Determinants of the Use of Health and Fitness Mobile Apps by Patients With Asthma: Secondary Analysis of Observational Studies.

BACKGROUND: Health and fitness apps have potential benefits to improve self-management and disease control among patients with asthma. However, inconsistent use rates have been reported across studies, regions, and health systems. A better understanding of the characteristics of users and nonusers is critical to design solutions that are effectively integrated in patients' daily lives, and to ensure that these equitably reach out to different groups of patients, thus improving rather than entrenching health inequities. OBJECTIVE: This study aimed to evaluate the use of general health and fitness apps by patients with asthma and to identify determinants of usage. METHODS: A secondary analysis of the INSPIRERS observational studies was conducted using data from face-to-face visits. Patients with a diagnosis of asthma were included between November 2017 and August 2020. Individual-level data were collected, including age, gender, marital status, educational level, health status, presence of anxiety and depression, postcode, socioeconomic level, digital literacy, use of health services, and use of health and fitness apps. Multivariate logistic regression was used to model the probability of being a health and fitness app user. Statistical analysis was performed in R. RESULTS: A total of 526 patients attended a face-to-face visit in the 49 recruiting centers and 514 had complete data. Most participants were ≤40 years old (66.4%), had at least 10 years of education (57.4%), and were in the 3 higher quintiles of the socioeconomic deprivation index (70.1%). The majority reported an overall good health status (visual analogue scale [VAS] score>70 in 93.1%) and the prevalence of anxiety and depression was 34.3% and 11.9%, respectively. The proportion of participants who reported using health and fitness mobile apps was 41.1% (n=211). Multivariate models revealed that single individuals and those with more than 10 years of education are more likely to use health and fitness mobile apps (adjusted odds ratio [aOR] 2.22, 95%CI 1.05-4.75 and aOR 1.95, 95%CI 1.12-3.45, respectively). Higher digital literacy scores were also associated with higher odds of being a user of health and fitness apps, with participants in the second, third, and fourth quartiles reporting aORs of 6.74 (95%CI 2.90-17.40), 10.30 (95%CI 4.28-27.56), and 11.52 (95%CI 4.78-30.87), respectively. Participants with depression symptoms had lower odds of using health and fitness apps (aOR 0.32, 95%CI 0.12-0.83). CONCLUSIONS: A better understanding of the barriers and enhancers of app use among patients with lower education, lower digital literacy, or depressive symptoms is key to design tailored interventions to ensure a sustained and equitable use of these technologies. Future studies should also assess users' general health-seeking behavior and their interest and concerns specifically about digital tools. These factors may impact both initial engagement and sustained use.

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.

Anaphylaxis in children and adolescents: The Portuguese Anaphylaxis Registry.

BACKGROUND: Anaphylaxis is increasing at pediatric age; however, its characterization is hampered by underdiagnosis and underreporting. The aim of this study was to identify the causes of anaphylaxis in children and adolescents in Portugal, thus contributing to a better knowledge of its etiology, clinical manifestations, and management. METHODS: During a 10-year period, a nationwide notification system for anaphylaxis was implemented, with voluntary reporting by allergists. Data on 533 patients under 18 years of age with anaphylaxis were included. RESULTS: Mean age was 8.5 ± 4.9 years, 61% were male; 45% had asthma. Mean age at the first anaphylaxis episode was 5.3 ± 4.7 years (ranging from 1 month to 17 years of age), 63% at pre-school age. Most reactions occurred at home (57%). Food-induced anaphylaxis was the leading cause (77%). The main culprit foods were cow's milk (32%), tree nuts (16%), shellfish (13%), egg (12%), fresh fruits (11%), fish (8%), and peanut (8%). Other causes included drugs (11%), insect sting (5%), cold-induced anaphylaxis (4%), exercise-induced anaphylaxis (2%), latex (1%), and idiopathic anaphylaxis (1%). Most patients (83%) were admitted to the emergency department; only 46% received adrenaline treatment. Recurrence of anaphylaxis occurred in 41% of the patients (3 or more episodes in 21%). An adrenaline autoinjector was used in 9% of the patients. CONCLUSIONS: In the Portuguese pediatric population, food is the leading cause of anaphylaxis. Undertreatment with adrenaline and high recurrence of anaphylaxis highlight the need to improve both the diagnosis and the therapeutic management of this life-threatening entity.

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.

The Dysfunctional Immune System in Common Variable Immunodeficiency Increases the Susceptibility to Gastric Cancer.

Gastric carcinoma (GC) represents the most common cause of death in patients with common variable immunodeficiency (CVID). However, a limited number of cases have been characterised so far. In this study, we analysed the clinical features, bacterial/viral infections, detailed morphology and immune microenvironment of nine CVID patients with GC. The study of the immune microenvironment included automated digital counts of CD20+, CD4+, CD8+, FOXP3+, GATA3+ and CD138+ immune cells, as well as the evaluation of PD-L1 expression. Twenty-one GCs from non-CVID patients were used as a control group. GC in CVID patients was diagnosed mostly at early-stage (n = 6/9; 66.7%) and at younger age (median-age: 43y), when compared to non-CVID patients (p < 0.001). GC pathogenesis was closely related to Helicobacter pylori infection (n = 8/9; 88.9%), but not to Epstein-Barr virus (0.0%) or cytomegalovirus infection (0.0%). Non-neoplastic mucosa (non-NM) in CVID-patients displayed prominent lymphocytic gastritis (100%) and a dysfunctional immune microenvironment, characterised by higher rates of CD4+/CD8+/Foxp3+/GATA3+/PD-L1+ immune cells and the expected paucity of CD20+ B-lymphocytes and CD138+ plasma cells, when compared to non-CVID patients (p < 0.05). Changes in the immune microenvironment between non-NM and GC were not equivalent in CVID and non-CVID patients, reflecting the relevance of immune dysfunction for gastric carcinogenesis and GC progression in the CVID population.

Determination of potential childhood asthma biomarkers using a powerful methodology based on microextraction by packed sorbent combined with ultra-high pressure liquid chromatography. Eicosanoids as case study.

Leukotrienes and prostaglandins are arachidonic acid bioactive derived eicosanoids and key mediators of bronchial inflammation and response modulation in the airways contributing to the pathophysiology of asthma. An easy-to-use ultra-high pressure liquid chromatography (UHPLC)-based strategy was developed to characterize biomarkers of lipid peroxidation: leukotrienes E (LTE4) and B4 (LTB4) and 11ß-prostaglandin F2α (11ßPGF2α), present in urine of asthmatic patients (N = 27) and healthy individuals (N = 17). A semi-automatic eVol®-microextraction by packed sorbent (MEPS) was used to isolate the target analytes. Several experimental parameters with influence on the extraction efficiency and on the chromatographic resolution, were evaluated and optimized. The method was fully validated under optimal extraction (R-AX sorbent, 3 conditioning-equilibration cycles with 250 µL of ACN-water at 0.1% FA, 10 extract-discard cycles of 250 µL of sample at a pH of 5.1, elution with 2 times 50 µL of MeOH and concentration of the eluate until half of its volume) and chromatographic conditions (14-min analysis at a flow rate of 300 µL min-1 in an UHPLC-PDA equipped with a BEH C18 column), according to IUPAC guidelines. The findings indicated good recoveries (>95%) in addition to excellent extraction efficiency (>95%) at three concentration levels (low mid and high) with precision (RSDs) less than 11%. The lack-of-fit test, goodness-of-fit test and Mandel's fitting test, revealed good linearity within the concentration range. Good selectivity and sensitivity were achieved with a limits of detection ranging from 0.04 µg L-1 for LTB4 to 1.12 µg L-1 for 11ßPGF2α, and limits of quantification from 0.10 µg L-1 for the LTB4 to 2.11 µg L-1 for 11ßPGF2α. The successful application of the fully validated method shows that, on average, the asthmatic patients had significantly higher concentrations of 11ßPGF2α (112.96 µg L-1vs 62.56 µg L-1 in normal controls), LTE4 (1.27 µg L-1vs 0.89 µg L-1 in normal controls), and LTB4 (1.39 µg L-1vs 0.76 µg L-1 in normal controls). The results suggest the potential of the target eicosanoids on asthma diagnosis, however, a larger and more extensive study will be necessary to confirm the data obtained and to guarantee a greater robustness to the approach.

Genetic polymorphisms and asthma: findings from a case-control study in the Madeira island population.

BACKGROUND: Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. RESULTS: Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold). CONCLUSION: In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.

Genetic polymorphisms and asthma: findings from a case - control study in the Madeira island population

BACKGROUND: Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set. RESULTS: Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590*CT/TT and IL4-RP2*253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16*AG is a risk factor (3.5-fold), while genotype GSDML-236*TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4*C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4*CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10mm) to house dust (1.4-fold) and storage mite (7.8-fold). CONCLUSION: In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.

Distribution of polymorphisms IL4-590 C/T and IL4 RP2 in the human populations of Madeira, Azores, Portugal, Cape Verde and Guinea-Bissau.

The IL4 gene is located on chromosome 5q23.3-31.2. Polymorphisms within this cytokine gene, like the derivative allele T of IL4-590, have been reported as being associated to elevated IgE serum levels and asthma. In the present work, the allelic and genotypic frequency of the IL4-590 and IL4 RP2 polymorphisms was carried out in 599 individuals from Madeira, Azores, Portugal mainland, Cape Verde and Guinea-Bissau and in a sample of 101 asthmatics from Madeira population. In all populations the polymorphisms were in LD and presented a significant dissimilar allelic and genotypic distribution (p<0.05) except between mainland Portugal and Madeira when compared to Azores. Significant differences regarding both loci were found between Madeira population and the group of asthmatics. Genotype 183183TT frequency is higher for African populations while 253253CC prevails in Caucasian populations. The existence of a Hardy-Weinberg Disequilibrium in Guinea-Bissau population not observed in neutral markers leads to the hypothesis of natural selection occurring in these loci probably associated to a rapid population growth an hypothesis strengthened by neutral STRs D5S818 and CSF1PO gene diversity.

Risk factors for asthma admissions in children.

Bronchial asthma is related to a high morbidity rate, leading to an increasing frequency of emergency room visits and hospital admissions. The aim of this study was to identify severity risk factors for childhood asthma related to hospitalization. The authors studied 124 children admitted to the hospital for asthma, during a 2-year period, correlating the obtained data with a sample of outpatients with asthma matched by age, gender, and socioeconomic status. A standardized questionnaire and skin-prick tests (SPTs) were performed on all children. The significant and independent risk factors identified for hospital admission were prior asthma hospitalization (OR = 7.63; 95% CI = 1.5-39.6; p = 0.01) and last-year admission (OR = 3.18; 95% CI = 1.1-8.9; p = 0.02), environmental tobacco-smoke exposure (OR = 6.63; 95% CI = 2.5-17.8; p = 0.002), allergen sensitization (OR = 3.86; 95% CI = 1.4-10.7; p = 0.009), family history of maternal asthma (OR = 3.58; 95% CI = 1.3-9.6; p = 0.01), and onset of symptoms before 12 months of age (OR = 2.76; 95% CI = 1.0-7.9; p = 0.06). Attendance at day care or kindergarten (OR = 0.38; 95% CI = 0.2-0.9; p = 0.04) and large family size (OR = 0.25; 95% CI = 0.1-0.8; p = 0.01) could be protective factors. Our results stress the importance of early diagnosis and specialized medical care of childhood asthma, mainly in high-risk children, with emphasis on medication planning and the establishment of preventive measures such as environmental tobacco smoke avoidance and limitation of aeroallergen exposure.