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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.

Asthma, rhinitis and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of "one-airway-one-disease", coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitisation and multimorbidity, (iii) advances in mHealth for novel phenotype definition, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut and neuropsychiatric multimorbidities, is the "Epithelial Barrier Hypothesis". This review determined that the "one-airway-one-disease" concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme "allergic" (asthma) phenotype combining asthma, rhinitis and conjunctivitis. Rhinitis alone and rhinitis and asthma multimorbidity represent two distinct diseases with the following differences: (i) genomic and transcriptomic background (Toll-Like Receptors and IL-17 for rhinitis alone as a local disease; IL-33 and IL-5 for allergic and non-allergic multimorbidity as a systemic disease), (ii) allergen sensitisation patterns (mono- or pauci-sensitisation versus polysensitisation), (iii) severity of symptoms and (iv) treatment response. In conclusion, rhinitis alone (local disease) and rhinitis with asthma multimorbidity (systemic disease) should be considered as two distinct diseases, possibly modulated by the microbiome, and may be a model for understanding the epidemics of chronic and auto-immune diseases.

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.

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. 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 one year. 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<0.001). Medication use peaked during the spring, with similar patterns across different European regions (defined geographically or by Google Trends). Oral H -antihistamines were the most common medication in single and co-medication. Each patient reported using an annual average of 2.7 drugs, with 80% reporting two or more. AR medication patterns are similar across European regions. One third of treatment days involved co-medication. These findings suggest that patients treat themselves according to their symptoms (irrespective of how they understand AR), and that co-medication use is driven by symptom severity.

Purpose: 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 wa

Azithromycin 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. In 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. Patients 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. Time to clinical improvement is not influenced by azithromycin in patients hospitalised with moderate to severe COVID-19.

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. 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. 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%). 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 I

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.

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 [...].

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 post-bronchodilation 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.

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.

Irritant-induced asthma (IIA) is a phenotype of asthma caused by the inhalation of irritant agents. Definite IIA, probable IIA, or possible IIA have been described depending on the concentration of the inhaled irritants and the onset of respiratory symptoms respective to the time of exposure. Definite IIA represents approximately 4% to 14% of all cases of new-onset work-related asthma. The agents responsible of IIA can be encountered as fumes, gases, aerosols, or dusts. The most frequent are chlorine, nitrogen oxides, sulphur dioxide, ammonia, acetic acid, solvents, and cleaning materials. Although the diagnosis of definite IIA is based upon a suggestive clinical history along with evidence of reversible airflow limitation and/or non-specific bronchial hyperresponsiveness, possible IIA cannot be diagnosed with certainty as the relationship between exposure and the onset of symptoms is difficult to establish. The present article reviews the epidemiology, pathophysiology, diagnostic approach, and management of IIA.

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<0.001). Forced oscillation technique (FOT) appears to be an interesting complement to routine PFTs in COPD assessment. Reactance parameters are correlated with dyspnea and their response to bronchodilators is a predictor of significantly improved inspiratory capacity (IC). All in all, FOT may be considered as a functional test with regard to pulmonary hyperinflation, a critical determinant of dyspnea.

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

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 changes of symptoms over time. We analyzed data from MASK-air® longitudinally, clustering weeks according to reported rhinitis symptoms. We analyzed MASK-air® data, assessing weeks when patients answered a rhinitis daily questionnaire on all seven 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 latent class mixture model to assess robustness of results. We analyzed 113,239 days (16,177 complete weeks) from 2,590 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 higher frequency of rhinitis co-medication, 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. 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.

Clinical heterogeneity in sensitizer-induced occupational asthma (OA) and its relationship to airway inflammatory profiles remain poorly elucidated. 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. 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. 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 b2-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 b2-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]). 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.

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. 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. 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. 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.

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 -rearranged lung adenocarcinoma who developed a 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 A598-T599insV mutation occurring in lung cancer, we discuss resistance mechanisms to ALK TKIs, implications of mutation in NSCLC, and A598-T599insV mutation in other cancers.

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.

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.

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<0.01). pIgR bronchiolar expression was reduced in transbronchial biopsies from BOS (p<0.05 vs BOS-free and pre-BOS), with further decrease in end-stage BOS explants (p<0.0001 vs BOS-free and pre-BOS). Conclusions: BAL S-IgA and pIgR decreased levels suggest that the pIgR/IgA system is impaired in BOS. This could play a pathogenic role by increasing susceptibility to local infections.

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<0.01). Serum IgA levels were similar across the studied groups, while both SC and S-IgA were increased in pre-BOS LT recipients (Fig 1B-C; S-IgA: 40.6 vs 21.2µg/ml, p<0.05; SC: 156.0 vs 97.2ng/ml, p<0.001). pIgR bronchiolar expression was reduced in transbronchial biopsies from BOS (Fig 1D-E; p<0.05 vs BOS-free and pre-BOS), with further decrease in end-stage BOS explants (p<0.0001 vs BOS-free and pre-BOS). Conclusions. BAL S-IgA and pIgR decreased levels suggest that the pIgR/IgA system is impaired in BOS. This alteration is even present prior to the functional diagnosis of CLAD. Serum SC and S-IgA increased levels in pre-BOS LT recipients may reflect a spill-over from bronchoalveolar f

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. 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. 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). 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.

Treatment of patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) continues to evolve expeditiously. This retrospective study investigated real-world treatment patterns and EGFR mutation testing in patients with EGFRm advanced NSCLC in Belgium. Data were extracted from medical records of adults diagnosed with EGFRm locally advanced/metastatic NSCLC between 1 September 2015 and 31 December 2017. Patients were followed retrospectively from diagnosis until 1 September 2018, end of clinical activity or death. Data on demographics, patient outcomes and disease characteristics, treatment patterns and EGFR mutation testing at diagnosis and progression were analyzed descriptively. A total of 141 patients were enrolled. At diagnosis, median age was 69 years, 63.1% were female, 88.7% had metastatic disease, 94.3% had adenocarcinoma histology, 76.6% had ECOG 0/1, 70.9% had common EGFR mutations and 29.1% had only rare mutations. In first line, 73.8% of patients received first/second-generation EGFR-tyrosine kinase inhibitors (1G/2G EGFR-TKIs), while 21.9% received other systemic treatments. Among 61 patients progressing on and discontinuing a first 1G/2G EGFR-TKI, 45 (73.8%) received subsequent systemic treatment while 16 (26.2%) did not; 20 (32.8%) received osimertinib. Among 65 patients progressing on a first 1G/2G EGFR-TKI, 47 (72.3%) were tested for T790M, of whom 25 (53.2%) were positive. These real-world data from Belgium show that a substantial fraction of patients with EGFRm NSCLC do not receive 1G/2G EGFR-TKIs in first line and do not receive subsequent systemic treatment after progression on 1G/2G EGFR-TKIs. Only a third receive osimertinib upon progression on 1G/2G EGFR-TKIs. These observations should be considered in first-line treatment decisions. ClinicalTrials.gov: NCT03761901-December 3, 2018.

Cet article décrit les avancées récentes relatives à la prise en charge diagnostique et thérapeutiques des cancers bronchiques à petites cellules. Une place particulière est faite au développement des inhibiteurs des protéines de contrôle de l’immunité. Il cite aussi les points encore débattus autour des explorations préthérapeutiques, de la radiothérapie thoracique, et de l’irradiation prophylactique cérébrale. Enfin, les pistes de thérapie ciblant les anomalies de réparation des dommages de l’ADN sont évoquées., This article describes recent advances in the diagnostic and therapeutic management of small cell lung cancer, particularly, the development of immune checkpoint inhibitors. He also cites still debatable issues such as pre-therapeutic explorations, thoracic radiotherapy, and prophylactic cerebral irradiation. Finally, therapeutic approaches targeting DNA damage repair abnormalities are discussed.

Multiple nonspecific symptoms in a patient treated by pembrolizumab Immune checkpoint inhibitors, such as the receptor programmed cell death protein 1 (PD-1) or PD-1 ligand 1 (PD-L1), which are new therapeutic weapons against cancer, which are increasingly sed nowadays. This case report concerns a 72-year-old man treated by pembrolizumab (Keytruda®), a PD-1 inhibitor, in first-line systemic treatment of an Stage IVA lung adenocarcinoma. Three weeks before his eighth cure, the patient’s general condition deteriorated, including loss of appetite, fatigue, nausea, and a slight weigh loss. He also reported headaches. As an adrenal insufficiency was suspected, a substitution treatment consisting of hydrocortisone was initiated. The originality of this case lies in the relevance of also considering non-specific symptoms in cancer patients under immunotherapy, the emergency of the diagnosis, and the recommended medical management. The aim of this article is direct your attention to this rare but potentially fatal adverse event of immunotherapy, with its new treatments that you will encounter increasingly often in your practice, and to revise some cases already published in the literature , in addition to another personal case.

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). Diagnosis 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. 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. MM automated analysis shows significant promise to diagnose moderate-to-severe pediatric OSA.

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<0.01). 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.

Introduction : Lung cancer is the most frequent and the deadliest cancer in the world. In non-small cell lung cancer (NSCLC), which represents 85% of all lung cancers, up to 55% patients relapse following surgery alone or in combination with chemotherapy or radiotherapy. Tumor-infiltrating lymphocytes play a key role in the control of the malignancy and display different phenotypes whilst interacting with cancer cells. Hence, immunoglobulin-A (IgA)-producing cells have been described to have an immunosuppressive function, promoting tumor development and growth in hepatocarcinoma and prostate cancer. Due to the important role of IgA in the lung, we aimed to study the prognostic significance of IgA+ cell infiltration in the epithelial and stromal compartments of resected NSCLCs. [...]

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.

Airway stenting offers good palliation and improves the quality of life in patients with inoperable bronchotracheal stenosis. However, in some cases, the management of stenting can be life-threatening. Hence, a strategy for maintaining oxygenation and hemodynamic stability should be anticipated to avoid critical situations. Herein, we report the use of extracorporeal membrane oxygenation (ECMO) in bronchotracheal stenting management to secure oxygenation and facilitate interventions. We retrospectively reviewed all patients who underwent rigid bronchoscopy under ECMO support for the management of bronchotracheal stenting at CHU UCL Namur hospital (Belgium), between January 2009 and December 2019. We included 14 bronchoscopy cases performed on 11 patients (3 patients underwent 2 bronchoscopies) in this study; 12 were performed on males and 2 on females. The median age was 54 years. There were 11 benign and 3 malignant etiologies for the central airway obstruction/stenosis. Eight cases were supported by venovenous ECMO and six by venoarterial ECMO. The median ECMO time was 267 minutes. The weaning of ECMO support was successful in all cases. In most cases, the procedures were performed effectively and safely. Only two local complications caused by the cannulation of ECMO were reported, and anticoagulation was adapted to avoid bleeding at the operating site and clot formation in the system. Elective ECMO support was helpful and safe for the high-risk management of bronchotracheal stenting with rigid bronchoscopy and was not associated with any additional significant complications.

[Voir la liste complète des auteurs : https://onlinelibrary.wiley.com/doi/10.1002/clt2.12014] INTRODUCTION : Allergen immunotherapy (AIT), the gradually increasing repeated administration of high doses of allergens to allergic patients, offers the potential for immune tolerance against reactions to the natural exposures to specific allergens. AIT may lead to the long‐lasting remission of allergic symptoms and is the only disease‐modifying intervention in IgE‐mediated allergic respiratory diseases. [...]

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.

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.

Osimertinib has become a standard of care in the first-line treatment of advanced-stage non-small-cell lung cancer (NSCLC) harboring exon 19 and 21 activating mutations in the gene. Nevertheless, the 18.9-month median progression-free survival emphasizes the fact that resistance to osimertinib therapy is inevitable. Acquired resistance mechanisms to osimertinib in EGFR-driven NSCLC include amplification, C797S mutation, neuroendocrine differentiation, small-cell lung carcinoma histologic transformation, and amplifications and and translocations, as well as V600 mutation. This last one represents 3% of the acquired resistance mechanisms to osimertinib. In this review, we discuss the rationale for EGFR/BRAF/MEK co-inhibition in the light of a clinical case of -mutant NSCLC developing a V600 mutation as an acquired resistance mechanism to osimertinib and responding to the association of osimertinib plus dabrafenib and trametinib. Additionally, we discuss the acquired resistance mechanisms to osimertinib plus dabrafenib and trametinib combination in that context.

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). To examine the clinical, functional, and inflammatory profile of QAC-induced OA compared with OA caused by other low-molecular weight (LMW) agents. 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. 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 < .001). 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.

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 bron, [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.

[This corrects the article DOI: 10.1186/s13601-020-00323-0.].

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day between those from Slovenia Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day in those starting anti-IgE (Slovenia Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.

In allergic rhinitis, a relevant outcome providing information on the effectiveness of interventions is needed. In MASK-air (Mobile Airways Sentinel Network), a visual analogue scale (VAS) for work is used as a relevant outcome. This study aimed to assess the performance of the work VAS work by comparing VAS work with other VAS measurements and symptom-medication scores obtained concurrently. All consecutive MASK-air users in 23 countries from 1 June 2016 to 31 October 2018 were included (14 189 users; 205 904 days). Geolocalized users self-assessed daily symptom control using the touchscreen functionality on their smart phone to click on VAS scores (ranging from 0 to 100) for overall symptoms (global), nose, eyes, asthma and work. Two symptom-medication scores were used: the modified EAACI CSMS score and the MASK control score for rhinitis. To assess data quality, the intra-individual response variability (IRV) index was calculated. A strong correlation was observed between VAS work and other VAS. The highest levels for correlation with VAS work and variance explained in VAS work were found with VAS global, followed by VAS nose, eye and asthma. In comparison with VAS global, the mCSMS and MASK control score showed a lower correlation with VAS work. Results are unlikely to be explained by a low quality of data arising from repeated VAS measures. VAS work correlates with other outcomes (VAS global, nose, eye and asthma) but less well with a symptom-medication score. VAS work should be considered as a potentially useful AR outcome in intervention studies.

Reported COVID-19 deaths in Germany are relatively low as compared to many European countries. Among the several explanations proposed, an early and large testing of the population was put forward. Most current debates on COVID-19 focus on the differences among countries, but little attention has been given to regional differences and diet. The low-death rate European countries (e.g. Austria, Baltic States, Czech Republic, Finland, Norway, Poland, Slovakia) have used different quarantine and/or confinement times and methods and none have performed as many early tests as Germany. Among other factors that may be significant are the dietary habits. It seems that some foods largely used in these countries may reduce angiotensin-converting enzyme activity or are anti-oxidants. Among the many possible areas of research, it might be important to understand diet and angiotensin-converting enzyme-2 (ACE2) levels in populations with different COVID-19 death rates since dietary interventions may be of great benefit.

RATIONALE: Accumulation of B cells and lymphoid follicles (LFs) has been described in chronic obstructive pulmonary disease (COPD) airways, but the functional status of lung B cells remains poorly known. OBJECTIVES: To characterize LFs for expression of IgA, the main mucosal antibody. METHODS: The presence of B cells and LFs, including intrafollicular IgA expression, were determined in the lung from patients with COPD (n = 37) versus control subjects (n = 34) by immunohistochemistry. We also evaluated follicular IgA responses in the lungs from mice infected with Pseudomonas aeruginosa (PAO1) (n = 10 per group) and in smoking mice. MEASUREMENTS AND MAIN RESULTS: Whereas in smokers B-cell numbers slightly increased, robust increases in B-cell and LF numbers (mainly in distal airways) were only observed in severe COPD. Most follicular B cells were IgM+ (70-80%), but IgA+ (and not IgG+) B-cell numbers were increased in LFs from severe COPD compared with control subjects (twofold, 44.7% vs. 25.2%), and this was significant in distal but not proximal airways. Follicular IgA response was also observed in PAO1-infected mouse lungs, but not after smoke exposure. Moreover, follicular IgA expression associated with expression of IL-21, which was very potent to activate immunoglobulin production in vitro. CONCLUSIONS: This study shows that IgA production occurs in peribronchiolar LFs from severe COPD, where IL-21-producing T cells are present, and presumably represents a feature of exacerbated mucosal adaptive immune responses against microbial and/or self-antigens.