Uncontrolled severe T2 asthma: Which biological to choose? A biomarker-based approach.

In recent years, advances in knowledge of molecular mechanisms involved in asthma have changed uncontrolled severe asthma (USA) treatment, with the appearance of biological treatment. USA is a heterogeneous entity with different endotypes and phenotypes. Nowadays, the biological drugs approved with asthma indication are omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab. Tezepelumab is approved by the Food and Drug Administration (FDA) in the United States and, recently, by the European Medicines Agency (EMA). All these biological drugs have shown their efficacy in clinical trials, especially in reducing exacerbations, improving asthma control, quality of life, pulmonary function, and withdrawing systemic corticosteroids or at least reducing their daily dose, with some differences between them. Except for mepolizumab and reslizumab, biological drugs have different targets and thus different therapeutic indications should be expected; however, in some patients, more than one drug could be indicated, making the election more difficult. Because there are no direct comparisons between biological drugs, some biomarkers are used to choose between them, but they are not unbeatable. In this article, an algorithm to choose the first biological drug in a specific patient is proposed based on different study results and patient' characteristics.

Corrigendum: Uncontrolled severe T2 asthma: Which biological to choose? A biomarker-based approach.

[This corrects the article DOI: 10.3389/falgy.2022.1007593.].

Effectiveness of Text Message Reminders on Adherence to Inhaled Therapy in Patients With Asthma: Prospective Multicenter Randomized Clinical Trial.

BACKGROUND: Poor adherence to inhaled medication in asthma patients is of great concern. It is one of the main reasons for inadequate asthma control. OBJECTIVE: The goal of the research was to determine if motivational messages using short message service (SMS, or text) improved adherence to inhaled medication in patients with asthma. METHODS: A prospective multicenter randomized parallel-group clinical trial was conducted in 10 asthma clinics in Spain. Adherence was assessed with electronic monitors (Smartinhaler, Adherium Ltd) connected to inhalers. Patients in the SMS group received psychologist-developed motivational messages every 3 days for 6 months. RESULTS: There were 53 patients in the SMS group and 88 patients in the control group. After 6 months, mean electronic adherence was 70% (SD 17%) in the intervention group and 69% (SD 17%) in the control group (P=.82). Significant differences between the study groups in morning and evening adherence to inhaled therapy, asthma control, exhaled nitric oxide levels, or improvement of lung functions were not observed. CONCLUSIONS: Motivational messages were not useful to improve adherence to inhaled asthma medication compared with usual care.

Mucus hypersecretion in asthma is associated with rhinosinusitis, polyps and exacerbations.

BACKGROUND: Bronchial hypersecretion is a poorly studied symptom in asthma. The aim of the study was to determine the specific characteristics of asthmatics with bronchial hypersecretion. METHODS: A total of 142 asthmatics (21.8% men; mean age 49.8 years) were prospectively followed for one year. Mucus hypersecretion was clinically classified into two severity categories: daily sputum production and frequent expectoration but not every day. Clinical and pulmonary function variables associated with mucus hypersecretion were assessed by multiple logistic regression analysis. RESULTS: Daily cough was recorded in 28.9% of patients and sputum production daily or most of the days in 52.1%. Patients with mucus hypersecretion had more dyspnoea, poorer asthma control and quality of life, had suffered from more exacerbations and showed anosmia associated with chronic rhinosinusitis and nasal polyposis more frequently. Factors associated to mucus hypersecretion were anosmia, one exacerbation or more in the previous year and FEV1/FVC <70% (AUC 0.75, 95% CI 0.66-0.85) for the first definition of hypersecretion, and anosmia, poor asthma control and age (AUC 0.75, 95% CI 0.67-0.83) for the second definition. CONCLUSIONS: Mucus hypersecretion is frequent in patients with asthma, and is associated with chronic upper airways disease, airway obstruction, poor asthma control and more exacerbations.

Multidisciplinary Consensus on the Nonadherence to Clinical Management of Inhaled Therapy in Spanish asthma patients.

PURPOSE: Rates of nonadherence to asthma treatment in Spain are between 24% and 76%, which results in poor disease control and increased health care costs. The main objective of this multidisciplinary consensus was to investigate the opinions of health professionals and patients regarding adherence to inhaled therapy in Spain. The results will help to identify the causes of nonadherence and to establish strategies to detect and correct the problem. METHODS: This research was conducted by using a modified Delphi method organized into 2 rounds and involving a panel of 64 physicians, 16 nurses, and 10 community pharmacists. In addition, 70 patients with asthma completed a simplified 1-round survey, based on the Delphi questionnaire. The items proposed to reach a consensus included topics such as impact and causes of nonadherence, as well as strategies to improve adherence to treatment. FINDINGS: Expert panelists reached a consensus on ~80% of the items proposed. They agreed that the lack of control in asthma has an important economic impact. The causes of nonadherence with more agreement were the patients' beliefs about treatment and the complexity of the inhalation devices. Panelists agreed that the most important strategies to improve adherence were modification of patients' beliefs, training of professionals in the management of adherence, and personalization of interventions. Most patients only agreed with items that referred to strategies to improve adherence. IMPLICATIONS: Although the problems, impact, causes, and interventions regarding nonadherence to asthma treatment are known, adequate monitoring of adherence to treatment is not performed. A multidisciplinary and personalized approach is necessary to control and improve adherence.

Th-2 signature in chronic airway diseases: towards the extinction of asthma-COPD overlap syndrome?

We aimed to describe the differences and similarities between patients with chronic obstructive airway disease classified on the basis of classical diagnostic labels (asthma, chronic obstructive pulmonary disease (COPD), or asthma-COPD overlap (ACOS)) or according to the underlying inflammatory pattern (Th-2 signature, either Th-2-high or Th-2-low).We performed a cross-sectional study of patients aged ≥40 years and with a post-bronchodilator forced expiratory volume in 1 s to forced vital capacity ratio ≤0.7 with a previous diagnosis of asthma (non-smoking asthmatics (NSA)), COPD or ACOS, the latter including both smoking asthmatics (SA) and patients with eosinophilic COPD (COPD-e). Clinical, functional and inflammatory parameters (blood eosinophil count, IgE and exhaled nitric oxide fraction (FeNO)) were compared between groups. Th-2 signature was defined by a blood eosinophil count ≥300 cells·µL-1 and/or a sputum eosinophil count ≥3%.Overall, 292 patients were included in the study: 89 with COPD, 94 NSA and 109 with ACOS (44 SA and 65 with COPD-e). No differences in symptoms or exacerbation rate were found between the three groups. With regards the underlying inflammatory pattern, 94 patients (32.2%) were characterised as Th-2-high and 198 (67.8%) as Th-2-low. The Th-2 signature was found in 49% of NSA, 3.3% of patients with COPD, 30% of SA and 49.3% of patients with COPD-e. This classification yielded significant differences in demographic, functional and inflammatory characteristics.We conclude that a classification based upon the inflammatory profile, irrespective of the taxonomy, provides a more clear distinction of patients with chronic obstructive airway disease.

Consensus on the Asthma-COPD Overlap Syndrome (ACOS) Between the Spanish COPD Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma (GEMA). / Consenso sobre el solapamiento de asma y EPOC (ACO) entre la Guía española de la EPOC (GesEPOC) y la Guía Española para el Manejo del Asma (GEMA).

Following a proposal by the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), sponsor of the Spanish COPD Guidelines (GesEPOC) and the Spanish Guidelines on the Management of Asthma (GEMA), authors of both papers have unified the criteria for the diagnosis of asthma-COPD overlap syndrome (ACOS). This consensus defines ACOS as the presence in a given patient of three elements: significant smoking exposure, chronic airflow limitation and asthma. Diagnosis is confirmed when a patient (35years of age or older), smoker or ex-smoker of more than 10 pack-years, presents airflow limitation (post-bronchodilator FEV1/FVC<0.7) that persists after treatment with bronchodilators and inhaled corticosteroids (even after systemic corticosteroids in selected cases), and an objective current diagnosis of asthma (according to GEMA criteria). In cases in which the diagnosis of asthma cannot be demonstrated, marked positive results on a bronchodilator test (FEV1≥15% and ≥400mL) or elevated blood eosinophil count (≥300eosinophils/µL) will also be diagnostic of ACOS. The opinion of another 33 experts who had not participated in the consensus was sought using a modified Delphi survey. Up to 80% of respondents gave a very positive opinion of the consensus, and declared that it was better than other previous proposals. The GesEPOC-GEMA consensus on ACOS provides a unique perspective of the diagnostic problem, using a simple proposal and a pragmatic diagnostic algorithm that can be applied at any healthcare level.

Differences in Adherence and Non-Adherence Behaviour Patterns to Inhaler Devices Between COPD and Asthma Patients.

Differences between COPD and asthma may also differentially affect adherence to inhaled drugs in each disease. We aimed to determine differences in behaviour patterns of adherence and non-adherence to inhaled therapy between patients with COPD and patients with asthma using the Test of Adherence to Inhalers (TAI) questionnaire. A total of 910 patients (55% with asthma, 45% with COPD) participated in a cross-sectional multicentre study. Data recorded included sociodemographics, education level, asthma or COPD history, TAI score, the Asthma Control Test (ACT), the COPD Assessment Test (CAT) and spirometry. Asthma patients were statistically significant less adherents, 140 (28%) vs. 201 (49%), and the pattern of non-adherence was more frequently erratic (66.8% vs. 47.8%) and deliberate (47.2% vs. 34.1%) than COPD patients; however unwitting non-adherence was more frequently observed in COPD group (31.2% vs. 22.8%). Moreover, taking together all sample studied, only being younger than 50 years of age (OR 1.88 [95% CI: 1.26-2.81]) and active working status (OR 1.45 [95% CI: 1.00-2.09]) were risk factors for non-adherence in the multivariate analysis, while having asthma remained in the limits of the significance (OR 1.44 [95%CI: 0.97-2.14]). Even though non-adherence to inhalers is more frequently observed in asthma than in COPD patients and exhibited a different non-adherence patterns, these differences are more likely to be related to sociodemographic characteristics. However, differences in non-adherence patterns should be considered when designing specific education programmes tailored to each disease.

Validation of the 'Test of the Adherence to Inhalers' (TAI) for Asthma and COPD Patients.

BACKGROUND: To validate the 'Test of Adherence to Inhalers' (TAI), a 12-item questionnaire designed to assess the adherence to inhalers in patients with COPD or asthma. METHODS: A total of 1009 patients with asthma or COPD participated in a cross-sectional multicenter study. Patients with electronic adherence ≥80% were defined as adherents. Construct validity, internal validity, and criterion validity were evaluated. Self-reported adherence was compared with the Morisky-Green questionnaire. RESULTS: Factor analysis study demonstrated two factors, factor 1 was coincident with TAI patient domain (items 1 to 10) and factor 2 with TAI health-care professional domain (items 11 and 12). The Cronbach's alpha was 0.860 and the test-retest reliability 0.883. TAI scores correlated with electronic adherence (ρ=0.293, p=0.01). According to the best cut-off for 10 items (score 50, area under the ROC curve 0.7), 569 (62.5%) patients were classified as non-adherents. The non-adherence behavior pattern was: erratic 527 (57.9%), deliberate 375 (41.2%), and unwitting 242 (26.6%) patients. As compared to Morisky-Green test, TAI showed better psychometric properties. CONCLUSIONS: The TAI is a reliable and homogeneous questionnaire to identify easily non-adherence and to classify from a clinical perspective the barriers related to the use of inhalers in asthma and COPD.

A repeated short educational intervention improves asthma control and quality of life.

We assessed the effectiveness of an asthma educational programme based on a repeated short intervention (AEP-RSI) to improve asthma control (symptom control and future risk) and quality of life. A total of 230 adults with mild-to-moderate persistent uncontrolled asthma participated in a 1-year cluster randomised controlled multicentre study. The AEP-RSI was given in four face-to-face sessions at 3-month intervals, and included administration of a written personalised action plan and training on inhaler technique. Centres were randomised to the AEP-RSI (intervention) group or usual clinical practice group. Specialised centres using a standard educational programme were the gold standard group. A significant improvement in the Asthma Control Test score was observed in all three groups (p<0.001), but improvements were higher in the intervention and gold standard groups than in the usual clinical practice group (p=0.042), which also showed fewer exacerbations (mean±sd; 1.20±2.02 and 0.56±1.5 versus 2.04±2.72, respectively) and greater increases in the Mini Asthma Quality of Life Questionnaire scores (0.95±1.04 and 0.89±0.84 versus 0.52±0.97, respectively). The AEP-RSI was effective in improving asthma symptom control, future risk and quality of life.

What pulmonologists think about the asthma-COPD overlap syndrome.

BACKGROUND: Some patients with COPD may share characteristics of asthma; this is the so-called asthma-COPD overlap syndrome (ACOS). There are no universally accepted criteria for ACOS, and most treatments for asthma and COPD have not been adequately tested in this population. MATERIALS AND METHODS: We performed a survey among pulmonology specialists in asthma and COPD aimed at collecting their opinions about ACOS and their attitudes in regard to some case scenarios of ACOS patients. The participants answered a structured questionnaire and attended a face-to-face meeting with the Metaplan methodology to discuss different aspects of ACOS. RESULTS: A total of 26 pulmonologists with a mean age of 49.7 years participated in the survey (13 specialists in asthma and 13 in COPD). Among these, 84.6% recognized the existence of ACOS and stated that a mean of 12.6% of their patients might have this syndrome. In addition, 80.8% agreed that the diagnostic criteria for ACOS are not yet well defined. The most frequently mentioned characteristics of ACOS were a history of asthma (88.5%), significant smoking exposure (73.1%), and postbronchodilator forced expiratory volume in 1 second/forced vital capacity <0.7 (69.2%). The most accepted diagnostic criteria were eosinophilia in sputum (80.8%), a very positive bronchodilator test (69.2%), and a history of asthma before 40 years of age (65.4%). Up to 96.2% agreed that first-line treatment for ACOS was the combination of a long-acting ß2-agonist and inhaled steroid, with a long-acting antimuscarinic agent (triple therapy) for severe ACOS. CONCLUSION: Most Spanish specialists in asthma and COPD agree that ACOS exists, but the diagnostic criteria are not yet well defined. A previous history of asthma, smoking, and not fully reversible airflow limitation are considered the main characteristics of ACOS, with the most accepted first-line treatment being long-acting ß2-agonist/inhaled corticosteroids.

Knowledge of their own allergic sensitizations in asthmatic patients and its impact on the level of asthma control.

BACKGROUND: Asthma guidelines recommend the adoption of allergen avoidance measures (AAM). To do so, patients need to know their own allergies. However, this degree of knowledge has not yet been assessed. The aims of this study were to determine, in allergic asthma patients: i)the degree of knowledge of their own allergic sensitizations; ii)the percentage of those who knew all their allergies and, in addition, adopted AAM against all of them, and iii)the possible impact of this degree of knowledge on the level of asthma control. PATIENTS AND METHODS: Descriptive, prospective and multicentre study, including 147patients from 9 Respiratory Medicine outpatient clinics. After confirming the previous allergic asthma diagnosis, a questionnaire was completed. It included asthma control and severity levels, results of previous allergy tests, and the description and number of allergic sensitizations known by the patients and AAM followed. RESULTS: Only 72 (49%) patients knew all their allergic sensitizations and only 48 (33%) were also following AAM against all the allergens to which they were allergic. No relationship was established between the degree of knowledge of their own allergies and the level of asthma control (P=.544). CONCLUSIONS: Overall knowledge about the allergic nature of their disease among asthmatic patients attending Spanish Respiratory Medicine Departments is inadequate. Furthermore, a higher degree of knowledge of their allergies does not seem to lead, by itself, to better asthma control. Both findings seem to question the effectiveness of current educational strategies in this field and consequently, they should be revised.

Factors related with the higher percentage of hospitalizations due to asthma amongst women: the FRIAM study.

INTRODUCTION: The reason why there is a higher hospitalization rate due to asthma exacerbations amongst women is unclear. The objective of this study is to explore the possible causes that may explain this fact. METHODS: A multi-center, prospective study including asthma patients hospitalized in the pulmonary medicine departments during a two-year period. By means of a questionnaire, the following data were collected: demographic characteristics and treatment compliance, anxiety-depression, hyperventilation and asthma control, both prior to and during the hospitalization. RESULTS: 183 patients were included, 115 (62.84%) of whom were women. The women were older (52.4 ± 18.3/43.4 ± 18.7; P=.02), were more frequently prescribed inhaled corticosteroids (63.2%/47.1%; P=.03) and had a higher rate of hyperventilation syndrome (57.3/35.9; P=.02) and a longer mean hospital stay (7.3 ± 3.4/5.9 ± 3.6; P=.02). The percentage of smokers among the women was lower (21.2%/38.8%; p=0.01) and the FEV(1) was lower at admittance (58.2% ± 15.9/67.5% ± 17.4; P=.03). In the 40 to 60-year-old age range, an association was demonstrated between being female and the 'previous hospitalizations' variable (OR, 16.1; 95% CI, 1.6-156.7); sex and obesity were also independently associated (OR, 4.8; 95% CI, 1.06-22). CONCLUSIONS: In this cohort, the rate of hospitalization for asthma was higher in women than in men. Being a woman between the ages of 40 and 60 is associated with previous hospitalizations and is a risk factor for asthma-related hospitalization. This situation could partially be explained by the hormonal changes during menopause, where polyposis and obesity are independent risk factors.

Involvement of Spanish pulmonology centers in patient care, postgraduate education and research in asthma: the results of the ATENEA survey.

UNLABELLED: Although asthma is one of the most prevalent chronic respiratory diseases, the participation of Spanish pulmonology units in the management of asthma may have room for improvement. OBJECTIVE: To determine the degree of involvement of the Spanish pulmonology services in the patient care, education and research related with asthma disease and especially in difficult-to-control asthma. METHODS: A survey made up of 75 questions was sent to the heads of several pulmonology departments. The survey asked questions pertaining to respiratory disease care in general, and in asthma in particular, as well as the educational activities and research in asthma during the previous five years. RESULTS: Out of the 107 surveys sent, 69 (645%) centers filled them out and returned them. Forty-seven (681%) met the criteria for an important level of health-care activity in asthma. However, only 29 (42%) had a monographic consultation for difficult-to-control asthma and 37 (536%) used an education program. As for postgraduate education, only 31 (449%) provided their resident physicians with specific asthma training. And in the research field, 12 (174%) reported having projects funded by SEPAR and 25 (362%) had published studies in journals with an impact factor. CONCLUSIONS: Although the majority of the pulmonology centers interviewed report a notable activity in asthma patient care, their involvement in the specialized approach for difficult-to-control asthma is insufficient. Likewise, participation in educational activities and research related with the disease is inconsistent and limited to few centers.