Multiple manifestations of uncontrolled asthma increase the risk of severe COVID-19.

OBJECTIVE: Asthma control is of importance when assessing the risk of severe outcomes of COVID-19. The aim of this study was to explore associations of clinical characteristics and the effect of multiple manifestations of uncontrolled asthma with severe COVID-19. METHODS: In 2014-2020, adult patients with uncontrolled asthma, defined as Asthma Control Test (ACT) ≤19 were identified in the Swedish National Airway Register (SNAR) (n = 24533). The SNAR database, including clinical data, was linked with national registers to identify patients with severe COVID-19 (n = 221). The effect of multiple manifestations of uncontrolled asthma was based on: 1) ACT ≤15, 2) frequent exacerbations and 3) previous asthma inpatient/secondary care and evaluated stepwise. Poisson regression analyses were conducted with severe COVID-19 as the dependent variable. RESULTS: In this cohort with uncontrolled asthma, obesity was the strongest independent risk factor for severe COVID-19 in both sexes, but even greater in men. Multiple manifestations of uncontrolled asthma were more common among those with severe COVID-19 vs. without: one, 45.7 vs. 42.3%, two, 18.1 vs. 9.1% and three, 5.0 vs. 2.1%. The risk ratio (RR) of severe COVID-19 increased with an increasing number of manifestations of uncontrolled asthma: one, RR 1.49 (95% CI 1.09-2.02), two, RR 2.42 (95% CI 1.64-3.57) and three, RR 2.96 (95% CI 1.57-5.60), when adjusted for sex, age, and BMI. CONCLUSIONS: It is important to consider the effect of multiple manifestations of uncontrolled asthma and obesity when assessing patients with COVID-19, as this increases the risk of severe outcomes substantially.

Pediatric asthma control during the COVID-19 pandemic.

BACKGROUND: The lockdown imposed by the COVID-19 pandemic resulted in a completely different style of life with possible effects on the attitude toward their disease in patients with chronic lung disease, such as asthma. The aim of our study was to investigate in asthmatic children the level of asthma control and the maintenance therapy used during the lockdown. METHODS: Among asthmatic children attending our clinic, we identified those who had been prescribed the same therapy in March-April 2019 and March-April 2020. The level of asthma control (GINA-score) and the maintenance therapy used during the lockdown (March-April 2020) were compared with those of March-April 2019. We separately analyzed a small group of children with severe asthma treated with Omalizumab during the lockdown. RESULTS: We enrolled 92 asthmatic children (67 males). Compared to 2019, in 2020 a higher proportion of children modified their maintenance therapy (38% vs. 15.2%, p < .001), with a significant increase in both the proportion of children who increased (p = .033) and in that of children who decreased their therapy (p = .026). The level of control resulted as significantly higher in 2020 (March p = .023; April p = .007). Also, the 13 children treated with Omalizumab showed a good level of control in 2020. CONCLUSIONS: In asthmatic children, the COVID-19 pandemic lockdown had a significant impact on their asthma control and on their attitude toward maintenance therapy.

Geographical differences in the use of oral corticosteroids in patients with severe asthma in Spain: heat map based on existing databases analyses.

BACKGROUND: Although there are currently alternative treatments to the long-term use of oral corticosteroids (OCS) in severe asthma, recent studies show excessive use depending on geography and differences in medical practice. The objective of the study was to describe the differences in OCS use for severe asthma across the Spanish geography. METHODS: This is a real-world study using existing databases (year 2019): longitudinal patient database (EMR), based on electronic medical records, and database of pharmacological consumption (Sell-in) in basic healthcare areas. With EMR, the percentage of OCS prescriptions corresponding to patients with severe asthma (ICD-9 "asthma" and prescription of biological treatment and/or high dose of inhaled corticosteroids/long-acting inhaled ß2 agonists) was calculated. This percentage was transferred to the OCS consumption of each basic healthcare area as reported in the Sell-in database and a national heat map was created. The estimation of OCS use in patients with severe asthma per 100,000 inhabitants for each region was calculated by grouping basic healthcare areas and the mean OCS use per patient for different regions in Spain was also estimated. RESULTS: Patients with severe asthma in Spain were mostly female (69.6%), with a mean age (SD) of 57.6 years (18.01). Median time (Pc25-Pc75) since asthma diagnosis was 83.1 months (34.65-131.56). Of all patients with OCS prescriptions in 2019 identified in EMR, 4.4% corresponded to patients with severe asthma. Regions with the highest OCS use were Asturias, Andalucía, and Galicia, whereas those with the lowest use were Navarra, Baleares, Madrid and País Vasco. The mean OCS use per patient with severe asthma in 2019 throughout Spain was 1099.85 mg per patient, ranging from 782.99 mg in Navarra to 1432.64 in Asturias. CONCLUSIONS: There are geographical differences between Spanish regions with respect to the use of OCS in patients with severe asthma. The national mean consumption of OCS per patient with severe asthma and year is above the limits that indicate good asthma control.

Factors associated with improved outcome of inhaled corticosteroid use in COVID-19: A single institutional study.

Asthmatics seem less prone to adverse outcomes in coronavirus disease 2019 (COVID-19) and some data shows that inhaled corticosteroids (ICS) are protective. We gathered data on anecdotal ICS and outcomes of patients hospitalized with COVID-19, given there is literature supporting ICS may reduce risk of severe infection. In addition, we fill gaps in current literature evaluating Charlson Comorbidity Index (CCI) as a risk assessment tool for COVID-19. This was a single-center, retrospective study designed and conducted to identify factors associated intubation and inpatient mortality. A multivariate logistic regression model was fit to generate adjusted odds ratios (OR). Intubation was associated with male gender (OR, 2.815; 95% confidence interval [CI], 1.348-5.881; P = .006) and increasing body mass index (BMI) (OR, 1.053; 95% CI, 1.009-1.099; P = .019). Asthma was associated with lower odds for intubation (OR, 0.283; 95% CI, 0.108-0.74; P = .01). 80% of patients taking pre-hospital ICS were not intubated (n = 8). In-patient mortality was associated with male gender (OR, 2.44; 95% CI, 1.167-5.1; P = .018), older age (OR, 1.096; 95% CI, 1.052-1.142; P = <.001), and increasing BMI (OR, 1.079; 95% CI, 1.033-1.127; P = .001). Asthma was associated with lower in-patient mortality (OR, 0.221; 95% CI, 0.057-0.854; P = .029). CCI did not correlate with intubation (OR, 1.262; 95% CI, 0.923-1.724; P = .145) or inpatient mortality (OR, 0.896; 95% CI, 0.665-1.206; P = .468). Asthmatics hospitalized for COVID-19 had less adverse outcomes, and most patients taking pre-hospital ICS were not intubated. CCI score was not associated with intubation or inpatient mortality.

The outcome of COVID-19 in children with chronic lung disease: Systematic review and meta-analyses.

BACKGROUND: Few studies have examined the impact of Coronavirus disease 2019 (COVID-19) infection on children with chronic lung disease (CLD). OBJECTIVE: To perform a systematic review and meta-analysis to determine the prevalence, risk factors for contracting COVID-19, and complications of COVID-19, in children with CLD. METHODS: This systematic review was based on articles published between January 1, 2020 and July 25, 2022. Children under 18 years old, with any CLD and infected with COVID-19 were included. RESULTS: Ten articles involving children with asthma and four involving children with cystic fibrosis (CF) were included in the analyses. The prevalence of COVID-19 in children with asthma varied between 0.14% and 19.1%. The use of inhaled corticosteroids (ICS) was associated with reduced risk for COVID-19 (risk ratio [RR]: 0.60, 95% confidence interval [CI]: 0.40-0.90). Uncontrolled asthma, younger age, AND moderate-severe asthma were not significant risk factors for contracting COVID-19. Children with asthma had an increased risk for hospitalization (RR: 1.62, 95% CI: 1.07-2.45) but were not more likely to require assisted ventilation (RR: 0.51, 95% CI: 0.14-1.90). The risk of COVID-19 infection among children with CF was <1%. Posttransplant and cystic fibrosis-related diabetes mellitus (CFRDM) patients were at an increased risk for hospitalization and intensive care treatment. CONCLUSION: Hospitalizations were higher in children with asthma with COVID-19 infection. However, using ICS reduced the risk of COVID-19 infection. As for CF, postlung transplantation and CFRDM were risk factors for severe disease.

The association of preexisting severe asthma with COVID-19 outcomes.

PURPOSE OF REVIEW: Three years after the emergence of coronavirus disease 2019 (COVID-19), many studies have examined the association between asthma and COVID-related morbidity and mortality, with most showing that asthma does not increase risk. However, the U.S. Centers for Disease Control (CDC) currently suggests that patients with severe asthma may, nonetheless, be particularly vulnerable to COVID-19-related morbidity. RECENT FINDINGS: With respect to poor COVID-19 outcomes, our search yielded nine studies that quantified associations with severe asthma, seven that considered use of monoclonal antibodies (mAB), and 14 that considered inhaled corticosteroids (ICS) use. mAb and ICS use have been used as measures of severe asthma in several studies. Severe asthma was significantly associated with poor COVID-19 outcomes. The results for mAb and ICS were mixed. SUMMARY: An increased risk of poor COVID-19 outcomes in patients with severe asthma is possible. However, these studies remain sparse and suffer from several methodological limitations that hinder their interpretation. Additional evidence is needed to provide clear, cogent guidance for health agencies seeking to inform patients with asthma about potential risks due to COVID-19.

Impact of the COVID-19 Pandemic on the Prescribing of Antiasthmatic Treatments in Portugal: A Nationwide Study.

PURPOSE: The coronavirus disease 2019 (COVID-19) pandemic has had a profound impact on everyday life, the environment, and health care services. A shift from in-person medical appointments to telemedicine was a main adjustment. Such changes can have repercussions on the control and management of chronic respiratory diseases, such as asthma. The available data suggest that there was an overall decrease in asthma-related morbidities during the first year of the pandemic. Therefore, the goal of this study was to quantify the effects of the pandemic on the prescribing of antiasthmatic treatments in outpatient care (public and private health care). METHODS: This before-after study used a time series approach based on data from monthly prescriptions of antiasthmatic drugs (anti-inflammatory drugs and bronchodilators) dated between April 2018 and March 2021. An interrupted time series (ITS) design was used for assessing changes in antiasthmatic prescribing patterns in the short and long terms after COVID-19 was recognized as a pandemic. The results are complemented with seasonal autoregressive integrated moving average (sARIMA) models. FINDINGS: The ITS analysis showed a non-significant increase in antiasthmatic prescribing in the short term. In the long term, after the pandemic was declared, a statistically significant decrease was observed in the prescribing of antiasthmatics (in anti-inflammatory drugs and, more pronounced, in bronchodilators). In the sARIMA model, the mean monthly volume of antiasthmatic prescriptions was 18.1% lower than predicted. The numbers of months outside of the 95% CIs were different between anti-inflammatory drugs (1 month) and bronchodilators (7 months). IMPLICATIONS: The prescribing of antiasthmatic drugs in the long term was significantly decreased with the COVID-19 pandemic, with a greater effect in the case of bronchodilators.

Biologic use and outcomes among adults with severe asthma treated by US subspecialists.

BACKGROUND: Multiple biologics are now available for severe asthma (SA) treatment and can improve outcomes for patients. However, few available data describe the real-world use and effectiveness of multiple approved biologics, including biologic switching, among subspecialists in the United States. OBJECTIVE: To evaluate biologic use and associated exacerbation outcomes in a large cohort of subspecialist-treated US adults with SA. METHODS: CHRONICLE is an ongoing, noninterventional study of subspecialist-treated US adults with SA receiving biologics, maintenance systemic corticosteroids, or those persistently uncontrolled by high-dose inhaled corticosteroids with additional controllers. For enrolled patients, sites report asthma exacerbations and medication use starting 12 months before enrollment. For patients enrolled between February 2018 and February 2021, biologic use and exacerbation outcomes before and after biologic initiation are described. RESULTS: Among 2793 enrolled patients, 66% (n = 1832) were receiving biologics. The most used biologic (> 1 biologic use per patient allowed) was omalizumab (47%), followed by benralizumab (27%), mepolizumab (26%), dupilumab (18%), and reslizumab (3%). Overall, 16% of patients had biologic switches, 13% had stops, and 89% had ongoing biologic use. Patients starting and switching biologics experienced a 58% (1.80 vs 0.76 per patient-year) and 49% (1.47 vs 0.75 per patient-year) reduction in exacerbations, respectively (both P < .001), with a numerically greater reduction observed among those starting non-anti-immunoglobulin E biologics compared with anti-immunoglobulin E. CONCLUSION: Real-world starting and switching of biologic therapies for SA were associated with meaningful reductions in exacerbations. With increasing biologic options available, individualized approaches to therapy may improve patient outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03373045.

Home-based treatment of biologics for asthma: who, what, where, when and why.

INTRODUCTION: The advent of biologic therapies for severe asthma has profoundly changed the management of this pathology. The introduction of home administration is therefore an important innovation to optimize the patients' management, even if there are many aspects that need to be clarified and pointed out. AREAS COVERED: This review summarizes the path that led to the possibility of self-administration of biologics, and what the pandemic has changed in the management of these patients. EXPERT OPINION: The growing understanding of asthma phenotypes and endotypes is enabling the careful selection of patients suitable for biologics. In this context, the availability of reliable and simple self-injection devices is important in implementing self-administration. The transition to self-injection is also possible thanks to the high safety profile of biologics. With attention, most patients may potentially be suitable for self-administration. The transition process from hospital to home administration can therefore be carried out correctly by clinicians with adequate expertise in the field of severe asthma and biologic therapies, with the support of other health professionals, pharmacists, and general practitioners. Home administration is probably the best way to guarantee high adherence and high-level satisfaction of patients, even in the long term.

Risk of serious COVID-19 outcomes among adults and children with moderate-to-severe asthma: a systematic review and meta-analysis.

BACKGROUND: The Joint Committee on Vaccination and Immunisation in the United Kingdom requested an evidence synthesis to investigate the relationship between asthma and coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: We conducted a systematic review and meta-analysis to summarise evidence on the risk of severe COVID-19 outcomes in people with uncontrolled asthma or markers of asthma severity. METHODS: High-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) were used as markers of asthma severity, following international or national asthma guidelines. Risk of bias was assessed using Joanna Briggs Institute tools. Adjusted point estimates were extracted for random-effects meta-analyses and subgroup analyses. RESULTS: After screening, 12 studies (11 in adults and one in children) met the eligibility criteria. Adults using high-dose ICS or OCS had a pooled adjusted hazard ratio (aHR) of 1.33 (95% CI 1.06-1.67, I2=0%) for hospitalisation and an aHR of 1.22 (95% CI 0.90-1.65, I2=70%) for mortality for COVID-19. We found insufficient evidence for associations between markers on COVID-19 mortality in the subgroup analyses. CONCLUSIONS: Adults with severe asthma are at increased risk of COVID-19 hospitalisation compared to nonusers. Our analysis highlighted the dearth of studies in children with asthma investigating serious COVID-19 outcomes.

REALITI-A Study: Real-World Oral Corticosteroid-Sparing Effect of Mepolizumab in Severe Asthma.

BACKGROUND: Patients with severe asthma may require maintenance oral corticosteroids (mOCS) for disease control as well as systemic corticosteroid (SCS) bursts for clinically significant exacerbations. However, mOCS and SCS use are associated with adverse effects, which increases patient disease burden. OBJECTIVE: To assess the real-world corticosteroid-sparing effect of mepolizumab in patients with severe asthma. METHODS: REALITI-A was a 24-month international, prospective, observational cohort study involving 84 centers across Europe, Canada, and the United States, with a 1-year pre-post mepolizumab treatment preplanned interim analysis. A total of 822 adults with a clinical diagnosis of asthma and a physician decision to initiate mepolizumab treatment (100 mg subcutaneously) were included. End points included daily mOCS dose at baseline (penultimate 28 days of pretreatment) and 1 year after treatment; percent reduction from baseline in mOCS dose; patients discontinuing mOCS 1 year after treatment; and the rate of clinically significant exacerbations (those requiring OCS for 3 days or more [or parenteral administration], emergency room visit, and/or hospital admission) before and after treatment. RESULTS: A total of 319 patients received mOCS at baseline (median [interquartile range]: 10.0 [5.0-15.0] mg/d). At 1 year after treatment, median mOCS dose was reduced by 75% (2.5 [0.0-5.0] mg/d); 64% of patients had a reduction in mOCS dose of 50% or greater compared with baseline and 43% discontinued mOCS. Clinically significant exacerbations decreased between pretreatment and posttreatment (rate ratio [95% confidence interval] 0.29 [0.26-0.32]; P < .001). CONCLUSION: This 1-year analysis demonstrates that real-world mepolizumab treatment is clinically effective in patients with severe asthma, providing disease control while reducing the need for mOCS and SCS bursts.

Application of XOLAIR® (Omalizumab) in adolescent refractory chest tightness variant asthma.

BACKGROUND: Asthma can manifest in a variety of clinical phenotypes like cough variant asthma, chest tightness variant asthma (CTVA), and masked asthma. Patients with CTVA usually have a singular or primary complaint of chest tightness, which is often overlooked or misdiagnosed due to the lack of characteristic asthma symptoms. We hereby report a case of CTVA managed by omalizumab. CASE REPORT: A 15-year-old female patient reported to us with repeated coughing persisting for 3 weeks. Initial treatment with standard asthma drugs had minimal effect. Later during the disease, chest tightness became the primary symptom, and she was managed with steroids, ß2 receptor agonists, and leukotriene receptor agonists but without complete relief. Based on clinical signs and symptoms, the response to baseline drugs, and results of bronchial provocation test, the diagnosis was revised to CTVA, and the patient was started on Omalizumab in addition to baseline drugs, which significantly improved her condition. CONCLUSIONS: CTVA is difficult to diagnose due to its insidious symptoms and poor characteristics. Improper treatment can lead to uncontrolled disease, negative psychological issues, and reduced quality of life. Comprehensive assessment of children's airway inflammation level, lung function, bronchial provocation test, and responsiveness to drug therapy should be performed for accurate diagnosis. Omalizumab in combination with standard drugs can significantly improve the outcomes of CTVA.

Edible algae (Ecklonia cava) bioprocessed with mycelia of shiitake (Lentinula edodes) mushrooms in liquid culture and its isolated fractions protect mice against allergic asthma.

BACKGROUND: Ecklonia cava is an edible marine brown alga harvested from the ocean that is widely consumed in Asian countries as a health-promoting medicinal food The objective of the present study is to evaluate the anti-asthma mechanism of a new functional food produced by bioprocessing edible algae Ecklonia cava and shiitake Lentinula edodes mushroom mycelia and isolated fractions. METHODS: We used as series of methods, including high performance liquid chromatography, gas chromatography, cell assays, and an in vivo mouse assay to evaluate the asthma-inhibitory effect of Ecklonia cava bioprocessed (fermented) with Lentinula edodes shiitake mushroom mycelium and its isolated fractions in mast cells and in orally fed mice. RESULTS: The treatments inhibited the degranulation of RBL-2H3 cells and immunoglobulin E (IgE) production, suggesting anti-asthma effects in vitro. The in vitro anti-asthma effects in cells were confirmed in mice following the induction of asthma by alumina and chicken egg ovalbumin (OVA). Oral administration of the bioprocessed Ecklonia cava and purified fractions suppressed the induction of asthma and was accompanied by the inhibition of inflammation- and immune-related substances, including eotaxin; thymic stromal lymphopoietin (TSLP); OVA-specific IgE; leukotriene C4 (LTC4); prostaglandin D2 (PGD2); and vascular cell adhesion molecule-1 (VCAM-1) in bronchoalveolar lavage fluid (BALF) and other fluids and organs. Th2 cytokines were reduced and Th1 cytokines were restored in serum, suggesting the asthma-induced inhibitory effect is regulated by the balance of the Th1/Th2 immune response. Serum levels of IL-10, a regulatory T cell (Treg) cytokine, were increased, further favoring reduced inflammation. Histology of lung tissues revealed that the treatment also reversed the thickening of the airway wall and the contraction and infiltration of bronchial and blood vessels and perialveolar inflammatory cells. The bioprocessed Ecklonia cava/mushroom mycelia new functional food showed the highest inhibition as compared with commercial algae and the fractions isolated from the bioprocessed product. CONCLUSIONS: The in vitro cell and in vivo mouse assays demonstrate the potential value of the new bioprocessed formulation as an anti-inflammatory and anti-allergic combination of natural compounds against allergic asthma and might also ameliorate allergic manifestations of foods, drugs, and viral infections.