COVID-19 vaccination acceptance, safety and side-effects in European patients with severe asthma.

Background: Vaccination is vital for achieving population immunity to severe acute respiratory syndrome coronavirus 2, but vaccination hesitancy presents a threat to achieving widespread immunity. Vaccine acceptance in chronic potentially immunosuppressed patients is largely unclear, especially in patients with asthma. The aim of this study was to investigate the vaccination experience in people with severe asthma. Methods: Questionnaires about vaccination beliefs (including the Vaccination Attitudes Examination (VAX) scale, a measure of vaccination hesitancy-related beliefs), vaccination side-effects, asthma control and overall safety perceptions following coronavirus disease 2019 (COVID-19) vaccination were sent to patients with severe asthma in 12 European countries between May and June 2021. Results: 660 participants returned completed questionnaires (87.4% response rate). Of these, 88% stated that they had been, or intended to be, vaccinated, 9.5% were undecided/hesitant and 3% had refused vaccination. Patients who hesitated or refused vaccination had more negative beliefs towards vaccination. Most patients reported mild (48.2%) or no side-effects (43.8%). Patients reporting severe side-effects (5.7%) had more negative beliefs. Most patients (88.8%) reported no change in asthma symptoms after vaccination, while 2.4% reported an improvement, 5.3% a slight deterioration and 1.2% a considerable deterioration. Almost all vaccinated (98%) patients would recommend vaccination to other severe asthma patients. Conclusions: Uptake of vaccination in patients with severe asthma in Europe was high, with a small minority refusing vaccination. Beliefs predicted vaccination behaviour and side-effects. Vaccination had little impact on asthma control. Our findings in people with severe asthma support the broad message that COVID-19 vaccination is safe and well tolerated.

Characteristics of severe asthma patients on biologics: a real-life European registry study.

Background: The use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs. Materials and methods: We performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies. Results: Patients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids. Conclusion: A large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.

Evaluation of real-world mepolizumab use in severe asthma across Europe: the SHARP experience with privacy-preserving federated analysis.

Background: An objective of the Severe Heterogeneous Asthma Registry, Patient-centered (SHARP) is to produce real-world evidence on a pan-European scale by linking nonstandardised, patient-level registry data. Mepolizumab has shown clinical efficacy in randomised controlled trials and prospective real-world studies and could therefore serve as a proof of principle for this novel approach. The aim of the present study was to harmonise data from 10 national severe asthma registries and characterise patients receiving mepolizumab, assess its effectiveness on annual exacerbations and maintenance oral glucocorticoid (OCS) use, and evaluate treatment patterns. Methods: In this observational cohort study, registry data (5871 patients) were extracted for harmonisation. Where harmonisation was possible, patients who initiated mepolizumab between 1 January 2016 and 31 December 2021 were examined. Changes of a 12-month (range 11-18 months) period in frequent (two or more) exacerbations, maintenance OCS use and dose were analysed in a privacy-preserving manner using meta-analysis of generalised estimating equation parameters. Periods before and during the coronavirus disease 2019 pandemic were analysed separately. Results: In 912 patients who fulfilled selection criteria, mepolizumab significantly reduced frequent exacerbations (OR 0.18, 95% CI 0.13-0.25), maintenance OCS use (OR 0.75, 95% CI 0.61-0.92) and dose (mean -3.93 mg·day-1, 95% CI -5.24-2.62 mg·day-1) in the pre-pandemic group, with similar trends in the pandemic group. Marked heterogeneity was observed between registries in patient characteristics and mepolizumab treatment patterns. Conclusions: By harmonising patient-level registry data and applying federated analysis, SHARP demonstrated the real-world effectiveness of mepolizumab on asthma exacerbations and maintenance OCS use in severe asthma patients across Europe, consistent with previous evidence. This paves the way for future pan-European real-world severe asthma studies using patient-level data in a privacy-proof manner.

Heterogeneity in the use of biologics for severe asthma in Europe: a SHARP ERS study.

Introduction: Treatment with biologics for severe asthma is informed by international and national guidelines and defined by national regulating bodies, but how these drugs are used in real-life is unknown. Materials and methods: The European Respiratory Society (ERS) SHARP Clinical Research Collaboration conducted a three-step survey collecting information on asthma biologics use in Europe. Five geographically distant countries defined the survey questions, focusing on seven end-points: biologics availability and financial issues, prescription and administration modalities, inclusion criteria, continuation criteria, switching biologics, combining biologics and evaluation of corticosteroid toxicity. The survey was then sent to SHARP National Leads of 28 European countries. Finally, selected questions were submitted to a broad group of 263 asthma experts identified by national societies. Results: Availability of biologics varied between countries, with 17 out of 28 countries having all five existing biologics. Authorised prescribers (pulmonologists and other specialists) also differed. In-hospital administration was the preferred deliverance modality. While exacerbation rate was used as an inclusion criterion in all countries, forced expiratory volume in 1 s was used in 46%. Blood eosinophils were an inclusion criterion in all countries for interleukin-5 (IL-5)-targeted and IL-4/IL-13-targeted biologics, with varying thresholds. There were no formally established criteria for continuing biologics. Reduction in exacerbations represented the most important benchmark, followed by improvement in asthma control and quality of life. Only 73% (191 out of 263) of surveyed clinicians assessed their patients for corticosteroid-induced toxicity. Conclusion: Our study reveals important heterogeneity in the use of asthma biologics across Europe. To what extent this impacts on clinical outcomes relevant to patients and healthcare services needs further investigation.

The effect of the COVID-19 pandemic on severe asthma care in Europe: will care change for good?

Background: The coronavirus disease 2019 (COVID-19) pandemic has put pressure on healthcare services, forcing the reorganisation of traditional care pathways. We investigated how physicians taking care of severe asthma patients in Europe reorganised care, and how these changes affected patient satisfaction, asthma control and future care. Methods: In this European-wide cross-sectional study, patient surveys were sent to patients with a physician-diagnosis of severe asthma, and physician surveys to severe asthma specialists between November 2020 and May 2021. Results: 1101 patients and 268 physicians from 16 European countries contributed to the study. Common physician-reported changes in severe asthma care included use of video/phone consultations (46%), reduced availability of physicians (43%) and change to home-administered biologics (38%). Change to phone/video consultations was reported in 45% of patients, of whom 79% were satisfied or very satisfied with this change. Of 709 patients on biologics, 24% experienced changes in biologic care, of whom 92% were changed to home-administered biologics and of these 62% were satisfied or very satisfied with this change. Only 2% reported worsening asthma symptoms associated with changes in biologic care. Many physicians expect continued implementation of video/phone consultations (41%) and home administration of biologics (52%). Conclusions: Change to video/phone consultations and home administration of biologics was common in severe asthma care during the COVID-19 pandemic and was associated with high satisfaction levels in most but not all cases. Many physicians expect these changes to continue in future severe asthma care, though satisfaction levels may change after the pandemic.

Effective Initial Treatment of Diffuse Pulmonary Lymphangiomatosis with Sirolimus and Propranolol: A Case Report.

Diffuse pulmonary lymphangiomatosis (DPL), an exceptionally rare disease, mainly occurs in children and young adults of both sexes. Even though DPL is considered to be a benign disease, its prognosis is relatively poor. Because of its rarity, little guidance on diagnosis and treatment is available, which makes working with patients with DPL challenging for clinicians. We present here a case of a young man with DPL in whom treatment with sirolimus and propranolol rapidly achieved positive radiological and clinical effects.

Post COVID-19 Organizing Pneumonia: The Right Time to Interfere.

The COVID-19 pandemic dramatically changed medical care. Healthcare professionals are faced with new issues. Patients who survived COVID-19 have plenty of different continuing symptoms, of which the most common are fatigue and breathlessness. It is not well known how to care for patients with persistent or worsening respiratory symptoms and changes on chest X-ray following COVID-19 pneumonia. In this article, we talk about a subgroup of patients with organizing pneumonia following COVID-19 pneumonia that could be effectively treated with systemic glucocorticoids. It is important that patients with COVID-19 pneumonia be followed-up at least three weeks after diagnosis, in order to recognize early lung damage. We are providing a management algorithm for early diagnosis of lung diseases after COVID-19 pneumonia.

Massive hemoptysis due to anastomosis between the left phrenic artery and pulmonary arteries/veins.

Massive hemoptysis is a serious medical condition or emergency which needs immediate treatment. It typically appears in the bronchial arteries and can be caused by a wide range of pulmonary diseases. This report is based on a very rare case of a patient bleeding from an anastomosis between the left phrenic artery and pulmonary arteries/veins. In this case, the chest computed tomography had detected changes which required doctors to perform a successful embolization.

ERS guidelines on the diagnosis and treatment of chronic cough in adults and children.

These guidelines incorporate the recent advances in chronic cough pathophysiology, diagnosis and treatment. The concept of cough hypersensitivity has allowed an umbrella term that explains the exquisite sensitivity of patients to external stimuli such a cold air, perfumes, smoke and bleach. Thus, adults with chronic cough now have a firm physical explanation for their symptoms based on vagal afferent hypersensitivity. Different treatable traits exist with cough variant asthma (CVA)/eosinophilic bronchitis responding to anti-inflammatory treatment and non-acid reflux being treated with promotility agents rather the anti-acid drugs. An alternative antitussive strategy is to reduce hypersensitivity by neuromodulation. Low-dose morphine is highly effective in a subset of patients with cough resistant to other treatments. Gabapentin and pregabalin are also advocated, but in clinical experience they are limited by adverse events. Perhaps the most promising future developments in pharmacotherapy are drugs which tackle neuronal hypersensitivity by blocking excitability of afferent nerves by inhibiting targets such as the ATP receptor (P2X3). Finally, cough suppression therapy when performed by competent practitioners can be highly effective. Children are not small adults and a pursuit of an underlying cause for cough is advocated. Thus, in toddlers, inhalation of a foreign body is common. Persistent bacterial bronchitis is a common and previously unrecognised cause of wet cough in children. Antibiotics (drug, dose and duration need to be determined) can be curative. A paediatric-specific algorithm should be used.

Expert opinion on the cough hypersensitivity syndrome in respiratory medicine.

In 2011, a European Respiratory Society Task Force embarked on a process to determine the position and clinical relevance of the cough hypersensitivity syndrome, a disorder characterised by troublesome coughing often triggered by low levels of thermal, mechanical or chemical exposure, in the management of patients with chronic cough. A 21-component questionnaire was developed by an iterative process supported by a literature review. 44 key opinion leaders in respiratory medicine were selected and interviewed as to their opinions. There was a high degree of unanimity in the responses obtained, with all opinion leaders supporting the concept of cough hypersensitivity as a clinically useful paradigm. The classic stratification of cough into asthmatic, rhinitic and reflux-related phenotypes was supported. Significant disparity of opinion was seen in the response to two questions concerning the therapy of chronic cough. First, the role of acid suppression in reflux cough was questioned. Secondly, the opinion leaders were split as to whether a trial of oral steroids was indicated to establish a diagnosis of eosinophilic cough. The cough hypersensitivity syndrome was clearly endorsed by the opinion leaders as a valid and useful concept. They considered that support of patients with chronic cough was inadequate and the Task Force recommends that further work is urgently required in this neglected area.

Reactive oxygen species in peripheral blood and sputum neutrophils during bacterial and nonbacterial acute exacerbation of chronic obstructive pulmonary disease.

Chronic airway inflammation can be mediated by an enhanced neutrophil oxidative burst. However, the role of bacteria in the pathogenesis of chronic obstructive pulmonary disease (COPD) exacerbations is highly controversial. The aim of this study was to evaluate the production of reactive oxygen species (ROS) in peripheral blood and sputum neutrophils during bacterial and nonbacterial acute exacerbations of COPD (AECOPD). A total of 40 patients with AECOPD, 10 healthy nonsmokers, and 10 "healthy" smokers were enrolled into the study. Peripheral blood and sputum samples were obtained during exacerbation and after recovery. Neutrophils were isolated by high-density gradient centrifugation and magnetic separation. ROS production by neutrophils was investigated after stimulation with phorbol-myristate-acetate and Staphylococcus aureus bacteria. ROS production by neutrophils was assessed as the mean fluorescent intensity using a flow cytometer. IL-8 levels in serum and induced sputum were determinant by ELISA. Spontaneous ROS production was significantly higher in neutrophils from the patients with bacterial AECOPD as compared with nonbacterial AECOPD and stable COPD (P <0.05). ROS production stimulated with PMA and with Staphylococcus aureus was significantly higher in neutrophils isolated from the patients with bacterial AECOPD as compared with nonbacterial and stable COPD (P <0.05). The serum and induced sputum IL-8 levels were significantly increased in the patients with bacterial AECOPD than nonbacterial AECOPD, stable COPS, and "healthy" smokers and nonsmokers (P <0.05) and higher in the induced sputum as the compared with serum in all studied groups (P <0.05). Enlarge CRP level was documented during AECOPD than in all other groups (P <0.05). A markedly increased ROS production in sputum neutrophils during bacterial AECOPD shows an inflammatory response reflecting enhanced local inflammation, which can be mediated by bacterial colonization.

Network analysis of quantitative proteomics on asthmatic bronchi: effects of inhaled glucocorticoid treatment.

BACKGROUND: Proteomic studies of respiratory disorders have the potential to identify protein biomarkers for diagnosis and disease monitoring. Utilisation of sensitive quantitative proteomic methods creates opportunities to determine individual patient proteomes. The aim of the current study was to determine if quantitative proteomics of bronchial biopsies from asthmatics can distinguish relevant biological functions and whether inhaled glucocorticoid treatment affects these functions. METHODS: Endobronchial biopsies were taken from untreated asthmatic patients (n = 12) and healthy controls (n = 3). Asthmatic patients were randomised to double blind treatment with either placebo or budesonide (800 µg daily for 3 months) and new biopsies were obtained. Proteins extracted from the biopsies were digested and analysed using isobaric tags for relative and absolute quantitation combined with a nanoLC-LTQ Orbitrap mass spectrometer. Spectra obtained were used to identify and quantify proteins. Pathways analysis was performed using Ingenuity Pathway Analysis to identify significant biological pathways in asthma and determine how the expression of these pathways was changed by treatment. RESULTS: More than 1800 proteins were identified and quantified in the bronchial biopsies of subjects. The pathway analysis revealed acute phase response signalling, cell-to-cell signalling and tissue development associations with proteins expressed in asthmatics compared to controls. The functions and pathways associated with placebo and budesonide treatment showed distinct differences, including the decreased association with acute phase proteins as a result of budesonide treatment compared to placebo. CONCLUSIONS: Proteomic analysis of bronchial biopsy material can be used to identify and quantify proteins using highly sensitive technologies, without the need for pooling of samples from several patients. Distinct pathophysiological features of asthma can be identified using this approach and the expression of these features is changed by inhaled glucocorticoid treatment. Quantitative proteomics may be applied to identify mechanisms of disease that may assist in the accurate and timely diagnosis of asthma. TRIAL REGISTRATION: ClinicalTrials.gov registration NCT01378039.