Daniela Linhares

Validation of Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) - a prospective multicenter study

Control of Allergic Rhinitis and Asthma Test for Children (CARATKids) is the first questionnaire that assesses simultaneously allergic rhinitis and asthma control in children. It was recently developed, but redundancy of questions and its psychometric properties were not assessed. This study aimed to (i) establish the final version of the CARATKids questionnaire and (ii) evaluate its reliability, responsiveness, cross‐sectional validity, and longitudinal validity.

Effects of atopy and rhinitis on exhaled nitric oxide values - a systematic review

BackgroundAtopy and rhinitis are among the factors affecting exhaled nitric oxide (FeNO) values and may contribute to difficulties in the clinical interpretation of FeNO measurements. However, data assessing their effects on FeNO values had never been summarized. This review aims to evaluate the effect of atopy and rhinitis in FeNO values in otherwise healthy individuals.MethodsA systematic review was performed in Pubmed, Scopus and ISI Web of Knowledge. A two-step selection process was completed, and from 2357 references 19 were included. The inclusion criteria were: participants without known diseases other than rhinitis; atopy assessement by SPT or Specific IgE; and FeNO measurements according to ATS/ERS recommendations.ResultsThe 8 articles measuring FeNO in children showed higher values in both allergic rhinitis and atopic children when compared with healthy children. The 11 articles performed in adults observed higher FeNO in AR patients comparatively with either healthy or atopic individuals. However, adult healthy and atopic individuals had similar FeNO values.ConclusionsFeNO values are higher in individuals with rhinitis and/or atopy without other health problems. These effects are small, seem to be independent and should be further studied using multivariate models. The effect of atopy was observed only in children. The combined effect of atopy and rhinitis produced higher FeNO values in adults. These results support that both atopy and rhinitis should be considered when interpreting or when defining FeNO reference values.

In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: A systematic review

Objectives This systematic review aimed to assess the in vivo and clinical effect of strontium (Sr)-enriched biomaterials in bone formation and/or remodelling. Methods A systematic search was performed in Pubmed, followed by a two-step selection process. We included in vivo original studies on Sr-containing biomaterials used for bone support or regeneration, comparing at least two groups that only differ in Sr addition in the experimental group. Results A total of 572 references were retrieved and 27 were included. Animal models were used in 26 articles, and one article described a human study. Osteoporotic models were included in 11 papers. All articles showed similar or increased effect of Sr in bone formation and/or regeneration, in both healthy and osteoporotic models. No study found a decreased effect. Adverse effects were assessed in 17 articles, 13 on local and four on systemic adverse effects. From these, only one reported a systemic impact from Sr addition. Data on gene and/or protein expression were available from seven studies. Conclusions This review showed the safety and effectiveness of Sr-enriched biomaterials for stimulating bone formation and remodelling in animal models. The effect seems to increase over time and is impacted by the concentration used. However, included studies present a wide range of study methods. Future work should focus on consistent models and guidelines when developing a future clinical application of this element. Cite this article: N. Neves, D. Linhares, G. Costa, C. C. Ribeiro, M. A. Barbosa. In vivo and clinical application of strontium-enriched biomaterials for bone regeneration: A systematic review. Bone Joint Res 2017;6:366–375. DOI: 10.1302/2046-3758.66.BJR-2016-0311.R1.

Development process and cognitive testing of CARATkids - Control of Allergic Rhinitis and Asthma Test for children

BackgroundAllergic 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.MethodsThe 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.ResultsFour 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.ConclusionCARATkids, 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.

Neuroimmune expression in hip osteoarthritis: a systematic review

BackgroundNeuroimmune axis is central in the physiopathology of hip osteoarthritis (OA), but its specific pathways are still unclear. This systematic review aims to assess the nervous and immune system profile of patients with hip osteoarthritis (OA) when compared to healthy controls.MethodsA systematic review followed PRISMA guidelines was conducted. A two-step selection process was completed, and from 609 references 17 were included. The inclusion criteria were: original articles on adult patients with hip OA, with assessment of neuroimmune expression. Articles with other interventions prior to analysis and those without a control group were excluded.ResultsThirty-nine relevant neuroimmune markers were identified, with assessments in bone, cartilage, synovial membrane, synovial fluid, whole blood, serum and/or immune cells. GM-CSF, IFN-γ, IL-1α, IL-6, IL-8, IL-1 and TNF-α presented variable expression among tissues studied when compared between hip OA and controls. VEGFs and TGF-ß isoforms showed similar tendencies among tissues and studies. On nervous expression, CGRP, Tuj-1 and SP were increased in synovial membrane. Overall, patients with hip OA presented a higher number of overexpressed markers.ConclusionsFor the first time a systematic review on neuroimmune expression in patients with hip OA found an upregulation of neuroimmune markers, with deregulated balance between pro and anti-inflammatory cytokines. However, no clear systematic pattern was found, and few information is available on nervous expression. This highlights the importance of future research with clear methodologies to guide the management of these patients.

The Editor recommends this issue's articles to the reader

Wheezing in small children is one of themost common symptoms leading parents to seekmedical advice worldwide. The course and especially the severity of these episodes are considerably variable. The prediction of chronic consequences, particularly the future risk of bronchial asthmadevelopment, is hardly possible in very young children.Moreover, to date there is little evidence as to whether these first clinical symptoms are already accompanied by remodeling changes of the bronchial wall. Presence of histological changes was found in school children before clinically diagnosed bronchial asthma (1). The keyquestion iswhether these changes are solely a consequence of repeated obstructive episodes or if some histological signs might precede the clinical course and predispose children to the development of asthma. The current study by Berankova et al. (2) supports the hypothesis of pre-existing discrete morphological changes of the bronchial wall in very young children considered to be at higher risk for developing asthma. Increased bronchial basement membrane thickness was found in children with atopic eczema or a parental history of asthma. On the basis of the immunohistochemical analysis, the authors suggest that this might be caused by higher subepithelial deposition of laminin. On the other hand, significant difference was not found in the expression of tenascin that is constantly present in chronic inflammatory processes. Based on their results, the authors suggest that initial remodeling changes might be found very early in life, even before the first clinical symptoms of asthma. Increased expression of laminin in the basement membrane might indicate a crucial role of bronchial epithelial cells in this process. This finding supports the idea of early initiation of preventative monitoring in children at risk for developing bronchial asthma.

P69 - Development and evaluation of CARATKids, Control of Allergic Rhinitis and Asthma Test for children

Evaluation Prospective multicenter validation study. In a 2 visits program scheduled 3-5 weeks apart, questionnaires (including cACT) and VAS were filled by children with ARA and their caregivers. Physicians blinded for questionnaire results assessed children’s ARA status. Logistic regression and reliability analysis were used to select the questions to be included in CARATKids final version; and discriminative properties, reliability and validity were evaluated. Results Development A 17-item preliminary version with dichotomous (Yes/ No) answer format accompanied by illustrative drawings was produced.