Obstructive Sleep Apnea: a risk for uncontrolled and more severe asthma in adults that we should keep an eye on.

Summary: Background. Asthma control can be influenced by several factors, including obstructive sleep apnea (OSA). The literature reports variable prevalence and magnitude of OSA impact on asthma outcomes. The aim of our study is to analyze the frequency of high-risk for OSA in asthma patients and its impact on disease severity and control. Methods. We conducted a cross-sectional study at an Allergy Department with adult asthma patients recruited while undergoing routine lung function tests. Data on sex, age, body mass index, allergen sensitization, smoking habits, risk of OSA (using the Berlin questionnaire), rhinitis control (through CARAT), asthma severity (based on GINA 2023), asthma control (using the ACT), adherence to asthma treatment (through Treatment Adherence Measure) and pulmonary function test results were collected. Results. We included 216 patients, predominantly women (70.4%), with a median (P25-P75) age of 29.0 (21.0-45.0) years, of whom 28.2% were on GINA treatment levels 4-5. In 75.5% of cases asthma was controlled. High-risk for OSA was identified in 21.8% of patients. Asthma patients with high-risk for OSA were more likely to have uncontrolled [(47.8%; n = 22) vs (15.8%; n = 26); p less than 0.001] and more severe disease [(44.7%; n = 21) vs (23.7%; n = 40), p = 0.006]. In multivariable analysis, high-risk for OSA (OR 2.81 [95%CI 1.1.28-6.17], p = 0.010), sex (women) (OR 5.21 [95% CI 1.70-15.96], p = 0.004), uncontrolled rhinitis (OR 3.65 [95%CI 1.38-9.64], p = 0.009) and GINA asthma treatment steps 4-5 (OR 2.46 [95%CI 1.15-5.26], p = 0.020) were associated with uncontrolled asthma. Conclusions. It is crucial to actively investigate OSA, especially in patients with uncontrolled and more severe forms of asthma.

Factors Associated With Asthma Control in 121 Preschool Children.

BACKGROUND AND OBJECTIVES: Data on risk factors for uncontrolled asthma in preschool children are controversial. Objective: This study aims to explore the association between clinical and functional parameters and the lack of asthma control in preschool children. METHODS: Children aged 3-5 years with asthma and healthy controls were recruited. A questionnaire was used to identify potential risk factors for uncontrolled asthma, as defined by the Global INitiative for Asthma criteria. Lung function and bronchial reversibility were evaluated through impulse oscillometry and spirometry. Adjusted odds ratios were estimated based on multivariable generalized additive regression models. The discriminative ability of the models was measured by the area under the receiver operating characteristic curve (AUC). RESULTS: The study population comprised 121 children (107 with asthma and 14 healthy controls). Fifty-three patients (50%) had uncontrolled asthma. After adjustment, the variables associated with an increased risk of lack of control were as follows: "More than 3 flare-ups in the last 12 months", "Moderate to severe rhinitis", and "Relative variation in postbronchodilator FVC and FEV1". The AUC of the final models that included variation in FVC or FEV1 were 0.82 and 0.81, respectively. The R5-20, R5-20%, and AX z-score values of the healthy group were lower than those of children with asthma. CONCLUSION: In preschool children, clinical and functional parameters are associated with uncontrolled asthma. More studies are needed to confirm the usefulness of impulse oscillometry.

Cross-cultural validation of the Portuguese from Portugal version of the Test for Respiratory and Asthma Control in Kids (TRACK) questionnaire.

SUMMARY: Introduction. The Test for Respiratory and Asthma Control in Kids (TRACK) is a tool to assess asthma control in preschool children. This study aims to validate the Portuguese from Portugal version of the TRACK questionnaire. Methods. A prospective cohort study was carried out to assess their psychometric characteristics. Caregivers of 141 children under age 5 with asthma symptoms were enrolled. Results. Internal reliability was close to 0.70 (Cronbach's α). The test-retest reliability was 0.87. TRACK scores were different between well, partially, and non-controlled asthma groups (p less than 0.001). Patients rated as having better control showed an increase in TRACK scores. Conclusions. The Portuguese version of the TRACK questionnaire is accurate and reliable for monitoring asthma control. Its use may help to overcome challenges with the management of this age group.

Machine Perfusion: Cold versus Warm, versus Neither. Update on Clinical Trials.

Machine perfusion (MP) preservation is potentially one of the most significant improvements in the field of liver transplantation in the last 20 years, and it has been considered a promising strategy for improved preservation and ex situ evaluation of extended criteria donor (ECD) organs. However, MP preservation adds significant cost and logistical considerations to liver transplantation. MP protocols are mainly classified according to the perfusion temperature with hypothermic machine perfusion (HMP) and normothermic machine perfusion (NMP) being the two categories most studied so far. After extensive preclinical work, MP entered the clinical setting, and there are now several studies that demonstrated feasibility and safety. However, because of the limited quality of clinical trials, there is no compelling evidence of superiority in preservation quality, and liver MP is still considered experimental in most countries. MP preservation is moving to a more mature phase, where ongoing and future studies will bring new evidence in order to confirm their superiority in terms of clinical outcomes, organ utilization, and cost-effectiveness. Here, we present an overview of all preclinical MP studies using discarded human livers and liver MP clinical trials, and discuss their results. We describe the different perfusion protocols, pitfalls in MP study design, and provide future perspectives. Recent trials in liver MP have revealed unique challenges beyond those seen in most clinical studies. Randomized trials, correct trial design, and interpretation of data are essential to generate the data necessary to prove if MP will be the new gold standard method of liver preservation.

Polymer-based actuators: back to the future.

Polymer-based actuators play a key role in the area of smart materials and devices, and for this reason different polymer-based actuators have appeared in recent years and are implemented in a broad range of fields, including biomedical, optical or electronics, among others. Although it is possible to find more types, they are mainly classified into two main groups according to their different working principles: electromechanical - with electrical to mechanical energy conversion - and magnetomechanical - with magnetic to mechanical energy conversion. The present work provides a comprehensive and critical review of the recent studies in this field. The operating principles, some representative designs, performance analyses and practical applications will be presented. The future development perspectives of this interesting field will be also discussed. Thus, the present work provides a comprehensive understanding of the effects reported in the past, introduces solutions to the present limitations and, back to the future, serves as a useful guidance for the design of new polymer-based actuators aiming to improve their output performances.

Asthma and COPD "overlap": a treatable trait or common several treatable-traits?

Summary: In the last years, disease classification of chronic respiratory diseases (CRD) has been vivaciously discussed and new concepts have been introduced, namely asthma-chronic obstructive pulmonary disease (COPD) overlap (ACO). Controversially the GOLD consensus document of 2020 considered that we should no longer refer to ACO, as they constitute two different diseases that may share some common traits and clinical features. The treatable traits approach has numerous strengths that are applicable to several levels of health care. In this paper we review the application of the treatable traits to CRD and describe in detail the ones already identified in patients with asthma and COPD. Treatable traits in CRD can be divided in pulmonary, extra-pulmonary and behavior/lifestyle risk factors. Patients with both asthma and COPD patients have clearly recognized treatable traits in all these subtopics but it is notorious the severe and frequent exacerbations, the associated cardiovascular disease and the low health related quality of life and productivity of these patients.

Phylogenetic diversity of aerobic spore-forming Bacillalles isolated from Brazilian soils.

The phylum Firmicutes comprises seven classes where most species are either aerobic or anaerobic endospore former. Inside Firmicutes, species allocated in the genus Bacillus and related genera are collectively named aerobic endospore-forming bacteria (AEFB), and the soil is their major reservoir. AEFB have great importance in health, agriculture, and biotechnology although the more studied species are Bacillus subtilis and the human pathogens Bacillus cereus and Bacillus anthracis. AEFB have great importance in health, agriculture, and biotechnology; although the knowledge about these organisms is based on few species, notably, Bacillus subtilis, Bacillus cereus, and Bacillus anthracis. In this work, we generated partial 16S rRNA gene sequences of both strands of 192 AEFB strains isolated from soils of Distrito Federal, Brazil (SDF strains). The resulting consensus sequences were used to obtain taxonomic assignment and establish the phylogenetic relationships among these strains. Through this approach, we could observe that classified SDF strains were distributed among genera Bacillus (169 strains; 88.02%), Paenibacillus (11; 5.73%), Lysinibacillus (6; 3.13%), Brevibacillus (4; 2.08%), Terribacillus (1; 0.52%), and Rummeliibacillus (1; 0.52%). Phylogenetic trees revealed these 192 SDF strains can be segregated into eight groups spanning families Bacillaceae and Paenibacillaceae belonging to the order Bacillales. To expand the knowledge about the diversity of these SDF strains, further studies regarding characterization with different methodologies are underway.

Short and extended provocation tests have similar negative predictive value in non-immediate hypersensitivity to beta-lactams in children.

INTRODUCTION AND OBJECTIVES: Drug provocation tests (DPTs) are the gold-standard method to diagnose non-immediate hypersensitivity reactions (NIHSR) to beta-lactam antibiotics (BL) in children. Our aim was to compare the negative predictive value (NPV) of one-day (short) DPT versus 3-7 days (extended) DPT for the diagnosis of NIHSR to BL in paediatric age. A secondary aim was to compare confidence on drug re-exposure after short and extended negative DPTs. METHODS: The occurrence of HSR on drug re-exposure and drug refusal after negative diagnostic DPTs were evaluated in children/adolescents with a history of NIHSR to BL using a questionnaire performed six months to ten years after DPT. Patients were divided into two groups according to the protocol performed: short DPT vs. extended DPT. RESULTS: We enrolled 212 children and adolescents (86 females, 126 males, mean age at DPT 5.52 years, p25=3 years, p75=7.25 years): 69 tested with short DPT, and 143 with extended DPT. The NPV of both types of DPT together was 95.2%. The NPV of short DPT was 97.5% and the NPV of extended DPT was 93.8% (p=0.419). After negative DPT, beta-lactams were refused by carers in 14.75% of the children requiring subsequent treatment, 6.98% in the short DPT group and 18.99% in the extended DPT group (p=0.074). CONCLUSIONS: In our paediatric sample, prolonging drug administration did not increase the NPV of diagnostic DPT for NIHSR to BL or reduce drug refusal. Altogether, the data here reported suggest that, however intuitive, prolonging DPT is not beneficial in the parameters analysed.

Treatment of allergic rhinitis using mobile technology with real-world data: The MASK observational pilot study.

BACKGROUND: Large observational implementation studies are needed to triangulate the findings from randomized control trials as they reflect "real-world" everyday practice. In a pilot study, we attempted to provide additional and complementary insights on the real-life treatment of allergic rhinitis (AR) using mobile technology. METHODS: A mobile phone app (Allergy Diary, freely available in Google Play and Apple App stores) collects the data of daily visual analog scales (VAS) for (i) overall allergic symptoms, (ii) nasal, ocular, and asthma symptoms, (iii) work, as well as (iv) medication use using a treatment scroll list including all medications (prescribed and over the counter (OTC)) for rhinitis customized for 15 countries. RESULTS: A total of 2871 users filled in 17 091 days of VAS in 2015 and 2016. Medications were reported for 9634 days. The assessment of days appeared to be more informative than the course of the treatment as, in real life, patients do not necessarily use treatment on a daily basis; rather, they appear to increase treatment use with the loss of symptom control. The Allergy Diary allowed differentiation between treatments within or between classes (intranasal corticosteroid use containing medications and oral H1-antihistamines). The control of days differed between no [best control], single, or multiple treatments (worst control). CONCLUSIONS: This study confirms the usefulness of the Allergy Diary in accessing and assessing everyday use and practice in AR. This pilot observational study uses a very simple assessment (VAS) on a mobile phone, shows novel findings, and generates new hypotheses.

Adsorption of flexible polymer chains on a surface: Effects of different solvent conditions.

Polymer chains undergoing a continuous adsorption-desorption transition are studied through extensive computer simulations. A three-dimensional self-avoiding walk lattice model of a polymer chain grafted onto a surface has been treated for different solvent conditions. We have used an advanced contact-density chain-growth algorithm, in which the density of contacts can be directly obtained. From this quantity, the order parameter and its fourth-order Binder cumulant are computed, as well as the corresponding critical exponents and the adsorption-desorption transition temperature. As the number of configurations with a given number of surface contacts and monomer-monomer contacts is independent of the temperature and solvent conditions, it can be easily applied to get results for different solvent parameter values without the need of any extra simulations. In analogy to continuous magnetic phase transitions, finite-size-scaling methods have been employed. Quite good results for the critical properties and phase diagram of very long single polymer chains have been obtained by properly taking into account the effects of corrections to scaling. The study covers all solvent effects, going from the limit of super-self-avoiding walks, characterized by effective monomer-monomer repulsion, to poor solvent conditions that enable the formation of compact polymer structures.

Piperacillin-tazobactam anaphylaxis: a rare cause of occupational disease.

Summary: Piperacillin is a beta-lactam antibiotic of penicillin family. Some penicillins were report-ed as occupational diseases cause, but piperacillin anaphylaxis with occupational sensi-tization is rare. We describe the case of a female nurse with recurrent anaphylaxis in last few months without apparent cause, only in work environment. Latex allergy was excluded after negative latex glove provocation. Later during diagnostic workup, the patient reported a similar reaction minutes after piperacillin preparation. She denied any previous antibiotic therapeutic exposure. Skin prick tests (SPT) to beta-lactams were positive to piperacillin, penicillin G and major and minor determinants. SPT to cefuroxime was negative but intradermic test was positive. The patient has indication for beta-lactams eviction and for adrenaline auto-injector kit. No further reactions occurred after patient's transfer to another department with minimum possible exposure. Allergic risk prevention is essential and must be rapidly implemented to avoid incapacitating occupational diseases development.

Work productivity in rhinitis using cell phones: The MASK pilot study.

Allergic rhinitis often impairs social life and performance. The aim of this cross-sectional study was to use cell phone data to assess the impact on work productivity of uncontrolled rhinitis assessed by visual analogue scale (VAS). A mobile phone app (Allergy Diary, Google Play Store and Apple App Store) collects data from daily visual analogue scales (VAS) for overall allergic symptoms (VAS-global measured), nasal (VAS-nasal), ocular (VAS-ocular) and asthma symptoms (VAS-asthma) as well as work (VAS-work). A combined nasal-ocular score is calculated. The Allergy Diary is available in 21 countries. The app includes the Work Productivity and Activity Impairment Allergic Specific Questionnaire (WPAI:AS) in six EU countries. All consecutive users who completed the VAS-work from 1 June to 31 October 2016 were included in the study. A total of 1136 users filled in 5818 days of VAS-work. Symptoms of allergic rhinitis were controlled (VAS-global <20) in approximately 60% of the days. In users with uncontrolled rhinitis, approximately 90% had some work impairment and over 50% had severe work impairment (VAS-work >50). There was a significant correlation between VAS-global calculated and VAS-work (Rho=0.83, P<0.00001, Spearman's rank test). In 144 users, there was a significant correlation between VAS-work and WPAI:AS (Rho=0.53, P<0.0001). This pilot study provides not only proof-of-concept data on the work impairment collected with the app but also data on the app itself, especially the distribution of responses for the VAS. This supports the interpretation that persons with rhinitis report both the presence and the absence of symptoms.

Pilot study of mobile phone technology in allergic rhinitis in European countries: the MASK-rhinitis study.

BACKGROUND: The use of Apps running on smartphones and tablets profoundly affects medicine. The MASK-rhinitis (MACVIA-ARIA Sentinel NetworK for allergic rhinitis) App (Allergy Diary) assesses allergic rhinitis symptoms, disease control and impact on patients' lives. It is freely available in 20 countries (iOS and Android platforms). AIMS: To assess in a pilot study whether (i) Allergy Diary users were able to properly provide baseline characteristics (ii) simple phenotypic characteristics based upon data captured by the Allergy Diary could be identified and (iii) information gathered by this study could suggest novel research questions. METHODS: The Allergy Diary users were classified into six groups according to the baseline data that they entered into the App: (i) asymptomatic; (ii) nasal symptoms excluding rhinorrhea; (iii) rhinorrhea; (iv) rhinorrhea plus 1-2 nasal/ocular symptoms; (v) rhinorrhea plus ≥3 nasal/ocular symptoms; and (vi) rhinorrhea plus all nasal/ocular symptoms. RESULTS: By 1 June 2016, 3260 users had registered with the Allergy Diary and 2710 had completed the baseline questionnaire. Troublesome symptoms were found mainly in the users with the most symptoms. Around 50% of users with troublesome rhinitis and/or ocular symptoms suffered work impairment. Sleep was impaired by troublesome symptoms and nasal obstruction. CONCLUSIONS: This is the first App (iOS and Android) to have tested for allergic rhinitis and conjunctivitis. A simple questionnaire administered by cell phones enables the identification of phenotypic differences between a priori defined rhinitis groups. The results suggest novel concepts and research questions in allergic rhinitis that may not be identified using classical methods.

Determining the health-related quality of life in individuals with haemophilia in developing economies: results from the Brazilian population.

INTRODUCTION: Several studies show the negative impact of haemophilia in health-related quality of life (HRQOL). This issue is not well explored in developing countries. OBJECTIVES: This cross-sectional study aimed to evaluate the HRQOL and its associated factors in patients with haemophilia A/B in Brazil. Data were collected by questionnaire and in medical records, including a Portuguese version of Haem-A-Qol. RESULTS: Brazilian patients were invited to the study and 175 participants (147 haemophilics A and 28 haemophilics B) were included. The total score of the Haem-A-QoL had a median of 36.96 (range of 0-100), with worse performance in 'sport and leisure' and best on 'relationships' fields. HRQOL was worst among the older participants, the less educated, non-white, non-working, who were hospitalized in the last year, who did not have a single medical consultation and among those with the highest number of affected joints. Moreover, patients with hepatitis B had a significantly worse HRQOL in the domain 'sports and leisure', also observed in married patients. Otherwise, married individuals reported better HRQOL on 'dealing with the disease' domain. Patients with haemophilia B reported worse HRQOL in the domain 'self-perception'. CONCLUSION: The results obtained could be helpful in guidance of haemophilia treatment which is determinant to improve HRQoL of the most vulnerable groups of patients. This work also reinforced the relevance of joint bleeds in all aspects of HRQoL in haemophilic patients. The use of prophylactic factor concentrates and multidisciplinary treatments could contribute to improve the quality of life in haemophilia.

Non-steroidal anti-inflammatory drug hypersensitivity in children.

INTRODUCTION: There are rather few publications about hypersensitivity reactions to non-steroidal anti-inflammatory drugs (NSAID) in the paediatric age. In this study, we aimed to assess the frequency of confirmed NSAID hypersensitivity in children with a previous reported reaction to NSAID in order to investigate the role of the drug provocation test (DPT) in the diagnostic workup and to explore the factors associated with confirmed NSAID hypersensitivity. METHODS: We conducted a retrospective analysis of the clinical files from every patient under 18 years old who attended two Portuguese paediatric allergy outpatient clinics, from January 2009 to August 2014, due to a suspected NSAID hypersensitivity. RESULTS: We included 119 patients, with a median age of nine years (P25-P75: 5-14). Ibuprofen was the commonest implicated NSAID in the patients' reports (n=94-79%). After DPT, NSAID hypersensitivity was confirmed in nine (7.6%) patients, excluded in 93 (78.2%) and was inconclusive in 17 (14.3%). In the majority (n=95-79.8%), the reaction occurred in the first 24h after intake. Eighty-four patients (70.6%) reported only cutaneous manifestations and 18 (15.1%) had systemic symptoms. Anaphylaxis represented a relative risk to NSAID hypersensitivity confirmation. No association was found for atopy and the number of previous reactions. CONCLUSION: In our study, NSAID hypersensitivity was confirmed in a small proportion of the patients with a previous reported reaction. Ibuprofen was the most implicated drug with urticaria/angio-oedema as the commonest manifestation. Anaphylaxis was associated with confirmed drug hypersensitivity. The drug provocation test was essential to establish the diagnosis.

Sensitivity of breeding values for carcass traits of meat-type quail to changes in dietary (methionine + cystine):lysine ratio using reaction norm models.

Our objective was to evaluate changes in breeding values for carcass traits of two meat-type quail (Coturnix coturnix) strains (LF1 and LF2) to changes in the dietary (methionine + cystine):lysine ([Met + Cys]:Lys) ratio due to genotype by environment (G × E) interaction via reaction norm. A total of 7000 records of carcass weight and yield were used for analyses. During the initial phase (from hatching to day 21), five diets with increasing (Met + Cys):Lys ratios (0.61, 0.66, 0.71, 0.76 and 0.81), containing 26.1% crude protein and 2900 kcal ME/kg, were evaluated. Analyses were performed using random regression models that included linear functions of sex (fixed effect) and breeding value (random effect) for carcass weight and yield, without and with heterogeneous residual variance adjustment. Both fixed and random effects were modelled using Legendre polynomials of second order. Genetic variance and heritability estimates were affected by both (Met + Cys):Lys ratio and strain. We observed that a G × E interaction was present, with changes in the breeding value ranking. Therefore, genetic evaluation for carcass traits should be performed under the same (Met + Cys):Lys ratio in which quails are raised.

Pilot Study Evaluating Regulatory T Cell-Promoting Immunosuppression and Nonimmunogenic Donor Antigen Delivery in a Nonhuman Primate Islet Allotransplantation Model.

The full potential of islet transplantation will only be realized through the development of tolerogenic regimens that obviate the need for maintenance immunosuppression. Here, we report an immunotherapy regimen that combines 1-ethyl-3-(3'-dimethylaminopropyl)-carbodiimide (ECDI)-treated donor lymphoid cell infusion (ECDI-DLI) with thymoglobulin, anti-interleukin-6 receptor antibody and rapamycin to achieve prolonged allogeneic islet graft survival in a nonhuman primate (NHP) model. Prolonged graft survival is associated with Treg expansion, donor-specific T cell hyporesponsiveness and a transient absence of donor-specific alloantibody production during the period of graft survival. This regimen shows promise for clinical translation.

Degree of food processing of household acquisition patterns in a Brazilian urban area is related to food buying preferences and perceived food environment.

OBJECTIVE: This cross-sectional study examined the association between local food environment and consumers' acquisition of ultra-processed food. METHODS: Households were randomly selected from 36 census tracts in Santos City, Brazil. Mothers, of varying economic status, who had children ages 10 or younger (n = 538) were interviewed concerning: their household food acquisition of 31 groups of food and beverages, perceptions of local food environment, food sources destinations, means of transportation used, and socioeconomic status. Food acquisition patterns were classified based on the degree of industrial food processing. Logistic regression models were fitted to assess the association between consumer behaviors and acquisition patterns. RESULTS: The large variety of fresh produce available in supermarkets was significantly related to lower odds of ultra-processed food purchases. After adjusting for sociodemographic characteristics, higher odds for minimally-processed food acquisition were associated with: frequent use of specialized markets to purchase fruits and vegetables (OR 1.89, 95% CI 1.01-2.34), the habit of walking to buy food (OR 1.58, 95% CI 1.08-2.30), and perceived availability of fresh produce in participants' neighborhood (OR 1.58, 95% CI 1.08-2.30). Acquisition of ultra-processed food was positively associated with the use of taxis as principal means of transportation to food sources (OR 2.35, 95% CI 1.08-5.13), and negatively associated with perceived availability of a variety of fruits and vegetables in the neighborhood (OR 0.57, 95% CI 0.37-0.88). CONCLUSION: The results suggest that interventions aiming to promote acquisition of less processed food in settings similar to Santos, may be most effective if they focus on increasing the number of specialized fresh food markets in local neighborhood areas, improve residents' awareness of these markets' availability, and provide appropriate transportation.