Asthma-like symptoms, diagnostic tests, and asthma medication use in children and adolescents: a population-based nationwide survey.

OBJECTIVE: This study aimed to estimate the prevalence of asthma-like symptoms, current asthma (CA), asthma diagnostic tests, and inhaled medication use in a nationwide pediatric population (<18 years). METHODS: Pediatric-specific data from a cross-sectional, population-based telephone survey (INAsma study) in Portugal were analyzed. CA was defined as lifetime asthma and (1) wheezing, (2) waking with breathlessness, or (3) asthma attack in the previous 12 months, and/or (4) taking asthma medication at the time of the interview. RESULTS: In total, 716 children were included. The prevalence of asthma-like symptoms was 39.4% [95% confidence interval (95% CI): 35.7-43.3]. The most common symptoms were waking with cough (30.9%) and wheezing (19.1%). The prevalence of CA was 8.4% (95% CI: 6.6-10.7). Among children with CA, 79.9% and 52.9% reported prior allergy testing and pulmonary function testing (PFT), respectively. Inhaled medication use in the previous 12 months was reported by 67.6% (reliever inhalers, 40.1%; controller inhalers, 41.5%). Those who only used inhaled reliever medications experienced more asthma attacks [odds ratio (OR): 2.69]. Significantly fewer children with CA living in rural areas than those living in urban areas had undergone PFT or used inhaled medication (OR: 0.06 for PFT, 0.20 for medication]. CONCLUSIONS: The prevalence of CA in the Portuguese pediatric population was 8.4%. Only half of children with CA had ever undergone PFT; more than half did not use controller inhalers, and those who only used reliever inhalers reported more asthma attacks. These findings suggest that asthma management has been substandard, mainly in rural areas.

Asthma control in children is associated with nasal symptoms, obesity, and health insurance: a nationwide survey.

BACKGROUND: This study aimed to estimate the prevalence of asthma control and determinants of poor control in the Portuguese pediatric population (<18 years); secondarily, we described asthma-related healthcare services and medication use. METHODS: Data of 98 children with current asthma, from the second phase of a nationwide population-based telephone survey (INAsma study), were analyzed. Asthma control definition was based on GINA criteria, grouping partially controlled and uncontrolled asthma as 'not-controlled asthma' (NCA). We used multivariate logistic regression to study factors associated with NCA and with unscheduled medical visits for asthma. RESULTS: About half of the children had NCA (49%, 95% CI 39-59%). In the multivariate model, risk factors for NCA were as follows: substantial nasal symptoms (a OR 6.80), overweight/obesity (a OR 3.44), and not having health insurance (a OR 3.78). All the children with NCA had nasal symptoms, and the lack of asthma control was also associated with the increasing number of nasal symptoms (p < 0.001). In the previous year, 90% (95% CI 84-96%) of children with current asthma had healthcare visits and 67% (95% CI 58-77%) used medication for asthma. The risk of unscheduled medical visits was higher in children with nasal symptoms (a OR 3.63) and in those without health insurance (a OR 2.79), and lower in adolescents (a OR 0.19). CONCLUSIONS: Half of the children with asthma were poorly controlled. Nasal symptoms and obesity are important determinants of asthma control. Children without health insurance are at greater risk of poor asthma outcomes; this association is reported for the first time in a European country.

Respiratory and non-respiratory outcomes of bronchopulmonary dysplasia in adolescents: A systematic review.

BACKGROUND: There is lack of evidence synthesis on the global consequences of bronchopulmonary dysplasia (BPD) in adolescence. AIM: Assess the impact of bronchopulmonary dysplasia on respiratory and non-respiratory outcomes in adolescents. METHODS: A systematic review of studies assessing the outcomes of adolescents aged 10 to 19 years-old with BPD was conducted. We independently screened studies published until 6th March 2023 in PubMed® and Scopus® databases. Data on methodologic design, sample descriptive and findings were extracted from each study. Risk of bias was assessed using quality assessment tools. RESULTS: Thirty-one studies were included. Adolescents with a history of BPD present with more respiratory symptoms (wheezing, respiratory exacerbations, need for respiratory medication) and twenty-five studies showed a reduction in pulmonary function, with varying impact according to BPD severity and no differences before and after the surfactant era. Spirometry evaluation throughout the years is not consensual, but methacholine and salbutamol response in BPD groups is increased compared to non-BPD groups. Markers of eosinophilic airway inflammation are not increased as in asthma patients. Exercise potential is identical, but data regarding physical capacity and activity are inconsistent. More frequent radiologic abnormalities translate into higher high-resolution computed tomography scores, with linear (72.2 %) and triangular subpleural opacities (58.3 %) as the most common findings. There is a higher risk for special needs in education, but quality of life seems to be equal to non-BPD adolescents. CONCLUSIONS: BPD negatively impacts both pulmonary and non-pulmonary outcomes in adolescents.

Symptoms of anxiety and depression in patients with persistent asthma: a cross-sectional analysis of the INSPIRERS studies.

OBJECTIVES: Anxiety and depression are relevant comorbidities in asthma, but, in Portugal and Spain, data on this topic are scarce. We assessed, in patients with asthma, the frequency of anxiety and depression using the Hospital Anxiety and Depression Scale (HADS) and the European Quality of Life Five Dimension Questionnaire (EQ-5D); the level of agreement between these questionnaires, and the factors associated with these symptoms. METHODS: This is a secondary analysis of the INSPIRERS studies. A total of 614 adolescents and adults with persistent asthma (32.6±16.9 years, 64.7% female) were recruited from 30 primary care centres and 32 allergy, pulmonology and paediatric clinics. Demographic and clinical characteristics, HADS and EQ-5D were collected. A score ≥8 on Hospital Anxiety and Depression Scale-Anxiety/Hospital Anxiety and Depression Scale-Depression or a positive answer to EQ-5D item 5 indicated the presence of these symptoms. Agreement was determined by Cohen's kappa. Two multivariable logistic regressions were built. RESULTS: According to HADS, 36% of the participants had symptoms of anxiety and 12% of depression. According to EQ-5D, 36% of the participants had anxiety/depression. The agreement between questionnaires in identifying anxiety/depression was moderate (k=0.55, 95% CI 0.48 to 0.62). Late asthma diagnosis, comorbidities and female gender were predictors of anxiety/depression, while better asthma control, health-related quality of life and perception of health were associated with lower odds for anxiety/depression. CONCLUSION: At least 1/3 of the patients with persistent asthma experience symptoms of anxiety/depression, showing the relevance of screening these disorders in patients with asthma. EQ-5D and HADS questionnaires showed a moderate agreement in the identification of anxiety/depression symptoms. The identified associated factors need to be further investigated in long-term studies.

Gut microbiota changes after metabolic surgery in adult diabetic patients with mild obesity: a randomised controlled trial.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery is one of the most efficient procedures for the treatment of obesity, also improving metabolic and inflammatory status, in patients with mild obesity. The underlying mechanisms have not been fully understood, but gut microbiota is hypothesized to play a key role. Our aim was to evaluate the association between gut microbiota changes and anthropometric, metabolic and inflammatory profiles after metabolic surgery compared with medical therapy, in type 2 diabetic (T2DM) adults with mild obesity (BMI 30-35 kg/m2). METHODS: DM2 was an open-label, randomised controlled clinical trial (RCT: ISRCTN53984585) with 2 arms: (i) surgical, and (ii) medical. The main outcome was gut microbiota changes after: metabolic surgery (Roux-en-Y gastric bypass-RYGB) versus standard medical therapy. Secondary outcomes included anthropometric, metabolic and inflammatory profiles. Clinical visits, blood workup, and stool samples were collected at baseline and months (M)1, 3, 6, 12. Gut microbiota was profiled using 16S rRNA targeted sequencing. RESULTS: Twenty patients were included: 10 in surgical and 10 in medical arm. Anthropometric and metabolic comparative analysis favoured RYGB over medical arm. At M12, the percentage of weight loss was 25.5 vs. 4.9% (p < 0.001) and HbA1c was 6.2 vs. 7.7% (p < 0.001) respectively. We observed a continuous increase of genus richness after RYGB up until M12. In the medical arm, genus richness ended-up being significantly lower at M12. Composition analysis indicated significant changes of the overall microbial ecosystem (permanova p = 0.004, [R2 = 0.17]) during the follow-up period after RYGB. There was a strong association between improvement of anthropometric/metabolic/inflammatory biomarkers and increase in microbial richness and Proteobacterial lineages. CONCLUSIONS: This was the first RCT studying composite clinical, analytic, and microbiome changes in T2DM patients with class 1 obesity after RYGB versus standard medical therapy. The remarkable phenotypic improvement after surgery occurred concomitantly with changes in the gut microbiome, but at a lower level. TRIAL REGISTRATION: ISRCTN53984585.

Profiling Persistent Asthma Phenotypes in Adolescents: A Longitudinal Diagnostic Evaluation from the INSPIRERS Studies.

We aimed to identify persistent asthma phenotypes among adolescents and to evaluate longitudinally asthma-related outcomes across phenotypes. Adolescents (13-17 years) from the prospective, observational, and multicenter INSPIRERS studies, conducted in Portugal and Spain, were included (n = 162). Latent class analysis was applied to demographic, environmental, and clinical variables, collected at a baseline medical visit. Longitudinal differences in clinical variables were assessed at a 4-month follow-up telephone contact (n = 128). Three classes/phenotypes of persistent asthma were identified. Adolescents in class 1 (n = 87) were highly symptomatic at baseline and presented the highest number of unscheduled healthcare visits per month and exacerbations per month, both at baseline and follow-up. Class 2 (n = 32) was characterized by female predominance, more frequent obesity, and uncontrolled upper/lower airways symptoms at baseline. At follow-up, there was a significant increase in the proportion of controlled lower airway symptoms (p < 0.001). Class 3 (n = 43) included mostly males with controlled lower airways symptoms; at follow-up, while keeping symptom control, there was a significant increase in exacerbations/month (p = 0.015). We have identified distinct phenotypes of persistent asthma in adolescents with different patterns in longitudinal asthma-related outcomes, supporting the importance of profiling asthma phenotypes in predicting disease outcomes that might inform targeted interventions and reduce future risk.

Monitoring Adherence to Asthma Inhalers Using the InspirerMundi App: Analysis of Real-World, Medium-Term Feasibility Studies.

Background: Poor medication adherence is a major challenge in asthma and objective assessment of inhaler adherence is needed. InspirerMundi app aims to monitor inhaler adherence while turning it into a positive experience through gamification and social support. Objective: We assessed the medium-term feasibility of the InspirerMundi app to monitor inhaler adherence in real-world patients with persistent asthma (treated with daily inhaled medication). In addition, we attempted to identify the characteristics of the patients related to higher app use. Methods: Two real-world multicenter observational studies, with one initial face-to-face visit and a 4-month telephone interview, were conducted in 29 secondary care centers from Portugal. During an initial face-to-face visit, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients took a photo of the medication (inhaler, blister, or others) using the image-based medication detection tool. Medication adherence was calculated as the number of doses taken as a percentage of the number scheduled. Interacting with the app ≥30 days was used as the cut-off for higher app use. Results: A total of 114 patients {median 20 [percentile 25 to percentile 75 (P25-P75) 16-36] years, 62% adults} were invited, 107 (94%) installed the app and 83 (73%) completed the 4-month interview. Patients interacted with the app for a median of 18 [3-45] days, translated on a median use rate of 15 [3-38]%. Median inhaler adherence assessed through the app was 34 [4-73]% when considering all scheduled inhalations for the study period. Inhaler adherence assessed was not significantly correlated with self-reported estimates. Median adherence for oral and other medication was 41 [6-83]% and 43 [3-73]%, respectively. Patients with higher app use were slightly older (p = 0.012), more frequently taking medication for other health conditions (p = 0.040), and more frequently prescribed long-acting muscarinic antagonists (LAMA, p = 0.024). After 4 months, Control of Allergic Rhinitis and Asthma Test (CARAT) scores improved (p < 0.001), but no differences between patients interacting with the app for 30 days or less were seen. Conclusions: The InspirerMundi app was feasible to monitor inhaler adherence in patients with persistent asthma. The persistent use of this mHealth technology varies widely. A better understanding of characteristics related to higher app use is still needed before effectiveness studies are undertaken.

Feasibility and Acceptability of an Asthma App to Monitor Medication Adherence: Mixed Methods Study.

BACKGROUND: Poor medication adherence is a major challenge in asthma, and objective assessment of inhaler adherence is needed. The InspirerMundi app aims to monitor adherence while providing a positive experience through gamification and social support. OBJECTIVE: This study aimed to evaluate the feasibility and acceptability of the InspirerMundi app to monitor medication adherence in adolescents and adults with persistent asthma (treated with daily inhaled medication). METHODS: A 1-month mixed method multicenter observational study was conducted in 26 secondary care centers from Portugal and Spain. During an initial face-to-face visit, physicians reported patients' asthma therapeutic plan in a structured questionnaire. During the visits, patients were invited to use the app daily to register their asthma medication intakes. A scheduled intake was considered taken when patients registered the intake (inhaler, blister, or other drug formulation) by using the image-based medication detection tool. At 1 month, patients were interviewed by phone, and app satisfaction was assessed on a 1 (low) to 5 (high) scale. Patients were also asked to point out the most and least preferred app features and make suggestions for future app improvements. RESULTS: A total of 107 patients (median 27 [P25-P75 14-40] years) were invited, 92.5% (99/107) installed the app, and 73.8% (79/107) completed the 1-month interview. Patients interacted with the app a median of 9 (P25-P75 1-24) days. At least one medication was registered in the app by 78% (77/99) of patients. A total of 53% (52/99) of participants registered all prescribed inhalers, and 34% (34/99) registered the complete asthma therapeutic plan. Median medication adherence was 75% (P25-P75 25%-90%) for inhalers and 82% (P25-P75 50%-94%) for other drug formulations. Patients were globally satisfied with the app, with 75% (59/79) scoring ≥4,; adherence monitoring, symptom monitoring, and gamification features being the most highly scored components; and the medication detection tool among the lowest scored. A total of 53% (42/79) of the patients stated that the app had motivated them to improve adherence to inhaled medication and 77% (61/79) would recommend the app to other patients. Patient feedback was reflected in 4 major themes: medication-related features (67/79, 85%), gamification and social network (33/79, 42%), symptom monitoring and physician communication (21/79, 27%), and other aspects (16/79, 20%). CONCLUSIONS: The InspirerMundi app was feasible and acceptable to monitor medication adherence in patients with asthma. Based on patient feedback and to increase the registering of medications, the therapeutic plan registration and medication detection tool were redesigned. Our results highlight the importance of patient participation to produce a patient-centered and engaging mHealth asthma app.

Probiotic Ingestion, Obesity, and Metabolic-Related Disorders: Results from NHANES, 1999-2014.

Gut microbiota dysbiosis has been recognized as having key importance in obesity- and metabolic-related diseases. Although there is increasing evidence of the potential benefits induced by probiotics in metabolic disturbances, there is a lack of large cross-sectional studies to assess population-based prevalence of probiotic intake and metabolic diseases. Our aim was to evaluate the association of probiotic ingestion with obesity, type 2 diabetes, hypertension, and dyslipidemia. A cross-sectional study was designed using data from the National Health and Nutrition Examination Survey (NHANES), 1999-2014. Probiotic ingestion was considered when a subject reported consumption of yogurt or a probiotic supplement during the 24-hour dietary recall or during the Dietary Supplement Use 30-Day questionnaire. We included 38,802 adults and 13.1% reported probiotic ingestion. The prevalence of obesity and hypertension was lower in the probiotic group (obesity-adjusted Odds Ratio (OR): 0.84, 95% CI 0.76-0.92, p < 0.001; hypertension-adjusted OR: 0.79, 95% CI 0.71-0.88, p < 0.001). Accordingly, even after analytic adjustments, body mass index (BMI) was significantly lower in the probiotic group, as were systolic and diastolic blood pressure and triglycerides; high-density lipoprotein (HDL) was significantly higher in the probiotic group for the adjusted model. In this large-scale study, ingestion of probiotic supplements or yogurt was associated with a lower prevalence of obesity and hypertension.

Patient-physician discordance in assessment of adherence to inhaled controller medication: a cross-sectional analysis of two cohorts.

OBJECTIVE: We aimed to compare patient's and physician's ratings of inhaled medication adherence and to identify predictors of patient-physician discordance. DESIGN: Baseline data from two prospective multicentre observational studies. SETTING: 29 allergy, pulmonology and paediatric secondary care outpatient clinics in Portugal. PARTICIPANTS: 395 patients (≥13 years old) with persistent asthma. MEASURES: Data on demographics, patient-physician relationship, upper airway control, asthma control, asthma treatment, forced expiratory volume in one second (FEV1) and healthcare use were collected. Patients and physicians independently assessed adherence to inhaled controller medication during the previous week using a 100 mm Visual Analogue Scale (VAS). Discordance was defined as classification in distinct VAS categories (low 0-50; medium 51-80; high 81-100) or as an absolute difference in VAS scores ≥10 mm. Correlation between patients' and physicians' VAS scores/categories was explored. A multinomial logistic regression identified the predictors of physician overestimation and underestimation. RESULTS: High inhaler adherence was reported both by patients (median (percentile 25 to percentile 75) 85 (65-95) mm; 53% VAS>80) and by physicians (84 (68-95) mm; 53% VAS>80). Correlation between patient and physician VAS scores was moderate (rs=0.580; p<0.001). Discordance occurred in 56% of cases: in 28% physicians overestimated adherence and in 27% underestimated. Low adherence as assessed by the physician (OR=27.35 (9.85 to 75.95)), FEV1 ≥80% (OR=2.59 (1.08 to 6.20)) and a first appointment (OR=5.63 (1.24 to 25.56)) were predictors of underestimation. An uncontrolled asthma (OR=2.33 (1.25 to 4.34)), uncontrolled upper airway disease (OR=2.86 (1.35 to 6.04)) and prescription of short-acting beta-agonists alone (OR=3.05 (1.15 to 8.08)) were associated with overestimation. Medium adherence as assessed by the physician was significantly associated with higher risk of discordance, both for overestimation and underestimation of adherence (OR=14.50 (6.04 to 34.81); OR=2.21 (1.07 to 4.58)), while having a written action plan decreased the likelihood of discordance (OR=0.25 (0.12 to 0.52); OR=0.41 (0.22 to 0.78)) (R2=44%). CONCLUSION: Although both patients and physicians report high inhaler adherence, discordance occurred in half of cases. Implementation of objective adherence measures and effective communication are needed to improve patient-physician agreement.

Dedicated Pediatricians in Emergency Department: Shorter Waiting Times and Lower Costs.

BACKGROUND: Dedicated pediatricians in emergency departments (EDs) may be beneficial, though no previous studies have assessed the related costs and benefits/harms. We aimed to evaluate the net benefits and costs of dedicated emergency pediatricians in a pediatric ED. METHODS: Cost-consequences analysis of visits to a pediatric ED of a tertiary hospital. Two pediatric ED Medical Teams (MT) were compared: MT-A (May-September 2012), with general pediatrics physicians only; and MT-B (May-September 2013), with emergency dedicated pediatricians. The main outcomes analyzed were relevant clinical outcomes, patient throughput time and costs. RESULTS: We included 8,694 children in MT-A and 9,417 in MT-B. Medication use in the ED increased from 42.3% of the children in MT-A to 49.6% in MT-B; diagnostic tests decreased from 24.2% in MT-A to 14.3% in MT-B. Hospitalization increased from 1.3% in MT-A to 3.0% in MT-B; however, there was no significant difference in diagnosis-related group relative weight of hospitalized children in MT-A and MT-B (MT-A, 0.979; MT-B, 1.075). No differences were observed in ED readmissions or in patients leaving without being seen by a physician. The patient throughput time was significantly shorter in MT-B, with faster times to first medical observation. Within the cost domains analyzed, the total expenditures per children observed in the ED were 16% lower in MT-B: 37.87 euros in MT-A; 31.97 euros in MT-B. CONCLUSION: The presence of dedicated emergency pediatricians in a pediatric ED was associated with significantly lower waiting times in the ED, reduced costs, and similar clinical outcomes.

[Streptococcus pneumoniae Vaccination in Children and Adolescents at High Risk of Invasive Pneumococcal Disease]. / Vacinação Contra Infeções por Streptococcus pneumoniae em Crianças e Adolescentes de Alto Risco para Doença Invasiva Pneumocócica.

BACKGROUND: In Portugal, pneumococcal vaccination is free of charge and recommended by the Directorate-General of Health for the pediatric population at high risk of invasive pneumococcal disease. Our main aim was to describe the vaccination uptake in a pediatric population attending a hospital outpatient clinic. MATERIAL AND METHODS: Cross-sectional observational survey of a pediatric population attending a referral hospital outpatient clinic, from July to December 2014. Data was collected from clinical records, Individual Health Bulletin or the registry from Plataforma de Dados da Saúde®. RESULTS: Of the 122 participants, 95.9% had, at least, one shot of pneumococcal vaccine, but only 64.8% of these completed the age recommended vaccination scheme. Uptake was higher in children < 5 years old. The proportion of complete vaccination schemes was 100% in hemoglobinopathies and human immunodeficiency virus infection groups, 66.7% in prematures, 62.5% in splenectomized and 54.7% in Down syndrome. Children had better complete vaccination schemes when they attended the Pediatric Infectious Disease (100%) and Pulmonology Clinics (88.2%). Children > 5 years old had a higher uptake of 23-valent polysaccharide vaccine than the 2 to 5-years old ones (74.5% vs 40.5%; p < 0.001). DISCUSSION: Most of our pediatric population at high risk of IPD was vaccinated; nevertheless, only two-thirds had completed the scheme for their age. The main failure was on the 23-valent polysaccharide vaccine administration. CONCLUSIONS: Although these results are better than those reported in other European countries with similar recommendations, it is essential to explore the causes for the observed flaws in order to optimize vaccination rates.

Introdução: Em Portugal, a vacinação anti-pneumocócica é gratuita e recomendada pela Direção-Geral da Saúde na população pediátrica de alto risco para doença invasiva pneumocócica. O objetivo deste estudo foi analisar o cumprimento vacinal numa população pediátrica seguida em consulta hospitalar. Material e Métodos: Estudo observacional transversal, em crianças com diagnóstico de alto risco de doença invasiva pneumocócica e consulta num hospital nível três, entre julho e dezembro de 2014. Os dados foram obtidos através do processo clínico, Boletim Individual de Saúde e Plataforma de Dados da Saúde®. Resultados: Dos 122 participantes, 95,9% realizaram, pelo menos, uma dose de vacina mas, destes, só 64,8% efetuaram o esquema completo. O cumprimento do esquema vacinal foi melhor nos de idade inferior a cinco anos (p < 0,01). A proporção de crianças com esquema completo foi de: 100% nas hemoglobinopatias, 100% nas infeções por vírus da imunodeficiência humana, 66,7% nos prematuros com idade gestacional ⤠28 semanas, 62,5% nos esplenectomizados e 54,7% na síndrome de Down. As crianças têm mais esquemas completos quando são seguidas em consulta de Infeciologia (100%) e de Pneumologia pediátricas (88,2%). O grupocom idade superior a cinco anos está mais vacinado com a vacina polissacarida 23-valente do que o dos 2-5 anos (74,5% vs 40,5%; p < 0,01).Discussão: A maioria da nossa população de alto risco para doença invasiva pneumocócica efetuou vacinação anti-pneumocócica, mas apenas dois terços completaram o esquema recomendado, sendo a maior falha na administração da vacina polissacarida 23-valente. Conclusões: Embora estes resultados sejam melhores do que em países europeus com recomendações semelhantes, é necessário explorar as causas das falhas observadas para otimizar a vacinação.