Parasympathetic nervous system: A key role in control and mood disorders in patients with asthma.

BACKGROUND: Patients with severe asthma often have uncontrolled disease and experience mood disorders, particularly anxiety and depression. The autonomic nervous system (ANS) plays an important role in asthma, mainly through the parasympathetic ANS system (PANS), which favors bronchoconstriction and mental health status. OBJECTIVE: To evaluate the role of the activation of the PANS in uncontrolled asthma and related mood disorders. METHODS: This was a proof-of-concept cross-sectional study that analyzed demographic and clinical variables reflecting asthma severity and control, lung function, inflammation (from induced sputum), evaluation of quality of life, and the risk for anxiety and depression according to validated questionnaires. The PANS analysis was conducted based on heart rate variability: SD of the difference between consecutive normal-to-normal (NN) intervals (SDNN), root mean square of the successive differences (RMSSD), percentage of consecutive NN intervals (pNN50), total power (TP), and respiratory-related power (Pr). RESULTS: A total of 30 patients with asthma were grouped according to asthma control and the risk for anxiety and depression; 10 patients with uncontrolled asthma compared with the patients with controlled asthma showed significant differences (P < .05) in SDNN (26.5 [8.2] vs 42.7 [29.7]), RMSSD (14.1 [6.5] vs 24 [20]), pNN50 (0.6 [1.5] vs 6.2 [11.8]), TP (0.0005 [0.00046] vs 0.0014 [0.00085]), and Pr (0.0003 [0.00025] vs 0.0007 [0.00060]) respectively. A total of 13 patients at risk for anxiety and depression compared with the patients without showed reduced values (P < .05) for SDNN (26.5 [7.9] vs 45.6 [31.3]), pNN50 (0.75 [1.4] to 7.12 [12.6]), TP (0.0005 [0.00048] to 0.0012 [0.0008]), and Pr (0.0003 [0.00027] to 0.0008 [0.00062]). CONCLUSION: Our results suggest that PANS activity is depressed in patients with uncontrolled asthma and common mood disorders such as depression and anxiety, and the evaluation of heart rate variability may be a useful means for follow-up of asthma control and related mood disorders.

Analysis of Differentially Expressed MicroRNAs in Serum and Lung Tissues from Individuals with Severe Asthma Treated with Oral Glucocorticoids.

Nowadays, microRNAs (miRNAs) are increasingly used as biomarkers due to their potential contribution to the diagnosis and targeted treatment of a range of diseases. The aim of the study was to analyze the miRNA expression profiles in serum and lung tissue from patients with severe asthma treated with oral corticosteroids (OCS) and those without OCS treatment. For this purpose, serum and lung tissue miRNAs of OCS and non-OCS asthmatic individuals were evaluated by miRNAs-Seq, and subsequently miRNA validation was performed using RT-qPCR. Additionally, pathway enrichment analysis of deregulated miRNAs was conducted. We observed altered expression by the next-generation sequencing (NGS) of 11 miRNAs in serum, of which five (hsa-miR-148b-3p, hsa-miR-221-5p, hsa-miR-618, hsa-miR-941, and hsa-miR-769-5p) were validated by RT-qPCR, and three miRNAs in lung tissue (hsa-miR-144-3p, hsa-miR-144-5p, and hsa-miR-451a). The best multivariate logistic regression model to differentiate individuals with severe asthma, treated and untreated with OCS, was to combine the serum miRNAs hsa-miR-221-5p and hsa-miR-769-5p. Expression of hsa-miR-148b-3p and hsa-miR-221-5p correlated with FEV1/FVC (%) and these altered miRNAs act in key signaling pathways for asthma disease and the regulated expression of some genes (FOXO3, PTEN, and MAPK3) involved in these pathways. In conclusion, there are miRNA profiles differentially expressed in OCS-treated individuals with asthma and could be used as biomarkers of OCS treatment.

Multi-ancestry genome-wide association study of asthma exacerbations.

BACKGROUND: Asthma exacerbations are a serious public health concern due to high healthcare resource utilization, work/school productivity loss, impact on quality of life, and risk of mortality. The genetic basis of asthma exacerbations has been studied in several populations, but no prior study has performed a multi-ancestry meta-analysis of genome-wide association studies (meta-GWAS) for this trait. We aimed to identify common genetic loci associated with asthma exacerbations across diverse populations and to assess their functional role in regulating DNA methylation and gene expression. METHODS: A meta-GWAS of asthma exacerbations in 4989 Europeans, 2181 Hispanics/Latinos, 1250 Singaporean Chinese, and 972 African Americans analyzed 9.6 million genetic variants. Suggestively associated variants (p ≤ 5 × 10-5 ) were assessed for replication in 36,477 European and 1078 non-European asthma patients. Functional effects on DNA methylation were assessed in 595 Hispanic/Latino and African American asthma patients and in publicly available databases. The effect on gene expression was evaluated in silico. RESULTS: One hundred and twenty-six independent variants were suggestively associated with asthma exacerbations in the discovery phase. Two variants independently replicated: rs12091010 located at vascular cell adhesion molecule-1/exostosin like glycosyltransferase-2 (VCAM1/EXTL2) (discovery: odds ratio (ORT allele ) = 0.82, p = 9.05 × 10-6 and replication: ORT allele  = 0.89, p = 5.35 × 10-3 ) and rs943126 from pantothenate kinase 1 (PANK1) (discovery: ORC allele  = 0.85, p = 3.10 × 10-5 and replication: ORC allele  = 0.89, p = 1.30 × 10-2 ). Both variants regulate gene expression of genes where they locate and DNA methylation levels of nearby genes in whole blood. CONCLUSIONS: This multi-ancestry study revealed novel suggestive regulatory loci for asthma exacerbations located in genomic regions participating in inflammation and host defense.

Prevalence of chronic cough and patient characteristics in adults in Spain: A population-based cross-sectional survey.

BACKGROUND: Chronic cough (CC) represents a significant health burden. This study assessed the prevalence of CC (defined as per international guidelines as cough duration >8 weeks) in Spanish adults and compared characteristics between CC and non-CC cohorts. METHODS: CC cohorts were compiled using data from adult respondents to the 2020 Spanish cross-sectional online National Health and Wellness Survey (NHWS). Using propensity scores, respondents experiencing CC during their lifetime and the previous 12 months were matched 3:1 to respondents without CC and their health characteristics were compared. The number of Spanish adults affected with CC was estimated using weighted CC prevalence. RESULTS: CC during their lifetime or the previous 12 months was experienced by 579 (8.2%) and 389 (5.5%) of 7074 NHWS respondents, of whom 233 (38.5%) and 171 (44.0%), respectively, had physician-diagnosed CC. Based on weighted prevalence rates, lifetime and 12-month CC were estimated to affect ≈3.3 million and ≈2.2 million Spanish adults, respectively. Relative to the non-CC cohort, the 12-month CC cohort consistently demonstrated poorer health status, poorer mental health, greater healthcare utilization, and lower productivity at work and home. CONCLUSION: This study contributes novel data regarding the prevalence of CC in Spain, suggests that CC is underdiagnosed, and reflects that CC and related comorbidities inflict a significant health burden in the affected population.

Current expert opinion and attitudes to optimize telemedicine and achieve control in patients with asthma in post-pandemic era: The COMETA consensus.

OBJECTIVE: To collect perspectives and explore consensus for expert recommendations related to asthma control and the use of telemedicine among professionals who manage patients with asthma. DESIGN: A Delphi-like questionnaire was designed to analyse the level of agreement about several recommendations formulated by an expert scientific committee about asthma control and the use of telemedicine with this purpose. A dedicated scientific committee validated the questionnaire, which included questions about the participants' profile and the use of technological tools at a personal level or in clinical practice. The experts expressed their agreement with a Likert-scale of 9 values: 1-3 was considered no agreement, 4-6 neutral, and 7-9 agreement. A rate ≥70% with the same answer was considered consensus. SITE: The questionnaire was programmed and distributed as an internet-based survey. PARTICIPANTS: A pre-selected sample of 75 experts with experience in telemedicine (pulmonology, allergology, family medicine, nursing and community pharmacy) responded to a Delphi-like questionnaire composed by six questions and 52 items. INTERVENTIONS: Consultation was performed in two consecutive waves: the first wave was carried out from 12th of July to 8th of September of 2021; the second wave, from 25th of October to 12th of November of 2021. MAIN MEASUREMENTS: Three questions about asthma control (actions for achieving or maintaining control of asthma at every visit, current problems that affect asthma control, and potential solutions to offset such problems), and three questions about the impact of telemedicine in asthma control (potential benefits of telemedicine, and potential reticence about telemedicine among both patients and healthcare professionals) were included. RESULTS: From the 52 items inquired, 35 were agreed by consensus. The actions for achieving or maintaining control of asthma, the problems that affect asthma control, and their potential solutions were agreed by consensus. The potential benefits of telemedicine were validated by consensus. None of the potential reservations of patients about telemedicine were validated, while five out of 14 potential reservations of healthcare professionals were agreed by consensus. CONCLUSIONS: The COMETA consensus provides a current picture of the main problems for achieving asthma control, the benefits and the reservations about the use of telemedicine in the Spanish setting, and offers solutions. A wide interest in implementing telemedicine has been observed, although current limitations need to be overcome.

Multidisciplinary consensus on sputum induction biosafety during the COVID-19 pandemic.

Sputum induction (SI) is the gold standard approach to the non-invasive study of airway inflammation. The differential count of inflammatory cells for SI allows patients with asthma to be classified according to inflammatory phenotypes and predicted therapeutic responses. Since SI involves the generation of aerosols, there is a need to establish a protocol to ensure biosafety in clinical practice during the current COVID-19 pandemic. The multidisciplinary consensus on SI described in this article was developed by 22 experts in SI from different Spanish hospitals who drew on available scientific evidence in achieving consensuated opinions, compiled by means of an electronic survey. We hope that these unified criteria and recommendations will guide health professionals in implementing SI sampling and processing procedures as safely as possible during the COVID-19 pandemic.

Characteristics and treatment regimens across ERS SHARP severe asthma registries.

Little is known about the characteristics and treatments of patients with severe asthma across Europe, but both are likely to vary. This is the first study in the European Respiratory Society Severe Heterogeneous Asthma Research collaboration, Patient-centred (SHARP) Clinical Research Collaboration and it is designed to explore these variations. Therefore, we aimed to compare characteristics of patients in European severe asthma registries and treatments before starting biologicals.This was a cross-sectional retrospective analysis of aggregated data from 11 national severe asthma registries that joined SHARP with established patient databases.Analysis of data from 3236 patients showed many differences in characteristics and lifestyle factors. Current smokers ranged from 0% (Poland and Sweden) to 9.5% (Belgium), mean body mass index ranged from 26.2 (Italy) to 30.6 kg·m-2 (the UK) and the largest difference in mean pre-bronchodilator forced expiratory volume in 1 s % predicted was 20.9% (the Netherlands versus Hungary). Before starting biologicals patients were treated differently between countries: mean inhaled corticosteroid dose ranged from 700 to 1335 µg·day-1 between those from Slovenia versus Poland when starting anti-interleukin (IL)-5 antibody and from 772 to 1344 µg·day-1 in those starting anti-IgE (Slovenia versus Spain). Maintenance oral corticosteroid use ranged from 21.0% (Belgium) to 63.0% (Sweden) and from 9.1% (Denmark) to 56.1% (the UK) in patients starting anti-IL-5 and anti-IgE, respectively.The severe asthmatic population in Europe is heterogeneous and differs in both clinical characteristics and treatment, often appearing not to comply with the current European Respiratory Society/American Thoracic Society guidelines definition of severe asthma. Treatment regimens before starting biologicals were different from inclusion criteria in clinical trials and varied between countries.

DuoResp® Spiromax® adherence, satisfaction and ease of use: findings from a multi-country observational study in patients with asthma and COPD in Europe (SPRINT).

Objective: Adherence and inhaler technique are often suboptimal in asthma and chronic obstructive pulmonary disease (COPD). New inhalers have been developed to improve these determinants of treatment effectiveness. We assessed treatment adherence, satisfaction, and ease of use of DuoResp® Spiromax® among SPRINT study participants.Methods: The Phase IV SPRINT study was conducted in 10 European countries. Asthma and COPD patients were receiving a fixed-dose combination of inhaled corticosteroid (ICS) and long-acting ß2-agonist (LABA), delivered via various inhalers including DuoResp Spiromax. DuoResp Spiromax users self-assessed adherence using the 8-item Morisky Medication Adherence Scale (MMAS-8®), and ease of use and satisfaction using 10-point scales, during a single physician's office visit.Results: Of 1661 (asthma: n = 1101; COPD: n = 560) SPRINT study participants, 342 (asthma: n = 235; COPD: n = 107) received DuoResp Spiromax prior to inclusion. Overall, 72.5% of DuoResp Spiromax users reported medium or high adherence (MMAS-8 score ≥6). Mean (standard deviation [SD]) satisfaction score for DuoResp Spiromax was 8.9 (1.6). Almost all (98.8%) DuoResp Spiromax users were at least satisfied with their inhaler; 85.4% were very satisfied. Mean (SD) ease of use score for DuoResp Spiromax was 9.1 (1.3).Conclusions: Asthma and COPD patients using DuoResp Spiromax reported moderate-to-high medication adherence, were very satisfied with their inhaler and found it easy to use.

Pseudomonas aeruginosa in Chronic Obstructive Pulmonary Disease Patients with Frequent Hospitalized Exacerbations: A Prospective Multicentre Study.

BACKGROUND: Pseudomonas aeruginosa (PA) is a common microorganism related to severe exacerbations in Chronic Obstructive Pulmonary Disease (COPD). However, their role in COPD patients with frequent hospitalized exacerbations (FHE) is not well described. OBJECTIVES: We aimed to determine prevalence, risk factors, susceptibility patterns and impact on outcomes of PA in COPD patients with FHE. METHODS: Prospective observational multicentre study that included COPD patients with FHE. The cohort was stratified in 2 groups according to the presence or absence of PA isolation in sputum. Patients were followed up for 12 months. RESULTS: We enrolled 207 COPD patients with FHE. In 119 patients (57%), a valid sputum culture was collected. Of them, PA was isolated in 21 patients (18%). The risk factors associated with PA were prior use of systemic corticosteroids (OR 3.3, 95% CI 1.2-9.7, p = 0.01) and prior isolation of PA (OR 4.36, 95% CI 1.4-13.4, p < 0.01). Patients with PA had an increased risk of having ≥3 readmissions (OR 4.1, 95% CI 1.3-12.8, p = 0.01) and higher PA isolation rate (OR 7.7, 95% CI 2.4-24.6, p < 0.001) during the follow-up period. In 14 patients (67%), PA was resistant to at least one antibiotic tested. PA persisted in the sputum in 70% of patients. CONCLUSIONS: The presence of PA was related to 3 or more readmissions during the 1-year follow-up and PA persisted in the sputum despite an appropriate antibiotic treatment. This finding suggested an important role of PA in the course of the disease of COPD patients with FHE.

Impact of patient satisfaction with his or her inhaler on adherence and asthma control.

Background: Asthma guidelines recommend considering patient preferences for inhaler choice. However, few studies have assessed the impact of patient satisfaction with an inhaler on adherence and health outcomes. Objective: To assess the impact of patient satisfaction with an inhaler on adherence and health outcomes in asthma. Methods: In a cross-sectional, observational, multicenter study, 778 patients with moderate or severe asthma and who were treated with maintenance inhalers completed a number of scales and questionnaires: the Feeling of Satisfaction with Inhaler (FSI-10) questionnaire, the Treatment Satisfaction Questionnaire for Medication, the Test of Adherence to Inhalers (TAI), the Morisky-Green questionnaire, and the Asthma Control Test (ACT). Results: The study population was categorized according to a median FSI-10 score as high (49.4%) and low (50.6%) satisfaction with their inhaler. Logistic regression analysis showed that high specific satisfaction with an inhaler was associated with the younger age group (odds ratio [OR] 0.976 [95% confidence interval {CI} 0.965-0.987]); male gender (OR 1.725 [95% CI 1.187-2.507]); controlled asthma: ACT score ≥ 20 (OR 1.664 [95% CI 1.133-2.445]); high general satisfaction with treatment (OR 4.861 [95% CI 3.335-7.085]); high adherence to inhaler: TAI score ≥ 46 (OR 1.546 [95% CI 1.025-2.332]); nonsevere asthma (OR 1.056 [95% CI 0.648-1.721]); and no trouble with inhaler use (OR 0.401 [95% CI 0.174-0.922]). Conclusion: High patient satisfaction with an inhaler, irrespective of received medication, was related to adherence and asthma control. Our results pointed out the relevance of inhaler choice in inhaled therapy; these results could be useful for designing new strategies targeted to increase adherence in patients with asthma.