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Dyspnea is reported in a minority of patients affected by coronavirus disease 2019 (COVID-19). Even patients with pneumonia can present hypoxemia without any respiratory distress, a phenomenon known as “silent” or “happy hypoxemia”. During the current pandemic there were only a few studies conducted on this subject and these were quite heterogeneous. Therefore, the prevalence of “silent hypoxemia” varied substantially. While studies did not show a clear tendency of “silent hypoxemia” to poorer outcomes compared to hypoxemia presenting with dyspnea, several showed that patients with “silent hypoxemia” are not protected from poor outcomes either. There is a need for a uniform definition of “silent hypoxemia”, in order to better guide clinicians and investigators. More studies are needed to shed light on the mechanisms of “silent hypoxemia”, as well as its presentation and influence in the disease's progression and outcomes, so as to better assist physicians in the care of COVID-19 patients.

Purpose of Review To provide an up-to-date on paediatric acute urticaria (AU) management, highlighting recent publications. Recent Findings In more than 30% of children with AU, no specific cause is identified. Infections are consistently the most reported potential triggers, followed by food and drug hypersensitivity. Specific triggers aren’t associated with AU severity. Older age and the presence of concomitant angioedema are associated with urticaria persistence. There are worldwide differences regarding available second-generation H1-antihistamines (2ndGAH) and also licensed doses. Evidence on up-dosing 2ndGAH in paediatric urticaria is scarce, but the use of cetirizine may result in increased dose-dependent sedation. Other topical and systemic treatments are being used; not all are evidence-based. Educational training sessions on urticaria management are effective in enhancing physicians’ compliance with current recommendations. Summary A comprehensive clinical history is the key factor for the identification of treatable AU causes. Oral 2ndGAH should be widely available as the first-line treatment. At least doubling the standard dose of low sedative potential 2ndGAH can be useful, if symptoms persist or in moderate-severe urticaria. Short-term oral corticosteroids may be added in severe AU, including children with significant or predominant angioedema. Clinical trials on larger paediatric populations are needed to support evidence-based recommendations.

Background Allergic rhinitis and asthma (ARA) are chronic inflammatory diseases of the airways that often coexist in children. The only tool to assess the ARA control, the Control of Allergic Rhinitis and Asthma Test (CARAT) is to be used by adults. We aimed to develop the Pediatric version of Control of Allergic Rhinitis and Asthma Test (CARATkids) and to test its comprehensibility in children with 4 to 12 years of age. Methods The questionnaire development included a literature review of pediatric questionnaires on asthma and/or rhinitis control and two consensus meetings of a multidisciplinary group. Cognitive testing was carried out in a cross-sectional qualitative study using cognitive interviews. Results Four questionnaires to assess asthma and none to assess rhinitis control in children were identified. The multidisciplinary group produced a questionnaire version for children with 17 questions with illustrations and dichotomous (yes/no) response format. The version for caregivers had 4-points and dichotomous scales. Twenty-nine children, 4 to 12 years old, and their caregivers were interviewed. Only children over 6 years old could adequately answer the questionnaire. A few words/expressions were not fully understood by children of 6 to 8 years old. The drawings illustrating the questions were considered helpful by children and caregivers. Caregivers considered the questionnaire complete and clear and preferred dichotomous over the 4-points scales. The proportion of agreement between children and their caregivers was 61%. The words/expressions that were difficult to understand were amended. Conclusion CARATkids, the first questionnaire to assess a child’s asthma and rhinitis control was developed and its content validity was assured. Cognitive testing showed that CARATKids is well-understood by children 6 to 12 years old. The questionnaire’s measurement properties can now be assessed in a validation study.

Purpose of review This review aims to describe some of the limitations in defining anaphylaxis and therefore the difficulties in studying its epidemiology. Despite these limitations we also aim to describe some of the trends observed in recent studies. Recent findings The epidemiological study of anaphylaxis is problematic. Although first described over 100 years ago, the definition of anaphylaxis has undergone revision in the last 2 decades, and a new international consensus definition was proposed in 2014. Clinical diagnostic criteria have been in use for little over a decade. Mast cell tryptase can be used to confirm the diagnosis, but is not always available, is of little use in determining immediate treatment and is not performed in many cases of suspected anaphylaxis. Epidemiological studies rely on clinical diagnosis and medical coding systems which have many limitations. Summary Recent changes adopted in the ICD-11 will aid the detection and classification of anaphylaxis cases. The absence of an objective gold standard and the difficulty in data quality at a population level mean that reliable epidemiologic data are difficult to obtain. Anaphylaxis seems to be increasing, with food-induced case in paediatrics and drug-induced cases in adults the main drivers.

Background Asthma affects the lives of hundred million people around the World. Despite notable progresses in disease management, asthma control remains largely insufficient worldwide, influencing patients’ wellbeing and quality of life. Poor patient handling of inhaling devices has been identified as a major persistent problem that significantly reduces inhaled drugs’ efficacy and is associated with poor adherence to treatment, impairing clinical results such as asthma control and increasing disease-related costs. We herein review key research and development (R&D) innovation in inhaler devices, highlighting major real-world critical errors in the handling and inhalation technique with current devices and considering potential solutions. Furthermore, we discuss current evidence regarding breath-triggered inhalers (BTI). Main body The two most common significant problems with inhalers are coordinating actuation and inhalation with pressurized metered-dose inhalers (pMDIs), and the need to inhale forcibly with a dry powder inhaler. BTI R&D plans were designed to overcome these problems. Its newest device k-haler® has several other important features, generating a less forceful aerosol plume than previous pMDIs, with efficient drug delivery and lung deposition, even in patients with low inspiratory flow. The local and systemic bioavailability of fluticasone propionate and formoterol (FP/FORM) administered via k-haler® has been shown to be therapeutically equivalent when administered via the previous FP/FORM pMDI. This device requires very few steps and has been considered easy to use (even at first attempt) and preferred by the patients in a randomized crossover study. In our country, FP/FORM k-haler is available without additional costs compared to FP/FORM pMDI. All devices continue to require education and regular checking of the correct inhalation technique. Conclusion BTI R&D can bring advantage over current available inhalers, avoiding the two most common identified critical errors in inhalation technique. K-haler® BTI is currently available, without an increased cost, and approved for adolescents and adults with asthma in whom treatment with inhaled combined therapy with long-acting beta 2 -agonists and corticosteroids is indicated. Its attractive and practical design to facilitate its use has been awarded. K-haler® represents added value through innovation to fulfill actual asthma patient needs, thus with potential relevant impact in asthma management and effective control.

In recent decades, both asthma prevalence and incidence have been increasing worldwide, not only due to the genetic background, but mainly because of the effect of a wide number of environmental and lifestyle risk factors. In many countries noncommunicable diseases, like asthma, are not yet considered a healthcare priority. This review will analyze and discuss disparities in asthma management in several countries and regions, such as access to healthcare human resources and medications, due to limited financial capacity to develop strategies to control and prevent this chronic disease. This review tries to explore the social and economic burden of asthma impact on society. Although asthma is generally accepted as a costly illness, the total costs to society (direct, indirect and intangible asthma costs) are difficult to estimate, mainly due to different disease definitions and characterizations but also to the use of different methodologies to assess the asthma socio-economic impact in different societies. The asthma costs are very variables from country to country, however we can estimate that a mean cost per patient per year, including all asthmatics (intermittent, mild, moderate and severe asthma) in Europe is $USD 1,900, which seems lower than USA, estimated mean $USD 3,100.

Background The concurrent management of allergic rhinitis and asthma (ARA) has been recommended by Allergic Rhinitis and its Impact on Asthma (ARIA) guidelines. However, a tool capable of assessing simultaneously the control of upper and lower airways diseases is lacking. Aim To describe the studies conducted to design the control of ARA test (CARAT) questionnaire. Methods We performed a literature review to generate a list of potentially important items for the assessment of control of ARA. A formal consensus development process, that used an innovative web-based application, was designed – 111 experts in ARA and 60 patients participated. At the final consensus meeting, 25 primary and secondary care physicians formulated the questions and response options. A qualitative feasibility study (n = 31 patients) was conducted to evaluate the comprehensibility of the questionnaire while testing two different designs. Results Thirty-four potentially important items were identified. All the steps of the consensus process were completed in 2.5 months. The opinions of experts and patients lead to the formulation of 17 questions. At the feasibility study the instructions and wording problems were corrected and a semi-tabular format was chosen. Conclusion A tool to measure the control of allergic rhinitis and asthma was developed using a comprehensive set of methodological steps ensuring the design quality and the face and content validity. Additional validation studies to assess the psychometric properties of the questionnaire have started.

The increasing knowledge of the mechanisms involved in metabolism is shifting the paradigms by which the pathophysiology of many pulmonary diseases is understood. Metabolic dysfunction is recognized in obesity-associated asthma, but other metabolic conditions have been shown to be independently related to asthma. Novel insights have also recently been brought by metabolomics in this filed. The purpose of this review is to discuss current perspectives regarding metabolic dysfunction in asthma, from obesity-related asthma to other metabolic conditions and the role of current pharmacological therapeutic strategies and lifestyle interventions. Obesity is a well-recognized risk factor for asthma across the lifespan, which is generally associated with poorer response to current available treatments, rendering a more severe, refractory disease status. Besides the epidemiological and clinical link, untargeted metabolomics studies have recently supported the obesity-associated asthma phenotype at the molecular level. Not only obesity-related, but also other aspects of metabolic dysregulation can be independently linked to asthma. These include hyperinsulinemia, dyslipidemia and hypertension, which need to be taken into account, even in the non-obese patient. Untargeted metabolomics studies have further highlighted several other metabolic pathways that can be altered in asthma, namely regarding oxidative stress and systemic inflammation, and also suggesting the importance of microbiota in asthma pathogenesis. Considering the reduced response to corticosteroids, other pharmacologic treatments have been shown to be effective regardless of body mass index. Non-pharmacologic treatments (namely weight reduction and dietary changes) may bring substantial benefit to the asthmatic patient. Taken together, this evidence points towards the need to improve our knowledge in this filed and, in particular, to address the influence of environmental factors in metabolic dysfunction and asthma development. Personalized medicine is definitely needed to optimize treatment, including a holistic view of the asthmatic patient in order to set accurate pharmacologic therapy together with dietary, physical exercise and lifestyle interventions. Keywords: asthma, diet, inflammation, metabolic, metabolomics, obesity

Objective The present narrative review provides a comprehensive update of the current knowledge on urticaria, both in adult and pediatric populations, and on the safety and efficacy of fexofenadine hydrochloride (HCl) as a treatment option. Data source A literature search was conducted on Embase and Medline. Study selection Clinical studies published in English and published between 1999 and 2020 were selected. Results Although the exact pathogenesis of urticaria is not fully understood, multiple pathways of mast cell activation are discussed to explain the existence of phenotypically different clinical manifestations of urticaria. An overview of the worldwide prevalence of chronic urticaria, including disease burden and patient’s quality of life is provided. The impact of urticaria on patient’s life differs on the basis of whether its form is acute or chronic, but pharmacological approaches are most often needed to control the disabling symptoms. A summary of the current management of urticaria recommended by different guidelines across countries (Global; European; American; Australian; Asian; Japanese) is presented. Non-sedating, second-generation H 1 -antihistamines are the preferred choice of treatment across several guidelines worldwide. Herein, the efficacy and safety of fexofenadine HCl, a representative second-generation H 1 -antihistamine approved for the treatment of urticaria, is discussed. The occurrence of urticaria manifestations in COVID-19 patients is also briefly presented. Conclusion The burden of acute and chronic urticaria is high for patients. Second generation anti-histamines such as fexofenadine HCl can help managing the symptoms.

Background and Objectives: Histamine H 1 -receptor antagonists (antihistamines) have been shown to be efficacious and safe in children and are recommended as first-line treatment for the symptoms of allergic rhinitis and urticaria. No published study to date has directly compared satisfaction with the different antihistamines in children in a real-life clinical setting. This study aimed to investigate parent and physician satisfaction with the efficacy and tolerability of oral antihistamine treatment in children and to compare satisfaction between levocetirizine and the other antihistamines used by children in this cohort. Methods: This was an international Observational Survey in Children with Allergic Rhinitis (OSCAR). Children aged 2–12 years, with a history of an allergic condition leading to a consultation, were enrolled from 424 primary-care/ specialist allergy clinics across Bulgaria, India, Portugal, Romania, Russia, South Korea and Spain. At the consultation, parents and physicians of eligible children completed questionnaires evaluating their satisfaction with specific antihistamines currently employed for management of the child’s allergic condition, as well as their intention for future use of that treatment. Parents’ satisfaction scores for efficacy, tolerability and global satisfaction with the antihistamine used were primary study outcomes, while physicians’ satisfaction scores for the same measures were secondary outcomes. Other secondary outcomes were parents’ rating of the impact of the antihistamine treatment on their child’s sleep and school performance, and parents’ and physicians’ willingness to use/recommend the same antihistamine in the future. Results: A total of 4581 patients were enrolled; 3048 (66.5%) had allergic rhinitis (55.9% persistent allergic rhinitis and 44.1% intermittent allergic rhinitis), and 663 (14.5%) had urticaria as primary conditions. Additionally, 2465 patients (53.8%) suffered from other allergic diseases, including allergic asthma (33.3%), atopic dermatitis (17.6%), food allergy (5.3%), other allergies (5.0%) and drug hypersensitivity (2.0%). Parents’ and physicians’ satisfaction scores were closely concordant and demonstrated significantly greater global satisfaction for the second-generation antihistamines than for the first-generation antihistamines. Levocetirizine (n = 2339) and fexofenadine (n = 42) generally scored highest for efficacy, tolerability and global satisfaction, as well as for impact on the child’s ability to function at school, quality of school activities and quality of sleep. Furthermore, >97% of parents and physicians indicated their desire to continue or recommend the use of levocetirizine in the future. Somnolence, the most commonly reported adverse event in this survey, was observed predominantly in patients treated with first-generation antihistamines. Among second-generation antihistamines, reports of somnolence were most frequent in the cetirizine group. Conclusion: Second-generation antihistamines have a better risk:benefit ratio than first-generation antihistamines, indicating that the latter should be avoided or their use limited in children whenever possible. Levocetirizine and fexofenadine were perceived by parents and physicians to produce significantly higher treatment satisfaction than the majority of the other antihistamines with respect to overall efficacy and tolerability, and impact on the child’s sleep and school activities. The newer antihistamine levocetirizine seems to be a preferred and appropriate future treatment choice for children with allergic diseases.