Regional, sex, and age inequities in asthma hospital admissions in Spain and Portugal.

BACKGROUND: Asthma presents a significant health challenge, imposing a considerable burden on healthcare services. Discrepancies in asthma-related hospitalisations may reflect underlying health disparities. We aimed to analyse inequities in asthma hospital admissions in mainland Portugal and Spain, from a regional perspective and considering sex and age. METHODS: We conducted a retrospective study using data from the Spanish and Portuguese national hospitalisations databases. We calculated crude national and regional yearly hospitalisation rates according per Nomenclature of Territorial Units for Statistics region. Additionally, we calculated hospitalisation rates adjusted for asthma prevalence and the female-to-male ratio in asthma hospital admissions per age group, considering the female-to-male ratio in the overall population. RESULTS: Between 2012 and 2016, there were 92,084 asthma hospital admissions in mainland Spain and 7717 in mainland Portugal. There was a trend for a higher-than-average rate of asthma-related hospitalisations in the Northern regions of both countries. Women had a hospitalisation rate that was 3.2 times higher than men. Age was associated with higher risk for asthma hospitalisation, with individuals aged 65 and older displaying a hospitalisation rate 4.5 times higher than those under 65. Additionally, while hospitalisations in women aged <65 years were 2.3 times more likely than in men of the same age, hospitalisations in women aged ≥65 years were 3.5 times higher than in men aged ≥65 years. CONCLUSION: This study suggests that marked regional inequities in asthma hospital admissions exist in Spain and Portugal. Additionally, women are particularly at risk of hospitalisation due to asthma, and such risk increases with age.

Adult Severe Asthma Registries: A Global and Growing Inventory.

Aim: The International Severe Asthma Registry (ISAR; http://isaregistries.org/) uses standardised variables to enable multi-country and adequately powered research in severe asthma. This study aims to look at the data countries within ISAR and non-ISAR countries reported collecting that enable global research that support individual country interests. Methods: Registries were identified by online searches and approaching severe asthma experts. Participating registries provided data collection specifications or confirmed variables collected. Core variables (results from ISAR's Delphi study), steroid-related comorbidity variables, biologic safety variables (serious infection, anaphylaxis, and cancer), COVID-19 variables and additional variables (not belonging to the aforementioned categories) that registries reported collecting were summarised. Results: Of the 37 registries identified, 26 were ISAR affiliates and 11 non-ISAR affiliates. Twenty-five ISAR-registries and 4 non-ISAR registries reported collecting >90% of the 65 core variables. Twenty-three registries reported collecting all optional steroid-related comorbidity variables. Twenty-nine registries reported collecting all optional safety variables. Ten registries reported collecting COVID-19 variables. Twenty-four registries reported collecting additional variables including data from asthma questionnaires (10 Asthma Control Questionnaire, 20 Asthma Control Test, 11 Asthma Quality of Life Questionnaire, and 4 EuroQol 5-dimension 5-level Questionnaire). Eight registries are linked to databases such as electronic medical records and national claims or disease databases. Conclusion: Standardised data collection has enabled individual severe asthma registries to collect unified data and increase statistical power for severe asthma research irrespective of ISAR affiliations.

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.

Development and validation of an electronic daily control score for asthma (e-DASTHMA): a real-world direct patient data study.

BACKGROUND: Validated questionnaires are used to assess asthma control over the past 1-4 weeks from reporting. However, they do not adequately capture asthma control in patients with fluctuating symptoms. Using the Mobile Airways Sentinel Network for airway diseases (MASK-air) app, we developed and validated an electronic daily asthma control score (e-DASTHMA). METHODS: We used MASK-air data (freely available to users in 27 countries) to develop and assess different daily control scores for asthma. Data-driven control scores were developed based on asthma symptoms reported by a visual analogue scale (VAS) and self-reported asthma medication use. We included the daily monitoring data from all MASK-air users aged 16-90 years (or older than 13 years to 90 years in countries with a lower age of digital consent) who had used the app in at least 3 different calendar months and had reported at least 1 day of asthma medication use. For each score, we assessed construct validity, test-retest reliability, responsiveness, and accuracy. We used VASs on dyspnoea and work disturbance, EQ-5D-VAS, Control of Allergic Rhinitis and Asthma Test (CARAT), CARAT asthma, and Work Productivity and Activity Impairment: Allergy Specific (WPAI:AS) questionnaires as comparators. We performed an internal validation using MASK-air data from Jan 1 to Oct 12, 2022, and an external validation using a cohort of patients with physician-diagnosed asthma (the INSPIRERS cohort) who had had their diagnosis and control (Global Initiative for Asthma [GINA] classification) of asthma ascertained by a physician. FINDINGS: We studied 135 635 days of MASK-air data from 1662 users from May 21, 2015, to Dec 31, 2021. The scores were strongly correlated with VAS dyspnoea (Spearman correlation coefficient range 0·68-0·82) and moderately correlated with work comparators and quality-of-life-related comparators (for WPAI:AS work, we observed Spearman correlation coefficients of 0·59-0·68). They also displayed high test-retest reliability (intraclass correlation coefficients range 0·79-0·95) and moderate-to-high responsiveness (correlation coefficient range 0·69-0·79; effect size measures range 0·57-0·99 in the comparison with VAS dyspnoea). The best-performing score displayed a strong correlation with the effect of asthma on work and school activities in the INSPIRERS cohort (Spearman correlation coefficients 0·70; 95% CI 0·61-0·78) and good accuracy for the identification of patients with uncontrolled or partly controlled asthma according to GINA (area under the receiver operating curve 0·73; 95% CI 0·68-0·78). INTERPRETATION: e-DASTHMA is a good tool for the daily assessment of asthma control. This tool can be used as an endpoint in clinical trials as well as in clinical practice to assess fluctuations in asthma control and guide treatment optimisation. FUNDING: None.

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.

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.

The impact of weight loss beyond lung function: benefit with respect to asthma outcomes.

OBJECTIVE: We evaluated the effect of weight loss (WL) on lung function (LF) in obese individuals who underwent bariatric surgery, and on asthma control, quality of life, LF, and controller medication in a sub-group of obese asthma (OA) patients. MATERIALS AND METHODS: Obese individuals who underwent bariatric surgery between July 2015 and July 2017 were included in this prospective longitudinal study. They were classified as OA or obese non-asthmatics (O-NA). LF was assessed preoperatively and 6-9 months postoperatively. In OA patients, asthma control, quality of life, and treatment step were evaluated. P < 0.05 was considered significant. RESULTS: Twenty-six patients (OA: n = 8; O-NA: n = 18), 84.6% with class III obesity were enrolled. Preoperatively, OA patients showed worse values of LF parameters, with upper and lower airway CARAT scores of 6.1 ±â€¯3.1 and 13.4 ±â€¯4.1, respectively, and 75% were in step 4 of treatment. After WL, improvements in dynamic volumes, lung capacities, and total resistance were observed in both groups. Despite greater increases in OA patients, no significant differences were observed between groups. In OA patients, improvements in CARAT score of upper (3.9 ±â€¯1.9, p = 0.017) and lower (4.2 ±â€¯4.4, p = 0.027) airways, and in Asthma Life Quality scores (8.1 ±â€¯5.6, p = 0.017) were observed along with a decrease (-1.8 ±â€¯1.0, p = 0.017) in treatment step. CONCLUSIONS: All LF parameters improved after WL. Although the improvement was greater in OA patients, the difference between groups was not significant. Significant improvement from baseline in uncontrolled symptoms of OA patients and quality of life was observed after WL, along with a significant decrease in treatment step.

The Portuguese Severe Asthma Registry: Development, Features, and Data Sharing Policies.

The Portuguese Severe Asthma Registry (Registo de Asma Grave Portugal, RAG) was developed by an open collaborative network of asthma specialists. RAG collects data from adults and pediatric severe asthma patients that despite treatment optimization and adequate management of comorbidities require step 4/5 treatment according to GINA recommendations. In this paper, we describe the development and implementation of RAG, its features, and data sharing policies. The contents and structure of RAG were defined in a multistep consensus process. A pilot version was pretested and iteratively improved. The selection of data elements for RAG considered other severe asthma registries, aiming at characterizing the patient's clinical status whilst avoiding overloading the standard workflow of the clinical appointment. Features of RAG include automatic assessment of eligibility, easy data input, and exportable data in natural language that can be pasted directly in patients' electronic health record and security features to enable data sharing (among researchers and with other international databases) without compromising patients' confidentiality. RAG is a national web-based disease registry of severe asthma patients, available at asmagrave.pt. It allows prospective clinical data collection, promotes standardized care and collaborative clinical research, and may contribute to inform evidence-based healthcare policies for severe asthma.

[Age as influence in the adrenergic/cholinergic bronchomotor response]. / Idade como variável na resposta broncomotora adrenérgica/colinérgica.

BACKGROUND: Changes of pulmonary mechanisms, receptor population and nervous control of the airway, that occur with ageing, are responsible for the different clinical presentation of pathologies like asthma, as well as different efficacy of bronchodilator therapeutics in the aged patient. To be explained are the effects of age in the bronchodilator response to beta-mimetics and cholinergics and the existent evidence is discordant. Some comparative studies of that pharmacological response, made on asthmatics, have shown an efficacy decline with age. Others didn't find any significant difference. OBJECTIVES: Individual evaluation of bronchodilator response in individuals of different age groups to salbutamol and ipratropium bromide. METHODS: Three groups of 12 patients - witness group (W), young healthy individuals; control group (C), elderly individuals without respiratory pathology; study group (S), elderly individuals with bronchial asthma - were submitted to functional ventilator evaluation followed by a bronchodilator test in two consecutive days (one day with salbutamol (s), other with ipratropium bromide (b). In S all were in a stable period, without anti-asthmatic medication in the previous 24 hours. Plethismography and spirometry followed ATS/ERS, 2005 criteria. To evaluate the bronchomotor response we used as criteria an increase of 12% or 200 ml in FEV1 or in FVC, after inhalation of 40 mcg of ipratropium bromide or 200+200 mcg of salbutamol. RESULTS: The variability of response was constant. With age, (W Vs C) there was an increase on negative responses to both drugs (4 Vs 8); a decrease on responses simultaneously positives to s and negatives to b (4 Vs 2) and an increase on responses simultaneously positives to b and negatives to s (0 Vs 1). With age and associated disease (W Vs S) the number of responses simultaneously positives to both drugs has raised (1 Vs 3); the number of responses simultaneously negatives to both drugs kept constant (4 Vs 4); the number of responses simultaneously positives to s and negatives to b decreased (4 Vs 1); number of responses simultaneously positives to b and negatives to s increased (0 Vs 2). CONCLUSIONS: An individual analysis of bronchomotricity in different groups leads to the conclusion that, with age, there was a decrease in bronchial lability, independently of the used drug. Globally, in aged asthmatics, the bronchial response was superior to the healthy ones, as expected. The individual analyses of the positive bronchodilatorresponses lead to the conclusion that, with age and disease, the ipratropium bromide showed an improvement in bronchomotricity, contrary to salbutamol. Such fact may be explained by the already, but not consensual, description of the decreasing efficacy of adrenergic drugs with age, aggravated by the chronic use of long acting betamimetics.

[Influence of age and bronchial obstruction on the elderly bronchodilation response]. / Influência da idade e da obstrução brônquica na resposta broncodilatadora em idosos.

INTRODUCTION: Bronchodilator response may be influenced by airway flow limitation, age and genetics. Evidence has shown that this response increases with higher levels of airway obstruction and is altered with age and presence of specific genetic polymorphisms of the ß2 adrenergic receptors. AIM: Correlate the airway flow limitation (FEV1, FVC, IC, RV) with the bronchodilation response, to ß-adrenergics (salbutamol (s)) and to anticholinergics (ipratropium bromide (b)), in a group of elderly people with diagnosed asthma. METHODS: We submitted a group of twelve aged individuals (>65Y), with diagnosed asthma, to a basal ventilatory lung function evaluation, followed by a bronchodilation test, in two consecutive days (in one day using s, in the other using b). They were submitted to a functional ventilatory evaluation followed by a bronchodilator test (one day with s, other day with b). The individuals were in a stable period, without anti-asthmatic medication in the previous 24 hours. Plethismography and spirometry followed ATS/ERS 2005 criteria. Statistic analysis used SPSS for Windows. Correlations were established using the Pearson coefficient (r value). RESULTS: The bronchodilation response after b correlated best, with basal ventilatory evaluated parameters, than bronchodilation response after. - The FEV1 response increased as lower were the basal IC/TLC values, only after b; - The FVC response was increased as lower were the basal IC/TLC values and as higher were basal RV/TLC values, only after b; - The IC/TLC response increased as lower were basal IC/TLC values, only after b; - For both b and s, the RV/TLC responses increased as lower were basal VR/TLC values. CONCLUSIONS: The found correlations point out the relation of increased airway flow limitation and better bronchodilation response to b, which assumed importance to the responses related with the RV basal variation. The responses to s didn't show such a grade of dependence. That might be explained by the probable concurrence of other variables for the grade of bronchodilation response to the ß-adrenergics. The existence of genetic polymorphisms of ADRB2 gene, already described in the literature, show an increasing in bronchodilation response of Arg/Arg homozygotes when ß-adrenergic therapeutic is replaced for the anticholinergic one.

Clinical and polysomnographic characteristics of patients with REM sleep disordered breathing.

There is a 10 -36% rate of obstructive sleep apnoea syndrome (OSAS) associated with rapid eye movement (REM) in the OSAS population. Prior studies have suggested an increased prevalence of psychiatric disorders and an effect of gender and age on these patients. Our aim was to study the clinical and polysomnograph (PSG) characteristics of our patients with REM- -related sleep disordered breathing (REM SDB). Inclusion criteria was the identification of REM SDB detected by PSG defined as apnea -hypopnea index (AHI) in REM sleep > or = 5h, AHI in non -REM sleep (NREM) < or = 15h and REM/NREM AHI > or = 2. Several Sleep Disorders Questionnaire (SDQ) version 1.02 parameters were analysed. The study comprised 19 patients with a mean age of 54.0 (SD+/-13.97), a mean BMI of 29.01 (SD +/- 4.10) and a 0.58 female / male ratio. The mean Epworth Sleepiness Scale score was 12.74 (SD +/-4.86). Mean AHI was 9.16/h (SD 4.09); mean AHI in REM sleep 37.08/h (SD 25.87) and mean REM -AHI/NREM- -AHI 8.86 (SD 8.63). The anxiety disorder rate was 33.3%; 44.4% in females, 16.7% in males. The average deep sleep was 20.7% (SD 10.42) and REM sleep 15.45% (SD 9.96), with a sleep efficiency of 85.3 (SD 8.70). No significant statistical correlation was found between the REM/NREM AHI index and anxiety symptoms, daytime sleepiness and sleep quality (REM and deep sleep percentages). These patients differ from the general OSAS population: on average, they are not obese, there are a greater number of females affected and they do not present a very significant diurnal hypersomnia. Reduced deep sleep and increased REM sleep were also present versus general population data, and sleep efficiency was just below the normal limit. Anxiety disorders were more prevalent in this group than described for the general population (3%) and OSAS patients.

Simultaneous sleep study and nasoendoscopic investigation in a patient with obstructive sleep apnoea syndrome refractory to continuous positive airway pressure: a case report.

INTRODUCTION: The standard treatment for obstructive sleep apnoea syndrome is nasal continuous positive airway pressure. In most cases the obstruction is located at the oropharyngeal level, and nasal continuous positive airway pressure is usually effective. In cases of non-response to nasal continuous positive airway pressure other treatments like mandibular advancement devices or upper airway surgery (especially bi-maxillary advancement) may also be considered. CASE PRESENTATION: We report the case of a 38-year-old Caucasian man with severe obstructive sleep apnoea syndrome, initially refractory to nasal continuous positive airway pressure (and subsequently also to a mandibular advancement devices), in which the visualization of the upper airway with sleep endoscopy and the concomitant titration of positive pressure were useful in the investigation and resolution of sleep disordered breathing. In fact, there was a marked reduction in the size of his nasopharynx, and a paresis of his left aryepiglotic fold with hypertrophy of the right aryepiglotic fold. The application of bi-level positive airway pressure and an oral interface successfully managed his obstructive sleep apnoea. CONCLUSION: This is a rare case of obstructive sleep apnoea syndrome refractory to treatment with nocturnal ventilatory support. Visualization of the endoscopic changes, during sleep and under positive pressure, was of great value to understanding the mechanisms of refractoriness. It also oriented the therapeutic option. Refractoriness to obstructive sleep apnoea therapy with continuous positive airway pressure is rare, and each case should be approached individually.