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.

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.

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.

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

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

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.

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.

Cut-off points for defining asthma control in three versions of the Asthma Control Questionnaire.

INTRODUCTION: The Asthma Control Questionnaire™ (ACQ) was developed to assess asthma control. The objective of this study is to determine the cut-off points that best differentiate between several types of asthma control in three versions of the ACQ used in clinical practice. MATERIALS AND METHODS: It appears 607 adult asthmatic patients (61% female) were recruited from 43 outpatient clinics in Spain. Once the patients were stratified by severity of asthma, they were then evaluated in an epidemiological study. To determine the optimum cut-off points, the area under the receiver operating characteristics (ROC) curve, as well as sensitivity, specificity, and positive and negative predictive values (PPV and NPV, respectively), was calculated for each version of the ACQ (ACQ-FEV1 (forced expiratory volume in the first second), ACQ-PEF (peak expiratory flow), and ACQ-wLF (without lung function)). RESULTS: The optimal cut-off for ACQ-FEV1 was 1.14 (the sum of 8 points/7 items), for ACQ-PEF 1.28 (the sum of 9 points/7 items), and for ACQ-wLF 0.83 (the sum of 5 points/6 items), and the percentage of correctly classified patients was 76.5%, 77.3%, and 77.2%, respectively. A comparison of ROCs obtained from the three versions of the ACQ shows that ACQ-wLF had a significantly greater area under the curves (AUC) (p = .004) than ACQ-FEV1. Patients were considered as having some control if their ACQ-FEV1 score fell between 1.14 and 1.57, if ACQ-PEF values were between 1.28 and 1.57, or if ACQ-wLF scores ranged between 0.83 and 1.5. CONCLUSIONS: Our study, which was carried out in a manner which more closely reflects clinical practice, reveals differences in cut-offs used to define well-controlled asthma among three versions of the ACQ.

Validation of the Spanish version of the Asthma Control Questionnaire.

BACKGROUND: The Asthma Control Questionnaire (ACQ) has not been validated in the Spanish population, and the fact that it requires spirometry poses an important limitation on its widespread use in the primary care setting in Spain. OBJECTIVE: The aim of this study was to evaluate the psychometric properties of the Spanish version of the ACQ. METHODS: In this multicenter, prospective study, consecutive adult patients with persistent asthma were recruited at 62 respiratory and allergy units across Spain. Patients were assessed at baseline and at weeks 2 and 6. The following clinical variables were recorded: lung function (forced expiratory volume in 1 second [FEV(1)]), symptoms, exacerbations, concomitant diseases, asthma severity according to the Global Initiative for Asthma international guideline, and asthma control as perceived by patients and physicians through direct ad hoc questions. The latter measures were derived specifically for this study. Patients self-completed the ACQ at all visits before the rest of the study variables were recorded. The ACQ's feasibility, validity, reliability, and sensitivity to change were assessed. Cross-sectional and longitudinal validity was assessed using the relationship between ACQ score and clinical parameters. Sensitivity to change was assessed by estimating the global effect size and the minimal important difference (MID). Reliability was assessed using estimation of the Cronbach alpha coefficient (CCalpha) and intraclass correlation coefficient (ICC). RESULTS: A total of 607 patients were included. The mean (SD) age was 45.6 (17.1) years and 61.4% of the patients were women. Of these 607, 235 (39%) had mild asthma; 246 (41%), moderate; and 126 (21%), severe. Mean (SD) time to complete the ACQ was 3.9 (4.4) minutes. The Pearson correlation coefficient in the relationship between ACQ and FEV(1) (% predicted value) was -0.23. ACQ was found to be significantly related to asthma severity and intensity and frequency of symptoms (coughing, wheezing, and dyspnea) (both, P < 0.001). Change in ACQ was significantly related to changes in FEV(1), intensity and frequency of symptoms, and number of exacerbations (all, P < 0.001). The global effect size of ACQ was 0.46 and the MID was 0.47 point of a maximum of 6. CCalpha was 0.90 and ICC was 0.86. CONCLUSION: In these adults with asthma in Spain, the Spanish version of the ACQ was found to be a reliable and valid questionnaire, suggesting that it can be used in this population as a discriminative and evaluative instrument.

[Knowledge of and attitudes and adherence to the Spanish Guidelines for Asthma Management (GEMA) among Spanish health care professionals: the GEMA test Project]. / Opinión, conocimientos y grado de seguimiento referidos por los profesionales sanitarios españoles de la Guía Española para el Manejo del Asma (GEMA). Proyecto GEMA-TEST.

OBJECTIVE: Health care professionals' adherence to asthma guidelines is believed to be low. The aim of the present study was to determine the knowledge, attitudes, and adherence of Spanish health care professionals with respect to the Spanish Guidelines for Asthma Management (GEMA). MATERIAL AND METHODS: A multiple choice test with 15 questions was constructed. Items assessed knowledge of and opinions and adherence to asthma guidelines in general and the GEMA in particular. Test completion was voluntary, individual, and anonymous. RESULTS: A total of 1,066 physicians and nurses took the test. The sample consisted of 241 (22.6%) respiratory medicine specialists and 244 (22.9%) nurses from the Spanish Society of Pulmonology and Thoracic Surgery (SEPAR), 221 (20.7%) pediatric pulmonologists from the Spanish Society of Pediatric Pulmonology (SENP), 220 (20.6%) general practitioners from the Spanish Society of Family and Community Medicine (semFYC), 181 (17%) general practitioners from the Spanish Society of Rural and General Medicine (SEMERGEN), and 38 (3.6%) others. Asthma guidelines were considered useful or very useful by 805 (76%), and 771 (72%) stated they were familiar with the GEMA. However, 388 (36%) admitted that they followed guidelines seldom or never. The level of adherence to the GEMA was poor for 243 (30.3%) respondents. The multivariate analysis revealed that low adherence was associated with the following characteristics: coming from the geographic center or south of Spain; being a primary care physician, unfamiliar with guidelines, or unconvinced of their utility; and not being a user of spirometry. CONCLUSIONS: Even though the majority of Spanish health care professionals surveyed seem to know of the GEMA, their adherence to those guidelines is very low. Educational programs that seek to improve knowledge of asthma guidelines should consider the profile of professionals with low adherence to the GEMA so as to include educational strategies that target them specifically.

[Assessment of the simplified versions of the Asthma Control Questionnaire]. / Evaluación de las versiones simplificadas del Cuestionario de Control del Asma.

BACKGROUND AND OBJECTIVE: The aim of this study was to assess the measurement properties of the Spanish version of Asthma Control Questionnaire (ACQ) when FEV1 item in the original version (ACQ-FEV1) is substituted by peak expiratory flow rate (ACQ-PEF) and when the lung function item is omitted (ACQ-wLF). MATERIAL AND METHOD: and 607 patients were enrolled in this study. Three study visits were carried out: at baseline, 2, and 6 weeks later. Validity, reliability and sensitivity to change of both ACQ versions were calculated. RESULTS: ACQ-PEF and ACQ-wLF had a correlation coefficient of 0.38 and 0.39 with no exacerbations. Both symptoms improvement and a better perception of asthma control, both by physicians and patients, were significantly related ro better scores in both versions (P <0.01). Cronbach a of ACQ-PEF and ACQ-wLF were 0.83 and 0.87, respectively. Intraclass correlation coefficients of both ACQ-PEF and ACQ-wLF were 0.9 and 0.87. Mean scores of all ACQ versions (ACQ-FEV1, ACQ-PEF and ACQ-wLF) were 1.31 (1), 1.34 (1) and 1.14 (1.1), respectively, being all differences statistically significant P < or = 0.003). CONCLUSIONS: Replacement of FEV1 by PEF, or its elimination, does not alter the measurement properties of the ACQ questionnaire. Use of ACQ simplified versions is recommended only for investigational purposes, without combining in the same analysis scores obtained with different versions of the questionnaire.

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.

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.

[Is the incidence of near-fatal asthma decreasing in Spain?]. / Disminuye la incidencia de asma de riesgo vital en España?

OBJECTIVE: A number of studies have shown that both mortality and hospital admissions due to severe asthma have decreased in recent years in many parts of the world. However, the situation is Spain has not yet been analyzed. The aim of this study was to determine the incidence of very severe, near-fatal asthma in recent years in various Spanish hospitals. PATIENTS AND METHODS: A retrospective review of hospital records from 6 hospitals in 5 Spanish autonomous communities was conducted for the period 1997 to 2004 to determine the annual number of patients who required orotracheal intubation and mechanical ventilation due to an asthma attack. RESULTS: Of the 130 patients included in the study, 81 (62%) were women and 61 (47%) were aged between 51 and 75 years. The number of cases observed for the periods 2001-2002 and 2003-2004 (32 and 18, respectively) was significantly lower than that observed for the 1997-1998 and 1999-2000 periods (40 in both cases; P=.019). A significant increase in the incidence was observed in autumn and winter (n=81 [62%]; P=.018). Seventeen patients (13%) died and 8 (6%) developed serious sequelae. CONCLUSIONS: Although our sample of 6 hospitals is not widely representative of the entire population of hospitals in Spain, our findings strongly suggest a decrease in the incidence of near-fatal asthma in Spain in recent years.

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.

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.