Systemic corticosteroids (SCS) are used to manage asthma exacerbations. Among the broad population of patients with asthma, SCS-related risk of adverse events (AEs), health care resource utilization (HCRU), and costs remain unclear.

This retrospective cohort study used the Optum Research Database claims to identify adults with asthma from 1/1/2017 to 6/30/2022. The index date was the earliest SCS claim for SCS users; non-SCS users were randomly selected and adjusted proportionally to SCS users by index year. SCS use was measured during the first 12 months of follow-up. Inverse probability of treatment weighting balanced the two cohorts for selected baseline demographic and clinical characteristics. SCS users were further stratified into low, medium, and high dose sub-cohorts. SCS-related AEs were assessed up to 48 months, while HCRU and costs were assessed during the first 12 months of follow-up. A generalized linear model (GLM) analyzed follow-up costs by SCS exposure.

The 130,739 patients included 55,363 non-SCS users (42.3%), while 75,376 were SCS users stratified into 60,319 low-, 12,235 medium-, and 2,822 high-dose users. The mean age was 49.6 years; 61.8% were female and 68.9% were non-Hispanic White. SCS users had a significantly greater risk of new-onset acute and chronic SCS-related AEs, increasing incrementally with dose exposure (all p < .001) across numerous physiological systems. Follow-up HCRU and costs also rose incrementally with dose exposure (all p < .001). Compared with non-users, SCS-related costs were 1.43, 1.97, and 3.21 times higher among low-, medium-, and high-dose users, respectively. The adjusted GLM predicted a 9.9% cost increase per 100 mg of prednisone equivalents.

Retrospective administrative claims studies cannot randomize patients and may not capture all patient events.

Among a broad population of adults with asthma, even low doses of SCS were associated with significantly increased risk of new-onset AEs, HCRU, and costs.

Gut microbiota imbalance is well-known as one important trigger of allergic asthma. Ma-Xing-Shi-Gan decoction (MXSG) is a traditional Chinese medicine prescription with ideal clinical efficacy on asthma. However, whether and how MXSG exerts its efficacy on asthma through gut microbiota remains unclear.

To investigate the underlying mechanism of MXSG against asthma using multi-omics technologies.

An asthma model was established using 8-week-old C57BL/6 J mice, after which they were daily administrated with high-, medium- and low-dose MXSG for 7 days. Histopathological examinations and flow cytometry were performed to evaluate the effects of MXSG on lung immune injury. Key regulatory pathways were predicted via network pharmacology and verified using 16S rRNA sequencing, metagenomics, metabolomics, and in vivo experiments including the knockout of the targeting gene.

MXSG alleviated asthma symptoms, elevated intestinal microbial diversities, and enriched potential beneficial microbes such as Lactococcus, Lactobacillus, and Limosilactobacillus. Network pharmacology and experimental validation highlighted the IL-17/Treg signaling as crucial for asthma treatment. IL-17 knockout experiments revealed its necessity for Treg differentiation during asthma. Moreover, IL-17-deficient asthmatic mice exhibited lower levels of Lactobacillus and significant changes in microbial genes involving histone deacetylases (HDAC) and short-chain fatty acids (SCFAs). Finally, MXSG significantly boosted SCFA production and reduced HDAC9 expression, which were correlated with Treg cell ratios.

Our study delineates a novel mechanism where MXSG synergizes with the IL-17 family to enrich intestinal beneficial microbes (e.g. Lactobacillus) and SCFAs. This inhibits the expression of SCFA-downstream HDAC9 to promote Treg differentiation, and thus potentially alleviates asthma.

Obesity and allergic diseases are global health concerns, both of which are seeing an increase in prevalence in recent years. Obesity has been recognised as an important comorbidity in subpopulations with allergic airway diseases, which represents a unique phenotype and endotype. Obesity-related allergic airway diseases are associated with exacerbated clinical symptom burden, altered immune response, increased disease severity and compromised predictive capability of conventional biomarkers for evaluating endotype and prognosis. Moreover, treatment of obesity-related allergic airway diseases is challenging because this unique endotype and phenotype is associated with poor response to standard therapeutic strategies. Therapeutic regimen that involves weight loss by non-surgical and surgical interventions, gut microbiome-targeted treatment, glucagon-like peptide-1 receptor agonist and other agents should be considered in this population. In this review, we outline the current knowledge of the impact of obesity on prevalence, endotypes, clinical symptom and management of allergic airway diseases. Increased understanding of the implications of obesity may contribute to better treatment options for the obesity-related refractory airway inflammation, particularly in precision medicine. KEY POINTS: Obesity can increase the prevalence of allergic airway diseases such as asthma, AR, and CRSwNP. Obesity alters the immune endotype and exacerbates clinical symptoms of respiratory allergic diseases. Obesity-related allergic airway diseases exhibit therapeutic resistance to standard treatment. Obesity-related allergic airway diseases constitute a distinct category of endotypes and phenotypes, requiring further in-depth research and novel therapeutic approaches.

The international and national guidelines for asthma management are typically comprehensive and designed for respiratory specialists, making them less practical for primary care physicians who handle most asthma cases. Recognizing the need for more accessible guidelines, the Japan Asthma Society developed the Practical Guidelines for Asthma Management (PGAM). PGAM aims to provide a concise summary of key asthma management principles, increasing awareness, education, and support among nonspecialists and patients alike. It includes user-friendly tables and lists outlining common symptoms, triggers, diagnostic criteria, and basic management strategies, along with frequently encountered treatable traits and comorbidities. These elements are presented through simple, clinically relevant algorithms. A notable feature of PGAM is the "Basic Roadmap for Asthma Management," which outlines a clear sequence for patient assessment, diagnosis, and treatment from initial consultation onward, offering an easy-to-follow visual guide. Additionally, the guidelines include methods for assessing airway inflammation, enabling patient phenotyping and endotyping. This supports a personalized treatment approach, particularly with biologics, aimed at achieving clinical remission.

For severe asthma (SA) management, real-world evidence on the effects of biologic therapies in reducing the burden of oral corticosteroid (OCS) use is limited.

To estimate the efficacy of biologic initiation on total OCS (TOCS) exposure in patients with SA from real-world specialist and primary care settings.

From the International Severe Asthma Registry (ISAR, specialist care) and the Optimum Patient Care Research Database (OPCRD, primary care, United Kingdom), adult biologic initiators were identified and propensity score-matched with non-initiators (ISAR, 1:1; OPCRD, 1:2). The impact of biologic initiation on TOCS (including bursts for exacerbations) daily dose in the first- and second-year follow-up period was estimated using multivariable generalized linear models.

Among 5,663 patients (ISAR 48%, OPCRD 52%), the odds ratios (ORs) of biologic initiators achieving TOCS cessation in the first and second years of follow-up were 2.38 (95% CI, 1.87-3.04) and 2.11 (95% CI, 1.65-2.70), whereas the ORs of low (0- to 5-mg) TOCS intake were 1.62 (95% CI, 1.40-1.86) and 1.40 (95% CI, 1.21-1.61), respectively. Compared with non-initiators, biologic initiators had a substantially higher chance of achieving greater than 75% reduction from baseline (OR [95% CI] = 2.35 [2.06-2.68] and 1.53 [1.35-1.73] in first and second years, respectively). These findings remained persistent and robust when analyses were repeated with one country setting removed at a time.

Biologic initiation in patients with SA led to substantial reduction in TOCS exposure, particularly in the first year. Future analyses will explore the impact on OCS-related adverse health events.

Oral corticosteroids (OCS) have been used for both maintenance and burst treatment of asthma since the 1950s owing to their beneficial effect on symptoms and exacerbations coupled with a historical lack of alternative therapies. Despite the current availability of well-tolerated and effective treatment with biologics, chronic OCS use remains high. This is of great concern because evidence suggests that a lifetime cumulative exposure even as low as 0.5 to 1.0 g prednisolone equivalent (about three to four bursts of OCS) significantly increases the risk of a wide range of acute and long-term adverse effects, some of which may not be fully reversible. Conversely, biologics have demonstrated a more favorable benefit-risk profile compared with OCS, while reducing exacerbations and improving symptom control. Here, we review the current situation, highlight the need for improved stewardship of OCS use, describe the cumulative and potentially irreversible toxicity seen with even short bursts of OCS, and discuss the role of biologics in minimizing their use. Finally, we provide our opinion on how maintenance OCS therapy in asthma can be relegated to history, with early patient risk evaluation to identify and measure biomarkers and/or clinical traits that may predict risk of future exacerbations, enabling proactive preventative intervention.

Background: Japanese guidelines recommend the addition of a long-acting muscarinic antagonist for patients with asthma uncontrolled on inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) therapy, the effectiveness of which is evaluated here. Methods: Retrospective, observational, single-arm cohort study in patients with asthma initiating fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) following ICS/LABA, using independently analyzed data from Japanese claims databases: JMDC and Medical Data Vision (MDV). The index date was that of the first FF/UMEC/VI prescription. Outcomes were assessed during a 12-month follow-up versus a 12-month pre-index period (baseline) and included asthma exacerbations, oral corticosteroid (OCS) use, and short-acting β2-agonist (SABA) use. P-values associated with rate ratios (RRs) were estimated using Conditional Poisson regression. Results: Overall, 3229 patients in the JMDC database and 1135 in the MDV database were included. Following FF/UMEC/VI initiation, the total annualized moderate-severe asthma exacerbation rate in the JMDC database reduced from 0.50 to 0.40 per-person-per-year (PPPY) (RR [95% confidence interval]: 0.78 [0.73, 0.84]; p < 0.001), with similar reductions in the MDV database: 0.53 to 0.42 PPPY (0.79 [0.70, 0.89]; p < 0.001). In both databases, there was a 20% reduction (JMDC: 0.80 [0.73, 0.88]; p < 0.001; MDV: 0.80 [0.68, 0.94]; p = 0.005) in patients with ≥1 OCS prescription after FF/UMEC/VI initiation. The proportion of patients with ≥1 SABA canister prescription dropped by 31% 0.69 [0.57, 0.84]; p < 0.001) in the JMDC database and 23% (0.77 [0.66, 0.90]; p < 0.001) in the MDV database. Conclusions: This suggests FF/UMEC/VI is effective in improving asthma exacerbations and reducing OCS and SABA use in Japanese patients previously using ICS/LABA in real-world clinical practice.

Understanding patient motivations for acute care-seeking behavior for asthma attacks could guide interventions to improve outcomes and mitigate health care resource use.

To characterize health care-seeking behaviors and motivations of patients in the United States who obtain care for an asthma attack in urgent care (UC), emergency department (ED), or hospital settings.

A cross-sectional survey was conducted online between July and August 2023 among adults in a market research panel treated for asthma in the past 12 months and who had experienced an asthma attack that required care in an UC, ED, or hospital or an oral corticosteroid prescription.

Of the 504 survey participants (female = 72%; White = 79%; Hispanic = 12%), 68% self-reported asthma of moderate severity and 72% had uncontrolled asthma. Oral corticosteroids were prescribed an average of 4.2 times in the past year. During their last asthma attack, 37% of participants took medicines at home, 20% went to UC, 15% went to the ED, and 5% were hospitalized. Participants who were younger, Asian, Hispanic, or with severe asthma were the most likely to go to the ED. Using a rescue inhaler was the most common action taken when first experiencing symptoms (72%). When participants considered seeking acute care, the severity of asthma symptoms was the most common factor considered (76%), followed by fast access to help (29%) and medication access (28%).

Most patients seeking acute asthma care reported moderately severe, uncontrolled disease. Seeking acute care seems to be motivated by symptom severity and the need for fast access to care after trying rescue medications. It would be of interest in a future study to also evaluate the acute care-seeking needs of patients who are at lower risk of seeking acute care.

Objective.Forced expiratory volume in one second (FEV1) is an important metric for patients to track at home for their self-management of asthma and chronic obstructive pulmonary disease (COPD). Unfortunately, the state-of-the-art for measuring FEV1 at home either depends on the patient's physical effort and motivation, or relies on bulky wearable devices that are impractical for long-term monitoring. This paper explores the feasibility of using a machine learning model to infer FEV1 from 270 seconds of a single-lead electrocardiogram (ECG) signal measured on the fingers with a mobile device.Methods.We evaluated the model's inferred FEV1 values against the ground truth of hospital-grade spirometry tests, which were performed by twenty-five patients with obstructive respiratory disease.Results.The model-inferred FEV1 compared to the spirometry-measured FEV1 with a correlation coefficient ofr = 0.73, a mean absolute percentage error of 23% and a bias of -0.08.Conclusions.These results suggest that the ECG signal contains useful information about FEV1, although a larger, richer dataset might be necessary to train a machine learning model that can extract this information with better accuracy.Significance.The benefit of a mobile ECG-based solution for measuring FEV1 is that it would require minimal effort, thus encouraging patient adherence and promoting successful self-management of asthma and COPD.

Although the effectiveness of molecular antibodies has been established, evidence is still lacking on objective predictors of response. The aim of this study was to assess whether the extent of previous endoscopic sinus surgeries, assessed by means of the Amsterdam Classification of Completeness of Endoscopic Sinus Surgery (ACCESS) score, may influence clinical outcomes in refractory CRSwNP patients treated with dupilumab.

A consecutive sample of patients treated with dupilumab for previously operated recalcitrant CRSwNP were enrolled in the study. Every patient was required to undergo a CT scan at baseline (T0), at 3 (T1), and 12 (T2) months after treatment start. ACCESS score was calculated at baseline, whilst at every timepoint patients underwent assessment of Nasal-Polyp-Score (NPS), Lund-Kennedy-Score (LKS), and had to fill in the 22-item Sinonasal-Outcome-Test (SNOT-22) and Visual-Analog-Scales (VAS) for sinonasal symptoms. Favorable outcome was considered based on EUFOREA guidelines, namely improving at least 3 of the followings: (i) NPS; (ii) SNOT-22; (iii) VAS-olfaction; and (iv) need for systemic corticosteroids.

Overall favorable outcome was achieved in 69.1% (n = 38/55) of cases at T1, while in 89.1% (n = 49/55) at T2. There were no differences in baseline characteristics between responders and non-responders at both timepoints. At T1, out of all the included variables, no statistically significant predictor of favorable outcome was observed. Conversely, at T2, ACCESS score was the only confirmed independent predictive factor of response to dupilumab treatment (OR = 0.81 [95% CI = 0.67-0.92], P = .010).

Our findings suggest that the extent of previous endoscopic sinus surgeries may have a role in influencing clinical outcomes in patients with refractory CRSwNP undergoing treatment with dupilumab.

Inhaled corticosteroid (ICS) and oral corticosteroid (OCS) are often used in asthma management.

To evaluate the long-term effect of ICS/OCS on osteoporosis, osteopenia, fractures, and bone metabolism in adult patients with asthma in real-world clinical practice.

This is a retrospective study investigating deidentified electronic health records from Ajou University Medical Center (Korea). Adult patients with asthma receiving maintenance ICS with/without OCS for at least 1 year were enrolled. They were classified into the high/low-dose of ICS or OCS group. Primary outcomes (incidences of osteoporosis, osteopenia, and fractures) and secondary outcomes (drug prescription and laboratory values related to bone metabolism including albumin and alkaline phosphatase) were compared after 5 years of follow-up.

After propensity score matching, both high- and low-dose OCS groups included 468 patients, and high/low-dose ICS groups each comprised 1252 patients. The risk of osteoporosis/major fracture was higher (hazard ratio [95% CI], 2.00 [1.15-3.57]/3.03 [1.04-11.11]) in the high-dose OCS group (especially in females aged ≥50 years) than in the low-dose group, although the ICS groups showed no significant differences. The high-dose ICS group showed a higher risk of osteopenia (1.92 [1.05-3.70]) than the low-dose ICS group. The linear mixed model of laboratory values showed significantly decreased serum albumin and increased alkaline phosphatase in the high-dose OCS group than in the low-dose OCS group.

The results of this study suggest that long-term use of OCS can increase the risk of osteoporosis and osteoporosis-related fractures, whereas long-term use of ICS may increase the risk of osteopenia in adult patients with asthma.

Oral corticosteroids (OCS) are recommended for the treatment of exacerbations in people with COPD; however, high cumulative lifetime doses (≥1000mg prednisolone-equivalent) are associated with adverse health effects. This issue is well defined in asthma but is less well understood in COPD. The aim of this study was to examine cumulative OCS dispensed to people with COPD over 12 months.

This was a secondary analysis of data from two randomised controlled trials involving people with COPD followed up for 12 months following pulmonary rehabilitation. Clinical and administrative (respiratory-related hospital admissions and emergency presentations, dispensed OCS and COPD maintenance medications) data were examined to determine cumulative OCS dose relative to the 1000mg threshold and the relationship with clinical features.

Of 232 participants (126 females, age mean 68 ± SD 9 years, FEV1 53 ± 22% predicted), 48% (n = 112) were dispensed OCS at least once over 12 months. Sixty-two participants (26%) were dispensed ≥1000mg. Participants with a high cumulative dose were more likely to have had a respiratory admission (OR 4.1, 95% CI 2.3 to 8.7) and greater breathlessness (modified Medical Research Council scale ≥2, OR 2.5, 95% CI 1.3 to 5.0); no relationship with disease severity or maintenance medications was demonstrated.

One in four people with COPD were dispensed unsafe lifetime cumulative OCS doses over a period of only 12 months. Further work is needed to determine the magnitude of this issue in COPD and strategies to address exposure to high doses of OCS.

The relationship between diabetes mellitus (DM) and asthma is complex and can impact disease trajectories.

To explore the bidirectional influences between the two conditions on clinical outcomes and disease control.

We systematically reviewed the literature on the relationship between DM and asthma, focusing on their impacts, mechanisms, and therapeutic implications. Various studies were assessed, which investigated the effect of glycemic control on asthma outcomes, lung function, and exacerbations. The study highlighted the role of specific diabetes medications in managing asthma.

The results showed that poor glycemic control in diabetes can exacerbate asthma, increase hospitalizations, and reduce lung function. Conversely, severe asthma, especially in obese individuals, can complicate diabetes management and make glycemic control more difficult. The diabetes-associated mechanisms, such as inflammation, microangiopathy, and oxidative stress, can exacerbate asthma and decrease lung function. Some diabetes medications exhibit anti-inflammatory effects that show promise in mitigating asthma exacerbations.

The complex interrelationship between diabetes and asthma suggests bidirectional influences that affect disease course and outcomes. Inflammation and microvascular complications associated with diabetes may worsen asthma outcomes, while asthma severity, especially in obese individuals, complicates diabetes control. However, the current research has limitations, and more diverse longitudinal studies are required to establish causal relationships and identify effective treatment strategies for individuals with both conditions.

Asthma is characterized by chronic airway inflammation as its primary pathological condition, which leads to various respiratory symptoms due to airway narrowing, with type 2 inflammation playing a central role. Asthma treatment, primarily centered on inhaled corticosteroids, aims to suppress type 2 inflammation and improve airway narrowing. However, severe asthma that cannot be controlled with high-dose inhaled corticosteroids or other asthma medications remains a clinical issue. The availability of multiple biological agents has recently improved the management of severe asthma. In addition, the concept of clinical remission has emerged as a treatment goal, further clarifying the objectives of asthma management. However, despite these advancements, the treatment of severe asthma driven primarily by non-type 2 inflammation remains a major challenge, and new biologics are currently being developed to address this issue.

Oral corticosteroids (OCS) are an effective treatment for severe uncontrolled asthma or asthma exacerbations, but frequent bursts or long-term use carry serious and sometimes irreversible adverse effects, or complications such as adrenal insufficiency upon discontinuation. Our aim was to survey people with asthma on their experiences of, and attitudes towards, using OCS.

This study was a national descriptive cross-sectional survey of people with asthma in Australia. An anonymous survey was hosted online with invitations to participate distributed by national consumer peak bodies. Survey free-text responses were coded to the Theoretical Domains Framework (TDF) to elicit determinants of OCS use.

1808 people with asthma participated between 3 and 16 May 2022. Most common reasons for using OCS were severe asthma symptoms (40%), doctor prescription (38%) or asthma action plan recommendations (20%). Approximately 55% of people had experienced adverse effects from OCS use. Commonly reported adverse effects were trouble sleeping (69%), weight gain (56%) and mood problems (41%). Of people who had OCS at home or an OCS script, 44% did not have an action plan that described when and how they should take them. People (33%) did not feel well informed about OCS adverse effects from their healthcare team. People had varied awareness (3-65%) of current available strategies to reduce OCS use. 'Knowledge', 'Environmental context and resources' and 'Social influences' were the most coded TDF domains influencing OCS use.

Adverse effects of OCS use are common. People with asthma are not adequately informed about optimal OCS use or strategies to reduce overuse. These findings can help guide the implementation of OCS stewardship initiatives.

Asthma is a chronic inflammatory disease and a leading cause of disability, posing a huge economic and social burden. Plant-based antioxidants have the potential to block proinflammatory pathways and protect against oxidative damage, which could improve asthma management.

This review examines the role of plant-based antioxidants as adjuvant therapy on inflammatory markers and clinical outcomes of adults with asthma.

Digital databases, including Scopus, MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane Airway Group's Specialized Register of Trials, were searched. Two independent authors performed initial and full-text screening of identified papers. The criteria for study inclusion and exclusion were predefined. Two authors independently performed data extraction and risk of bias as per the PRISMA checklist.

After full-text screening, nine randomized controlled trials were included in the final review. Seven of the included studies highlighted the efficacy of plant-based antioxidants in modulating the inflammatory cytokines in asthmatics. The benefits of antioxidants were also observed for improving oxidative status, lung functioning, and airway inflammatory markers. Furthermore, the overall quality of asthmatic patients' lives was improved with fewer exacerbations such as night coughs and wheezing. Despite having some limitations, the overall risk of bias was low in this review.

The review indicated that plant-based antioxidants could have adjuvant beneficial effects in the management of asthma inflammatory markers, which may help improve asthma-related clinical outcomes. However, due to the small number of study subjects, further research is required on the effect of plant-based antioxidants on asthma-inflammatory markers and clinical outcomes.

Characteristic symptoms of NSAID-exacerbated respiratory disease (N-ERD) include asthma, chronic eosinophilic rhinosinusitis with nasal polyposis, cysteinyl LT (CysLT) overproduction and NSAIDs hypersensitivity. Some N-ERD patients present with episodic treatment-resistant extra-respiratory symptoms (CysLT-associated coronary artery vasospasm, gastroenteritis, or skin rash). Even when using standard treatments for respiratory and extra-respiratory symptoms, including systemic corticosteroids and aspirin desensitization, it is difficult to control the clinical symptoms and severe type 2 inflammation involved with mast cells, eosinophils, ILC2s, and platelet activation. Few treatment options are applicable in a clinical setting. Therefore, identifying effective treatments is essential for managing N-ERD patients who suffer from these conditions. Our previous observational study demonstrated 12-month omalizumab treatment of N-ERD was clinically effective against respiratory symptoms. Despite the remaining eosinophilia, omalizumab significantly reduced urinary LTE4 and PGD2 metabolites to near normal levels at steady state. Based on the preliminary study, we demonstrated that omalizumab induced tolerance to aspirin in N-ERD patients 3 months after therapy initiation and suppressed activation of mast cells during 24 h of initiation in a randomized manner. Moreover, omalizumab had significant efficacy against extra-respiratory symptoms at baseline (lacking aspirin exposure) as well as throughout aspirin challenge. This review addresses the latest discoveries related to N-ERD pathogenesis and the significant effectiveness of omalizumab on N-ERD as a mast cell stabilizer. Our findings regarding omalizumab-associated mast cell inhibitory effects are indirect evidence that mast cell dysregulation and, possibly, IgE are pivotal components of N-ERD.

Asthma is a prevalent chronic respiratory condition that significantly impacts public health, with severe asthma subtypes, such as severe eosinophilic asthma, imposing substantial socioeconomic burdens.

Real-world data from the Italian Health Information System were analyzed to evaluate the economic consequences of asthma in Italy. An in-depth comparative analysis was conducted to investigate the economic implications of various asthma subtypes, focusing on severe eosinophilic asthma. Additionally, the study projected the potential cost-effectiveness of novel treatments aimed at reducing hospitalization rates, specialist visits, and oral corticosteroid use for patients with severe eosinophilic asthma in Italy.

The analysis revealed that severe asthma, and notably severe eosinophilic asthma, places a substantial economic burden on the Italian National Health System. Estimates demonstrated that implementing innovative treatments to mitigate the risks of hospitalization and specialist visits, as well as reducing oral corticosteroid usage in severe eosinophilic asthma patients, could lead to significant cost savings. The cost-consequence analysis indicated potential yearly reductions of €50.0 million (27%) for the treatment of severe asthma and €31.7 million (26%) for severe eosinophilic asthma.

This study presents a comprehensive evaluation of the economic repercussions of severe asthma in Italy. The findings emphasize the necessity of identifying and developing effective therapeutic strategies to improve the management of severe asthma while simultaneously reducing the economic burden on the healthcare system. These results offer valuable insights for healthcare policymakers and practitioners, facilitating evidence-based decisions in asthma management and healthcare policy in Italy.

Patients with asthma in Singapore often have complex patient journeys, with diagnosis and management across various primary and speciality care settings. Real-world population health data is needed to identify care gaps and inform policies.

This retrospective, longitudinal cohort study assessed real-world data from adults (aged ≥18 years) with asthma in the SingHealth Chronic Obstructive Pulmonary Disease and Asthma Data Mart, an integrated database of electronic medical records of patients who attended primary and/or speciality care clinics in the SingHealth Regional Health System 01/01/2015-12/31/2020. Patients were indexed by first asthma diagnosis and categorized into cohorts of index year. Patient characteristics, asthma management and outcomes were described during baseline (1-year pre-index) and follow-up periods (1-year post-index).

Overall, 21,215 patients were included across 4 cohorts: 2016, N=12,947; 2017, N=3419; 2018, N=2816; 2019, N=2033. Most common baseline asthma medication changed from inhaled corticosteroids (ICS) alone in the 2016 cohort (32.8% [n=4252]) to ICS/long-acting β2-agonist in the 2019 cohort (33.3% [n=677]). Asthma symptom control (mean [SD] Asthma Control Test scores) improved from 2016 to 2019 during baseline (18.38 [4.93] vs 19.87 [4.56]; p<0.001) and follow-up (18.34 [4.23] vs 21.07 [3.51]; p<0.001). Mean (standard deviation [SD]) number of exacerbations per patient during follow-up decreased from 2016 to 2019 (1.91 [3.11] vs 0.89 [2.07]; p<0.001). Mean (SD) number of emergency department visits per patient during follow-up decreased from 0.21 (0.75) in 2016 to 0.17-0.18 (0.60-0.65; p<0.001) between 2017 and 2019.

Health status at first asthma diagnosis improved for each succeeding cohort from 2016 to 2019, along with improvements in patient management and outcomes. This reflects greater awareness of the condition and improved use of medication and referrals in recent years, suggesting policy changes and their implementation, including promotion of disease awareness and adoption of guideline recommendations, may improve asthma outcomes in Singapore.

To compare the efficacy and adverse events of different oral corticosteroids (OCSs) withdrawal methods for chronic rhinosinusitis with nasal polyp after endoscopic sinus surgery (ESS).

This was a randomized prospective study conducted from Oct 2019 to Jan, 2021. 35 patients who underwent ESS were randomly divided into 2 groups. Regular group (n = 18) received 0.4mg/kg/day of methylprednisolone orally for 10 days, tapering group (n = 17) received 0.4mg/kg/day of methylprednisolone orally for 7 days, followed by progressive reduction of 8 mg of methylprednisolone per week for 3 weeks. The visual analogue scale (VAS) score, the Lund-Kennedy endoscopy (LKE) score, and the E score were assessed preoperatively and at half and 1, 2, and 12 months postoperatively. Statistical analyses were performed using SPSS.

There was no statistical difference in the baseline characteristics between the 2 groups. The postoperative VAS scores and LKE scores of patients were significantly improved from those preoperatively (P-values < 0.05). There was no statistical difference in the LKE score, E score, and VAS score between the 2 groups both preoperatively and postoperatively (P-values > 0.05). There was no statistical difference in adverse events between the 2 groups (P-values > 0.05).

The combination of OCSs and ESS can improve the clinical symptoms of patients and the recovery of nasal mucosa. There was no difference between the 2 drug withdrawal methods in efficacy and adverse events. Drug withdrawal gradually is more complicated therefore, in clinical practice, OCSs withdrawal directly would be the better option for patients.

We aimed to characterize intravenous (IV) methylprednisolone (MP) dosing regimens and clinical outcomes for children hospitalized for critical asthma (CA).

A single-center, retrospective review was performed of children admitted to the pediatric intensive care unit (PICU) for CA between September 2015 and October 2019. Patients 5-to 17-year-olds, initiated on continuous nebulized albuterol, and prescribed at least one dose of IV MP were included. The primary outcome was to characterize PICU MP dosing. Cohorts were then compared by MP dosing: conservative-dose methylprednisolone (CDMP, ≤ 0.5 mg/kg/dose every 6 h) and standard-dose methylprednisolone (SDMP, > 0.5 mg/kg/dose every 6 h). Clinical efficacy endpoints were the duration of continuous nebulized albuterol and PICU length of stay (LOS). Safety endpoints included corticosteroid-related adverse events.

Of 168 children studied, 50 (29.8%) were prescribed CDMP and 118 (70.2%) SDMP. The overall mean MP dose was 31.3 ± 19.6 mg (weight-adjusted: 0.77 ± 0.32 mg/kg/dose). Compared to those prescribed SDMP, those prescribed CDMP had a shorter median duration of continuous nebulized albuterol (12.8 [IQR: 10.5-20] versus 17.3 [IQR: 11.3-29.7] hours, p = 0.019) and median PICU LOS (0.9 [IQR: 0.7-1.4] versus 1.2 [IQR: 0.9-1.8] days, p = 0.012). No corticosteroid-related adverse events were observed. In adjusted models, weight-adjusted IV MP dose was not associated with PICU LOS or duration of continuous nebulized albuterol.

Intravenous MP dosing for pediatric CA varied widely in our study sample. Prospective, controlled trials are required to validate our observations including clinical efficacy and safety endpoints.

The Nucala Effectiveness Study (NEST) assessed the effectiveness of mepolizumab in patients with severe asthma (SA) in countries previously underrepresented in real-world studies.

A multi-country, bi-directional, self-controlled, observational cohort study conducted in Colombia, Chile, India, Türkiye, Saudi Arabia, United Arab Emirates, Kuwait, Oman, and Qatar. Historical and/or prospective data from patients with SA were assessed 12 months pre- and post-mepolizumab initiation.

incident rate ratio (IRR) of clinically significant exacerbations (CSEs). Key secondary endpoints: healthcare resource utilisation (HCRU), oral corticosteroid (OCS) use, lung function and symptom control (Asthma Control Test [ACT] scores).

Overall, 525 patients with SA burden pre-initiation (geometric mean blood eosinophil count [BEC] 490.7 cells/µl; 31.4% prior biologic use; 37.3% obese) received at least one dose of mepolizumab 100 mg subcutaneously. Post-initiation, a significant reduction in CSEs was observed (76% [p < 0.001]; IRR [95% confidence interval] 0.24 [0.19-0.30]); 72.0% of patients had no CSEs. Mepolizumab treatment led to a reduction in OCS use (52.8% pre-initiation vs. 16.6% post-initiation) and a mean (standard deviation [SD]) change in OCS dose of - 18.1 (20.7) mg post-initiation; 36.1% of patients became OCS-free. Fewer patients were hospitalised post-initiation (22.5% pre-initiation vs. 6.9% post-initiation). Improvements in mean (SD) forced expiratory volume in 1 s (62.8 [20.2]% pre-initiation vs. 73.0 [22.7]% post-initiation) and ACT scores (15.0% pre-initiation vs. 64.5% of patients post-initiation with well-controlled asthma) were observed. Proportion of patients with BEC ≥ 500 cells/µl decreased from 84.4% pre-initiation to 18.1% post-initiation.

Mepolizumab was effective in reducing the burden of SA by significantly reducing CSEs, reducing OCS use and HCRU, and improving lung function and asthma control, which could translate to improvements in health-related quality of life in patients with SA and high OCS dependency in the countries studied. A graphical abstract is available with this article.

Chronic respiratory diseases such as asthma and chronic obstructive pulmonary disease (COPD) are characterized by airway inflammation. While corticosteroids (CS) are frequently prescribed during exacerbations of these conditions, their repeated use is associated with numerous side effects. The aim of this review is to synthesize the recent literature on the indications, benefits, and risks of short-term CS therapy for these two diseases. French guidelines recommend short-term CS as a first-line treatment during asthma exacerbation (0,5 to 1mg/kg/day, not exceeding 60mg/day, for at least 5 to 7 days) or as a second-line treatment for COPD exacerbation (5 days, 30 to 40mg/day). However, these recommendations are not without limitations; they are primarily based on studies conducted in hospital settings, raising questions about the generalizability of their results to primary care, and as they employ a "one size fits all" strategy, they do not take into account the phenotypic heterogeneity of different patients. Moreover, repeated short-term CS courses generate side effects that even at low doses can appear early in young asthma patients, and they can exacerbate pre-existing comorbidities in COPD patients. The concept of a threshold dose should be employed in routine practice in view of accurately assessing the risk of side effects. In the near future, it will be important to consider recently published data supporting the use of predictive biomarkers for responses to CS, particularly in COPD cases.

Asthma is affecting 4-5% of all adults (10% of children) in Germany, ≥ half are inadequately controlled. In 2019 up to 54 thousand patients suffered from severe uncontrolled asthma, 52% were treated/co-treated by pneumonologists. 45% of them had continuous oral corticosteroid (OCS)- and short-acting β2-agonist (SABA) overuse for ≥2 years. The aim of the current study was to analyze the main treatments, escalation schemes and the adherence to the GINA recommendations.

Retrospective analysis in 2021 based on data from January to December 2019 in Germany, using the IQVIA™ LRx prescription database and the IQVIA™ Disease Analyzer database containing anonymized electronic medical records as the main data sources.

In 2019 25,200 patients with severe, uncontrolled asthma treated in a pneumonologist´s practice in Germany received GINA 3 (0,4%), GINA 4 (76%) or GINA 5 therapy (24%) during the study year compared to 59% GINA 5 therapy in the 5-10% (1,500-3,000) co-treated in a specialized outpatient department. In Pneumonologists` practices the most frequent choice in GINA 5 was OCS in 69% of patients (biologicals 37%, long-acting muscarinic antagonist (LAMA) 20%) compared to 66% biologicals, 55% OCS, and 25% LAMA in the outpatient department. 54,958 of 613,000 GINA 4/5 patients were treated with OCS, 9,725 even with doses above the so called "Cushing threshold" for prednisolone of 2700 mg/year. After introduction of a biological treatment, patients reduced their SABA prescriptions by 28%, OCS by 55%, and OCS overall exposure by 40%, one-third did not need OCS anymore.

In 75% of patients with uncontrolled asthma for ≥2 years therapy was not escalated beyond GINA 4 or low dose OCS was used as the most frequent add-on treatment in GINA 5 contradictory to treatment recommendations. Use of biologics reduced on demand rescue medication and OCS use.

Over the last two decades, we have witnessed great advancements in our understanding of the immunological pathways of asthma, leading to the development of targeted therapies, such as biologic drugs, that have radically and definitively changed the clinical outcomes of severe asthma. Despite the numerous therapeutic options available, ~4-10% of all people with asthma have severe or uncontrolled asthma, associated with an increased risk of developing chronic oral corticosteroid use, fixed airflow limitation, exacerbations, hospitalization and, finally, increased healthcare costs. The new concept of disease modification in asthma comes from the evolution of asthma management, which encompasses phenotyping patients with different inflammatory endotypes characterizing the disease, followed by the advent of more effective therapies capable of targeting the proximal factors of airway inflammation. This treat-to-target approach aims to achieve remission of the disease. Because the novel treatment paradigm for severe asthma with the advent of biologic therapies is no longer clinical control but rather clinical remission - a step closer to the concept of cure - a deeper and more accurate understanding of the critical causal mechanisms and endotypes of asthma is necessary to achieve the goal of clinical remission, which has the potential to generate real life-changing benefits for patients. This review aims to frame the evolution of the debated concept of clinical remission and provide clinicians with insights that may be helpful in achieving remission in the greatest number of patients.

Initiated by the Severe Asthma Network Italy (SANI), this study aims to explore asthma patients' perceptions of disease severity, differentiating between mild and severe asthma. The objective is to identify factors influencing tailored treatment strategies for varying disease severities and to provide insights into asthma care in Italy.

Conducted between November 2020 and January 2021, a survey using Computer-Assisted Personal Interviewing (CAPI) collected data from 308 Italian adults, representing the population. A 25 item multiple choice questionnaire covered asthma diagnosis, symptoms, treatment approaches, associated conditions, and quality of life.

Among participants, 83.8% reported having mild asthma, while 16.2% had severe asthma. Severe asthma patients had longer disease durations, more severe symptoms, frequent exacerbations, and higher hospital/ER visits. Although treatment adherence and symptom profiles generally aligned with international guidelines for self reported severe asthma, 22% of self identified mild asthmatics experienced severe respiratory symptoms. Oral corticosteroid (OCS) use was observed in 50% of severe cases and 22% of mild cases. Adherence was higher in severe asthma patients (76%) versus mild asthma patients (28%). Both groups experienced comorbidities, with 96% of severe asthmatics and 72% of mild asthmatics reporting impaired quality of life.

This study highlights the disparity between clinical categorization and patient perceptions of asthma severity. The prevalence of self reported severe asthma exceeds literature data. The burden of mild asthma remains significant, with treatment approaches not fully aligned, particularly regarding disproportionate OCS use. Addressing this gap requires enhancing patient education, improving diagnostic practices, and promoting adherence.

People with severe asthma remain at risk of toxicity from maintenance oral corticosteroid (OCS) use and/or frequent OCS burst therapy. Cumulative exposures above 500-1000 mg prednisolone are associated with adverse effects, and recently OCS stewardship principles were promulgated to guide OCS prescription.

To examine real-world registry data to quantify OCS burden, ascertain trends over time in prescription and assess whether opportunities to implement steroid-sparing strategies were utilised.

Participants were enrolled in the Australasian Severe Asthma Registry for the period 2013-2021. Assessments were taken at enrolment and then annual follow-up, which included asthma control and OCS use. Descriptive analyses were performed, and subgroups were compared at baseline and over time.

Nine hundred and twenty-four participants were evaluated and 215/924 (23%) were taking maintenance OCS at baseline, with 44% and 32% of participants having exposure to ≥500 or 1000 mg of OCS respectively in the prior year. Twelve months later, an additional 10% and 9% of participants reached cumulative doses of 500 or 1000 mg. People exceeding thresholds had ongoing poor asthma control. At baseline, 240/924 (26%) people were treated with asthma biological therapy. An additional 83 (12%) participants were identified as potentially benefiting from this steroid-sparing medication. Of these patients, only 23% commenced a biologic agent in the next 12 months.

A large national asthma registry identifies exposure to toxic cumulative doses of OCS in more than a third of participants, with further subsequent cumulative dose escalation over 2 years. Steroid-sparing strategies were often not employed, highlighting the need for implementation of OCS stewardship initiatives.

In the Middle East and Africa (MEA) region, overuse of oral corticosteroids (OCS) for asthma management, both as burst and maintenance therapy, poses a significant challenge. Gaps in knowledge regarding the need to taper OCS in patients with severe asthma and the use of OCS in comorbid conditions have been noted. OCS stewardship can help attain optimal and effective OCS tapering along with reducing OCS overuse and over-reliance. In this paper, we discuss current practices regarding the use of OCS in asthma, globally and in the MEA region. Expert recommendations for achieving OCS stewardship in the MEA region have also been presented. Regional experts recommend increasing awareness among patients about the consequences of OCS overuse, engaging community pharmacists, and educating primary healthcare professionals about the benefits of prompt appropriate referral. Innovative local referral tools like ReferID can be utilized to refer patients with asthma to specialist care. The experts also endorse a multidisciplinary team approach and accelerating access to newer medicines like biologics to implement OCS stewardship and optimize asthma care in the MEA region.

The use of oral corticosteroids for prolonged periods may be associated with adverse events (AEs). Nevertheless, the risk of AEs with oral corticosteroids, especially among patients with atopic dermatitis (AD), has not been comprehensively investigated and lacks evidence on duration of treatment.

To assess the association between long-term exposure to oral corticosteroids and AEs among adult patients with AD.

This nested case-control study used data from the Health Insurance Review and Assessment Service database of South Korea between January 1, 2012, and October 31, 2021, which included 1 year prior to the cohort entry date of January 1, 2013, for assessing exclusion criteria and baseline characteristics, and 1 year after the study end date of October 31, 2020, to ensure a minimum duration for assessing exposure. Among the population of adults with AD, patients diagnosed with any of 11 AEs were matched with patients who had never received a diagnosis of any of the 11 AEs.

Long-term use of oral corticosteroids was defined as cumulative supply of more than 30 days or more than 90 days of oral corticosteroid prescription per year.

We used multivariable conditional logistic regression analyses to measure the risk of 11 individual outcomes (osteoporosis, fracture, type 2 diabetes, hyperlipidemia, hypertension, myocardial infarction, stroke, heart failure, avascular necrosis, cataract, or glaucoma) as the composite outcome, controlling for potential confounders. We further classified the composite outcome to individual outcomes to evaluate the AE-specific risk.

Among 1 025 270 patients with AD between 2013 and 2020, 164 809 cases (mean [SD] age, 39.4 [14.8]; 56.9% women) were matched with 328 303 controls (mean [SD] age, 39.3 [14.7]; 56.9% women) for sex, age, cohort entry date, follow-up duration, and severity of AD, where the balance of most baseline characteristics was achieved. A total of 5533 cases (3.4%) and 10 561 controls (3.2%) were exposed to oral corticosteroids for more than 30 days, while 684 cases (0.4%) and 1153 controls (0.4%) were exposed to oral corticosteroids for more than 90 days. Overall, there was no increased risk of AEs with use of oral corticosteroids for more than 30 days (adjusted odds ratio [AOR], 1.00; 95% CI, 0.97-1.04), whereas the risk was slightly higher with use of oral corticosteroids for more than 90 days (AOR, 1.11; 95% CI, 1.01-1.23). The small elevation in experiencing an AE was observed with each cumulative or consecutive year of ever long-term use.

This case-control study found a slightly increased risk of AEs associated with use of oral corticosteroids for more than 90 days per year, which warrants future research to fully elucidate the observed findings.

Background: The standard therapeutic regimen for idiopathic chronic eosinophilic pneumonia (ICEP) involves the administration of oral corticosteroids (OCS). However, a notable proportion of individuals experience recurrent episodes after the tapering or cessation of OCS during the course of ICEP. There has been a growing interest in exploring alternative treatment modalities for patients with ICEP at heightened risk of relapse. Objective: The aim of this study was to assess the efficacy of mepolizumab at a dose of 100 mg administered every 4 weeks in preventing relapses of ICEP and its impact on the clinical outcomes. Methods: This retrospective clinical observational study used real-world data to assess the impact of mepolizumab on patients diagnosed with ICEP accompanied by severe asthma. Demographic information and clinical characteristics were extracted from medical records. The study examined the effect of mepolizumab on the annual relapse rate, OCS dose, eosinophil count, and respiratory function parameters. Results: All patients included in the study, with a median (range) follow-up period of 19 months (4-40 months), the annual relapse rate decreased from 0.33 to 0 after the initiation mepolizumab. In addition, the maintenance OCS dose, expressed in methylprednisolone equivalents, declined from 4 mg/day to 0 mg/day. A reduction in the blood eosinophil count was observed, alongside a partial improvement in respiratory function test results among the patients. Conclusıon: A dose regimen of 100 mg of mepolizumab administered every 4 weeks emerges as a promising and well-tolerated therapeutic approach for averting relapses of ICEP.

To evaluate dexamethasone prescribing practices, patient adherence, and outcomes by dosing regimen in children with acute asthma discharged from the emergency department (ED).

Prospective study of children 2-18 years treated with dexamethasone for acute asthma prior to discharge from an urban, tertiary care ED between 2018 and 2022. Demographics, clinical characteristics, ED treatment, and discharge prescriptions were collected via chart review. The exposure was discharge prescription (additional dose) versus no discharge prescription for dexamethasone. The primary outcome was treatment failure, defined as return ED visit, unplanned primary care visit, and/or ongoing bronchodilator use. Secondary outcomes included medication adherence, symptom persistence, quality-of-life, and school/work absenteeism. Outcomes were assessed by telephone 7-10 days after discharge.

564 subjects were enrolled; 338 caregivers (60%) completed follow-up. Children were a median age 7 years, 30% Black or African American, 49% Hispanic, and 79% had public insurance. A discharge prescription for dexamethasone was written for 482 (86%) children and was significantly associated with exacerbation severity, number of combined albuterol/ipratropium treatments, and longer length of stay. There was no difference in treatment failure between the discharge prescription and no discharge prescription groups (RR 0.87; 0.67, 1.12), including after adjusting for potential confounders; there was no difference between groups in secondary outcomes.

Prescription for an additional dexamethasone dose was not associated with reduced treatment failure or improved outcomes for children with acute asthma discharged from the ED. Single, ED-dose of dexamethasone prior to discharge may be sufficient for children with mild to moderate asthma exacerbations.

Severe asthma is associated with an increased risk for exacerbations, reduced lung function, fixed airflow obstruction, and substantial morbidity and mortality. The concept of remission in severe asthma as a new treatment goal has recently gained attention due to the growing use of monoclonal antibody therapies, which target specific pathologic pathways of inflammation. This review evaluates the current definitions of asthma remission and unveils some of the barriers for achieving this state in the severe asthma population. Although there is no unified definition, the concept of clinical remission in asthma should be based on a sustained period of symptom control, elimination of oral corticosteroid exposure and exacerbations, and stabilization of pulmonary function. The conjugation of these criteria seems a realistic treatment target in a minority of asthmatic patients. Some unmet needs in severe asthma may affect the achievement of clinical remission. Late intervention with targeted therapies in the severe asthma population may increase the risk of corticosteroid exposure and the development of irreversible structural airway changes. Moreover, airway infection is an important component in persistent exacerbations in patients on biologic therapies. Phenotyping exacerbations may be useful to guide therapy decisions and to avoid the liberal use of oral corticosteroids. Another challenge associated with the aim of clinical remission in severe asthma is the multifaceted interaction between the disease and its associated comorbidities. Behavioural factors should be evaluated in case of persistent symptoms despite optimised treatment, and assessing biomarkers and targeting treatable traits may allow for a more objective way of reaching remission. The concept of clinical remission will benefit from an international consensus to establish unifying criteria for its assessment, and it should be addressed in the future management guidelines.