A survey study on antibiotic prescription practices for acute asthma exacerbations: An European academy of allergy and clinical immunology task force report.

INTRODUCTION: Guidelines recommend treating asthma exacerbations (AAEs) with bronchodilators combined with inhaled and/or systemic corticosteroids. Indications for antibiotic prescriptions for AAEs are usually not incorporated although the literature shows antibiotics are frequently prescribed. AIM: To investigate the antibiotic prescription rates in AAEs and explore the possible determining factors of those practices. METHODS: A digital survey was created to determine the antibiotic prescription rates in AAEs and the influencing factors for the prescription practices. The survey was distributed among European academy of allergy and clinical immunology (EAACI) members by mass emailing and through regional/national societies in the Netherlands, Italy, Greece, and Poland. Furthermore, we retrieved local antibiotic prescription rates. RESULTS: In total, 252 participants completed the survey. Respondents stated that there is a lack of guidelines to prescribe antibiotics in AAEs. The median antibiotic prescription rate in this study was 19% [IQR: 0%-40%] and was significantly different between 4 professions: paediatrics 0% [IQR: 0%-37%], pulmonologists 25% [IQR: 10%-50%], general practitioners 25% [IQR: 0%-50%], and allergologists 17% [IQR: 0%-33%]) (p = 0.046). Additional diagnostic tests were performed in 71.4% of patients before prescription and the most common antibiotic classes prescribed were macrolides (46.0%) and penicillin (42.9%). Important clinical factors for health care providers to prescribe antibiotics were colorised/purulent sputum, abnormal lung sounds during auscultation, fever, and presence of comorbidities. CONCLUSION: In 19% of patients with AAEs, antibiotics were prescribed in various classes with a broad range among different subspecialities. This study stresses the urgency to compose evidence-based guidelines to aim for more rational antibiotic prescriptions for AAE.

Telemedicine with special focus on allergic diseases and asthma-Status 2022: An EAACI position paper.

Efficacious, effective and efficient communication between healthcare professionals (HCP) and patients is essential to achieve a successful therapeutic alliance. Telemedicine (TM) has been used for decades but during the COVID-19 pandemic its use has become widespread. This position paper aims to describe the terminology and most important forms of TM among HCP and patients and review the existing studies on the uses of TM for asthma and allergy. Besides, the advantages and risks of TM are discussed, concluding that TM application reduces costs and time for both, HCP and patients, but cannot completely replace face-to-face visits for physical examinations and certain tests that are critical in asthma and allergy. From an ethical point of view, it is important to identify those involved in the TM process, ensure confidentiality and use communication channels that fully guarantee the security of the information. Unmet needs and directions for the future regarding implementation, data protection, privacy regulations, methodology and efficacy are described.

Prevalence and clinical implications of respiratory viruses in asthma during stable disease state and acute attacks: Protocol for a meta-analysis.

INTRODUCTION: Viruses are detected in over 50% of acute asthma attacks and in a notable proportion of patients with asthma during stable disease state They are associated with worse outcomes. We will conduct a series of systematic reviews and meta-analyses to quantify the prevalence and clinical burden of various respiratory viruses in stable asthma and acute asthma attacks. In addition, we will assess the viral loads of respiratory viruses during stable and acute asthma, to explore whether viral load could differentiate attacks triggered by viruses versus those where viruses are present as "innocent bystanders". MATERIALS AND METHODS: Based on a prospectively registered protocol (PROSPERO, ID: CRD42023375108) and following standard methodology recommended by Cochrane, we will systematically search Medline/PubMed, EMBASE, the Cochrane Library and relevant conference proceedings for studies assessing the prevalence or clinical burden of respiratory viruses in asthma. Methodological rigour of the included studies will be appraised using a tool specific for prevalence studies and the Newcastle-Ottawa Scale respectively. In anticipation of significant clinical and methodological heterogeneity, we will conduct random effect meta-analyses. For evaluating the prevalence of viruses, we will perform meta-analyses of proportions using the inverse variance method, and the Freeman-Tukey transformation. We will conduct meta-regression analyses for exploring heterogeneity. CONCLUSION: We envisage that these systematic reviews and meta-analyses will quantify the prevalence and burden of respiratory viruses in stable and acute asthma and will drive future research and clinical practice.

Mepolizumab Improves Outcomes of Chronic Rhinosinusitis with Nasal Polyps in Severe Asthmatic Patients: A Multicentric Real-Life Study.

Objective: The upcoming introduction of mepolizumab represents a promising treatment for chronic rhinosinusitis with nasal polyps (CRSwNP). The present study aimed to evaluate the effectiveness of mepolizumab on sinonasal outcomes of comorbid CRSwNP and severe asthma in a real-life setting. The primary endpoint was to evaluate changes in the SinoNasal Outcome Test (SNOT)-22 score, Nasal Polyp (NP) score, and blood eosinophil count during a 12-month treatment with mepolizumab. Secondary endpoints were to quantify mepolizumab's effects on the mentioned parameters, identify clinical variables influencing the degree of response to treatment, and portray responder and nonresponder patients. Methods: A multicentric retrospective no-profit observational study on severe asthmatic patients, treated with mepolizumab, and comorbid CRSwNP was conducted. All patients were followed for at least 12 months. SNOT-22 score, NP score, and blood eosinophil count (and other CRS-specific variables) were collected at baseline and after 12 months. Results: Forty-three patients were included. A statistically significant reduction was observed for SNOT-22 score (mean t0 SNOT-22 54.8 ± 25.9; mean t12 SNOT-22 31.5 ± 21.3, p < 0.0001), NP score (median t0 NPS 3 (IQR 3); median t12 NPS 2 (IQR 4), p < 0.0001), and blood eosinophil count (mean t0 blood eosinophils 804.7 ± 461.5 cell/µL; mean t12 blood eosinophils 107.5 ± 104.6 cell/µL, p < 0.0001) after 12 months of treatment. Twenty patients (47%) gained improvement both in clinical and endoscopic outcome. Mepolizumab responder patients presented a t0 SNOT-22 significantly higher than nonresponders (p = 0.0011). Conclusions: Mepolizumab improved CRSwNP outcomes in a population of severe asthmatic patients. No clinical feature emerged to outline the profile of a "typical" responder patient, except for baseline SNOT-22 score, which seemed to affect the response to treatment. Further studies would be necessary to supplement these preliminary evaluations.

Short-term lung function changes predict mortality in patients with fibrotic hypersensitivity pneumonitis.

BACKGROUND AND OBJECTIVE: A proportion of patients with fibrotic hypersensitivity pneumonitis (fHP) follow a progressive disease course despite immunosuppressive treatment. Little is known about predictors of mortality in fHP. We aimed to investigate the impact of short-term lung function changes in fHP on mortality. METHODS: Baseline demographics for 145 consecutive patients with a multi-disciplinary team diagnosis of fHP, as well as baseline and 1-year follow-up of lung function, baseline echocardiographic findings, bronchoalveolar lavage (BAL) cellularity and all-cause mortality were recorded. Changes in forced vital capacity (FVC) ≥ 5% and ≥10%, and diffusion capacity of the lung for carbon monoxide (DLCO) ≥ 10% and ≥15% at 1 year were calculated. Cox proportional hazards analysis was performed to test for associations with mortality. RESULTS: Baseline lung function severity, age, presence of honeycombing on computed tomography (CT) and echocardiographic pulmonary arterial systolic pressure (PASP) ≥ 40 mm Hg were associated with early mortality, while BAL lymphocytosis was associated with improved survival. A decline in FVC ≥ 5% (hazard ratio [HR]: 3.10, 95% CI: 2.00-4.81, p < 0.001), FVC ≥ 10% (HR: 3.11, 95% CI: 1.94-4.99, p < 0.001), DLCO ≥ 10% (HR: 2.80, 95% CI: 1.78-4.42, p < 0.001) and DLCO ≥ 15% (HR: 2.92, 95% CI: 1.18-4.72, p < 0.001) at 1 year was associated with markedly reduced survival on univariable and multivariable analyses after correcting for demographic variables, disease severity, honeycombing on CT and treatment, as well as BAL lymphocytosis and PASP ≥ 40 mm Hg on echocardiography, in separate models. CONCLUSION: Worsening in FVC and DLCO at 1 year, including a marginal decline in FVC ≥ 5% and DLCO ≥ 10%, is predictive of markedly reduced survival in fHP.

EAACI position paper on the clinical use of the bronchial allergen challenge: Unmet needs and research priorities.

Allergic asthma (AA) is a common asthma phenotype, and its diagnosis requires both the demonstration of IgE-sensitization to aeroallergens and the causative role of this sensitization as a major driver of asthma symptoms. Therefore, a bronchial allergen challenge (BAC) would be occasionally required to identify AA patients among atopic asthmatics. Nevertheless, BAC is usually considered a research tool only, with existing protocols being tailored to mild asthmatics and research needs (eg long washout period for inhaled corticosteroids). Consequently, existing BAC protocols are not designed to be performed in moderate-to-severe asthmatics or in clinical practice. The correct diagnosis of AA might help select patients for immunomodulatory therapies. Allergen sublingual immunotherapy is now registered and recommended for controlled or partially controlled patients with house dust mite-driven AA and with FEV1 ≥ 70%. Allergen avoidance is costly and difficult to implement for the management of AA, so the proper selection of patients is also beneficial. In this position paper, the EAACI Task Force proposes a methodology for clinical BAC that would need to be validated in future studies. The clinical implementation of BAC could ultimately translate into a better phenotyping of asthmatics in real life, and into a more accurate selection of patients for long-term and costly management pathways.

When one plus one means more than two: the blockade of both IL-4 and IL-13 inflammatory pathways with dupilumab in a case of severe refractory T2-high asthma.

Novel approach of asthma includes personalised therapy involving specific immune pathways. We describe here a case of T2-high asthma in a 66-year-old woman treated with maximal inhaled therapy and inappropriate usage of oral corticosteroids showing poor symptoms control. Both anti-IgE and (omalizumab) and anti-interleukin (IL)-5 (mepolizumab) monoclonal antibodies treatments were prescribed without significant benefit. Add-on subcutaneous dupilumab, a monoclonal antibody directed against the IL-4 receptor subunit alpha, inhibiting signalling from both IL-4 and IL-13, proved to be an effective and safe medication to obtain rapid asthma control. Considering the previous lack of response to both anti-IgE and anti-eosinophilic strategies, we hypothesise that dupilumab upstream activity could exert different and more relevant effects than the simple inhibition of the two single downstream pathways. The current case highlights the need for a deeper analysis of biomolecular interactions in the framework of different asthma endotypes, to identify peculiar profiles associated with specific treatment responses.

Dangerous liaisons: Bacteria, antimicrobial therapies, and allergic diseases.

Microbiota composition and associated metabolic activities are essential for the education and development of a healthy immune system. Microbial dysbiosis, caused by risk factors such as diet, birth mode, or early infant antimicrobial therapy, is associated with the inception of allergic diseases. In turn, allergic diseases increase the risk for irrational use of antimicrobial therapy. Microbial therapies, such as probiotics, have been studied in the prevention and treatment of allergic diseases, but evidence remains limited due to studies with high heterogeneity, strain-dependent effectiveness, and variable outcome measures. In this review, we sketch the relation of microbiota with allergic diseases, the overuse and rationale for the use of antimicrobial agents in allergic diseases, and current knowledge concerning the use of bacterial products in allergic diseases. We urgently recommend 1) limiting antibiotic therapy in pregnancy and early childhood as a method contributing to the reduction of the allergy epidemic in children and 2) restricting antibiotic therapy in exacerbations and chronic treatment of allergic diseases, mainly concerning asthma and atopic dermatitis. Future research should be aimed at antibiotic stewardship implementation strategies and biomarker-guided therapy, discerning those patients that might benefit from antibiotic therapy.

Management of asthma in childhood: study protocol of a systematic evidence update by the Paediatric Asthma in Real Life (PeARL) Think Tank.

INTRODUCTION: Clinical recommendations for childhood asthma are often based on data extrapolated from studies conducted in adults, despite significant differences in mechanisms and response to treatments. The Paediatric Asthma in Real Life (PeARL) Think Tank aspires to develop recommendations based on the best available evidence from studies in children. An overview of systematic reviews (SRs) on paediatric asthma maintenance management and an SR of treatments for acute asthma attacks in children, requiring an emergency presentation with/without hospital admission will be conducted. METHODS AND ANALYSIS: Standard methodology recommended by Cochrane will be followed. Maintenance pharmacotherapy of childhood asthma will be evaluated in an overview of SRs published after 2005 and including clinical trials or real-life studies. For evaluating pharmacotherapy of acute asthma attacks leading to an emergency presentation with/without hospital admission, we opted to conduct de novo synthesis in the absence of adequate up-to-date published SRs. For the SR of acute asthma pharmacotherapy, we will consider eligible SRs, clinical trials or real-life studies without time restrictions. Our evidence updates will be based on broad searches of Pubmed/Medline and the Cochrane Library. We will use A MeaSurement Tool to Assess systematic Reviews, V.2, Cochrane risk of bias 2 and REal Life EVidence AssessmeNt Tool to evaluate the methodological quality of SRs, controlled clinical trials and real-life studies, respectively.Next, we will further assess interventions for acute severe asthma attacks with positive clinical results in meta-analyses. We will include both controlled clinical trials and observational studies and will assess their quality using the previously mentioned tools. We will employ random effect models for conducting meta-analyses, and Grading of Recommendations Assessment, Development and Evaluation methodology to assess certainty in the body of evidence. ETHICS AND DISSEMINATION: Ethics approval is not required for SRs. Our findings will be published in peer reviewed journals and will inform clinical recommendations being developed by the PeARL Think Tank. PROSPERO REGISTRATION NUMBERS: CRD42020132990, CRD42020171624.

Real-life impact of COVID-19 pandemic lockdown on the management of pediatric and adult asthma: A survey by the EAACI Asthma Section.

BACKGROUND: The restrictions imposed by the COVID-19 pandemic impact heavily the management of chronic diseases like asthma. This study aimed to evaluate the management of adults and children with asthma during COVID-19-related lockdown. METHODS: A survey was launched by the European Academy of Allergy and Clinical Immunology (EAACI) via e-mail, website, and social media to EAACI members and members of peer societies. RESULTS: The survey was completed by 339 healthcare professionals from 52 countries. 79% of follow-up consultations were replaced by phone calls, whereas 49% of newly referred patients attended the clinic. 62%, 76%, 66%, 76%, and 87% of responders did not conduct spirometry, impulse oscillometry, bronchodilator test, FeNO, or methacholine provocation, respectively, for asthma diagnosis in adults. The numbers were similar for children. 73% of responders based the initial asthma diagnosis and the prescription of inhaled therapy on clinical parameters only. Lung function tests were used in 29% of cases to monitor asthma worsening, and only 56% of participants were recommended to their patients ambulatory peak expiratory flow (PEF) measurements. Using a 1 (not at all) to 5 (very much) scale, the responders considered that the quality of healthcare provided and the patients' asthma status had deteriorated during the lockdown with 3.2 points and 2.8 points, respectively. CONCLUSION: Collectively, these results suggest that all necessary resources should be allocated to ensure the performance of lung function tests for initial diagnosis, whereas digital remote monitoring should be reinforced for the follow-up of children and adults with asthma.

Anti-muscarinic drugs as preventive treatment of exercise-induced bronchoconstriction (EIB) in children and adults.

Regular physical activity is strongly recommended to prevent chronic respiratory diseases, including asthma. On the other hand, vigorous physical training may trigger airway symptoms and bronchoconstriction. The transient airway narrowing occurring because of exercise is named exercise-induced bronchoconstriction (EIB). Despite management according to guidelines, a significant proportion of patients experiences uncontrolled EIB, which thus represents a relevant unmet medical need. In particular, although prevention and treatment of EIB are effectively based on the use of beta-2 bronchodilator drugs, high heterogeneity in individual responses has been reported. Furthermore, even though beta-2 adrenergic drugs remain the mainstay of EIB management, occurrence of tolerance and side effects, as well as doping concerns have been reported with their use. In regard to this, inhaled antimuscarinics could represent an alternative or additional effective and safe bronchodilator therapeutic option for achieving optimal EIB control and minimize adverse events. The present systematic review aims to collect and provide the most updated and evidence-based literature findings on the efficacy and safety of short- and long-acting inhaled anti-muscarinic drugs for the preventive treatment of EIB in both children and adults. Take-Home Message: Anti-muscarinic drugs are effective and safe in preventing EIB, despite response variability is reported. Further studies should focus on long-acting molecules, chronic administration and phenotype-driven effects.

A compendium answering 150 questions on COVID-19 and SARS-CoV-2.

In December 2019, China reported the first cases of the coronavirus disease 2019 (COVID-19). This disease, caused by the severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2), has developed into a pandemic. To date, it has resulted in ~9 million confirmed cases and caused almost 500 000 related deaths worldwide. Unequivocally, the COVID-19 pandemic is the gravest health and socioeconomic crisis of our time. In this context, numerous questions have emerged in demand of basic scientific information and evidence-based medical advice on SARS-CoV-2 and COVID-19. Although the majority of the patients show a very mild, self-limiting viral respiratory disease, many clinical manifestations in severe patients are unique to COVID-19, such as severe lymphopenia and eosinopenia, extensive pneumonia, a "cytokine storm" leading to acute respiratory distress syndrome, endothelitis, thromboembolic complications, and multiorgan failure. The epidemiologic features of COVID-19 are distinctive and have changed throughout the pandemic. Vaccine and drug development studies and clinical trials are rapidly growing at an unprecedented speed. However, basic and clinical research on COVID-19-related topics should be based on more coordinated high-quality studies. This paper answers pressing questions, formulated by young clinicians and scientists, on SARS-CoV-2, COVID-19, and allergy, focusing on the following topics: virology, immunology, diagnosis, management of patients with allergic disease and asthma, treatment, clinical trials, drug discovery, vaccine development, and epidemiology. A total of 150 questions were answered by experts in the field providing a comprehensive and practical overview of COVID-19 and allergic disease.

Effect of ambulatory oxygen on quality of life for patients with fibrotic lung disease (AmbOx): a prospective, open-label, mixed-method, crossover randomised controlled trial.

BACKGROUND: In fibrotic interstitial lung diseases, exertional breathlessness is strongly linked to health-related quality of life (HRQOL). Breathlessness is often associated with oxygen desaturation, but few data about the use of ambulatory oxygen in patients with fibrotic interstitial lung disease are available. We aimed to assess the effects of ambulatory oxygen on HRQOL in patients with interstitial lung disease with isolated exertional hypoxia. METHODS: AmbOx was a prospective, open-label, mixed-method, crossover randomised controlled clinical trial done at three centres for interstitial lung disease in the UK. Eligible patients were aged 18 years or older, had fibrotic interstitial lung disease, were not hypoxic at rest but had a fall in transcutaneous arterial oxygen saturation to 88% or less on a screening visit 6-min walk test (6MWT), and had self-reported stable respiratory symptoms in the previous 2 weeks. Participants were randomly assigned (1:1) to either oxygen treatment or no oxygen treatment for 2 weeks, followed by crossover for another 2 weeks. Randomisation was by a computer-generated sequence of treatments randomly permuted in blocks of constant size (fixed size of ten). The primary outcome, which was assessed by intention to treat, was the change in total score on the King's Brief Interstitial Lung Disease questionnaire (K-BILD) after 2 weeks on oxygen compared with 2 weeks of no treatment. General linear models with treatment sequence as a fixed effect were used for analysis. Patient views were explored through semi-structured topic-guided interviews in a subgroup of participants. This study was registered with ClinicalTrials.gov, number NCT02286063, and is closed to new participants with all follow-up completed. FINDINGS: Between Sept 10, 2014, and Oct 5, 2016, 84 patients were randomly assigned, 41 randomised to ambulatory oxygen first and 43 to no oxygen. 76 participants completed the trial. Compared with no oxygen, ambulatory oxygen was associated with significant improvements in total K-BILD scores (mean 55·5 [SD 13·8] on oxygen vs 51·8 [13·6] on no oxygen, mean difference adjusted for order of treatment 3·7 [95% CI 1·8 to 5·6]; p<0·0001), and scores in breathlessness and activity (mean difference 8·6 [95% CI 4·7 to 12·5]; p<0·0001) and chest symptoms (7·6 [1·9 to 13·2]; p=0·009) subdomains. However, the effect on the psychological subdomain was not significant (2·4 [-0·6 to 5·5]; p=0·12). The most common adverse events were upper respiratory tract infections (three in the oxygen group and one in the no-treatment group). Five serious adverse events, including two deaths (one in each group) occurred, but none were considered to be related to treatment. INTERPRETATION: Ambulatory oxygen seemed to be associated with improved HRQOL in patients with interstitial lung disease with isolated exertional hypoxia and could be an effective intervention in this patient group, who have few therapeutic options. However, further studies are needed to confirm this finding. FUNDING: UK National Institute for Health Research.

ERS International Congress 2018: highlights from best-abstract awardees.

A summary of the ERS International Congress 2018 from the best-abstract awardees for each ERS Assembly and their views on the evolving field of research of their respective Assemblies http://ow.ly/c0eq30ntKuw.

Are newly launched pharmacotherapies efficacious in treating idiopathic pulmonary fibrosis? Or is there still more work to be done?

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a challenging and multifactorial disease that has been thought for some time to lack effective treatments. The approval of two drugs, nintedanib and pirfenidone, has heralded a new era in its management. Areas covered: Currently, there is a growing interest on therapeutic strategies. Many studies have been designed and performed, although few of them turned out to be successful. Nowadays, nintedanib and pirfenidone are considered disease modifying drugs, recommended treatments by current evidence-based guidelines. A combined approach with more than one drug could be an effective strategy in IPF. However, data on combination therapy of the two approved drugs are still scarce, and ongoing trials are evaluating pharmacodynamic interactions and safety. The approved disease modifying drugs are also being assessed in combination with new molecules, showing promising results in preclinical models. Expert opinion: A deeper understanding of pathogenesis and key molecular mechanisms driving disease inception and progression will be key to identify novel agents to be tested both pre-clinically and clinically, possibly in combination with approved treatments. Looking at the near future, it is likely that clinical trials will adopt a phenotype-specific and pathway-specific approach, thus leading towards a personalized approach to IPF management.

Weaknesses of histological analysis in celiac disease diagnosis: new possible scenarios.

INTRODUCTION: Celiac disease (CD) is an autoimmune disorder triggered by the ingestion of gluten. Serology and organ culture system can support CD diagnosis, despite histology being the gold standard. AIM: We wanted to test the uniformity of application of Marsh-Oberhuber criteria by five different histologists. We also compared histological and serological data with cultural results to consider new possible strategies in CD diagnosis. METHODS: We studied 114 patients, who were divided in two groups. Group A was composed of 66 patients on a gluten-containing diet, with gluten-related signs and symptoms, showing positive serological anti-endomysial antibodies (EMA) and anti-tissue transglutaminase (anti- tTG). Group B was composed of 48 disease-control patients, presenting serological EMA and anti-tTG negative results. All patients studied underwent esophagogastroduodenoscopy with duodenal biopsy and duodenal mucosa organ culture. All histological samples were evaluated by five different histologists according to an appropriate questionnaire following Marsh-Oberhuber classification. Cohen κ inter-test was used for evaluating the agreement between histologists regarding group A. RESULTS: Strength of agreement was fair/moderate for villous:crypt ratio, moderate/good for villous height and crypt depth, and poor for intraepithelial lymphocytosis. Patients belonging to group A presented positive serological as well as cultural results in 100% of cases. None of the patients belonging to group B presented serological or cultural positive results. DISCUSSION: Our study stresses the limits of histological interpretation due to the lack of uniformity in the use of Marsh-Oberhuber classification. These findings could cast doubt on the role of histology as CD gold standard and could open a debate on the most appropriate CD diagnostic procedure.