GINA Step Research Articles

Clinical Features and Outcomes Associated with Bronchial Asthma Among COVID-19 Hospitalized Patients.

BackgroundThe impact of diagnosis treatment and bronchial asthma on coronavirus disease 2019 (COVID-19) associated outcomes remains unclear.ObjectiveTo identify the prevalence and outcomes associated with asthma among hospitalized patients with COVID-19.MethodsElectronic health records of 130 patients with asthma among hospitalized patients with COVID-19 were reviewed. Two subgroups of asthmatic patients were compared according to clinical outcomes during hospitalization. Patients with death results, intubation, and/or need of intensive care unit (ICU) stay were grouped as asthmatic patients with severe COVID-19 outcomes, and the rest were grouped as asthmatic patients with non-severe COVID-19 outcomes. Multivariable analyses were conducted with logistic regression to identify independent risk factors for severe outcomes.ResultsThe prevalence of asthma in COVID-19 hospitalized patients was 5%. The mean age was 59.4 years and 54% were women. 17% received treatment in GINA step 4–5 asthma at the time of admission. An allergic asthma phenotype was determined in 38%. There was no significant difference in hospital length of stay or need for intubation between asthmatic patients and global COVID-19 admitted patients. 17% of asthmatic patients developed a severe outcome, and 5% had a death result. Elevated Lactate Dehydrogenase (LDH) level, low transcutaneous pulse oximetry (SpO2), the coexistence of atrial fibrillation (AF), and need for moderate or high ICS at admission were independent risk factors for a worse outcome in asthmatics COVID-19 hospitalized patients.ConclusionThe prevalence of asthma in COVID-19 hospitalized patients was 5%, consistent with the asthma prevalence in the general population. The asthmatic patients with the previous prescription of moderate or high doses of ICS and/or coexistence of atrial fibrillation at admission had a higher risk of the severe outcome.

Clinical Characteristics of Irritant-Induced Occupational Asthma

Work is a substantial contributing factor of adult-onset asthma. A subtype of occupational asthma (OA) is caused by irritant agents, but knowledge of the clinical outcomes of irritant-induced asthma (IIA) is incomplete. To evaluate whether the clinical picture of IIA differs from that of sensitizer-induced OA. This retrospective study analyzed acute and subacute IIA patients diagnosed in an occupational medicine clinic during 2004 to 2018. Sixty-nine patients fulfilled the inclusion criteria, and their characteristics were analyzed at the time of the diagnosis and 6 months later. The results were compared with those of 2 subgroups of sensitizer-induced OA: 69 high-molecular-weight (HMW) and 89 low-molecular-weight (LMW) agent-induced OA patients. Six months after the diagnosis, 30% of the patients with IIA needed daily short-acting β-agonists (SABA), 68% were treated with Global Initiative for Asthma, 2020 report (GINA) step 4-5 medication, and 24% of the patients had asthma exacerbation after the first appointment. IIA depicted inferiority to LMW-induced OA in daily need for SABA (odds ratio [OR]: 3.80, 95% confidence interval [CI]: 1.38-10.46), treatment with GINA step 4-5 medication (OR: 2.22, 95% CI: 1.08-4.57), and exacerbation (OR: 3.85, 95% CI: 1.35-11.04). IIA showed poorer results than HMW-induced OA in the latter 2 of these features (OR: 2.49, 95% CI: 1.07-5.79 and OR: 6.29, 95% CI: 1.53-25.83, respectively). Six months after the OA diagnosis, a significant proportion of the patients with IIA remain symptomatic and the majority of these patients use asthma medications extensively suggesting uncontrolled asthma. The short-term outcomes of IIA appear poorer than that of sensitizer-induced OA.

The role of interleukin-33 in the pathogenesis, and treatment of severe asthma

Interleukin-33 (IL-33) belongs to the IL-1 family of cytokines, which has 11 members, including IL-1α, IL-1β, IL-1Ra, IL-18, IL-36α, IL-36β, and IL-37. Unlike its family members, IL-33 mediates T helper type-2 (Th2) immune responses, and promotes eosinophilic inflammation, similar to the other epithelial-derived cytokines, such as IL-25, and thymic stromal lymphopoietin (TSLP). Epithelial injury due to viral, and bacterial infections, allergens, chemical irritants, and trauma lead to secretion of alarmin cytokines, including IL-25, IL-33, and TSLP. IL-33 plays an important role in activating Th2 lymphocytes, group 2 innate lymphoid cells, dendritic cells, mast cells, basophils, and eosinophils, which result in secretion of cytokines, such as IL-4, IL-13, and IL-5; chemokines, including CCL2, and CXCL8, and adhesion molecules. The inflammatory mediators promote eosinophilic airway inflammation, airway hyperresponsiveness, and remodeling. IL-33 signaling is via a complex heterodimeric receptor comprising of IL-1 receptor-like 1 (IL-1RL1), and IL-1 receptor accessory protein. Downstream signaling cascade leads to the transcription of multiple cytokines and chemokines, which orchestrate eosinophilic asthma. Treatment of severe eosinophilic asthma include long-acting beta2-agonists, and inhaled corticosteroids, and addition of biologics at GINA step 4/5, such as omalizumab, mepolizumab, dupilumab, and tezepelumab. Currently, there are no anti-IL-33 biologics which have been approved for the treatment of eosinophilic asthma. Etokimab is a first-in-class IgG1 monoclonal antibody which blocks the activity of IL-33, thereby, inhibiting its biological effects. Phase 2a proof-of-concept clinical trial in 25 patient with severe eosinophilic asthma, showed that a single intravenous dose of etokimab (330 mg) resulted in a rapid and sustained improvement in lung function, and reduction in the asthma control questionnaire-5 scores throughout the study period of 64 days. Recently, itepekimab has been shown to improve asthma control, lung function, and quality of life, although the effects of itepekimab were slightly lesser than those observed for dupilumab. The dual therapy of itepekimab plus dupilumab did not achieve optimal outcomes, moreover, treatment with the doublet resulted in minimal change in pre-bronchodilator FEV1 compared with placebo. Dual blockade of interleukins incriminated in the pathogenesis of eosinophilic asthma need further careful studies, because of the immunological consequences in the era of SARS-CoV-2.

Omalizumab and modification of bronchial asthma natural course

Clinical and molecular heterogeneity of bronchial asthma has been documented in recent years. The search for novel solutions to enhance efficient patient support related first of all to understanding of asthma heterogenic nature and allows to personalize each patient treatment. Biological therapy application can influence to achieve better control at greater extent for patients with severe uncontrolled asthma. Nowadays 5 biological drugs are registered on Russian Federation territory and implemented according to severe asthma phenotypes: anti-IgE, anti-IL-4,13 and anti-IL-5 class therapies. Omalizumab become the first target drug for uncontrolled allergic asthma patients (monoclonal antibody against IgE). This medication is prescribed for uncontrolled moderate and severe allergic (atopic) asthma in patients on basic asthma therapy according GINA step 4 and 5 (Level of evidence A). Clinical trials confidently reported that anti- IgE-therapy reduces the rate of asthma exacerbations, severity of disease in patients with chronic severe asthma on high doses of inhaled steroids or systemic steroids and allows to reduce or withdraw systemic steroids doses in case of steroid-dependent asthma. For the last years special attention led to and demonstrated omalizumab positive effect on airways remodeling and modification of bronchial asthma natural course in adults and children. Antiinflammatory effect of omalizumab is documented. Omalizumab significantly reduces eosinophilic infiltration of submucosal bronchi layer among patients with atopic asthma, sputum eosinophilia, which correlates with reduction of FeNO during biologic treatment, reduces mast cells infiltration of smooth muscle cells in bronchi. Omalizumab significantly reduces the thickness of the bronchial wall, increases the lumen of the bronchi (positive dynamics of CT-scan parameters), which is clinically manifested by increased of FEV1.

The role of fixed dose combinations of inhaled cortikosteroids, long acting beta-2 agonists, and long acting muscarinic antagonists (ICS/LABA/LAMA) in the treatment of asthma

The effective treatment of asthma is important in terms of improving the quality of life and decreasing the number of hospital admissions due to acute exacerbations. Parasymphatic activity is increased in patients with asthma. This is one of most important part of airway obstruction which has a great potential for reversibility. The evidence about the synergic interaction between inhaled corticosteroids (ICS), long acting beta-2 agonists (LABA), and long acting muscarinic antagonists (LAMA) encourages the use of LAMA in asthma. Tiotropium treatment was found to be successful in patients with recurrent exacerbations in whom asthma was uncontrolled despite treatment with other add on treatments that were recommended at GINA step 4. These findings triggered several clinical studies on fixed dose ICS/LABA/LAMA for asthma treatment. Three studies that have been published recently showed that fixed dose ICS/LABA/LAMA improved the lung functions and decreased the exacerbation rate without increasing the dose of ICS or LABA in asthma. In this review, the mechanisms of action of LAMA in asthma were summarized and possible role of fixed dose ICS/LABA/ LAMA in asthma treatment was discussed under the light of current literature.

Overuse of Oral Corticosteroids, Underuse of Inhaled Corticosteroids, and Implications for Biologic Therapy in Asthma

Background: Asthma patients using high cumulative doses of oral corticosteroids (OCSs) are at risk of serious adverse events and are increasingly being treated with steroid-sparing asthma biologics. However, it is unknown whether prescribing these expensive biologics is always justified. Objectives: This study aimed to (1) assess the prevalence of asthma patients using high cumulative doses of OCSs, (2) explore the role of suboptimal inhaler therapy, and (3) estimate the proportion of patients to whom asthma biologics might be prescribed unnecessarily. Methods: All adults (n = 5,002) with at least 1 prescription of high-dose inhaled corticosteroids (≥500–1,000 mcg/day fluticasone-equivalent) and/or OCSs (GINA step 4–5) in 2010 were selected from a pharmacy database including 500,500 Dutch inhabitants, and sent questionnaires. Of 2,312 patients who returned questionnaires, 929 had asthma. We calculated the annual cumulative OCS dose and prescription fillings and checked inhaler technique in a sample of 60 patients. Patients estimated to have good adherence and inhaler proficiency who still required high doses of OCSs (≥420 mg/year) were considered candidates for initiating biologic treatment. Results: 29.5% of asthma patients on GINA 4–5 therapy used high doses of OCSs, of which 78.1% were likely to have poor therapy adherence or inadequate inhaler technique. Only 21.9% were considered definitive candidates for biologic therapy. Conclusion: High OCS use in Dutch GINA 4–5 asthma patients was common. However, in 4 out of 5 patients adherence to inhaled corticosteroid therapy and/or inhalation technique was considered suboptimal. Since optimizing inhaler therapy may reduce the need for OCSs, this should be mandatory before prescribing expensive steroid-sparing drugs.

Severe asthma in Kuwait population: Phenotype-based approach

BackgroundThere is increasing recognition of marked phenotypic heterogeneity within severe asthma patients. MethodsSevere asthma patients on GINA step 4 or 5 treatment, followed up at Al-Rashed Allergy center Kuwait, were evaluated for: demographics (gender, age, age of asthma onset), comorbidities (allergic rhinitis (AR), chronic rhinosinusitis (CRS), chronic rhinosinusitis with nasal polyposis (CRSwNP), obesity), blood biomarkers (total serum Immunoglobulin E (IgE), peripheral eosinophils), and sensitization to inhalants allergens. ResultsA total of 169 patients were candidates for biological treatment. Patients were divided in two groups based on level of total IgE as a “low” group with IgE<160 IU/ml (n = 55) and “high” group with IgE≥ 160 IU/ml (n = 114). Both groups were further divided in subgroups, “low” and “high”, based on absolute number of eosinophils (Eos) in peripheral blood with <300 cells/μl or ≥ 300 cells/μl. Only 10% of patients were in low IgE/low Eos while majority (46%) were in the high IgE/high Eos group. Mean age of patients was 44.1 year with domination of females (n = 123). Majority of patients were obese. AR, CRS and CRSwNP were more common in group with IgE ≥160 IU/ml, while CRS and CRSwNP in group with Eos ≥300 cells/μl. ConclusionThe majority of severe asthma patients in Kuwait are obese females with adult-onset asthma (>18 years of age) who were allergic with comorbid conditions including AR, CRS and CRSwNP, which correlates well with the level of Eos.

Characteristics of Reliever Inhaler Users and Asthma Control: A Cross-Sectional Multicenter Study in Portuguese Community Pharmacies.

PurposeSABA overuse might indicate poorly managed or uncontrolled asthma and be responsible for poor health outcomes. The aim of this study integrated in new fourth multi-design SABINA+ pillar was to characterize the population using short-acting β2-agonists for asthma and examine the patterns of its use among community pharmacy customers in Portugal, as well as identify characteristics associated with disease control and explore potential differences between GINA treatment steps.Patients and MethodsThis cross-sectional multicenter study was conducted in Portuguese community pharmacies between 29 May 2018 and 15 August 2018. Participants were adults (age ≥18 years) self-reporting asthma diagnosis recruited in the context of a short-acting β2-agonist dispense. A two-part questionnaire (pharmacist interview and self-administered) was used to collect information about sociodemographic characteristics, comorbidities, reliever inhaler use, healthcare resource consumption and self-reported disease control (assessed by the Control of Allergic Rhinitis and Asthma Test – CARAT®). Descriptive statistics was done to characterize the study sample. After categorizing patients according to GINA steps, based on their therapeutic regimen, we performed an exploratory subgroup analysis to evaluate if there were any differences between such groups in terms of the variables collected. A logistic regression was used to identify the potential determinants of overall disease control.ResultsAround 50.8% of patients were male, and the average age was 52 years old. Half of the patients never smoked, and 51.9% were employed. More than half of the patients report inhaler overreliance – purchasing more than 1 pack in 3 months (65.0%) or using the inhaler on more than 8 days over the previous 4 weeks (50.2%). Of the total number of patients in the study, 79.1% had poorly controlled asthma symptoms, and 78.7% had overall poorly controlled respiratory symptoms. We found statistically significant differences between GINA treatment steps in all sociodemographic characteristics (sex, mean age, education level, employment status); maximum number of SABA uses in 24h, CARAT score (total an asthma sub-score); history of exacerbations requiring ED visits or treatment with OCS for at least 3 days in the previous 12 months. Logistic regression revealed that patients reporting SABA use in more than 8 days in the previous 4 weeks and patients with at least 1 exacerbation requiring treatment with OCS for at least 3 days in the previous 12 months have greater odds of poor disease control [adjusted OR (95% CI): 2.6 (1.3–5.2) and 3.0 (1.3–6.6)].ConclusionBased on the results of this study, it can be inferred that the asthma population using SABA is largely uncontrolled and uses reliever inhalers excessively.

Characterization of uncontrolled, severe asthma patients with type 2 inflammation (T2): results from a physician survey across countries from Latin American, Eurasian Middle East regions and China

ABSTRACT Objective The 2019 GINA guidance incorporates the presence of T2 inflammation in severe asthma patients to determine eligibility for add-on biologic therapy, though little data exists to characterize this population. The objective of this manuscript is to conduct a descriptive analysis to characterize patients with severe asthma in emerging countries based on disease severity, patient exacerbation history, and T2 phenotype. Methods A cross-sectional survey of physicians treating asthma patients ages 12 years and older was conducted in eight countries. Physicians characterized their severe asthma patients and reported data from their patients’ medical charts. Medical chart data was selected from the physicians’ six most recent asthma patients taking prescription medication. Results A total of 550 physicians completed the survey and filled out 3,300 patient record forms. A total of 876 patients have been characterized with uncontrolled severe asthma. Of the 420 patients with available EOS lab data, 40% are indicated with T2 inflammation (EOS ≥150/µL). Ninety-one percent of all patients with available IgE lab data (n = 498) had IgE 30 − 1500 IU/mL indicating allergy-driven asthma. Finally, chronic OCS use (as reported by physicians) was reported in 11% of patients. Conclusion This research revealed that 65% of patients had at least one of three T2 inflammation comorbidities assessed: allergic rhinitis, chronic rhinosinusitis with nasal polyps, and atopic dermatitis. Discrepancies were observed between patients’ treatment regimens and GINA step reported, suggesting there may be room to improve understanding of asthma severity as defined per GINA guidelines as well as asthma control assessment in clinical practice.

Asthma in a large COVID-19 cohort: Prevalence, features, and determinants of COVID-19 disease severity

BackgroundAsthma prevalence among COVID-19 patients seems to be surprisingly low. However the clinical profile of COVID-19 asthmatic patients and potential determinants of higher susceptibility/worse outcome have been scarcely investigated. We aimed to describe the prevalence and features of asthmatic patients hospitalized for COVID-19 and to explore the association between their clinical asthma profile and COVID-19 severity. MethodsMedical records of patients admitted to COVID-Units of six Italian cities major hospitals were reviewed. Demographic and clinical data were analyzed and compared according to the COVID-19 outcome (death/need for ventilation vs discharge at home without requiring invasive procedures). ResultsWithin the COVID-Units population (n = 2000) asthma prevalence was 2.1%. Among the asthmatics the mean age was 61.1 years and 60% were females. Around half of patients were atopic, blood eosinophilia was normal in most of patients. An asthma exacerbation in the 6 months before the Covid-Unit admittance was reported by 18% of patients. 24% suffered from GINA step 4–5 asthma, and 5% were under biologic treatment. 31% of patients were not on regular treatment and a negligible use of oral steroid was recorded. Within the worse outcome group, a prevalence of males was detected (64 vs 29%, p = 0.026); they suffered from more severe asthma (43 vs 14%, p = 0.040) and were more frequently current or former smokers (62 vs 25%, p = 0.038). ConclusionsOur report, the first including a large COVID-19 hospitalized Italian population, confirms the low prevalence of asthma. On the other side patients with GINA 4/5 asthma, and those not adequately treated, should be considered at higher risk.

Clinical characteristics of patients with not well-controlled severe asthma in Japan: Analysis of the Keio Severe Asthma Research Program in Japanese population (KEIO-SARP) registry

BackgroundMultiple phenotypes exist within the classification of severe asthma. However, characteristics of patients with not well-controlled severe asthma have not been well identified. MethodsJapanese patients with asthma (age ≥ 20 years) were enrolled at the Keio University Hospital and its affiliated hospitals in this observational study (Keio Severe Asthma Research Program). Among them, patients with severe asthma (those undergoing Global Initiative for Asthma [GINA] 2018 step 4 or 5 treatment) were included in this analysis and investigated clinical characteristics based on asthma control status. ResultsOf the 154 patients (men, 46.8%; age, 60.1 ± 14.9 years), 87 (56.5%) had not well-controlled (partly controlled and uncontrolled) asthma (GINA step 4, 42 patients; step 5, 45 patients). Overall, there were no significant differences in clinical characteristics between patients with well-controlled and not well-controlled asthma. However, cluster analysis revealed that distinct 5 clusters (cluster 1, well-controlled; cluster 2, eosinophilic; cluster 3, non–type 2 inflammation; cluster 4, high periostin; and cluster 5, late-onset type 2 inflammation), and clusters 2–5 were not well-controlled. Among them, cluster 3 was characterized by low eosinophil counts, low periostin levels, and less frequent olfactory disturbance, and this cluster had the worst asthma control. ConclusionsJapanese patients with severe asthma were divided into well-controlled and not-well controlled asthma, and we confirmed heterogeneity of not well-controlled severe asthma. These patients, especially non-type 2 phenotype, require a further therapeutic approach. (University Hospital Medical Information Network Clinical Trials Registry, UMIN000002980)

Lung clearance index and steroid response in pediatric severe asthma.

Lung clearance index (LCI) is a measure of airway disease that has been shown to be abnormal in asthma. We hypothesized that LCI would be higher (worse) in children with severe therapy-resistant asthma (STRA) compared with difficult asthma (DA) and healthy controls and that LCI would fall in response to parenteral steroids in STRA. Sixty-four children with asthma who were prescribed high-dose asthma therapy (GINA steps 4 or 5) performed LCI and spirometry. Forty-three had STRA and 21 DA. Thirty-nine of forty-three STRA patients attended for a clinically indicated bronchoscopy during which an intramuscular injection of triamcinolone was given. LCI, spirometry, and fractional exhaled nitric oxide (FeNO) were performed on the day of the bronchoscopy and repeated 4 weeks later. LCI was more abnormal in STRA (median: 7.40, range: 5.58-12.34) than in DA (6.55, 5.77-7.75), P = .0006, and healthy controls (6.53, 5.57-7.35), P = .005. In contrast to the first second forced expired volume (FEV1 ), LCI improved following systemic steroids; of 20 STRA patients with an abnormal LCI at baseline, 13 improved following triamcinolone. LCI and FeNO responses were concordant. There is a subgroup of children with STRA in whom LCI is elevated who improve following parenteral steroids. LCI may be a valuable additional domain in assessing steroid response in pediatric asthma.

Treatment response according to small airways disease status: The effects of high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate in fixed dose combination in moderate uncontrolled asthmatic patients

BackgroundInflammation in small airways is particularly clinically active in severe asthma but they still continue to be ignored as considered silent. Recently, the Atlantis study reports small airways involvement in 91% of the asthma population. Therefore in the era of phenotype driven therapy, the aim of this study was to verify if high-strength extrafine ICS/LABA in fixed dose increases clinical efficacy in moderate asthmatic patients with small airways dysfunction and it could be proposed as phenotype driven therapy. MethodsIn this prospective, non-interventional, real-life pilot study we enrolled 37 consecutive patients with moderate asthma who were uncontrolled despite GINA step 3 treatment. All subjects at enrollment were divided in two groups according to the presence of small airways dysfunction:1) small airways phenotype (SAP) group: smokers (≥10 packs/die), ex-smokers (>20 packs/year) with air trapping (FVC <80% - VR >100% - FEF 25–75%<60%); 2) non-small airways phenotype (NSAP) group: non-smokers, without air trapping (FVC ≥80% - VR ≤ 100% - FEF 25–75%≥60%). We later proceeded in both groups with a step up in therapy with high-strength extrafine pMDI beclomethasone dipropionate/formoterol fumarate (BDP/FF) (200/6 μg) in fixed dose to achieve a better control and followed patients for 6 months. ResultsTreatment with extrafine BDP/FF(200/6 μg) in SAP group showed a more significant improvement of FEF25-75%, FVC, RV, and a reduction of alveolar inflammatory markers such as FENO350 and alveolar exhaled pH compared with NSAP patients. ConclusionsOur preliminary results support the use of high-strength extrafine pMDI BDP/FF (200/6 μg) as phenotype driven treatment directed to small airways dysfunction demonstrating an increase of clinical efficacy in moderate asthmatics with SAP.

Efficacy of immunoglobulin replacement therapy and azithromycin in severe asthma with antibody deficiency

BackgroundAlthough antibody deficiency (AD) is a well-known cause of recurrent respiratory infections, there are few data on its impact in adults with asthma. The objective of the present study was to assess outcomes in adults with severe asthma and AD after treatment with either azithromycin or subcutaneous immunoglobulins (SCIg). MethodsWe performed a 5-year, prospective, observational, two-centre study of adults with severe asthma and AD in France. Bronchiectasis was ruled out by high-resolution computed tomography. Patients were treated for one year with either azithromycin (250 mg every other day) or SCIg (0.4–0.6 g/kg/months, weekly). All patients were evaluated for exacerbations, asthma control and lung function at baseline and then one year after treatment initiation. ResultsThirty-nine patients with severe asthma were included in the study: 14 had been treated with azithromycin and 25 had been treated with SCIg. Before the initiation of treatment for AD, all patients had an Asthma Control Questionnaire (ACQ-7) score > 1.5 (mean ± SD: 2.71 ± 0.53) despite treatment at GINA step 4 or 5, and had a high exacerbation rate requiring oral corticosteroids and/or rescue antibiotics (∼7.2 ± 2.1/patient/year). One year after treatment initiation, we observed a significantly higher FEV1 (mean: 0.18 ± 0.22 L) and ACQ-7 score (1.26 ± 0.68), and a significantly lower exacerbation rate (1.63 ± 1.24/patient/year). ConclusionsTreatment of AD dramatically improved asthma outcomes - suggesting that adults with severe asthma and recurrent respiratory infections should be screened and (if appropriate) treated for AD.

As-needed ICS-LABA in Mild Asthma: What Does the Evidence Say?

For the last three decades, the guidelines for asthma management have supported a stepwise therapeutic approach, based on the administration of controller medications (especially inhaled corticosteroids) complemented by on-demand use of rescue medication. Classically, the rescue medication recommended comprised short-acting β agonists (SABA). Some years ago, the use of Symbicort Maintenance and Reliever Therapy (SMART) demonstrated the benefits of a combination of budesonide-formoterol, an inhaled corticosteroid, and a long-acting β agonist (ICS-LABA) as rescue medication in moderate and severe asthma. The results were enthusiastically received, and this therapeutic option was adopted in the guidelines for moderate to severe asthma patients. Recently, four trials (two randomised placebo control trials under the auspices of the SYGMA project and two real-life studies, Novel START, and the PRACTICAL trial) have explored the potential benefits of substituting SABA with budesonide-formoterol as rescue medication in mild asthma patients. The SYGMA 1 and 2 studies showed that the combination with formoterol-budesonide as rescue medication provides better asthma control than short-acting β-agonists alone in GINA step 2 patients, although the superiority was slight. Compared to budesonide maintenance therapy, the fixed combination of ICS-LABA on demand provides poorer asthma control. Regarding exacerbations, the fixed dose ICS-LABA combination on demand showed the same benefits for the prevention of exacerbations as chronic ICS treatment in mild asthma patients. The Novel START study, which assessed a population with milder symptoms, concluded that the fixed dose ICS-LABA combination used as needed was superior to SABA (albuterol) as needed for the prevention of asthma exacerbations. These results in fact show that, in undertreated GINA step 2 with only SABA as needed, ICS-LABA is more effective than SABA. The authors of PRACTICAL concluded that the study provided modest evidence that the ICS-LABA combination used as-needed for symptom relief reduces the rate of severe exacerbations compared with maintenance low-dose budesonide plus terbutaline as needed, although the study was not limited to mild asthma since according to the treatment consumed, it was evident that they had recruited some moderate asthma patients. Despite this poor evidence, and ignoring the clinical histological benefits of chronic inhaled corticosteroids (especially when administered promptly), GINA 2019 recently recommended daily low dose ICS or ICS-LABA as needed as a first option for step 2 patients. For step 1, symptom-driven or as-needed treatment with ICS-LABA is recommended rather than SABA alone (the preferred option until the last GINA update). Finally, the SIENA study showed that 73% of patients with mild asthma do not have an eosinophilic phenotype and that these patients have a similar clinical response to ICS (mometasone) and antimuscarinic drugs (tiotropium), results that challenge the indication of a drug combination that incorporates ICS as a first option. Overall, we believe there is insufficient evidence for the systematic recommendation of as-needed ICS-LABA instead of SABA on request for GINA step 1 or as a replacement for chronic ICS in GINA step 2.

Asthma severity in four countries of Latin America

BackgroundIn Latin America, there is scarce information about severe asthma (SA) according to the ERS/ATS 2014 criteria. This study aimed to compare the demographic, socio, clinical characteristics, treatment, and use of healthcare resources between SA and non-severe asthma (NSA) patients in Argentina, Colombia, Chile and Mexico.MethodsA cross-sectional study was conducted including 594 asthma patients from outpatient specialized sites. A descriptive analysis was performed comparing SA patients and NSA. Chi-square and Mann Whitney tests were used to assess associations between asthma severity and outcome variables.ResultsUsing ERS/ATS 2014 criteria, 31.0% of the patients were identified as SA. SA patients were older at diagnosis (mean age 31.64 years vs 24.71 years, p < 0.001) and had higher proportion of uncontrolled asthma than the NSA patients (64.1% vs 53.2%, p < 0.001). SA patients reported a significantly higher proportion of both hospital admission and emergency room (ER) visits due to asthma in the last year, compared with NSA patients, 8.7% vs. 3.7% (p = 0.011) and 37.0% vs. 21.7% (p < 0.001), respectively.ConclusionsSA patients were older, had greater proportions in some comorbidities and experienced increased healthcare utilization. Also, our results showed that even in patients using the last steps of treatment (GINA step 4 or 5), there was still a higher proportion of uncontrolled disease.

Effects of a structured educational intervention in moderate-to-severe elderly asthmatic subjects

BackgroundAdherence to inhaled drugs is linked to patients’ satisfaction with their device, and an incorrect use can negatively affect the outcomes of asthma treatment. We speculated that this is particularly true in elderly asthmatic subjects. AimWe performed a national pre-post interventional multicentre study, enrolling moderate-to-severe asthmatic subjects aged ≥65 ​years treated with fixed inhaled combination drugs by dry powder inhaler (DPI) or pressurized metered dose inhaler (pMDI). Adherence and critical errors were evaluated by means of validated questionnaires at first visit (V1) and after 3–6 months (V2). At V1, subjects underwent intensive training on the correct use of their device by physical demonstration. ResultsA total of 411 asthmatics (F/M: 238/173, mean age±SD: 72 ​± ​5 ​years) participated to the study. At V1, 50% of the study subjects showed an Asthma Control Test (ACT) score ≤19 despite GINA step 3 and 4 treatment, and 40% had experienced at least one severe asthma exacerbation in the previous year. Poor adherence to treatment was recorded in 43% of subjects, and at least one error in using the device was registered in 56% of subjects. At V2, available for 318 patients, both the percentage of individuals with poor adherence and with at least one critical error significantly decreased (from 46% to 25%, and from 49% to 25%, respectively; p ​< ​0.001 for both comparisons) with a significant increase of the ACT score (from 19 ​± ​4.9 to 20 ​± ​4.0, p ​< ​0.001). ConclusionsAsthma in the elderly is characterized by low levels of symptom control. Educational interventions are strongly advocated in this age group in order to increase adherence to treatment and inhaler techniques.

Les patients de la cohorte IDEAL : une photographie de l’asthme sévère en France

This paper reports the French data from a post-hoc analysis of the international IDEAL study, which aimed to describe a recent cohort of patients with severe asthma, the impact of the disease on quality of life, as well as the population of patients eligible for treatment with omalizumab, mepolizumab and reslizumab. Eligible patients were≥12 years of age, with severe asthma (GINA steps 4 and 5). A total of 129 patients were included in this post-hoc analysis. Their mean age was 53 years, the majority were overweight, they were mainly women (64%) and had at least one medical comorbidity (85%). More than half had suffered from asthma for more than 25 years and were non-smokers. Lung function was moderately impaired. Blood eosinophil count was≥150 cells/μL in 66% of patients,≥300 cells/μL in 34% of patients, and≥500 cells/μL in 12% of patients. One out of three patients was currently treated with omalizumab and 24% had maintenance oral corticosteroids. Asthma was poorly controlled with a negative impact on quality of life (ACQ≥1.5) in 67% of patients. In this population 40% of patients were eligible for omalizumab, 27% for mepolizumab and 2% for reslizumab. These findings show that a considerable proportion of patients with severe asthma remain uncontrolled and are not eligible for any of the available biological treatments. This underlines the need for therapeutic innovations in this disease.

ADD-ON TIOTROPIUM: CLINICAL IMPROVEMENT OF MODERATE ASTHMA REGARDLESS OF BASELINE IGE/EOSINOPHIL STATUS ACROSS AGE GROUPS

Introduction The influence of biomarker status on add-on tiotropium efficacy was analyzed across age groups using data from four phase 3 clinical trials. Methods Analyses involved four randomized, double-blind, placebo-controlled, parallel-group trials in patients with moderate persistent asthma (MezzoTinA-asthma® [NCT01172808/NCT01172821]: two replicate trials in adults; RubaTinA-asthma® [NCT01257230]: adolescents [12–17 years]; and CanoTinA-asthma® [NCT01634139]: children [6–11 years]). Patients received once-daily tiotropium 2.5 or 5.0 µg or placebo via a soft-mist inhaler as add-on to ICS±controllers. Results for the US-approved dose (2.5 µg) are reported here. Post hoc modeling analyses, including serum IgE levels and blood eosinophil counts as continuous covariates, were conducted for peak and trough FEV1. Results Overall, 779 and 792 patients received tiotropium and placebo, respectively. Statistically significant (all P1(0-3 h) (pooled MezzoTinA-asthma®: 223 [185–262] mL; pooled RubaTinA-asthma®+CanoTinA-asthma®: 159 [98–219] mL) and trough FEV1 (pooled MezzoTinA-asthma®: 180 [138–221] mL; pooled RubaTinA-asthma®+CanoTinA-asthma®: 105 [39–170] mL) at week 24. Differences similar to these overall analyses were observed with modeling of mean treatment differences between tiotropium and placebo for peak FEV1(0-3 h) and trough FEV1 by baseline IgE levels and blood eosinophil counts. Conclusions In adult and pediatric patients with moderate symptomatic asthma, once-daily add-on tiotropium improved lung function versus placebo, irrespective of IgE levels and blood eosinophil counts. These findings support addition of tiotropium to ICS/LABA at GINA step 4 and 5 before considering biologics in these variably phenotypic patients.

Systematic literature review of the clinical, humanistic, and economic burden associated with asthma uncontrolled by GINA Steps 4 or 5 treatment

Objective: This study sought to characterize the epidemiologic, clinical, humanistic, and economic burden of patients with asthma uncontrolled by GINA Steps 4 or 5 treatment (severe, uncontrolled asthma [SUA]).Methods: A systematic literature review adhering to PRISMA guidelines was performed. Relevant publications were searched for in MEDLINE and EMBASE from January 2004 to September 2016 and in a conference proceedings database from January 2012 to October 2016. Studies were screened using the Population, Intervention, Comparator, Outcomes, Study Design, and Time (PICOS-T) framework. Studies of SUA with observational (prospective and retrospective), randomized, or nonrandomized study designs; adult patient populations; sample sizes ≥20 patients; epidemiologic or clinical outcomes, patient-reported outcomes (PROs), or economic outcomes were included. For our analysis, SUA was defined as inadequate control of asthma, despite the use of medium- to high-dosage inhaled corticosteroids and at least one additional treatment.Results: A total of 195 articles reporting unique study populations were included. Prevalence of SUA was as great as 87.4% for patients with severe asthma, although values varied depending on the criteria used to define asthma control. Compared with patients with severe asthma who were controlled, patients with SUA experienced more symptoms, night-time awakenings, rescue medication use, and worse PROs. SUA-associated costs were 3-times greater than costs for patients with severe, controlled disease.Conclusion: Despite the availability of approved asthma treatments, this literature analysis confirms that SUA poses a substantial epidemiologic, clinical, humanistic, and economic burden. Published data are limited for certain aspects of SUA, highlighting a need for further research.