Concepts for the development of person-centred, digitally-enabled, Artificial Intelligence-assisted ARIA care pathways (ARIA 2024).

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own life based on their lived experiences. Improving healthcare safety, quality and coordination, as well as quality of life, are important aims in the care of patients with chronic conditions. Person-centred care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (i) digital care pathways for rhinitis and asthma multimorbidity and (ii) digitally-enabled person-centred care (1). It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally-enabled, patient-centred care. The paper includes (i) Allergic Rhinitis and its Impact on Asthma (ARIA), a two-decade journey, (ii) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (iii) mHealth impact on airway diseases, (iv) from guidelines to digital care pathways, (v) embedding Planetary Health, (vi) novel classification of rhinitis and asthma, (vi) embedding real-life data with population-based studies, (vii) the ARIA-EAACI strategy for the management of airway diseases using digital biomarkers, (viii) Artificial Intelligence, (ix) the development of digitally-enabled ARIA Person-Centred Care and (x) the political agenda. The ultimate goal is to propose ARIA 2024 guidelines centred around the patient in order to make them more applicable and sustainable.

Total IgE Trends in Children with Allergic Diseases.

Background/Objectives: The importance of non-invasive biomarkers for the diagnosis and monitoring of allergic diseases in childhood is currently unknown. From this perspective, data on the role of the total (t) immunoglobulin E (IgE) in relation to different allergic diseases across different age groups until adulthood remain unclear. The potential association of tIgE levels with types of allergic diseases diagnosed in an specialized tertiary allergy center, in relation to sex and the age group spanning from birth to 20 years, are evaluated in the present study. Methods: In this retrospective study, the tIgE values were obtained from children assessed for allergy-associated symptoms in our department from January 2015 to December 2020. The tIgE values were analyzed in relation to age and diagnosis. Results: Data from 2127 patients (1321 boys (62.1%)), with a median age of 6.31 (3.01-9.95) years, were available. The tIgE median values for the studied population were 132 (37.7-367.5) kU/lt. The tIgE values showed a significant increase from 0-2 years to 2-5 and 5-12 years, but not from 5-12 to 12-20 years. Boys exhibited significantly higher tIgE values compared to girls. Furthermore, the tIgE levels were significantly increased in children with asthma, allergic rhinitis, food allergy, and atopic dermatitis in comparison to children without these diagnoses. Conclusions: The total IgE values exhibit a significant and progressive longitudinal increase in children with allergic diseases, particularly notable in the 0-2 and 5-12 age groups, in boys, and in children diagnosed with atopic conditions.

Type 2 Inflammation and Asthma in Children: A Narrative Review.

Increased understanding of the underlying pathophysiology has highlighted the heterogeneity of asthma and identified that most children with asthma have type 2 inflammation with elevated biomarkers, such as blood eosinophils and/or fractional exhaled nitric oxide. Although in the past most of these children may have been categorized as having allergic asthma, identifying the type 2 inflammatory phenotype provides a mechanism to explain both allergic and non-allergic triggers in pediatric patients with asthma. Most children achieve control with low-to-medium doses of inhaled corticosteroids, however, in a small but significant proportion of children, asthma remains uncontrolled despite maximum conventional treatment, with an increased risk of severe exacerbations. In this review, we focus on the role of type 2 inflammation and allergic processes in children with asthma, together with evidence of the efficacy of available treatment options for those who experience severe symptoms.

Risks of cutaneous immune-related adverse events in long COVID: Multinational cohort studies in South Korea, Japan, and the UK.

Previous research has not investigated the persistent cutaneous immune-related adverse events (cirAEs) related to long COVID to investigate the long-term sequelae. This multinational study, using a propensity-matched overlap weighting method, utilizes large national claims-based cohorts, using ICD-10 code diagnosis, focusing on patients aged ≥20 years from three countries: South Korean, Japanese, and the British cohorts. To estimate the risk of cirAEs in long COVID, the persistence or emergence of cirAEs occurring 4 weeks after the initial SARS-CoV-2 infection, we employed a Cox proportional hazard regression model. The Korean cohort (n = 5,937,373; mean age 49.2 years [SD: 13.2]), the Japanese cohort (n = 4,307,587; 42.5 years [13.6]), and the UK cohort (n = 395,435; 71.0 years [8.07]) were presented. An increased risk of cirAEs in long COVID was observed (HR, 1.10; 95% CI, 1.06-1.14) in Korean cohort, while a similar association was observed in Japanese and UK cohorts. The long-term risk of cirAEs in long COVID was higher in more severe COVID-19 cases (1.31; 1.22-1.39). Unlike the increased risk of cirAEs in long COVID, COVID-19 vaccination attenuated the risk, especially with two or more doses (1.03; 0.95-1.11) or heterologous regimens (0.98; 0.76-1.27). The time attenuation effect indicated a sustained risk for up to 6 months postinfection (<3 months: 1.13 [1.07-1.19]; 3-6 months: 1.14 [1.06-1.22]). SARS-CoV-2 infection is associated with an increased risk of cirAEs in the aspect of long COVID. Vaccination might reduce this risk, highlighting the need for preventive strategies in long COVID management.

Relevance of the bacteriophage adherence to mucus model for Pseudomonas aeruginosa phages.

Pseudomonas aeruginosa infections are getting increasingly serious as antimicrobial resistance spreads. Phage therapy may be a solution to the problem, especially if improved by current advances on phage-host studies. As a mucosal pathogen, we hypothesize that P. aeruginosa and its phages are linked to the bacteriophage adherence to mucus (BAM) model. This means that phage-host interactions could be influenced by mucin presence, impacting the success of phage infections on the P. aeruginosa host and consequently leading to the protection of the metazoan host. By using a group of four different phages, we tested three important phenotypes associated with the BAM model: phage binding to mucin, phage growth in mucin-exposed hosts, and the influence of mucin on CRISPR immunity of the bacterium. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. Improved phage growth was likely the result of phage exploitation of mucin-induced physiological changes in the host. We could not detect CRISPR activity in our system but identified two putative anti-CRISPR proteins coded by the phage. Overall, the differential responses seen for the phages tested show that the same bacterial species can be targeted by mucosal-associated phages or by phages not affected by mucus presence. In conclusion, the BAM model is relevant for phage-bacterium interactions in P. aeruginosa, opening new possibilities to improve phage therapy against this important pathogen by considering mucosal interaction dynamics.IMPORTANCESome bacteriophages are involved in a symbiotic relationship with animals, in which phages held in mucosal surfaces protect them from invading bacteria. Pseudomonas aeruginosa is one of the many bacterial pathogens threatening humankind during the current antimicrobial resistance crisis. Here, we have tested whether P. aeruginosa and its phages are affected by mucosal conditions. We discovered by using a collection of four phages that, indeed, mucosal interaction dynamics can be seen in this model. Three of the tested phages significantly bound to mucin, while two had improved growth rates in mucin-exposed hosts. These results link P. aeruginosa and its phages to the bacteriophage adherence to the mucus model and open opportunities to explore this to improve phage therapy, be it by exploiting the phenotypes detected or by actively selecting mucosal-adapted phages for treatment.

Dietary Intake, Diet Diversity, and Weight Status of Children With Food Allergy.

BACKGROUND: Adoption of allergen avoidance diets may increase the risk of nutritional deficiencies and affect growth in children with food allergy (FA). How these dietary restrictions have an impact on diet diversity, a health-promoting eating behavior, remains unclear. OBJECTIVE: To evaluate diet diversity, dietary intake, and weight status of children with FA. DESIGN: Observational study. PARTICIPANTS/SETTING: One hundred children with immunoglobulin E (IgE)-mediated milk, egg, or nut FA or multiple FAs and 60 children with perennial respiratory allergies (RA) matched as controls, aged 3 to 18 years, were consecutively recruited into the study. MAIN OUTCOME MEASURES: Dietary intake and diet diversity (number of different foods consumed/day) were assessed through 4 24-hour recalls. Weight status (underweight, healthy weight, overweight, or obesity) was also evaluated. STATISTICAL ANALYSES PERFORMED: Chi-squared test and 2-sample independent t test were used to test differences between groups. Adjustment for sex, age, and energy intake was made using linear regression. RESULTS: The percentage of underweight was higher in children with FA (19.6%) compared with children in the control group (5.1%). Children with FA compared with children in the control group consumed more servings of meat (1.7, 95% CI, 1.6, 1.9 vs. 1.5, 95% CI, 1.3, 1.7 servings/day [Padj = 0.031]). No difference was observed in the diet diversity between the 2 groups (11-12 different foods/day). Within the FA group, children with allergy to milk proteins had lower energy intake from protein, lower intake of calcium, lower consumption of commercially prepared sweets, and higher consumption of eggs, compared with children with nut or egg allergy, but no difference in diet diversity was observed. CONCLUSIONS: Diet diversity did not differ between children with FA and children with no FA, despite some differences in the intake from specific food groups. However, the higher percentage of underweight in children with FA suggests the need for targeted nutrition intervention as early as possible after FA diagnosis.

Pediatric asthma comorbidities: Global impact and unmet needs.

Real-world data on the range and impact of comorbid health conditions that affect pediatric asthma are scant, especially from developing countries. Lack of data hinders effective diagnosis, treatment, and overall management of these complex cases. We, hereby, describe the common pediatric asthma comorbid conditions in terms of evidence for association, potential mechanisms of impact on asthma control, and treatment benefit. Obesity, upper airway allergies, dysfunctional breathing, multiple sensitizations, depressive disorders, food allergy, and gastro-esophageal reflux are common associations with difficult-to-treat asthma. On the other hand, asthma symptoms and/or management may negatively impact the well-being of children through drug adverse effects, worsening of anaphylaxis symptoms, and disturbing mental health. Awareness of these ailments may be crucial for designing the optimum care for each asthmatic child individually and may ultimately improve the quality of life of patients and their families. A multidisciplinary team of physicians is required to identify and manage such comorbidities aiming to mitigate the over-use of asthma pharmacotherapy. Asthma research should target relevant real-world difficulties encountered at clinical practice and focus on interventions that would mitigate the impact of such comorbidities. Finally, policymakers and global healthcare organizations are urged to recognize pediatric asthma control as a healthcare priority and allocate resources for research and clinical interventions. In other words, global asthma control needs support by compassionate scientific partnership.

Lysogeny destabilizes computationally simulated microbiomes.

Microbiomes are ecosystems, and their stability can impact the health of their hosts. Theory predicts that predators influence ecosystem stability. Phages are key predators of bacteria in microbiomes, but phages are unusual predators because many have lysogenic life cycles. It has been hypothesized that lysogeny can destabilize microbiomes, but lysogeny has no direct analog in classical ecological theory, and no formal theory exists. We studied the stability of computationally simulated microbiomes with different numbers of temperate (lysogenic) and virulent (obligate lytic) phage species. Bacterial populations were more likely to fluctuate over time when there were more temperate phages species. After disturbances, bacterial populations returned to their pre-disturbance densities more slowly when there were more temperate phage species, but cycles engendered by disturbances dampened more slowly when there were more virulent phage species. Our work offers the first formal theory linking lysogeny to microbiome stability.

Real-world biologics response and super-response in the International Severe Asthma Registry cohort.

BACKGROUND: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma. METHODS: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV1) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day. RESULTS: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria. CONCLUSIONS: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria.

Digitally-enabled, person-centred care (PCC) in allergen immunotherapy: An ARIA-EAACI Position Paper.

In rhinitis and asthma, several mHealth apps have been developed but only a few have been validated. However, these apps have a high potential for improving person-centred care (PCC), especially in allergen immunotherapy (AIT). They can provide support in AIT initiation by selecting the appropriate patient and allergen shared decision-making. They can also help in (i) the evaluation of (early) efficacy, (ii) early and late stopping rules and (iii) the evaluation of (carried-over) efficacy after cessation of the treatment course. Future perspectives have been formulated in the first report of a joint task force (TF)-Allergic Rhinitis and Its Impact on Asthma (ARIA) and the European Academy of Allergy and Clinical Immunology (EAACI)-on digital biomarkers. The TF on AIT now aims to (i) outline the potential of the clinical applications of mHealth solutions, (ii) express their current limitations, (iii) make proposals regarding further developments for both clinical practice and scientific purpose and (iv) suggest which of the tools might best comply with the purpose of digitally-enabled PCC in AIT.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XII - Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

Association between pre-biologic T2-biomarker combinations and response to biologics in patients with severe asthma.

Background: To date, studies investigating the association between pre-biologic biomarker levels and post-biologic outcomes have been limited to single biomarkers and assessment of biologic efficacy from structured clinical trials. Aim: To elucidate the associations of pre-biologic individual biomarker levels or their combinations with pre-to-post biologic changes in asthma outcomes in real-life. Methods: This was a registry-based, cohort study using data from 23 countries, which shared data with the International Severe Asthma Registry (May 2017-February 2023). The investigated biomarkers (highest pre-biologic levels) were immunoglobulin E (IgE), blood eosinophil count (BEC) and fractional exhaled nitric oxide (FeNO). Pre- to approximately 12-month post-biologic change for each of three asthma outcome domains (i.e. exacerbation rate, symptom control and lung function), and the association of this change with pre-biologic biomarkers was investigated for individual and combined biomarkers. Results: Overall, 3751 patients initiated biologics and were included in the analysis. No association was found between pre-biologic BEC and pre-to-post biologic change in exacerbation rate for any biologic class. However, higher pre-biologic BEC and FeNO were both associated with greater post-biologic improvement in FEV1 for both anti-IgE and anti-IL5/5R, with a trend for anti-IL4Rα. Mean FEV1 improved by 27-178 mL post-anti-IgE as pre-biologic BEC increased (250 to 1000 cells/µL), and by 43-216 mL and 129-250 mL post-anti-IL5/5R and -anti-IL4Rα, respectively along the same BEC gradient. Corresponding improvements along a FeNO gradient (25-100 ppb) were 41-274 mL, 69-207 mL and 148-224 mL for anti-IgE, anti-IL5/5R, and anti-IL4Rα, respectively. Higher baseline BEC was also associated with lower probability of uncontrolled asthma (OR 0.392; p=0.001) post-biologic for anti-IL5/5R. Pre-biologic IgE was a poor predictor of subsequent pre-to-post-biologic change for all outcomes assessed for all biologics. The combination of BEC + FeNO marginally improved the prediction of post-biologic FEV1 increase (adjusted R2: 0.751), compared to BEC (adjusted R2: 0.747) or FeNO alone (adjusted R2: 0.743) (p=0.005 and <0.001, respectively); however, this prediction was not improved by the addition of IgE. Conclusions: The ability of higher baseline BEC, FeNO and their combination to predict biologic-associated lung function improvement may encourage earlier intervention in patients with impaired lung function or at risk of accelerated lung function decline.

Exploring Definitions and Predictors of Response to Biologics for Severe Asthma.

BACKGROUND: Biologic effectiveness is often assessed as response, a term that eludes consistent definition. Identifying those most likely to respond in real-life has proven challenging. OBJECTIVE: To explore definitions of biologic responders in adults with severe asthma and investigate patient characteristics associated with biologic response. METHODS: This was a longitudinal cohort study using data from 21 countries, which shared data with the International Severe Asthma Registry. Changes in four asthma outcome domains were assessed in the 1-year period before and after biologic initiation in patients with a predefined level of prebiologic impairment. Responder cutoffs were 50% or greater reduction in exacerbation rate, 50% or greater reduction in long-term oral corticosteroid daily dose, improvement in one or more category in asthma control, and 100 mL or greater improvement in FEV1. Responders were defined using single and multiple domains. The association between prebiologic characteristics and postbiologic initiation response was examined by multivariable analysis. RESULTS: A total of 2,210 patients were included. Responder rate ranged from 80.7% (n = 566 of 701) for exacerbation response to 10.6% (n = 9 of 85) for a four-domain response. Many responders still exhibited significant impairment after biologic initiation: 46.7% (n = 206 of 441) of asthma control responders with uncontrolled asthma before the biologic still had incompletely controlled disease postbiologic initiation. Predictors of response were outcome-dependent. Lung function responders were more likely to have higher prebiologic FeNO (odds ratio = 1.20 for every 25-parts per billion increase), and shorter asthma duration (odds ratio = 0.81 for every 10-year increase in duration). Higher blood eosinophil count and the presence of type 2-related comorbidities were positively associated with higher odds of meeting long-term oral corticosteroid, control, and lung function responder criteria. CONCLUSIONS: Our findings underscore the multimodal nature of response, showing that many responders experience residual symptoms after biologic initiation and that predictors of response vary according to the outcome assessed.

A systematic review and meta-analysis of nutritional and dietary interventions in randomized controlled trials for skin symptoms in children with atopic dermatitis and without food allergy: An EAACI task force report.

This systematic review and meta-analysis aimed to consolidate evidence on dietary interventions for atopic eczema/dermatitis (AD) skin symptoms in children without food allergies, following PRISMA 2020 guidelines. Systematic review updates were conducted in May 2022 and June 2023, focusing on randomized placebo-controlled trials (RCTs) involving children with AD but without food allergies. Specific diets or supplements, such as vitamins, minerals, probiotics, prebiotics, symbiotics, or postbiotics, were explored in these trials. Exclusions comprised descriptive studies, systematic reviews, meta-analyses, letters, case reports, studies involving elimination diets, and those reporting on food allergens in children and adolescents. Additionally, studies assessing exacerbation of AD due to food allergy/sensitization and those evaluating elimination diets' effects on AD were excluded. Nutritional supplementation studies were eligible regardless of sensitization profile. Evaluation of their impact on AD clinical expression was performed using SCORAD scores, and a meta-analysis of SCORAD outcomes was conducted using random-effect models (CRD42022328702). The review encompassed 27 RCTs examining prebiotics, Vitamin D, evening primrose oil, and substituting cow's milk formula with partially hydrolyzed whey milk formula. A meta-analysis of 20 RCTs assessing probiotics, alone or combined with prebiotics, revealed a significant reduction in SCORAD scores, suggesting a consistent trend in alleviating AD symptoms in children without food allergies. Nonetheless, evidence for other dietary interventions remains limited, underscoring the necessity for well-designed intervention studies targeting multiple factors to understand etiological interactions and propose reliable manipulation strategies.

Current options in the management of tree nut allergy: A systematic review and narrative synthesis.

Tree nut allergy is a lifelong and potentially life-threatening condition. The standard of care is strictly avoiding the culprit nut and treating accidental reactions symptomatically. To evaluate potential therapeutic options for desensitizing patients with IgE-mediated tree nut allergy, we systematically searched three bibliographic databases for studies published until January 2024. We looked for active treatments of IgE-mediated allergy to tree nuts (walnut, hazelnut, pistachio, cashew, almond, pecan, macadamia nut, and brazil nut). We focused on allergen-specific immunotherapy (AIT) using oral (OIT), sublingual (SLIT), epicutaneous (EPIT), or subcutaneous (SCIT) delivery, or other disease-modifying treatments. We found 19 studies that met our criteria: 3 studies investigated sublingual immunotherapy, 5 studied oral immunotherapy to a single tree nut, and 6 used multi-food oral immunotherapy with or without omalizumab. The remaining studies investigated the effectiveness of monoclonal antibodies or IgE-immunoadsorption in multi-food allergic patients, including patients with tree nut allergy. The heterogeneity of the studies prevented pooling and meta-analysis. Oral immunotherapy, single or multi-nut, with or without omalizumab, was the most studied approach and appears effective in conferring protection from accidental exposures. Omalizumab monotherapy is the only approved alternative management for reducing allergic reactions that may occur with accidental exposure.

Incidence of primary hepatitis C infection among people who inject drugs during 2012-2020 in Athens, Greece.

One of the World Health Organization's targets for the 2030 viral hepatitis elimination strategy is to reduce new hepatitis C (HCV) infections. In Athens, Greece, people who inject drugs (PWID) have a high HCV prevalence, with increasing trends since the 2000s. This analysis aims to assess primary HCV incidence among PWID during 2012-2020. Two community-based interventions were implemented in 2012-2013 and 2018-2020 with repeated sero-behavioural surveys in each period. Participants enrolled in multiple surveys were identified through linkage. To assess trends in HCV transmission, three indicators were estimated: (i) anti-HCV prevalence among 'new' injectors (those injecting ≤2 years), (ii) indirect HCV incidence among 'new' injectors, assuming infection occurred at the midpoint between initiating injection and the first positive test, and (iii) HCV incidence from repeat participants. There were 431 and 125 'new' injectors, respectively, in 2012-2013 and 2018-2020. Αnti-HCV prevalence [95% CI] declined from 53.6% [48.8%, 58.3%] in 2012-2013 to 40.0% [31.3, 49.1%] in 2018-2020 (25.4% reduction, p = .007). The indirect estimate [95% CI] of HCV incidence among 'new' injectors decreased from 56.1 [49.3, 63.8] to 39.0/100 person-years (PYs) [29.6, 51.5] (30.5% reduction, p = .020). HCV incidence [95% CI] based on seroconversions in repeat participants (16/63 in 2012-2013 and 9/55 in 2018-2020) declined from 64.6 [39.6105.4] to 13.8/100 PYs [7.2, 26.5], respectively (78.6% reduction, p < .001). Primary HCV incidence remains high among PWID in Athens. Consistent implementation of combined interventions, including high-coverage harm reduction programs and initiatives tailored to increase access to HCV treatment, is essential to sustain the declining trends documented during 2012-2020.

Relevance of individual bronchial symptoms for asthma diagnosis and control in patients with rhinitis: A MASK-air study.

RATIONALE: It is unclear how each individual asthma symptom is associated with asthma diagnosis or control. OBJECTIVES: To assess the performance of individual asthma symptoms in the identification of patients with asthma and their association with asthma control. METHODS: In this cross-sectional study, we assessed real-world data using the MASK-air® app. We compared the frequency of occurrence of five asthma symptoms (dyspnea, wheezing, chest tightness, fatigue and night symptoms, as assessed by the Control of Allergic Rhinitis and Asthma Test [CARAT] questionnaire) in patients with probable, possible or no current asthma. We calculated the sensitivity, specificity and predictive values of each symptom, and assessed the association between each symptom and asthma control (measured using the e-DASTHMA score). Results were validated in a sample of patients with a physician-established diagnosis of asthma. MEASUREMENT AND MAIN RESULTS: We included 951 patients (2153 CARAT assessments), with 468 having probable asthma, 166 possible asthma and 317 no evidence of asthma. Wheezing displayed the highest specificity (90.5%) and positive predictive value (90.8%). In patients with probable asthma, dyspnea and chest tightness were more strongly associated with asthma control than other symptoms. Dyspnea was the symptom with the highest sensitivity (76.1%) and the one consistently associated with the control of asthma as assessed by e-DASTHMA. Consistent results were observed when assessing patients with a physician-made diagnosis of asthma. CONCLUSIONS: Wheezing and chest tightness were the asthma symptoms with the highest specificity for asthma diagnosis, while dyspnea displayed the highest sensitivity and strongest association with asthma control.

Ehf controls mammary alveolar lineage differentiation and is a putative suppressor of breast tumorigenesis.

The transcription factor EHF is highly expressed in the lactating mammary gland, but its role in mammary development and tumorigenesis is not fully understood. Utilizing a mouse model of Ehf deletion, herein, we demonstrate that loss of Ehf impairs mammary lobuloalveolar differentiation at late pregnancy, indicated by significantly reduced levels of milk genes and milk lipids, fewer differentiated alveolar cells, and an accumulation of alveolar progenitor cells. Further, deletion of Ehf increased proliferative capacity and attenuated prolactin-induced alveolar differentiation in mammary organoids. Ehf deletion also increased tumor incidence in the MMTV-PyMT mammary tumor model and increased the proliferative capacity of mammary tumor organoids, while low EHF expression was associated with higher tumor grade and poorer outcome in luminal A and basal human breast cancers. Collectively, these findings establish EHF as a non-redundant regulator of mammary alveolar differentiation and a putative suppressor of mammary tumorigenesis.

Exploring the Impact of Airway Microbiome on Asthma Morbidity: A Focus on the "Constructing a 'Eubiosis Reinstatement Therapy' for Asthma-CURE" Project.

The asthma pandemic imposes a huge burden on patients and health systems in both developed and developing countries. Despite available treatments, symptom control is generally suboptimal, and hospitalizations and deaths remain at unacceptably high levels. A pivotal aspect of asthma that warrants further exploration is the influence of the respiratory microbiome and virome in modulating disease activity. A plethora of studies report that the respiratory microbiome is characteristically dysbiotic in asthma. In addition, our data suggest that dysbiosis is also observed on the respiratory virome, partly characterized by the reduced abundance of bacteriophages (phages). Even though phages can naturally infect and control their bacterial prey, phage therapy has been grossly neglected in the Western world, although more recently it is more widely used as a novel tool against bacterial infections. However, it has never been used for tackling microbiome dysbiosis in human non-communicable diseases. This review provides an up-to-date understanding of the microbiome and virome's role within the airways in relation to asthma morbidity. It also advances the rationale and hypothesis for the CURE project. Specifically, the CURE project suggests that managing the respiratory microbiome through phage therapy is viable and may result in restoring eubiosis within the asthmatic airway. This entails controlling immune dysregulation and the clinical manifestation of the disease. To accomplish this goal, it is crucial to predict the effects of introducing specific phage mixtures into the intricate ecology of the airways and devise suitable interventions.

The impact of exposure to tobacco smoke and e-cigarettes on asthma-related outcomes: Systematic review informing the EAACI guidelines on environmental science for allergic diseases and asthma.

To inform the clinical practice guidelines' recommendations developed by the European Academy of Allergy and Clinical Immunology systematic reviews (SR) assessed using GRADE on the impact of environmental tobacco smoke (ETS) and active smoking on the risk of new-onset asthma/recurrent wheezing (RW)/low lung function (LF), and on asthma-related outcomes. Only longitudinal studies were included, almost all on combustion cigarettes, only one assessing e-cigarettes and LF. According to the first SR (67 studies), prenatal ETS increases the risk of RW (moderate certainty evidence) and may increase the risk of new-onset asthma and of low LF (low certainty evidence). Postnatal ETS increases the risk of new-onset asthma and of RW (moderate certainty evidence) and may impact LF (low certainty evidence). Combined in utero and postnatal ETS may increase the risk of new-onset asthma (low certainty evidence) and increases the risk of RW (moderate certainty evidence). According to the second SR (24 studies), ETS increases the risk of severe asthma exacerbations and impairs asthma control and LF (moderate certainty evidence). According to the third SR (25 studies), active smoking increases the risk of severe asthma exacerbations and of suboptimal asthma control (moderate certainty evidence) and may impact asthma-related quality-of-life and LF (low certainty evidence).