, Stallergenes, Ursapharm, HAL BV, grants from Leti, Optima, BitopAG, Hulka, Inmunotek, Cassella‐med GmbH & Co. KG, ASIT biotech, grants, personal fees and non‐financial support from Lofarma, non‐financial support from Roxall, Atmos, Bionorica, Otonomy, Ferrero, personal fees and non‐financial support from Novartis. OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., GlaxoSmithKline, personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS, Paul‐Martini‐Stiftung (PMS), Regeneron Pharmaceuticals Inc., RG Aerztefortbildung, Institut für Disease Management, Springer GmbH, AstraZeneca, IQVIA Commercial, Ingress Health, grants from Pohl‐Boskamp, Inmunotek S.L., Biomay, Circassia. NGPapadopoulos reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. ATB reports personal fees from AstraZeneca, GSK, Novartis, IQVIA/Abbvie, Mylan, Bial, Leti, grants and personal fees from Teva. STS reports personal fees from ERT, Roche products, Novartis, Sanofi Pharma, AstraZeneca, ALK‐ Abelló grants from Glaxo Smith Kline. IT reports grants from GSK, Boehringer Ingelheim, AZ, personal fees from Novartis, Astra Zeneca, Chiesi, TZ reports Organizational affiliations: Committee member: WHO‐Initiative “Allergic Rhinitis and Its Impact on Asthma” (ARIA); Member of the Board: German Society for Allergy and Clinical Immunology (DGAKI); Head: European Centre for Allergy Research Foundation (ECARF). President: Global Allergy and Asthma European Network (GA2LEN); Member: Committee on Allergy Diagnosis and Molecular Allergology, World Allergy Organization (WAO). Funding Information: MASK‐air® has been supported by EU grants (POLLAR, EIT Health; Structural and Development Funds, Twinning, EIP on AHA and H2020) and educational grants from Mylan‐Viatris, ALK, GSK, Novartis and Uriach 1 1 Publisher Copyright: © 2022 European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd. Background: Different treatments exist for allergic rhinitis (AR), including pharmacotherapy and allergen immunotherapy (AIT), but they have not been compared using direct patient data (i.e., “real-world data”). We aimed to compare AR pharmacological treatments on (i) daily symptoms, (ii) frequency of use in co-medication, (iii) visual analogue scales (VASs) on allergy symptom control considering the minimal important difference (MID) and (iv) the effect of AIT. Methods: We assessed the MASK-air® app data (May 2015–December 2020) by users self-reporting AR (16–90 years). We compared eight AR medication schemes on reported VAS of allergy symptoms, clustering data by the patient and controlling for confounding factors. We compared (i) allergy symptoms between patients with and without AIT and (ii) different drug classes used in co-medication. Results: We analysed 269,837 days from 10,860 users. Most days (52.7%) involved medication use. Median VAS levels were significantly higher in co-medication than in monotherapy (including the fixed combination azelastine-fluticasone) schemes. In adjusted models, azelastine-fluticasone was associated with lower average VAS global allergy symptoms than all other medication schemes, while the contrary was observed for oral corticosteroids. AIT was associated with a decrease in allergy symptoms in some medication schemes. A difference larger than the MID compared to no treatment was observed for oral steroids. Azelastine-fluticasone was the drug class with the lowest chance of being used in co-medication (adjusted OR = 0.75; 95% CI = 0.71–0.80). Conclusion: Median VAS levels were higher in co-medication than in monotherapy. Patients with more severe symptoms report a higher treatment, which is currently not reflected in guidelines. publishersversion published

The goal of the present study is to assess the relationship between functional respiratory parameters measured by the forced oscillation technique (FOT) in COPD patients and (1) dyspnea; (2) inspiratory capacity (IC), along with the variations occurring subsequent to bronchodilation. This cross-sectional study analyzed 40 stable COPD patients. Dyspnea was assessed by means of the San Diego Shortness of Breath Questionnaire. Forced oscillations were measured before and after bronchodilation by means of routine pulmonary function tests (PFTs). The reactance parameters measured by the FOT correlated with dyspnea (AX5: r=0.46; P=0.003) similarly to IC (r=-0.46; P=0.003). Changes in AX5 following bronchodilation led to a predicted 12% and 200mL improvement in IC, AX5 (area under the ROC curve=0.85, P

International audience; Bruxism is a heterogeneous condition related to various underlying mechanisms, including the presence of OSA. This case report illustrates that sleep mandibular movement monitoring and analysis could provide a useful opportunity for detection of both sleep bruxism and respiratory effort. The current case suggests that tracking of respiratory effort could enable evaluation of bruxism and its potential interactions. Successful treatment of sleep-related respiratory effort may lead to improved or resolution of bruxism in cases where such a causal relationship does exist.

Background and objectivesAzithromycin was rapidly adopted as a repurposed drug to treat coronavirus disease 2019 (COVID-19) early in the pandemic. We aimed to evaluate its efficacy in patients hospitalised for COVID-19.MethodsIn a series of randomised, open-label, phase 2 proof-of-concept, multicentre clinical trials (Direct Antivirals Working against the novel coronavirus (DAWn)), several treatments were compared with standard of care. In 15 Belgian hospitals, patients hospitalised with moderate to severe COVID-19 were allocated 2:1 to receive standard of care plus azithromycin or standard of care alone. The primary outcome was time to live discharge or sustained clinical improvement, defined as a two-point improvement on the World Health Organization (WHO) ordinal scale sustained for at least 3 days.ResultsPatients were included between April 22 and December 17, 2020. When 15-day follow-up data were available for 160 patients (56% of preset cohort), an interim analysis was performed at request of the independent Data Safety and Monitoring Board. Subsequently, DAWn-AZITHRO was stopped for futility. In total, 121 patients were allocated to the treatment arm and 64 patients to the standard-of-care arm. We found no effect of azithromycin on the primary outcome with a hazard ratio of 1.044 (95% CI 0.772–1.413; p=0.7798). None of the predefined subgroups showed significant interaction as covariates in the Fine–Gray regression analysis. No benefit of azithromycin was found on any of the short- and longer-term secondary outcomes.ConclusionTime to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19.

Jean-Louis Pepin,1,* Nhat-Nam Le-Dong,2,* Valérie Cuthbert,3 Nathalie Coumans,3 Renaud Tamisier,1 Atul Malhotra,4 Jean-Benoit Martinot3,5 1HP2 Laboratory, Inserm U1300, University Grenoble Alpes, Grenoble, France; 2Sunrise, Namur, Belgium; 3Sleep Laboratory, CHU Université Catholique de Louvain (UCL) Namur Site Sainte-Elisabeth, Namur, Belgium; 4University of California San Diego, La Jolla, CA, USA; 5Institute of Experimental and Clinical Research, UCL Bruxelles Woluwe, Brussels, Belgium*These authors contributed equally to this workCorrespondence: Jean-Benoit Martinot, Centre du Sommeil et de la Vigilance, CHU-UCL Namur Site Ste Elisabeth, 15 Place Louise Godin, Namur, 5000, Belgium, Tel +32 495502608, Fax +32 81570754, Email martinot.j@respisom.bePurpose: Differentiation between obstructive and central apneas and hypopneas requires quantitative measurement of respiratory effort (RE) using esophageal pressure (PES), which is rarely implemented. This study investigated whether the sleep mandibular movements (MM) signal recorded with a tri-axial gyroscopic chin sensor (Sunrise, Namur, Belgium) is a reliable surrogate of PES in patients with suspected obstructive sleep apnea (OSA).Patients and Methods: In-laboratory polysomnography (PSG) with PES and concurrent MM monitoring was performed. PSGs were scored manually using AASM 2012 rules. Data blocks (n=8042) were randomly sampled during normal breathing (NB), obstructive or central apnea/hypopnea (OA/OH/CA/CH), respiratory effort-related arousal (RERA), and mixed apnea (MxA). Analyses were evaluation of the similarity and linear correlation between PES and MM using the longest common subsequence (LCSS) algorithm and Pearson’s coefficient; description of signal amplitudes; estimation of the marginal effect for crossing from NB to a respiratory disturbance for a given change in MM signal using a mixed linear-regression.Results: Participants (n=38) had mild to severe OSA (median AH index 28.9/h; median arousal index 23.2/h). MM showed a high level of synchronization with concurrent PES signals. Distribution of MM amplitude differed significantly between event types: median (95% confidence interval) values of 0.60 (0.16– 2.43) for CA, 0.83 (0.23– 4.71) for CH, 1.93 (0.46– 12.43) for MxA, 3.23 (0.72– 18.09) for OH, and 6.42 (0.88– 26.81) for OA. Mixed regression indicated that crossing from NB to central events would decrease MM signal amplitude by – 1.23 (CH) and – 2.04 (CA) units, while obstructive events would increase MM amplitude by +3.27 (OH) and +6.79 (OA) units (all p< 10− 6).Conclusion: In OSA patients, MM signals facilitated the measurement of specific levels of RE associated with obstructive, central or mixed apneas and/or hypopneas. A high degree of similarity was observed with the PES gold-standard signal.Keywords: obstructive sleep apnea, respiratory effort, mandibular movements, esophageal pressure

Chronic obstructive pulmonary disease (COPD), asthma and cystic fibrosis (CF) are distinct respiratory diseases that share features such as the obstruction of small airways and disease flare-ups that are called exacerbations and are often caused by infections. Along the airway epithelium, immunoglobulin (Ig) A contributes to first line mucosal protection against inhaled particles and pathogens. Dimeric IgA produced by mucosal plasma cells is transported towards the apical pole of airway epithelial cells by the polymeric Ig receptor (pIgR), where it is released as secretory IgA. Secretory IgA mediates immune exclusion and promotes the clearance of pathogens from the airway surface by inhibiting their adherence to the epithelium. In this review, we summarize the current knowledge regarding alterations of the IgA/pIgR system observed in those major obstructive airway diseases and discuss their implication for disease pathogenesis.

Background: Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. Objectives: To further characterize the interactions between induced sputum inflammatory patterns, asthma-related outcomes and the high- or low-molecular-weight category of causal agents in a large cohort of subjects with OA. Methods: This multicenter, retrospective, cross-sectional study was conducted among 296 subjects with OA ascertained by a positive specific inhalation challenge who completed induced sputum assessment before and 24 hours after challenge exposure. Results: Multivariate logistic regression analysis revealed that sputum eosinophilia ≥3% was significantly associated with a high dose of inhaled corticosteroid (odds ratio [95% confidence interval], 1.31 [1.11-1.55] for each 250-μg increment in daily dose), short-acting 2-agonist use less than once a day (3.54 [1.82-7.00]), and the level of baseline nonspecific bronchial hyperresponsiveness (mild: 2.48 [1.21-5.08]); moderate/severe: 3.40 [1.44-8.29]). Sputum neutrophilia ≥76% was associated with age (1.06 [1.01-1.11]), male gender (3.34 [1.29-9.99]), absence of corticosteroid use (5.47 [2.09-15.16]), short-acting 2-agonist use once or more a day (4.09 [1.71-10.01]), ≥2 severe exacerbations during the last 12 months at work (4.22 [1.14-14.99]), and isolated early reactions during the SIC (4.45 [1.85-11.59]). Conclusion: The findings indicate that sputum inflammatory patterns in subjects with OA are associated with distinct phenotypic characteristics and further highlight the differential effects of neutrophils and eosinophils on asthma-related outcomes. These associations between inflammatory patterns and clinical characteristics share broad similarities with what has been reported in nonoccupational asthma and are not related to the type of causal agent.

INTRODUCTION: The PROOF registry is a prospective, observational study that aimed to monitor disease progression in a real-world cohort of patients with idiopathic pulmonary fibrosis (IPF). Here, longitudinal quality-of-life (QoL) outcomes, healthcare resource use (HCRU), and the association between QoL and mortality in patients enrolled in the PROOF registry are presented. METHODS: QoL outcomes (St. George's Respiratory Questionnaire [SGRQ], EuroQoL-5 dimensions-5 levels Health Questionnaire [EQ-5D-5L], EuroQoL-5 dimensions Health Questionnaire [EQ-5D] visual analogue scale [VAS] and cough VAS) and HCRU were collected for all patients. Associations between baseline QoL and mortality were assessed using univariate and multivariate analyses. During multivariate analyses, individual QoL measures were adjusted for the following covariates: age, sex, percent predicted forced vital capacity, percent predicted diffusing capacity of the lungs for carbon monoxide, smoking status, and supplementary oxygen use at registry inclusion. RESULTS: In total, 277 patients were enrolled in the PROOF registry. During the follow-up period, worsening in cough VAS score, SGRQ symptom score, and SGRQ activity score was observed, while EQ-5D VAS, SGRQ total score, and SGRQ impact score remained stable. During univariate analyses, EQ-5D VAS and all SGRQ sub-scores and total score at baseline were associated with mortality; however, during multivariate analyses, only the SGRQ total score, SGRQ impact score, and SGRQ symptom score at baseline were associated with mortality. During the follow-up period, 261 (94.2%) patients required an outpatient consultation (IPF- or non-IPF-related) and there were 182 hospitalizations in total, most of which were respiratory related (66.5%). CONCLUSIONS: The PROOF registry provided valuable, real-world data on the association between baseline QoL and mortality, and longitudinal HCRU and QoL outcomes in patients with IPF over 24 months and identified that SGRQ may be an independent prognostic factor in IPF. ispartof: PULMONARY THERAPY vol:8 issue:2 pages:181-194 ispartof: location:United States status: published

Intracameral cefuroxime is recommended at the end of cataract surgery, since it has been shown to substantially reduce the rate of postoperative endophthalmitis, a severe postoperative infectious complication [...].

Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) have improved the prognosis of advanced-stage non-small cell lung cancer (NSCLC) with ALK rearrangement, but resistance mechanisms limit their efficacy. We describe the case of a 63-year-old man with a stage cIVA ALK-rearranged lung adenocarcinoma who developed a BRAF A598-T599insV mutation as a potential resistance mechanism to alectinib, a second-generation ALK TKI. He was treated with an association of BRAF and MEK inhibitors but death occurred two months after treatment initiation in a context of tumor progression and toxicity. Based on this first report of BRAF A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of BRAF mutation in NSCLC, and BRAF A598-T599insV mutation in other cancers.

International audience; Over recent years positive airway pressure (PAP) remote monitoring has transformed the management of obstructive sleep apnea and produced a large amount of data. Accumulated PAP data provide valuable and objective information regarding patient treatment adherence and efficiency. However, the majority of studies analyzing longitudinal PAP remote monitoring summarize data trajectories in static and simplistic metrics for PAP adherence and the residual apnea-hypopnea index (AHI) by using mean or median values. The aims of this article are to suggest directions for improving data cleaning and processing and to address major concerns for data science applications including: 1) conditions for rAHI reliability, 2) lack of standardization of indicators provided by different PAP models, 3) missing values and 4) consideration of treatment interruptions. To allow fair comparison between studies and to avoid biases in computation, PAP data processing and management should be conducted rigorously with these points in mind. PAP remote monitoring data contain a wealth of information that is currently underused in the field of sleep research. Improving the quality and standardizing data handling could facilitate data sharing among specialists worldwide and enable artificial intelligence strategies to be applied in the field of sleep apnea.

Data de publicació electrònica: 03-11-2022 Introduction: Data from mHealth apps can provide valuable information on rhinitis control and treatment patterns. However, in MASK-air®, these data have only been analyzed cross-sectionally, without considering the changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. Methods: We analyzed MASK-air® data, assessing the weeks for which patients had answered a rhinitis daily questionnaire on all 7 days. We firstly used k-means clustering algorithms for longitudinal data to define clusters of weeks according to the trajectories of reported daily rhinitis symptoms. Clustering was applied separately for weeks when medication was reported or not. We compared obtained clusters on symptoms and rhinitis medication patterns. We then used the latent class mixture model to assess the robustness of results. Results: We analyzed 113,239 days (16,177 complete weeks) from 2590 patients (mean age ± SD = 39.1 ± 13.7 years). The first clustering algorithm identified ten clusters among weeks with medication use: seven with low variability in rhinitis control during the week and three with highly-variable control. Clusters with poorly-controlled rhinitis displayed a higher frequency of rhinitis co-medication, a more frequent change of medication schemes and more pronounced seasonal patterns. Six clusters were identified in weeks when no rhinitis medication was used, displaying similar control patterns. The second clustering method provided similar results. Moreover, patients displayed consistent levels of rhinitis control, reporting several weeks with similar levels of control. Conclusions: We identified 16 patterns of weekly rhinitis control. Co-medication and medication change schemes were common in uncontrolled weeks, reinforcing the hypothesis that patients treat themselves according to their symptoms.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background: Co-medication is common among patients with allergic rhinitis (AR), but its dimension and patterns are unknown. This is particularly relevant since AR is understood differently across European countries, as reflected by rhinitis-related search patterns in Google Trends. This study aims to assess AR co-medication and its regional patterns in Europe, using real-world data. Methods: We analysed 2015–2020 MASK-air® European data. We compared days under no medication, monotherapy and co-medication using the visual analogue scale (VAS) levels for overall allergic symptoms (‘VAS Global Symptoms’) and impact of AR on work. We assessed the monthly use of different medication schemes, performing separate analyses by region (defined geographically or by Google Trends patterns). We estimated the average number of different drugs reported per patient within 1 year. Results: We analysed 222,024 days (13,122 users), including 63,887 days (28.8%) under monotherapy and 38,315 (17.3%) under co-medication. The median ‘VAS Global Symptoms’ was 7 for no medication days, 14 for monotherapy and 21 for co-medication (p, This study was funded by ARIA. MASK-air® has been supported by EU grants (EU Structural and Development grant, POLLAR: EIT Health and Structural and Development Funds) and educational grants from Mylan-Viatris, ALK, GSK, Novartis and Uriach. Open Access funding enabled and organized by Projekt DEAL

Medical writing and editorial assistance were provided by Tim Ibbotson, PhD, of ApotheCom (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Statistical analysis was done by Herbert Thijs, Sofie Van Waes, and Filip Deforce (DICE). This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. The authors thanks to Hermine Leroi for the operational support and assistance during this project. The authors thank Katrien Willaert for the initiation of the study and its study design.

Aims. Long-term survival after lung transplantation (LT) is hampered by the occurrence of chronic lung allograft dysfunction (CLAD). CLAD may manifest as bronchiolitis obliterans syndrome (BOS) or restrictive allograft syndrome (RAS), and may be triggered by several factors, e.g. recurrent post-transplant infections (1). As immunoglobulin (Ig) A is crucial to ensure mucosal immunity and limit airway microbial load(2), we explored whether IgA and its epithelial receptor, the polymeric Ig receptor (pIgR) are impaired in BOS. Methods. Bronchoalveolar lavages (BAL, n=120) and sera (n=179) from LT recipients included in the Cohort for Lung Transplantation (COLT) were collected at pre-defined timepoints after LT, and prior to the diagnosis of functional stability (BOS-free, n=30) or BOS (pre-BOS, n=30). BAL were assessed for secretory (S)-IgA, while sera were assessed for IgA, S-IgA and secretory component (SC, released by pIgR apical cleavage following transcytosis). pIgR expression at the bronchiolar epithelium pIgR level was quantified in transbronchial biopsies from BOS-free (n=20), pre-BOS (n=19) and BOS LT recipients (n=12), as well as in end-stage BOS explants (n=15). Results. S-IgA levels were reduced in BAL from pre-BOS LT recipients versus BOS-free (Fig 1A; 16.1 vs 33.4 µg/ml, p

Objective: Metastasized non-small cell lung cancer (NSCLC) with an anaplastic lymphoma kinase (ALK) rearrangement is usually sensitive to a range of ALK-tyrosine kinase inhibitors. ALK-positive NSCLC have been identified in pivotal phase III trials with fluorescence in situ hybridization (ALK FISH +). These tumors are also expressing the fusion product (ALK immunohistochemistry (IHC) +). However, discrepant cases occur, including ALK IHC + FISH-. The aim of this study was to collect ALK IHC + cases and compare within this group response to crizotinib treatment of ALK FISH + cases with ALK FISH- cases.Materials and methods: In this European prospective multicenter research study patients with Stage IV ALK IHC + NSCLC treated with crizotinib were enrolled. Tumor slides were validated centrally for ALK IHC and ALK FISH.Results: Registration of 3523 ALK IHC tests revealed a prevalence of 2.7% (n = 94) ALK IHC + cases. Local ALK FISH analysis resulted in 48 concordant (ALK IHC + /FISH +) and 16 discordant (ALK IHC + /FISH-) cases. Central validation revealed 37 concordant and 7 discordant cases, 5 of which had follow-up. Validation was hampered by limited amount of tissue in biopsy samples. The PFS at 1 year for ALK concordant and discordant was 58% and 20%, respectively (HR = 2.4; 95% CI: 0.78-7.3; p = 0.11). Overall survival was significantly better for concordant cases than discordant cases after central validation (HR = 4.5; 95% CI = 1.2-15.9; p = 0.010.Conclusion: ALK IHC + FISH- NSCLC is infrequent and associated with a worse outcome on personalized treatment. A suitable predictive testing strategy may be to screen first with IHC and then confirm with FISH instead of considering ALK IHC equivalent to ALK FISH according to the current guidelines.

CONTEXTE : Bien que l’évaluation de l’inflammation bronchique, par expectoration induite, permette d’identifier différents phénotypes, chez les patients asthmatiques, il n’y a que peu d’informations sur le déterminant du pattern d’inflammation bronchique chez les patients présentant un asthme professionnel par sensibilisation. OBJECTIF : Déterminer si le pattern d’inflammation bronchique, déterminé par expectoration induite, permet de définir des phénotypes cliniques distincts. MÉTHODE : Cette étude multicentrique rétrospective a été réalisée auprès de 372 patients, présentant un asthme professionnel diagnostiqué par test d’exposition spécifique, qui étaient recrutés par le biais de la cohorte du groupe European network for Phenotypique of Ocupational Asthma. Chaque patient a bénéficié d’une expectoration induite avant et après test d’exposition spécifique. L’éosinophilie bronchique était définie par un pourcentage d’éosinophiles supérieur ou égal à 3 % dans l’expectoration induite, après test d’exposition spécifique, alors que la neutrophilie bronchique était définie par un pourcentage de neutrophiles supérieur ou égal à 76 %. RÉSULTATS : Au total, 268 (72 %) et 42 patients (11 %) présentaient respectivement une éosinophilie et une neutrophilie bronchique. Les analyses de régression logistique ont mis en évidence une association entre l’éosinophilie bronchique et l’exposition aux agents de haut poids moléculaire (odds ratio [OR], 1,89 ; IC 95 % 1,18–3,04), l’asthme persistant modéré (OR, 3,17 ; IC 95 %, 1,43–7,0) et l’asthme persistant sévère (OR, 2,39 ; IC 95 %, 1,06–5,43). La neutrophilie bronchique était associée à l’âge (OR pour chaque année supplémentaire, 1,04 ; IC 95 % 1,01–1,08), au genre masculin (OR, 2,83 : IC 95 %, 1,14–6,87), à l’asthme persistant léger (OR, 3,26 ; IC 95 %, 1,24–8,88), et à la dysphonie (OR, 2,83 ; IC95 %, 1,14–6,87). CONCLUSIONS : La majorité des patients avec un asthme professionnel par sensibilisation présentait une éosinophilie bronchique post-test d’exposition spécifique. L’éosinophilie et la neutrophilie, dans les expectorations induites, permettaient de définir des phénotypes cliniques différents, notamment en termes de sévérité et selon l’agent causal. [Phenotypes of occupational asthma defined with induced sputum after specific inhalation challenge] RATIONALE : Although the non-invasive assessment of airway inflammation through the induced sputum (IS) technique identified distinct asthma phenotypes, there is few information on the determinants of airway inflammatory pattern in sensitizer-induced occupational asthma (OA). AIM : To investigate whether the pattern of airway inflammation in IS is associated with distinct clinical phenotypes of OA. METHODS : This retrospective multicentric study was conducted among 372 patients with OA confirmed by a positive specific inhalation challenge (SIC) who were recruited in the European network for the Phenotyping of OCupational Asthma cohort (2006–2018). Each patient underwent an analysis of IS before and 24 hours after the SIC. Sputum eosinophilia and neutrophilia were defined by the presence of ≥ 3% eosinophils and ≥ 76% neutrophils in sputum samples collected after the SIC. RESULTS : In total, 268 (72%) and 42 patients (11%) exhibited sputum eosinophilia and neutrophilia, respectively. Multivariate logistic regression analysis revealed that eosinophilia was associated with exposure to a high molecular weight agent (odds ratio [OR], 1.89; 95% CI, 1.18–3.04), moderate asthma (OR, 3.17; 95% CI, 1,43–7.0) and severe asthma (OR, 2.39; 95% CI, 1.06–5.43). Sputum neutrophilia was associated with age (OR for each additional year, 1.04; 95% CI, 1.01–1.08), male gender (OR, 2.74; 95% CI, 1,21–6.8), mild asthma (OR, 3.26; 95% CI, 1.24–8.88), and dysphonia (OR, 2.83; 95% CI, 1.14–6.87). CONCLUSIONS : Sputum eosinophilia post-SIC was predominant in OA patients. Sputum eosinophilia and neutrophilia were associated with distinct clinical phenotypes of OA, especially in terms of causal agents and asthma severity.

Introduction: Health Care System - The kingdom of Belgium with its capital Brussels is located in Western Europe (Fig. 1) and has a population of 11,492,641 inhabitants (January 2020) for a surface of 30,689 km2. The country is a member of the European Union (EU) and federally organized with a Dutch-speaking majority in the northern Flemish region, a French-speaking region (Wallonia) in the south, and the Brussels capital region. Its population is mainly of Caucasian ethnicity, with 10% immigrants from different non-EU countries, mostly Africa and Middle East. [...]

Purpose Lung transplant recipients (LTR) are at higher risk to develop severe SARS-CoV2 pneumonia, due to the immunosuppressive regimen, which further hampers their immune response to vaccination. Indeed, is has been shown that LTR mount weak antibody response after SARS-CoV2 mRNA vaccination. Nevertheless, the immunogenicity of ChAdOx1 nCoV-19 vaccine has not yet been studied in LTR. Methods 49 lung-transplant SARS-CoV2 seronegative recipients were enrolled in a prospective cohort study and received the two doses regimen, day 0 and day 90, of the ChAdOx1 nCoV-19 vaccine. Immune response was assessed by measuring total anti-SARS-CoV2 antibodies (Anti-SARS-CoV2 total Ig immunoassay, Ortho Clinical Diagnostics, USA) at D0, D24, D84, D112 and D180. Endpoints At D180, 25% of LTR had positive total antibody levels (positivity threshold, > 1 (sample signal/threshold value). Age, CMV status, gender and initial respiratory disease had no influence on the immune response. Immune response was improved in patients whose immunosuppressive regimen did not include mycophenolate mofetil (53% versus 0%, p < 0.0001), and in patients who were transplanted for more than 18 months (0% versus 41%, p < 0.05), probably due to more aggressive immunosuppressive regimen in recently transplanted patients. Conclusions Immunogenicity of ChAdOx1 nCoV-19 vaccine is poor in LTR, with only one in four patients mounting significant anti-SARS-CoV2 immune response at D180. Of note, according to expert recommendations, most LTR received an heterologous booster dose with a SARS-CoV2 mRNA vaccine (BNT162b2). Additional serological analyses are planned to decipher whether vaccinal response is improved after the third dose in LTR. Results will be updated accordingly and presented at the 42nd ISHLT Congress.

Mucosal surfaces are lined by epithelial cells, which provide a complex and adaptive module that ensures first-line defense against external toxics, irritants, antigens, and pathogens. The underlying mechanisms of host protection encompass multiple physical, chemical, and immune pathways. In the lung, inhaled agents continually challenge the airway epithelial barrier, which is altered in chronic diseases such as chronic obstructive pulmonary disease, asthma, cystic fibrosis, or pulmonary fibrosis. In this review, we describe the epithelial barrier abnormalities that are observed in such disorders and summarize current knowledge on the mechanisms driving impaired barrier function, which could represent targets of future therapeutic approaches.

Funding Information: BSreports personal fees from Allergopharma, during the conduct of the study; grants from National Health Programm, grant, personal fees from Polpharma, ASTRA, personal fees from Mylan, Adamed, patient ombudsman, national Centre for Research and Development, Polish Allergology Society. Funding Information: NGP reports personal fees from Novartis, Nutricia, HAL, MENARINI/FAES FARMA, SANOFI, MYLAN/MEDA, BIOMAY, AstraZeneca, GSK, MSD, ASIT BIOTECH, Boehringer Ingelheim, grants from Gerolymatos International SA, Capricare. Funding Information: CA reports grants from Allergopharma, grants from Idorsia, Swiss National Science Foundation, Christine Kühne‐Center for Allergy Research and Education, European Commission's Horison's 2020 Framework Programme, Cure, Novartis Research Institutes, Astra Zeneca, scibase, advisory role in Sanofi/Regeneron, grants from Glakso Smith‐Kline, advisory role in scibase. Funding Information: MJTreports grants from European Commission, SEAIC, ISCIII, personal fees from Diater laboratory, Leti laboratory, Aimmune Therapeutics. Funding Information: LK reports grants and personal fees from Allergopharma, MEDA/Mylan, LETI Pharma, Sanofi, grants from Stallergenes, Quintiles, ASIT biotech, grants from ALK Abelló, Lofarma, AstraZeneca, GSK, Inmunotk, personal fees from Allergy Therapeut., HAL Allergie, Cassella med; and Membership: AeDA, DGHNO, Deutsche Akademie für Allergologie und klinische Immunologie, HNO‐BV, GPA, EAACI. Funding Information: DPreports grants and personal fees from GlaxoSmithKline, personal fees from Menarini, Pliva, Belupo, AbbVie, Novartis, MSD, Chiesi, Revenio, personal fees and non‐financial support from Boehringer Ingelheim, non‐financial support from Philips. Funding Information: OP reports grants and personal fees from ALK‐Abelló, Allergopharma, Stallergenes Greer, HAL Allergy Holding B.V./HAL Allergie GmbH, Bencard Allergie GmbH/Allergy Therapeutics, Lofarma, ASIT Biotech Tools S.A., Laboratorios LETI/LETI Pharma, Anergis S.A., Glaxo Smith Kline, grants from Biomay, Circassia, Pohl‐Boskamp, Inmunotek S.L., personal fees from MEDA Pharma/MYLAN, Mobile Chamber Experts (a GA2LEN Partner), Indoor Biotechnologies, Astellas Pharma Global, EUFOREA, ROXALL Medizin, Novartis, Sanofi‐Aventis and Sanofi‐Genzyme, Med Update Europe GmbH, streamedup! GmbH, John Wiley and Sons, AS. Copyright: Copyright 2021 Elsevier B.V., All rights reserved. publishersversion published

TO THE EDITOR, In industrialized and developing countries, occupational asthma (OA) is one of the most common chronic occupational respiratory diseases. Worldwide, especially in developing countries, OA remains under-recognized and poorly diagnosed. [...]

BACKGROUND: Asthmatics have accelerated lung function decline over time compared with healthy individuals. OBJECTIVE: To evaluate risk factors for accelerated lung function decline. METHODS: In a longitudinal analysis on severe asthmatics enrolled in the Belgian Severe Asthma Registry with at least 2 visits a minimum of 12 months apart, we compared characteristics of patients with and without decline (loss of postbronchodilation forced expiratory volume in 1 s [FEV1] (% predicted)/y greater than zero) over time. Multiple linear regression was applied to study the factors independently associated with FEV1 decline. RESULTS: In the overall population (n = 318), median annual FEV1 decline was 0.27 (-4.22 to 3.80) % predicted/y over a period of 23 months (12-41 months). Asthma was less controlled at baseline in nondecliners than in decliners (53%). Lung function and residual volume at baseline were higher in the declining group. Decliners presented with increased bronchial reactivity (ie, a lower provocative concentration of methacholine causing a 20% fall in FEV1) at baseline. Twenty-five percent of nondecliners were started on anti-interleukin-5 (anti-IL-5) for severe eosinophilic asthma during the study compared with 10% of decliners. The multivariable model suggested that Asthma Control Questionnaire score at baseline, late-onset asthma, and addition of anti-IL-5 during follow-up were associated with lower FEV1 decline, independently from other variables such as evolution in exacerbations, smoking status, inhaled corticosteroids or oral corticosteroids dose, or add-on anti-immunoglobulin E over time, whereas reversibility to salbutamol and higher FEV1 were associated with accelerated FEV1 decline. CONCLUSIONS: Add-on therapy with anti-IL-5 in severe eosinophilic asthma was associated with an attenuated FEV1 decline. The causality of this observation should, however, be confirmed in future prospective controlled studies. (C) 2021 American Academy of Allergy, Asthma & Immunology

Background: ANDHI was done to assess the efficacy of benralizumab, including onset of effect and impact on health-related quality of life (HRQOL), exacerbation rate, lung function, and nasal polyposis symptoms. Methods: This phase 3b, randomised, double-blind, parallel-group, placebo-controlled ANDHI study was completed in adults (aged 18–75 years) with severe eosinophilic asthma with at least 2 exacerbations in the previous year, despite high-dose inhaled corticosteroid plus additional controllers, screening blood eosinophil counts of at least 150 cells per μL, and an Asthma Control Questionnaire 6 (ACQ-6) score of 1·5 or more. Patients who met eligibility criteria were randomly assigned (2:1; stratified by previous exacerbation count [two, or three or more], maintenance oral corticosteroid use, and region), using an integrated web-based response system, to receive benralizumab at 30 mg every 8 weeks (first three doses given 4 weeks apart) or matched placebo for 24 weeks. Primary efficacy measure was annualised asthma exacerbation rate, with rate ratio (RR) calculated over the approximate 24-week follow-up. Secondary efficacy measures included change from baseline to end of treatment (week 24) in St George's Respiratory Questionnaire (SGRQ) total score (key secondary endpoint), FEV1, peak expiratory flow (PEF), ACQ-6, Predominant Symptom and Impairment Assessment (PSIA), Clinician Global Impression of Change (CGI-C), Patient Global Impression of Change (PGI-C), and Sino-Nasal Outcome Test-22 (SNOT-22). All efficacy analyses, except for SNOT-22, were summarised and analysed using the full analysis set on an intention-to-treat population (all randomly assigned patients receiving investigational product, regardless of protocol adherence or continued participation in the study). SNOT-22 was summarised for the subgroup of patients with physician-diagnosed nasal polyposis with informed consent. This study is registered with ClinicalTrials.gov, NCT03170271. Findings: Between July 7, 2017, and Sept 25, 2019, 656 patients received benralizumab (n=427) or placebo (n=229). Baseline characteristics were consistent with severe eosinophilic asthma. Benralizumab significantly reduced exacerbation risk by 49% compared with placebo (RR estimate 0·51, 95% CI 0·39–0·65; p5%) were nasopharyngitis (30 [7%]), headache (37 [9%]), sinusitis (28 [7%]), bronchitis (22 [5%]), and pyrexia (26 [6%]). Fewer serious adverse events were reported for benralizumab (23 [5%]) versus placebo (25 [11%]), and the only common serious adverse event (experienced by >1% of patients) was worsening of asthma, which was reported for nine (2%) patients in the benralizumab group and nine (4%) patients in the placebo group. Interpretation: Our results extend the efficacy profile of benralizumab for patients with severe eosinophilic asthma, showing early clinical benefits in patient-reported outcomes, HRQOL, lung function, and nasal polyposis symptoms. Funding: AstraZeneca.

Objective The earliest possible detection of individuals with COVID-19 has been essential to curb the spread of infection. Existing digital tools have been scaled up to address this issue. Every night telemonitoring data on continuous positive airway pressure (CPAP) device use, the first-line therapy for obstructive sleep apnoea (OSA), is collected worldwide. We asked whether the changes in CPAP adherence patterns of might constitute an alert for COVID-19. Methods We analysed preliminary results of telemonitoring data, recorded between February 1 and April 30, 2020, on OSA patients followed by our sleep clinics and diagnosed with COVID-19. Results CPAP telemonitoring data from the first 19 patients diagnosed with COVID-19 showed a clear decrease or halt in adherence in the 20 days immediately preceding COVID-19 diagnosis compared to an earlier period (p Conclusion Patterns of continuous positive airway pressure device use by obstructive sleep apnoea patients collected through telemonitoring can indicate the onset of COVID-19 symptoms. Existing telemonitoring platforms could be immediately used to screen for COVID-19, and for other respiratory infections, in this large at-risk population.

TO THE EDITOR : We all sleep, and sleep patterns and architecture influence our health and wellbeing. At present, the gold standard method for recording detailed sleep patterns to detect and monitor sleep disorders is in-laboratory overnight polysomnography (PSG), requiring specialized equipment and trained staff. This is no longer feasible in view of the size of the population with suspected sleep disorders, and especially in the coronavirus disease (COVID-19) era. [...]

Purpose Sleep bruxism (SBx) activity is classically identified by capturing masseter and/or temporalis masticatory muscles electromyographic activity (EMG-MMA) during in-laboratory polysomnography (PSG). We aimed to identify stereotypical mandibular jaw movements (MJM) in patients with SBx and to develop rhythmic masticatory muscles activities (RMMA) automatic detection using an artificial intelligence (AI) based approach. Patients and Methods This was a prospective, observational study of 67 suspected obstructive sleep apnea (OSA) patients in whom PSG with masseter EMG was performed with simultaneous MJM recordings. The system used to collect MJM consisted of a small hardware device attached on the chin that communicates to a cloud-based infrastructure. An extreme gradient boosting (XGB) multiclass classifier was trained on 79,650 10-second epochs of MJM data from the 39 subjects with a history of SBx targeting 3 labels: RMMA episodes (n=1072), micro-arousals (n=1311), and MJM occurring at the breathing frequency (n=77,267). Results Validated on unseen data from 28 patients, the model showed a very good epoch-by-epoch agreement (Kappa = 0.799) and balanced accuracy of 86.6% was found for the MJM events when using RMMA standards. The RMMA episodes were detected with a sensitivity of 84.3%. Class-wise receiver operating characteristic (ROC) curve analysis confirmed the well-balanced performance of the classifier for RMMA (ROC area under the curve: 0.98, 95% confidence interval [CI] 0.97–0.99). There was good agreement between the MJM analytic model and manual EMG signal scoring of RMMA (median bias −0.80 events/h, 95% CI −9.77 to 2.85). Conclusion SBx can be reliably identified, quantified, and characterized with MJM when subjected to automated analysis supported by AI technology., Video Abstract Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/M7LqfF1ZCyk

Background Quaternary ammonium compounds (QACs) are used extensively for cleaning and disinfection and have been documented in scattered reports as a cause of occupational asthma (OA) through bronchoprovocation tests (BPTs). Objective To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low–molecular weight (LMW) agents. Methods The study was conducted in a retrospective multicenter cohort of 871 subjects with OA ascertained by a positive BPT. Subjects with QAC-induced OA (n = 22) were identified based on a positive BPT to QACs after exclusion of those challenged with cleaning products or disinfectants that contained other potential respiratory sensitizers. They were compared with 289 subjects with OA caused by other LMW agents. Results Most subjects with QAC-induced OA were working in the health care sector (n = 14). A twofold or greater increase in the postchallenge level of nonspecific bronchial hyperresponsiveness was recorded in eight of 11 subjects with QAC-induced OA (72.7%) and in 49.7% of those with OA caused by other LMW agents. Although sputum assessment was available in only eight subjects with QAC-induced OA, they showed a significantly greater median (interquartile) increase in sputum eosinophils (18.1% [range, 12.1% to 21.1%]) compared with those with OA caused by other LMW agents (2.0% [range, 0% to 5.2%]; P Conclusions This study indicates that QAC-induced OA is associated with a highly eosinophilic pattern of airway response and provides further evidence supporting the sensitizing potential of QACs. The findings highlight the heterogeneous nature of the pathobiologic pathways involved in OA caused by LMW agents.

Background Given the high prevalence and risk for outcomes associated with pediatric obstructive sleep apnea (OSA), there is a need for simplified diagnostic approaches. A prospective study in 140 children undergoing in-laboratory polysomnography (PSG) evaluates the accuracy of a recently developed system (Sunrise) to estimate respiratory efforts by monitoring sleep mandibular movements (MM) for the diagnosis of OSA (Sunrise™). Methods Diagnostic and severity were defined by an obstructive apnea/hypopnea index (OAHI) ≥ 1 (mild), ≥ 5 (moderate), and ≥ 10 events/h (severe). Agreement between PSG and Sunrise™ was assessed by Bland-Altman method comparing respiratory disturbances hourly index (RDI) (obstructive apneas, hypopneas, and respiratory effort-related arousals) during PSG (PSG_RDI), and Sunrise RDI (Sr_RDI). Performance of Sr_RDI was determined via ROC curves evaluating the device sensitivity and specificity at PSG_OAHI ≥ 1, 5, and 15 events/h. Results A median difference of 1.57 events/h, 95% confidence interval: -2.49 to 8.11 was found between Sr_RDI and PSG_RDI. Areas under the ROC curves of Sr_RDI were 0.75 (interquartile range [IQR]: 0.72-0.78), 0.90 (IQR: 0.86-0.92) and 0.95 (IQR: 0.90-0.99) for detecting children with PSG_OAHI ≥ 1, PSG_OAHI ≥ 5, or PSG_ OAHI ≥ 10, respectively. Conclusion MM automated analysis shows significant promise to diagnose moderate-to-severe pediatric OSA.