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Abstract Patient‐reported outcome measures (PROMs) are used to assess a patient's health status at a particular point in time. They are essential in the development of person‐centred care. This paper reviews studies performed on PROMs for assessing AR and asthma control, in particular VAS scales that are included in the app MASK‐air® (Mobile Airways Sentinel networK) for asthma and rhinitis. VASs were initially developed on paper and pencil and tested for their criterion validity, cut‐offs and responsiveness. Then, a multicentric, multinational, double‐blind, placebo‐controlled, randomised control trial (DB‐PC‐RCT) using an electronic VAS form was carried out. Finally, with the development of MASK‐air® in 2015, previously validated VAS questions were adapted to the digital format and further methodologic evaluations were performed. VAS for asthma, rhinitis, conjunctivitis, work and EQ‐5D are included in the app. Additionally, two control‐medication scores for allergic symptoms of asthma (e‐DASTHMA) were validated for their criterion validity, cut‐offs and responsiveness.

Myriad digital health interventions, applications, devices and technologies have, and are, being developed to help refine and personalise medicine from the patient, healthcare professional (HCP), healthcare system and industry perspectives. At a gathering of leaders in digital health, discussion included the current landscape of such digital health tools (DHTs), with specific examples from cardiology and respiratory medicine, and both the benefits and sometime downfalls of such tools. While DHTs can help patients and HCPs detect and monitor health conditions, the experts discussed how adoption of DHTs may be hampered by issues such as access to technology; data privacy and security concerns; technology integration into current healthcare systems; cost and reimbursement; and lack of guidelines and regulatory hurdles. The experts suggested solutions to such issues, including wider availability of healthcare ‘booths’ local to a patient; easy to understand and use phone applications; patient and HCP incentives to use DHTs and clear paths to adoption within a healthcare system. These should help with integration of DHTs into the healthcare system to aid shared decision-making and, ultimately, streamline and personalise healthcare for all.

BackgroundChatGPT was not intended for use in health care, but it has potential benefits that depend on end-user understanding and acceptability, which is where health care students become crucial. There is still a limited amount of research in this area. ObjectiveThe primary aim of our study was to assess the frequency of ChatGPT use, the perceived level of knowledge, the perceived risks associated with its use, and the ethical issues, as well as attitudes toward the use of ChatGPT in the context of education in the field of health. In addition, we aimed to examine whether there were differences across groups based on demographic variables. The second part of the study aimed to assess the association between the frequency of use, the level of perceived knowledge, the level of risk perception, and the level of perception of ethics as predictive factors for participants’ attitudes toward the use of ChatGPT. MethodsA cross-sectional survey was conducted from May to June 2023 encompassing students of medicine, nursing, dentistry, nutrition, and laboratory science across the Americas. The study used descriptive analysis, chi-square tests, and ANOVA to assess statistical significance across different categories. The study used several ordinal logistic regression models to analyze the impact of predictive factors (frequency of use, perception of knowledge, perception of risk, and ethics perception scores) on attitude as the dependent variable. The models were adjusted for gender, institution type, major, and country. Stata was used to conduct all the analyses. ResultsOf 2661 health care students, 42.99% (n=1144) were unaware of ChatGPT. The median score of knowledge was “minimal” (median 2.00, IQR 1.00-3.00). Most respondents (median 2.61, IQR 2.11-3.11) regarded ChatGPT as neither ethical nor unethical. Most participants (median 3.89, IQR 3.44-4.34) “somewhat agreed” that ChatGPT (1) benefits health care settings, (2) provides trustworthy data, (3) is a helpful tool for clinical and educational medical information access, and (4) makes the work easier. In total, 70% (7/10) of people used it for homework. As the perceived knowledge of ChatGPT increased, there was a stronger tendency with regard to having a favorable attitude toward ChatGPT. Higher ethical consideration perception ratings increased the likelihood of considering ChatGPT as a source of trustworthy health care information (odds ratio [OR] 1.620, 95% CI 1.498-1.752), beneficial in medical issues (OR 1.495, 95% CI 1.452-1.539), and useful for medical literature (OR 1.494, 95% CI 1.426-1.564; P

Abstract 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.

Abstract Recommendations for or against the use of interventions need to consider both desirable and undesirable effects as well as patients' values and preferences (V&P). In the decision‐making context, patients' V&P represent the relative importance people place on the outcomes resulting from a decision. Therefore, the balance between desirable and undesirable effects from an intervention should depend not only on the difference between benefits and harms but also on the value that patients place on them. V&P are therefore one of the criteria to be considered when formulating guideline recommendations in the Evidence‐to‐Decision framework developed by the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) Working Group. Patients' V&P may be quantified through utilities, which can be elicited using direct methods (e.g., standard gamble or time trade‐off) or indirect methods (using validated instruments to measure health‐related quality of life, such as EQ‐5D). The GRADE approach recommends conducting systematic reviews to summarise all the available evidence and assess the degree of certainty on V&P. In this article, we discuss the importance of considering patients' V&P and provide examples of how they are considered in the 2024 person‐centred Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines.

Abstract Conifers are long-lived and slow-evolving, thus requiring effective defences against their fast-evolving insect natural enemies. The copy number variation (CNV) of two key acetophenone biosynthesis genes Ugt5/Ugt5b and βglu-1 may provide a plausible mechanism underlying the constitutively variable defence in white spruce (Picea glauca) against its primary defoliator, spruce budworm. This study develops a long-insert sequence capture probe set (Picea_hung_p1.0) for quantifying copy number of βglu-1-like, Ugt5-like genes and single-copy genes on 38 Norway spruce (Picea abies) and 40 P. glauca individuals from eight and nine provenances across Europe and North America respectively. We developed local assemblies (Piabi_c1.0 and Pigla_c.1.0), full-length transcriptomes (PIAB_v1 and PIGL_v1), and gene models to characterise the diversity of βglu-1 and Ugt5 genes. We observed very large copy numbers of βglu-1, with up to 381 copies in a single P. glauca individual. We observed among-provenance CNV of βglu-1 in P. glauca but not P. abies. Ugt5b was predominantly single-copy in both species. This study generates critical hypotheses for testing the emergence and mechanism of extreme CNV, the dosage effect on phenotype, and the varying copy number of genes with the same pathway. We demonstrate new approaches to overcome experimental challenges in genomic research in conifer defences.

Abstract Background An innovation to better manage cat‐allergic patients utilises anti‐Fel d 1 IgY antibodies to neutralise Fel d 1 after its production by the cat. However, there is no published study showing its clinical efficacy in humans in a home setting. A longitudinal, open‐label, proof‐of‐concept study was carried out to approach clinical efficacy of the cat food in cat‐allergic patients. Methods After a baseline evaluation, the cats ate only the cat food for the following 4 months. Daily evaluation of efficacy was performed for 2 weeks at baseline and after 1, 2 and 3 months of intervention for periods of 2 weeks. The MASK‐air app was used daily to assess symptoms, work productivity and medications. Results Of the 49 patients screened, 42 were followed up and 33 (78.5%) reported MASK‐air data at all 3 evaluation periods. The primary end point (visual analogue scale [VAS] for global allergy symptoms) was significantly improved (p 20/100) decreased from 64% at baseline to 35% at 1 month (p

Abstract Background Asthma presents a significant health challenge, imposing a considerable burden on healthcare services. Discrepancies in asthma‐related hospitalisations may reflect underlying health disparities. We aimed to analyse inequities in asthma hospital admissions in mainland Portugal and Spain, from a regional perspective and considering sex and age. Methods We conducted a retrospective study using data from the Spanish and Portuguese national hospitalisations databases. We calculated crude national and regional yearly hospitalisation rates according per Nomenclature of Territorial Units for Statistics region. Additionally, we calculated hospitalisation rates adjusted for asthma prevalence and the female‐to‐male ratio in asthma hospital admissions per age group, considering the female‐to‐male ratio in the overall population. Results Between 2012 and 2016, there were 92,084 asthma hospital admissions in mainland Spain and 7717 in mainland Portugal. There was a trend for a higher‐than‐average rate of asthma‐related hospitalisations in the Northern regions of both countries. Women had a hospitalisation rate that was 3.2 times higher than men. Age was associated with higher risk for asthma hospitalisation, with individuals aged 65 and older displaying a hospitalisation rate 4.5 times higher than those under 65. Additionally, while hospitalisations in women aged

Allergic rhinitis (AR) is a chronic respiratory condition that internationally continues to be burdensome and impacts quality of life. Despite availability of medicines and guidelines for healthcare providers for the optimal management of AR, optimisation of its management in the community continues to be elusive. The reasons for this are multi-faceted and include both environmental and healthcare related factors. One factor that we can no longer ignore is that AR management is no longer limited to the domain of healthcare provider and that people with AR make their own choices when choosing how to manage their condition, without seeking advice from a health care provider. We must build a bridge between healthcare provider knowledge and guidelines and patient decision-making. With this commentary, we propose that a shared decision-making approach between healthcare professionals and people with AR be developed and promoted, with a focus on patient health literacy. As custodians of AR knowledge, we have a responsibility to ensure it is accessible to those that matter most—the people with AR.

IntroductionExposure to respiratory viruses is a significant cause of morbidity and affects virus-specific antibody levels. Little is known about determinants associated with immune response to these viruses. We aimed to investigate the determinants of respiratory syncytial virus (RSV)- and rhinovirus (RV)- specific IgG responses in both children and adults.MethodsThe study is based on the EGEA cohort, composed of 530 samples of children in EGEA1 (1991-95) and 1241 samples of adults in EGEA2 (2003-07). Cumulative RV-specific IgG levels (species A, B and C) and IgG levels to RSV-G protein were measured by using micro-array technoloy. Multiple linear mixed models (random effect to account for familial dependence) were performed to assess associations between age, sex, body mass index (BMI), tobacco smoke exposure and season of blood sampling with RSV-and RV-specific IgG levels.ResultsIn children (11.1 ± 2.8 years old, 57% boys), higher RV-specific IgG levels were associated with older age (only for RV-B), female sex and lower BMI, while only older age was associated with higher RSV-specific IgG levels. In adults (43.5 ± 16.7 years old, 48% men), younger age, female sex, lower BMI, active smoking and all seasons except summer were associated with higher RV-specific IgG levels. Older age, active smoking and all seasons except summer were associated with higher RSV-specific IgG levels.ConclusionPersonal and seasonal determinants of RSV- and RV-specific IgG levels seem to vary according to the respiratory virus type and between children and adults, suggesting different patterns of responses along the life course.

Abstract The concept of “one-airway-one-disease”, coined over 20 years ago, may be an over-simplification of the links between allergic diseases. Genomic studies suggest that rhinitis alone and rhinitis with asthma are operated by distinct pathways. In this MeDALL (Mechanisms of the Development of Allergy) study, we leveraged the information of the human interactome to distinguish the molecular mechanisms associated with two phenotypes of allergic rhinitis: rhinitis alone and rhinitis in multimorbidity with asthma. We observed significant differences in the topology of the interactomes and in the pathways associated to each phenotype. In rhinitis alone, identified pathways included cell cycle, cytokine signalling, developmental biology, immune system, metabolism of proteins and signal transduction. In rhinitis and asthma multimorbidity, most pathways were related to signal transduction. The remaining few were related to cytokine signalling, immune system or developmental biology. Toll-like receptors and IL-17-mediated signalling were identified in rhinitis alone, while IL-33 was identified in rhinitis in multimorbidity. On the other hand, few pathways were associated with both phenotypes, most being associated with signal transduction pathways including estrogen-stimulated signalling. The only immune system pathway was FceRI-mediated MAPK activation. In conclusion, our findings suggest that rhinitis alone and rhinitis and asthma multimorbidity should be considered as two distinct diseases.

Drought frequency and intensity are projected to increase with climate change, thus amplifying stress on forest trees. Resilience to drought implicates physiological traits such as xylem conductivity and wood anatomical traits, which are related to growth and wood density. Integrating drought-stress response traits at the juvenile stage into breeding criteria could help promote the survival of planted seedlings under current and future climate and thus, improve plantation success. We assessed in greenhouse the influence of drought-induced stress on 600 two-year-old white spruce (Picea glauca) seedlings from 25 clonal lines after two consecutive growing seasons. Three levels of drought-induced stress were applied: control, moderate and severe. Seedlings were also planted at a 45° angle to clearly separate compression from normal wood. We looked at the phenotypic and genetic effects of drought stress on xylem specific hydraulic conductivity, lumen diameter, tracheid diameter and length, and the number of pits per tracheid in the normal wood. We detected no significant effects of drought stress except for tracheid length, which decreased with increasing drought stress. We found low to high estimates of trait heritability, which generally decreased with increasing drought stress. Genetic correlations were higher than phenotypic correlations for all treatments. Specific conductivity was genetically highly correlated positively with lumen diameter and tracheid length under all treatments. Tracheid length and diameter were always negatively correlated genetically, indicating a trade-off in resource allocation. Moderate to high genetic correlations sometimes in opposite direction were observed between physico-anatomical and productivity traits, also indicating trade-offs. A large variation was observed among clones for all physico-anatomical traits, but clonal ranks were generally stable between control and drought-induced treatments. Our results indicate the possibility of early screening of genetic material for desirable wood anatomical attributes under normal growing conditions, thus allowing to improve the drought resilience of young trees.

Background: The Allergic Rhinitis Clinical Management Pathway (AR-CMaP) was developed to overcome the challenge of implementing current AR guidelines in the Australian community pharmacy practice and support pharmacists in optimally managing patients' AR. Objective(s): To evaluate the impact of AR-CMaP on patients' behaviour and pharmacists' needs in managing AR in the pharmacy. Methods: This study used a cross-sectional, pre-post study design in which the primary outcome was the appropriateness of medications purchased from community pharmacies in Australia. Patient data were collected before and after the implementation of AR-CMaP. Pharmacist needs were recorded before and after AR-CMaP training. Data were analysed descriptively. Results: Six pharmacies, 19 pharmacists and a total of 416 patients were included in the study; 206 pre-AR-CMaP implementation and 210 post-AR-CMaP implementation. Pre-AR-CMaP, 22.4% of patients purchased appropriate AR medication compared with 29.0% post-AR-CMaP implementation. Over half the patient cohort (52%) consulted a pharmacist pre-AR-CMaP and 37% consulted a pharmacist post-AR-CMaP implementation. Post-AR-CMaP, pharmacists reported increased awareness of barriers such as patients' lack of time, patients' perceptions about the pharmacist's role and patient choice to self-manage. Pharmacists also rated an increased desire to interact with other health care providers (HCPs) in caring for patients with AR. Conclusions: While there was a non-statistically significant increase in the proportion of patients purchasing optimal AR medication, AR-CMaP did empower patients to self-select their own medication without further detriment. Moreover, following the implementation of AR-CMaP, pharmacists developed a greater awareness of their role in AR management, exemplified by their increased desire to be actively involved in AR management and increased interaction with other HCPs. Future research needs to explore more effective tools to support pharmacists' clinical decision-making and target patients' self-selection of AR medications. This study highlights that there is an ingrained self-reliance of AR decision-making that has become a habit for people living with AR.

Abstract Background Few population‐based studies have described allergic rhinitis (AR) according to the Allergic Rhinitis and its Impact on Asthma (ARIA) classification, and none have assessed the impact of asthma on this classification. Our aims were to 1) describe AR according to four ARIA classes and 2) within each of the four ARIA classes, compare participants with AR alone versus those with AR and asthma. Methods Cross‐sectional analyses were performed using data from the 2014 annual follow‐up questionnaire of the French adult population‐based cohort Constances. Current AR was defined by the report of sneezing, runny, or blocked nose in the last 12 months and the report of nasal allergies. Following ARIA recommendations, rhinitis was classified according to its severity (mild or moderate‐severe) and duration (intermittent or persistent). Ever asthma was also defined by a questionnaire. Results Among the 4675 participants with AR (57% women, mean age 50.2 ± 12.7 years), 44% were classified as mild/intermittent, 16% mild/persistent, 25% moderate‐severe/intermittent, and 15% moderate‐severe/persistent. Within each of the four ARIA classes, compared to participants with rhinitis alone, participants with rhinitis and asthma had significantly more severe symptoms, more conjunctivitis, a higher mean eosinophil count and more treatments with intra‐nasal corticosteroids and oral antihistamines co‐medication. Conclusions This is a paradigm shift study as for the first time this large population‐based study in adults showed that asthma status has a profound effect on the ARIA classification. Rhinitis alone and rhinitis with asthma represent two distinct phenotypes. These results reinforce the need to include asthma status in the ARIA classification and guidelines.

Introduction Intranasal antihistamines and corticosteroids are some of the most frequently used drug classes in the treatment of allergic rhinitis. However, there is uncertainty as to whether effectiveness differences may exist among different intranasal specific medications. This systematic review aims to analyse and synthesise all evidence from randomised controlled trials (RCTs) on the effectiveness of intranasal antihistamines and corticosteroids in rhinitis nasal and ocular symptoms and in rhinoconjunctivitis-related quality-of-life.Methods and analysis We will search four electronic bibliographic databases and three clinical trials databases for RCTs (1) assessing patients ≥12 years old with seasonal or perennial allergic rhinitis and (2) comparing the use of intranasal antihistamines or corticosteroids versus placebo. Assessed outcomes will include the Total Nasal Symptom Score (TNSS), the Total Ocular Symptom Score (TOSS) and the Rhinoconjunctivitis Quality-of-Life Questionnaire (RQLQ). We will assess the methodological quality of included primary studies by using the Cochrane risk-of-bias tool. Certainty in the body of evidence for the analysed outcomes will be assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. We will perform a random-effects meta-analysis for each assessed medication and outcome, presenting results as pooled mean differences and standardised mean differences. Heterogeneity will be explored by sensitivity and subgroup analyses, considering (1) the risk of bias, (2) the follow-up period and (3) the drug dose.Ethics and dissemination Ethical considerations will not be required. Results will be disseminated in a peer-review journal.PROSPERO registration number CRD42023416573.

Abstract Background Allergic diseases—rhinitis and asthma—are the most common chronic conditions affecting adults. Traditional approaches to allergy diagnosis and treatment do not meet the health needs of all patients. Treatment adherence remains a challenge for physicians. The ubiquity of Internet access paired with limited in‐person contact with medical personnel in the course of the COVID‐19 pandemic demonstrated the potential of mHealth in communicating health information. Body The abundance of new applications dedicated to various medical specialties encourages reflection on the informed use of such tools. The paper takes a closer look at the potential of mHealth and presents conclusions of selected studies focusing on the use of good apps. The strength weakness opportunities threats analysis was used to illustrate the strengths of the mHealth strategy, as well as its advantages, limitations and areas in need of further development. Conclusion The strength of mHealth depends on the quality and quantity of the collected patient data, its reliable processing, as well as publication of outcomes and conclusions from analyses. Therefore, it is necessary to promote the use of validated applications among patients, physicians and medical staff.

BackgroundAzelastine hydrochloride (AZE) is a selective, non-sedating H1 antagonist with anti-inflammatory and mast cell stabilizing properties, which can be used as an alternative to intranasal corticosteroids. The objective of this study was to evaluate the efficacy of the new formulation of 0.15% AZE compared to that of the placebo at a dosage of two sprays per nostril twice daily for 4 weeks in patients with perennial allergic rhinitis (PAR).Materials and methodsA total of 581 subjects were randomized in this double-blind (DB) placebo-controlled trial (NCT00712920) that compared 0.10% (1,096 μg daily) and 0.15% AZE (1,644 μg daily) to the placebo in PAR patients. The study consisted of a 7-day single-blind placebo lead-in period and a 28-day DB treatment period. The primary endpoint was the change from baseline in the 12-h reflective total nasal symptom score (rTNSS) for the entire 28-day study period of 0.15% AZE, two sprays per nostril BID compared to the placebo. The efficacy and safety of 0.15% AZE were compared to the placebo.ResultsLeast square (LS) mean improvement from baseline in the morning (AM) and evening (PM) combined rTNSS was statistically significant for the 0.15% AZE group (p = 0.04) compared to the placebo group. LS mean improvement from baseline in the AM and PM combined rTNSS was 4.10 (4.26) units for 0.15% AZE and 3.81 (3.99) for 0.10% AZE. For individual symptoms, there was a statistically significant change in the LS mean (p = 0.04) improvement from baseline on the 12-h reflective assessment for the 0.15% AZE group for runny nose. Further numerical improvements were shown for itchy nose, nasal congestion, runny nose, and sneezing compared to the placebo. No deaths or serious adverse events related to the study medication were reported.ConclusionThe present formulation of 0.15% AZE is safe and effective in relieving PAR symptoms. It effectively relieves nasal and non-nasal symptoms. Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT00712920.

Abstract Introduction The integrated care pathways for atopic dermatitis (AD‐ICPs) aim to bridge the gap between existing AD treatment evidence‐based guidelines and expert opinion based on daily practice by offering a structured multidisciplinary plan for patient management of AD. ICPs have the potential to enhance guideline recommendations by combining interventions and aspects from different guidelines, integrating quality assurance, and describing co‐ordination of care. Most importantly, patients can enter the ICPs at any level depending on AD severity, resources available in their country, and economic factors such as differences in insurance reimbursement systems. Methods The GA2LEN ADCARE network and partners as well as all stakeholders, abbreviated as the AD‐ICPs working group, were involved in the discussion and preparation of the AD ICPs during a series of subgroup workshops and meetings in years 2020 and 2021, after which the document was circulated within all GAL2EN ADCARE centres. Results The AD‐ICPs outline the diagnostic procedures, possible co‐morbidities, different available treatment options including differential approaches for the pediatric population, and the role of the pharmacists and other stakeholders, as well as remaining unmet needs in the management of AD. Conclusion The AD‐ICPs provide a multidisciplinary plan for improved diagnosis, treatment, and patient feedback in AD management, as well as addressing critical unmet needs, including improved access to care, training specialists, implementation of educational programs, assessment on the impact of climate change, and fostering a personalised treatment approach. By focusing on these key areas, the initiative aims to pave the way for a brighter future in the management of AD.

Societal Impact Statement Syntheses clearly show that global warming is affecting ecosystems and biodiversity around the world. New methods and measures are needed to predict the climate resilience of plant species critical to ecosystem stability, to improve ecological management and to support habitat restoration and human well‐being. Widespread keystone species such as aspen are important targets in the study of resilience to future climate conditions because they play a crucial role in maintaining various ecosystem functions and may contain genetic material with untapped adaptive potential. Here, we present a new framework in support of climate‐resilient revegetation based on comprehensively understood patterns of genetic variation in aspen. Summary Elucidating species' genetic makeup and seed germination plasticity is essential to inform tree conservation efforts in the face of climate change. Populus tremuloides Michx. (aspen) occurs across diverse landscapes and reaches from Alaska to central Mexico, thus representing an early‐successional model for ecological genomics. Within drought‐affected regions, aspen shows ploidy changes and/or shifts from sexual to clonal reproduction, and reduced diversity and dieback have already been observed. We genotyped over 1000 individuals, covering aspen's entire range, for approximately 44,000 single‐nucleotide polymorphisms (SNPs) to assess large‐scale and fine‐scale genetic structure, variability in reproductive type (sexual/clonal), polyploidy and genomic regions under selection. We developed and implemented a rapid and reliable analysis pipeline (FastPloidy) to assess the presence of polyploidy. To gain insights into plastic responses, we contrasted seed germination from western US and eastern Canadian natural populations under elevated temperature and water stress. Four major genetic clusters were identified range wide; a preponderance of triploids and clonemates was found within western and southern North American regions, respectively. Genomic regions involving approximately 1000 SNPs under selection were identified with association to temperature and precipitation variation. Under drought stress, western US genotypes exhibited significantly lower germination rates compared with those from eastern North America, a finding that was unrelated to differences in mutation load (ploidy). This study provided new insights into the adaptive evolution of a key indicator tree that provisions crucial ecosystem services across North America, but whose presence is steadily declining within its western distribution. We uncovered untapped adaptive potential across the species' range which can form the basis for climate‐resilient revegetation.

Abstract Background Asthma with NSAID‐exacerbated respiratory disease (NERD) is associated with uncontrolled or severe asthma. NERD patients are more prone to severe allergic reactions and their asthma exacerbations lead to hospitalisations twice as often compared to patients with non‐NERD‐asthma. NERD patients are prone to recurrent nasal polyposis requiring frequent endoscopic sinus surgeries. However, the early risk factors of NERD are not fully understood. The aim was to identify risk factors of NERD among patients with adult‐onset asthma. Methods We used data from 1350 population‐based adult asthmatics with adult‐onset asthma from Finnish national registers. NERD was defined as self‐reported wheeze or other typical respiratory symptoms after ingestion of NSAIDs. Thirty‐six covariates covering several domains (personal characteristics, life‐style, early life factors, asthma characteristics and multimorbidities) were selected based on literature and were studied in association with NERD using logistic regressions. Results The study population included 153 (11.3%) asthmatics with NERD. Thirty‐six covariates were entered in univariate logistic regression analysis, in which 23 were associated with NERD (p

Abstract We explored antibody response after first and second BNT162b2 vaccinations, to predict the need for subsequent injections in nursing home (NH) residents. 369 NH residents were tested for IgG against SARS-CoV-2 Receptor-Binding Domain (RBD-IgG) and nucleoprotein-IgG (SARS-CoV-2 IgG II Quant and SARS-CoV-2 IgG Alinity assays, Abbott Diagnostics). In NH residents with prior SARS-CoV-2 infection, the first dose elicited high RBD-IgG levels (≥ 4160 AU/mL) in 99/129 cases (76.9%), with no additional antibody gain after the second dose in 74 cases (74.7%). However, a low RBD-IgG level (

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

Abstract Background GA2LEN‐ADCARE is a branch of the largest multidisciplinary network of research centres and clinical care in allergy and asthma, GA2LEN, focussing on the field of atopic dermatitis (AD). AD is a chronic inflammatory skin disease with high burden and many comorbidities requiring different levels of treatment. The need for aligned information from all involved healthcare providers led to the discussion of an integrated care pathway (ICP) plan for AD patient care involving all stakeholders and considering the complexity and variability of the disease, with a particular focus placed on the large number of patients with milder forms of AD. Methods The GA2LEN ADCARE network and all stakeholders, abbreviated the AD‐ICPs working group, were involved in the discussion and preparation of the AD‐ICPs during a series of subgroup workshops and meetings in years 2020 and 2021. Results Here we discuss the unmet needs in AD, the methodology for devising an AD‐ICP and the ICP action plan. Conclusion The GA2LEN ADCARE network has outlined the unmet needs in AD and provided an action plan for devising AD‐ICPs, considering the complexity and variability of the disease.

IntroductionGenomic selection is becoming a standard technique in plant breeding and is now being introduced into forest tree breeding. Despite promising results to predict the genetic merit of superior material based on their additive breeding values, many studies and operational programs still neglect non-additive effects and their potential for enhancing genetic gains.MethodsUsing two large comprehensive datasets totaling 4,066 trees from 146 full-sib families of white spruce (Picea glauca (Moench) Voss), we evaluated the effect of the inclusion of dominance on the precision of genetic parameter estimates and on the accuracy of conventional pedigree-based (ABLUP-AD) and genomic-based (GBLUP-AD) models.ResultsWhile wood quality traits were mostly additively inherited, considerable non-additive effects and lower heritabilities were detected for growth traits. For growth, GBLUP-AD better partitioned the additive and dominance effects into roughly equal variances, while ABLUP-AD strongly overestimated dominance. The predictive abilities of breeding and total genetic value estimates were similar between ABLUP-AD and GBLUP-AD when predicting individuals from the same families as those included in the training dataset. However, GBLUP-AD outperformed ABLUP-AD when predicting for new unphenotyped families that were not represented in the training dataset, with, on average, 22% and 53% higher predictive ability of breeding and genetic values, respectively. Resampling simulations showed that GBLUP-AD required smaller sample sizes than ABLUP-AD to produce precise estimates of genetic variances and accurate predictions of genetic values. Still, regardless of the method used, large training datasets were needed to estimate additive and non-additive genetic variances precisely.DiscussionThis study highlights the different quantitative genetic architectures between growth and wood traits. Furthermore, the usefulness of genomic additive-dominance models for predicting new families should allow practicing mating allocation to maximize the total genetic values for the propagation of elite material.

Contact with natural environments enriches the human microbiome, promotes immune balance and protects against allergies and inflammatory disorders. In Finland, the allergy & asthma epidemic became slowly visible in mid 1960s. After the World War II, Karelia was split into Finnish and Soviet Union (now Russia) territories. This led to more marked environmental and lifestyle changes in the Finnish compared with Russian Karelia. The Karelia Allergy Study 2002–2022 showed that allergic conditions were much more common on the Finnish side. The Russians had richer gene-microbe network and interaction than the Finns, which associated with better balanced immune regulatory circuits and lower allergy prevalence. In the Finnish adolescents, a biodiverse natural environment around the homes associated with lower occurrence of allergies. Overall, the plausible explanation of the allergy disparity was the prominent change in environment and lifestyle in the Finnish Karelia from 1940s to 1980s. The nationwide Finnish Allergy Programme 2008–2018 implemented the biodiversity hypothesis into practice by endorsing immune tolerance, nature contacts, and allergy health with favorable results. A regional health and environment programme, Nature Step to Health 2022–2032, has been initiated in the City of Lahti, EU Green Capital 2021. The programme integrates prevention of chronic diseases (asthma, diabetes, obesity, depression), nature loss, and climate crisis in the spirit of Planetary Health. Allergic diseases exemplify inappropriate immunological responses to natural environment. Successful management of the epidemics of allergy and other non-communicable diseases may pave the way to improve human and environmental health.

Abstract Forest tree improvement helps provide adapted planting stock to ensure growth productivity, fibre quality and carbon sequestration through reforestation and afforestation activities. However, there is increasing doubt that conventional pedigree provides the most accurate estimates for selection and prediction of performance of improved planting stock. When the additive genetic relationships among relatives is estimated using pedigree information, it is not possible to take account of Mendelian sampling due to the random segregation of parental alleles. The use of DNA markers distributed genome-wide (multi-locus genotypes) makes it possible to estimate the realized additive genomic relationships, which takes account of the Mendelian sampling and possible pedigree errors. We reviewed a series of papers on conifer and broadleaf tree species in which both pedigree-based and marker-based estimates of genetic parameters have been reported. Using metadata analyses, we show that for heritability and genetic gains, the estimates obtained using only the pedigree information are generally biased upward compared to those obtained using DNA markers distributed genome-wide, and that genotype-by-environment (GxE) interaction can be underestimated for low to moderate heritability traits. As high-throughput genotyping becomes economically affordable, we recommend expanding the use of genomic selection to obtain more accurate estimates of genetic parameters and gains.

Abstract With climate change, increasingly intense and frequent drought episodes will be affecting water availability for boreal tree species, prompting tree breeders and forest managers to consider adaptation to drought stress as a priority in their reforestation efforts. We used a 19‐year‐old polycross progeny test of the model conifer white spruce (Picea glauca) replicated on two sites affected by distinct drought episodes at different ages to estimate the genetic control and the potential for improvement of drought response in addition to conventional cumulative growth and wood quality traits. Drought response components were measured from dendrochronological signatures matching drought episodes in wood ring increment cores. We found that trees with more vigorous growth during their lifespan resisted better during the current year of a drought episode when the drought had more severe effects. Phenotypic data were also analyzed using genomic prediction (GBLUP) relying on the genomic relationship matrix of multi‐locus gene SNP marker information, and conventional analysis (ABLUP) based on validated pedigree information. The accuracy of predicted breeding values for drought response components was marginally lower than that for conventional traits and comparable between GBLUP and ABLUP. Genetic correlations were generally low and nonsignificant between drought response components and conventional traits, except for resistance which was positively correlated to tree height. Heritability estimates for the components of drought response were slightly lower than for conventional traits, but similar single‐trait genetic gains could be obtained. Multi‐trait genomic selection simulations indicated that it was possible to improve simultaneously for all traits on both sites while sacrificing little on gain in tree height. In a context of rapid climate change, our results suggest that with careful phenotypic assessment, drought response may be considered in multi‐trait improvement of white spruce, with accelerated screening of large numbers of candidates and selection at young age with genomic selection.

The utilization of genotyping has gained significant popularity in tree improvement programs, aiding in enhancing the precision of breeding values, removing pedigree errors, the assessment of genetic diversity, and evaluating pollen contamination. Our study explores the impact of utilizing 5308 SNP markers to genotype seed orchard parents (166), progeny in progeny trials (667), and seedlot orchard seedlings (780), to simultaneously enhance variance components, breeding values, genetic diversity estimates, and pollen flow in the Region I white spruce (Picea glauca) breeding program in central Alberta (Canada). We compared different individual tree mixed models, including pedigree-based (ABLUP), genomic-based (GBLUP), and single-step pedigree-genomic-based (ssGBLUP) models, to estimate variance components and predict breeding values for the height and diameter at breast height traits. The highest heritability estimates were achieved using the ssGBLUP approach, resulting in improved breeding value accuracy compared to the ABLUP and GBLUP models for the studied growth traits. In the six orchard seedlots tested, the genetic diversity of the seedlings remained stable, characterized by an average of approximately 2.00 alleles per SNP, a Shannon Index of approximately 0.44, and an expected and observed heterozygosity of approximately 0.29. The pedigree reconstruction of seed orchard seedlings successfully identified consistent parental contributions and equal genotype contributions in different years. Pollen contamination levels varied between 11% and 70% using SNP markers and 8% to 81% using pollen traps, with traps both over- and under-estimating contamination. Overall, integrating genomic information from parents and offspring empowers forest geneticists and breeders in the Region I white spruce breeding program to correct errors, conduct backward and forward selections with greater precision, gain a deeper understanding of the orchard’s genetic structure, select superior seedlots, and accurately estimate the genetic worth of each orchard lot, which can ultimately result in increased and more precise estimates of genetic gain in the studied growth traits.

Abstract 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.

Abstract Digital health is an umbrella term which encompasses eHealth and benefits from areas such as advanced computer sciences. eHealth includes mHealth apps, which offer the potential to redesign aspects of healthcare delivery. The capacity of apps to collect large amounts of longitudinal, real‐time, real‐world data enables the progression of biomedical knowledge. Apps for rhinitis and rhinosinusitis were searched for in the Google Play and Apple App stores, via an automatic market research tool recently developed using JavaScript. Over 1500 apps for allergic rhinitis and rhinosinusitis were identified, some dealing with multimorbidity. However, only six apps for rhinitis (AirRater, AllergyMonitor, AllerSearch, Husteblume, MASK‐air and Pollen App) and one for rhinosinusitis (Galenus Health) have so far published results in the scientific literature. These apps were reviewed for their validation, discovery of novel allergy phenotypes, optimisation of identifying the pollen season, novel approaches in diagnosis and management (pharmacotherapy and allergen immunotherapy) as well as adherence to treatment. Published evidence demonstrates the potential of mobile health apps to advance in the characterisation, diagnosis and management of rhinitis and rhinosinusitis patients.

Abstract Background Allergic rhinitis (AR) management requires a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication‐related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians. Methods Allergic Rhinitis and its Impact on Asthma (ARIA) first published a reference document on the pharmacist's role in allergic rhinitis management in 2004. Several guidelines were developed over the past 20 years improving the care of allergic rhinitis patients through an evidence‐based, integrated care approach. Results This ARIA/EAACI/FIP Position Paper is based on the latest ARIA in the Pharmacy guidelines and provides: (a) a structured approach to pharmacists identifying people with AR and/or allergic conjunctivitis as well as those at risk of poor disease control; (b) an evidence‐based clinical decision support tool for optimising the management of allergic rhinitis in the community pharmacy; and (c) a framework of referral to the physician. Conclusion This document is not intended to be a mandatory standard of care but is provided as a basis for pharmacists and their staff to develop relevant local standards of care for their patients, within their local practice environment. Pharmacy care varies between countries, and the guide should be adapted to the local situation.

Background: Present guidelines recommend a life-long therapy with mepolizumab in patients suffering from severe eosinophilic asthma as several studies proved the disadvantages of treatment cessation. This study evaluated the possibility of extending the dosage intervals of mepolizumab in those patients with severe eosinophilic asthma after being well controlled. Methods: Eighteen patients diagnosed with severe eosinophilic asthma were started on treatment with mepolizumab in regular 4-week intervals. Symptom control was measured using the asthma control test (ACT) and pulmonary function test every 3 months. The amount of oral corticosteroids needed to maintain symptom control was monitored at every visit. After achieving good symptom control, defined as well controlled ACT ≥20, injection intervals were prolonged from 4 up to 6 to 8 weeks. The evaluation of this data was approved by the ethics committee. Results: ACT and pulmonary function values significantly improved after initiating therapy with mepolizumab on a regular 4-weekly injection interval. After extending the dosage intervals, both ACT and pulmonary function remained on a stable level without significant changes during the follow-up visits for 1 year. Median dosage of prednisolone declined significantly in the studied group under mepolizumab therapy and stayed on a low level during the follow-up visits with only a single patient using prednisolone after 1 year. Conclusion: In patients with fully or well controlled eosinophilic asthma treated with mepolizumab extending the dosage intervals between the injections up to 8 weeks bears the potential to save costs for the health care system.

Abstract Background MASK‐air® is an app whose aim is to reduce the global burden of allergic rhinitis (AR) and asthma. A transfer of innovative practices was performed to disseminate and implement MASK‐air® in European regions. The aim of the study was to examine the implementation of the MASK‐air® app in Lithuanian adults in order to investigate (i) the rate of acceptance in this population, (ii) the duration of app use and (iii) the evaluation of the app after its use. Methods In a longitudinal study, Lithuanian adults with AR and/or asthma were recruited by allergists. They were informed about how to use MASK‐air® and were followed closely. They were reviewed after one to 3 months to evaluate satisfaction and were asked to continue using the app. Results Among the 149 patients recruited (37.2 ± 10.4 years), 52.4% had rhinitis alone, 42.9% had rhinitis, asthma and/or conjunctivitis multimorbidity, and 2.7% isolated asthma. According to the MASK‐air® baseline questionnaire, 88.3% of patients considered that their symptoms were troublesome. Data were available for 102 (68.4%) patients. The duration of app usage in patients ranged from 1 to 680 days (median, 25–75 percentile: 54, 23.2–151 days). Forty‐two (41.1% of patients who were reviewed) patients agreed to share their opinion on MASK‐air®. Most users of the app were satisfied, from 46.5% thinking their allergy was treated more successfully to 90.4% recommending this app to other allergy sufferers. Discussion When recommended by physicians, MASK‐air® was used for a longer period of time.

Abstract The Control of Allergic Rhinitis and Asthma Test (CARAT) is a patient‐reported outcome measurement (PROM) assessing the control of asthma and allergic rhinitis (AR) at a 4 week interval. This systematic review aimed to evaluate the measurement properties of CARAT. Following PRISMA and COSMIN guidelines, we searched five bibliographic databases and retrieved studies concerning the development, assessment of properties, validation, and/or cultural adaption of CARAT. The studies' methodological quality, the quality of measurement properties, and the overall quality of evidence were assessed. We performed meta‐analysis of CARAT measurement properties. We included 16 studies. Control of Allergic Rhinitis and Asthma Test displayed sufficient content validity and very good consistency (meta‐analytical Cronbach alpha = 0.83; 95% CI = 0.80–0.86;I2 = 62.6%). Control of allergic rhinitis and Asthma Test meta‐analytical intraclass correlation coefficient was 0.91 (95% CI = 0.64–0.98;I2 = 93.7%). It presented good construct validity, especially for correlations with Patient‐reported outcome measures assessing asthma (absolute Spearman correlation coefficients range = 0.67–0.73; moderate quality of evidence), and good responsiveness. Its minimal important difference is 3.5. Overall, CARAT has good internal consistency, reliability, construct validity and responsiveness, despite the heterogeneous quality of evidence. Control of Allergic Rhinitis and Asthma Test can be used to assess the control of asthma and AR. As first of its kind, this meta‐analysis of CARAT measurement properties sets a stronger level of evidence for asthma and/or AR control questionnaires.

Abstract Background The aim was to identify risk factors for severe adult-onset asthma. Methods We used data from a population-based sample (Adult Asthma in Finland) of 1350 patients with adult-onset asthma (age range 31–93 years) from Finnish national registers. Severe asthma was defined as self-reported severe asthma and asthma symptoms causing much harm and regular impairment and ≥ 1 oral corticosteroid course/year or regular oral corticosteroids or waking up in the night due to asthma symptoms/wheezing ≥ a few times/month. Sixteen covariates covering several domains (personal characteristics, education, lifestyle, early-life factors, asthma characteristics and multiple morbidities) were selected based on the literature and were studied in association with severe asthma using logistic regressions. Results The study population included 100 (7.4%) individuals with severe asthma. In a univariate analysis, severe asthma was associated with male sex, age, a low education level, no professional training, ever smoking, ≥ 2 siblings, ≥ 1 chronic comorbidity and non-steroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (NERD) (p

We report a case of severe uncontrolled allergic and eosinophilic asthma in which omalizumab had led to a fast remission. After 18 months, mepolizumab was added to omalizumab because of increased blood eosinophils and a deterioration of asthma control. Asthma was then under control for the next 18 months. Discontinuation of mepolizumab in the ensuing 6 months led to a decrease in asthma control and an increased eosinophilia. The introduction of benralizumab resulted in an immediate increase of lung function, asthma control test (ACT), and symptom relief. Before the introduction of biologics, the patient was on the list for transplantation due to respiratory insufficiency. High-resolution CT scans before and after biologic therapy demonstrated a reduction of bronchial wall thickening and mucous plugging as well as an increase in bronchial caliber. The patient did therefore not need a transplant. We conclude that the dual use of biologics may be efficient in some cases of severe asthma.

Real-world data represent an increasingly important source of knowledge in health care. However, assessing their representativeness can be challenging. We compared (i) real-world data from a mobile app for allergic rhinitis (MASK-air®) on the usage of oral H1-antihistamines from 2016 to 2020 in 10 European countries with (ii) Google Trends data on the relative volume of searches for such antihistamines. For each country, we sorted 5 different oral H1-antihistamines by their frequency of use and volume of searches. We found perfect agreement on the order of antihistamine use in MASK-air® and in Google Trends searches in 4 countries (France, Germany, Sweden, and the United Kingdom). Different levels of agreement were observed in the remaining countries (kappa coefficient from −0.50 to 0.75). Oral H1-antihistamine data from Google Trends and MASK-air® were consistent with nationwide medication sales data from France, Germany, and the United Kingdom. These results suggest that MASK-air® data may be consistent with other sources of real-world data, although assessing the representativeness of their users may require further studies.

Global warming is predicted to extend the growing season of trees and plants, and advance spring phenology. However, intensification of extreme climate events in mid-latitude forests, from weakening of the jet stream and atmospheric blockings, may expose trees to increased risk associated with more frequent late-spring frosts. Still, little is known regarding the intraspecific variation in frost tolerance and how it may be shaped by local adaptation to the climate of seed origin. As part of an assisted migration trial located in different bioclimatic zones in the province of Quebec, Canada, and following an extensive late-spring frost that occurred at the end of May 2021, we evaluated the frost damages on various white spruce (Picea glauca) seed sources tested on three sites (south, central, and north). The severity of frost damages was assessed on 5,376 trees after the cold spell and an early spring warming which advanced bud flush by approximately 10 days on average. The frost damage rate was similar among sites and seed sources and averaged 99.8%. Frost damage severity was unrelated to the latitude of seed origin but was variable among sites. The proportion of severely damaged trees was higher in the northern site, followed by central and southern sites. The proportion of severely damaged trees was linearly and inversely related to tree height before the frost event. Apical growth cancelation was not significantly different among seed sources including local ones, and averaged 74, 46, and 22%, respectively, in central, northern, and southern plantation sites. This study provides recommendations to limit the loss of plantation productivity associated with such a succession of spring climate anomalies. Implications for seed transfer models in the context of climate change and productivity of spruce plantations are discussed in the light of lack of local adaptation to such pronounced climate instability and ensuing large-scale maladaptation.

Olfactory dysfunction is common in COVID-19, and sudden-onset dysosmia is an early marker for wild-type SARS-CoV-2 infection. Over 10 000 mutations of SARS-CoV-2 have been registered, with variants of concern (VOC) under particular scrutiny. We report a telemedicine-based, multicentre, prospective cohort study with quantitative olfaction testing comparing 79 patients with a confirmed VOC-Delta (n = 21) or wild-type (WT) SARS-CoV-2 infection. Acute SARS-CoV-2 infection led to significant decrease of olfactory function in both cohorts. A majority of patients suffered from hyposmia or anosmia at inclusion with only 26 individuals performing normosmic. Sniffin'Sticks total scores were significantly higher for VOC-Delta patients at onset of illness, compared to WT patients (p

Abstract Accurate monitoring of genetic diversity levels of seedlots and mating patterns of parents from seed orchards are crucial to ensure that tree breeding programs are long-lasting and will deliver anticipated genetic gains. We used SNP genotyping to characterize founder trees, five bulk seed orchard seedlots, and trees from progeny trials to assess pollen contamination and the impact of severe roguing on genetic diversity and parental contributions in a first-generation open-pollinated white spruce clonal seed orchard. After severe roguing (eliminating 65% of the seed orchard trees), we found a slight reduction in the Shannon Index and a slightly negative inbreeding coefficient, but a sharp decrease in effective population size (eightfold) concomitant with sharp increase in coancestry (eightfold). Pedigree reconstruction showed unequal parental contributions across years with pollen contamination levels between 12 and 51% (average 27%) among seedlots, and 7–68% (average 30%) among individual genotypes within a seedlot. These contamination levels were not correlated with estimates obtained using pollen flight traps. Levels of pollen contamination also showed a Pearson’s correlation of 0.92 with wind direction, likely from a pollen source 1 km away from the orchard under study. The achievement of 5% genetic gain in height at rotation through eliminating two-thirds of the orchard thus generated a loss in genetic diversity as determined by the reduction in effective population size. The use of genomic profiles revealed the considerable impact of roguing on genetic diversity, and pedigree reconstruction of full-sib families showed the unanticipated impact of pollen contamination from a previously unconsidered source.

Abstract With climate change, the pressure on tree breeding to provide varieties with improved resilience to biotic and abiotic stress is increasing. As such, pest resistance is of high priority but has been neglected in most tree breeding programs, given the complexity of phenotyping for these traits and delays to assess mature trees. In addition, the existing genetic variation of resistance and its relationship with productivity should be better understood for their consideration in multitrait breeding. In this study, we evaluated the prospects for genetic improvement of the levels of acetophenone aglycones (AAs) in white spruce needles, which have been shown to be tightly linked to resistance to spruce budworm. Furthermore, we estimated the accuracy of genomic selection (GS) for these traits, allowing selection at a very early stage to accelerate breeding. A total of 1,516 progeny trees established on five sites and belonging to 136 full‐sib families from a mature breeding population in New Brunswick were measured for height growth and genotyped for 4,148 high‐quality SNPs belonging to as many genes along the white spruce genome. In addition, 598 trees were assessed for levels of AAs piceol and pungenol in needles, and 578 for wood stiffness. GS models were developed with the phenotyped trees and then applied to predict the trait values of unphenotyped trees. AAs were under moderate‐to‐high genetic control (h2: 0.43–0.57) with null or marginally negative genetic correlations with other traits. The prediction accuracy of GS models (GBLUP) for AAs was high (PAAC: 0.63–0.67) and comparable or slightly higher than pedigree‐based (ABLUP) or BayesCπ models. We show that AA traits can be improved and that GS speeds up the selection of improved trees for insect resistance and for growth and wood quality traits. Various selection strategies were tested to optimize multitrait gains.

Background: Chronic cough management necessitates a clear integrated care pathway approach. Primary care physicians initially encounter the majority of chronic cough patients, yet their role in proper management can prove challenging due to limited access to advanced diagnostic testing. A multidisciplinary approach involving otolaryngologists and chest physicians, allergists, and gastroenterologists, among others, is central to the optimal diagnosis and treatment of conditions which underly or worsen cough. These include infectious and inflammatory, upper and lower airway pathologies, or gastro-esophageal reflux. Despite the wide armamentarium of ancillary testing conducted in cough multidisciplinary care, such management can improve cough but seldom resolves it completely. This can be due partly to the limited data on the role of tests (eg, spirometry, exhaled nitric oxide), as well as classical pharmacotherapy conducted in multidisciplinary specialties for chronic cough. Other important factors include presence of multiple concomitant cough trigger mechanisms and the central neuronal complexity of chronic cough. Subsequent management conducted by cough specialists aims at control of cough refractory to prior interventions and includes cough-specific behavioral counseling and pharmacotherapy with neuromodulators, among others. Preliminary data on the role of neuromodulators in a proof-of-concept manner are encouraging but lack strong evidence on efficacy and safety. Objectives: The World Allergy Organization (WAO)/Allergic Rhinitis and its Impact on Asthma (ARIA) Joint Committee on Chronic Cough reviewed the recent literature on management of chronic cough in primary, multidisciplinary, and cough-specialty care. Knowledge gaps in diagnostic testing, classical and neuromodulator pharmacotherapy, in addition to behavioral therapy of chronic cough were also analyzed. Outcomes: This third part of the WAO/ARIA consensus on chronic cough suggests a management algorithm of chronic cough in an integrated care pathway approach. Insights into the inherent limitations of multidisciplinary cough diagnostic testing, efficacy and safety of currently available antitussive pharmacotherapy, or the recently recognized behavioral therapy, can significantly improve the standards of care in patients with chronic cough.

Abstract Introduction Although rhinitis is among the most common diseases worldwide, rhinitis prevalence in the general adult population is unclear and definitions differ widely. Objective To summarize the literature on rhinitis prevalence in the general adult population and to assess: (1) the prevalence according to different rhinitis definitions overall and in different regions of the world, and (2) the evolution of rhinitis prevalence over time. Methods We conducted an extensive literature review of publications including rhinitis prevalence using Pubmed and Scopus databases up to October 2020. We classified the definitions into three categories: unspecified rhinitis, allergic rhinitis (AR), and nonallergic rhinitis (NAR). Results Among 5878 articles screened, 184 articles were included, presenting 156 different definitions of rhinitis. Rhinitis prevalence ranged from 1% to 63%. The overall median prevalences of unspecified rhinitis, AR and NAR were 29.4%, 18.1% and 12.0%, and they varied according to the geographical location. Rhinitis prevalence tended to increase over time. Conclusions This review highlights the great heterogeneity of the definitions. The majority of studies had focused on AR, while only a few epidemiological data exist on NAR. We found geographical variability in rhinitis prevalence. Most of studies reported an increase of rhinitis prevalence over the last decades.

Abstract Background Evidence regarding the effectiveness of allergen immunotherapy (AIT) on allergic rhinitis has been provided mostly by randomised controlled trials, with little data from real‐life studies. Objective To compare the reported control of allergic rhinitis symptoms in three groups of users of the MASK‐air® app: those receiving sublingual AIT (SLIT), those receiving subcutaneous AIT (SCIT), and those receiving no AIT. Methods We assessed the MASK‐air® data of European users with self‐reported grass pollen allergy, comparing the data reported by patients receiving SLIT, SCIT and no AIT. Outcome variables included the daily impact of allergy symptoms globally and on work (measured by visual analogue scales—VASs), and a combined symptom‐medication score (CSMS). We applied Bayesian mixed‐effects models, with clustering by patient, country and pollen season. Results We analysed a total of 42,756 days from 1,093 grass allergy patients, including 18,479 days of users under AIT. Compared to no AIT, SCIT was associated with similar VAS levels and CSMS. Compared to no AIT, SLIT‐tablet was associated with lower values of VAS global allergy symptoms (average difference = 7.5 units out of 100; 95% credible interval [95%CrI] = −12.1;−2.8), lower VAS Work (average difference = 5.0; 95%CrI = −8.5;−1.5), and a lower CSMS (average difference = 3.7; 95%CrI = −9.3;2.2). When compared to SCIT, SLIT‐tablet was associated with lower VAS global allergy symptoms (average difference = 10.2; 95%CrI = −17.2;−2.8), lower VAS Work (average difference = 7.8; 95%CrI = −15.1;0.2), and a lower CSMS (average difference = 9.3; 95%CrI = −18.5;0.2). Conclusion In patients with grass pollen allergy, SLIT‐tablet, when compared to no AIT and to SCIT, is associated with lower reported symptom severity. Future longitudinal studies following internationally‐harmonised standards for performing and reporting real‐world data in AIT are needed to better understand its ‘real‐world’ effectiveness.

Abstract Vaccination is a highly effective preventive measure against COVID‐19. However, complementary treatments are needed to better control the disease. Fermented vegetables and spices, agonists of the antioxidant transcription factor nuclear factor (erythroid‐derived 2)‐like 2 (Nrf2) and TRPA1/V1 channels (Transient Receptor Potential Ankyrin 1 and Vanillin 1), may help in the control of COVID‐19. Some preliminary clinical trials suggest that curcumin (spice) can prevent some of the COVID‐19 symptoms. Before any conclusion can be drawn and these treatments recommended for COVID‐19, the data warrant confirmation. In particular, the benefits of the foods need to be assessed in more patients, through research studies and large trials employing a double‐blind, placebo‐controlled design.

Abstract Background An increase in online searches on health topics may either mirror epidemiological changes or reflect media coverage. In the context of COVID-19, this is particularly relevant, as COVID-19 symptoms may be mistaken for those of respiratory disease exacerbations. Therefore, we aimed to assess Internet search patterns on asthma and chronic obstructive pulmonary disease (COPD) in the context of COVID-19, as compared to searches on other chronic diseases. Methods We retrieved Google Trends (GTs) data on two respiratory (asthma and COPD) and three non-respiratory (diabetes, hypertension, and Crohn’s disease) chronic diseases over the past 5 years (up to May 31, 2020). For 54 countries, and for each disease, we built autoregressive integrated moving average (ARIMA) models to predict GTs for 2020 based on 2015–2019 search patterns. In addition, we estimated the proportion of searches in which COVID-19-related terms were used. To assess the potential impact of media coverage on online searches, we assessed whether weekly “asthma” GTs correlated with the number of Google News items on asthma. Results Over the past 5 years, worldwide search volumes for asthma and COPD reached their maximum values in March 2020. Such was not observed for diabetes, hypertension and Crohn’s disease. In 38 (70%) countries, GTs on asthma were higher in March 2020 than the respective maximum predicted values. This compares to 19 countries for COPD, 23 for hypertension, 11 for Crohn’s disease, and 9 for diabetes. Queries with COVID-19-related terms represented up to 47.8% of the monthly searches on asthma, and up to 21.3% of COPD searches. In most of the assessed countries, moderate-strong correlations were observed between “asthma” GTs and the number of news items on asthma. Conclusions During March 2020, there was a peak in searches on asthma and COPD, which was probably mostly driven by media coverage, as suggested by their simultaneity in several countries with different epidemiological situations.

Abstract Background Despite availability of clinical guidelines, underdiagnosis, undertreatment, and poor adherence are still significant concerns in allergic rhinitis (AR) therapeutic management. We investigated clinical practice patterns and prescribing behavior of Italian healthcare professionals (HCPs) specialized in AR. Methods One-hundred allergologists, 100 ear, nose and throat (ENT) specialists, and 150 general practitioners (GPs) were recruited. The survey assessed: socio-demographic, work experience, monthly caseload, prescription drivers. Next, HCPs were invited to retrospectively recover patients’ clinical data to investigate: AR clinical characteristics, therapy management, prescription patterns, patient adherence. Descriptive statistics, Chi square, One-Way analysis of variance, and Two-Way Analysis of Variance were performed. Results Allergologists visited more AR patients (31% of monthly caseload) than ENTs (21%, p 7). Conclusions This survey describes the therapeutic approach adopted by Italian physicians to cope with AR and shows that HCPs underestimated AR severity and had a non-realistic perception of patients’ adherence. These findings suggest that further efforts are required to improve AR clinical management in Italy.

Abstract Genome wide association studies (GWASs) have revealed several airway disease-associated risk loci. Their role in the onset of asthma, allergic rhinitis (AR) or chronic rhinosinusitis (CRS), however, is not yet fully understood. The aim of this review is to evaluate the airway relevance of loci and genes identified in GWAS studies. GWASs were searched from databases, and a list of loci associating significantly (p