Pulmonary Therapy最新文献

The latest advances in asthma treatment have highlighted the significance of eosinophilia and the possible role of some pro-eosinophilic mediators, like interleukins (IL) IL-5, IL-4/IL-13, and IL-33 in the disease's pathogenesis. Considering that a subgroup of patients with chronic obstructive pulmonary disease (COPD) may have blood eosinophilia akin to that seen in asthma, numerous studies in the last decade have suggested that eosinophilic COPD is a separate entity. While the exact role of blood eosinophils in the pathophysiology of COPD remains unclear, eosinophilia seems to increase the effectiveness of corticosteroid therapy. Currently, monoclonal antibodies targeting the interleukins (IL-5, IL-4, IL-13, and IL-33) or their receptors are being investigated in patients with COPD belonging in T2-high endotype. This review focuses on the mechanisms of eosinophilia in COPD, the effects of eosinophilia on disease outcome, and examines the most recent data on the use of peripheral blood eosinophilia in treating patients with COPD. Finally, we emphasize the current implication of monoclonal antibodies in COPD in the context of eosinophilic airway inflammation.

Introduction: The MERIT study in Malaysia is a real-world retrospective, observational, multicenter study that evaluated asthma control in patients with uncontrolled asthma who were switched from as-needed (pro re nata [PRN]) budesonide/formoterol or inhaled corticosteroid (ICS) whenever a short-acting beta-agonist (SABA) was taken, to proactive regular dosing of fluticasone propionate/salmeterol (FP/SAL PRD).

Methods: Data from the medical records of patients who were stepped up to FP/SAL PRD were extracted retrospectively at baseline and follow-up (between 3 and 6 months after stepping up to FP/SAL PRD). The primary endpoint was the percentage of patients with improvement in asthma control assessed via the Asthma Control Test (ACT). Secondary endpoints included safety and the percentage of patients with moderate and severe exacerbations. Additionally, patient-reported use of reliever medication, systemic corticosteroids, emergency department visits, or hospitalization was also analyzed.

Results: One hundred twenty patients with uncontrolled asthma who were stepped up to FP/SAL PRD were enrolled in the study. Of these, 76 (63.3%) patients were on prior budesonide/formoterol PRN, and 44 (36.7%) were on prior ICS with SABA PRN treatment. After stepping up to FP/SAL PRD with a mean follow-up of 5.8 months, 110 (91.7%) patients achieved asthma control at the follow-up visit (p < 0.001). Similar improvements were observed regardless of prior PRN regimen. A statistically significant improvement was observed in the mean ACT score at the follow-up visit (p < 0.0001). The proportion of patients with moderate and severe exacerbations was also reduced after stepping up to FP/SAL PRD, with no adverse events reported. Over 80% of patients reported a decrease in the use of systemic corticosteroids, visits to the emergency department, or hospitalization.

Conclusion: This study highlights the effectiveness of the FP/SAL PRD treatment approach in patients with uncontrolled asthma on a PRN treatment regimen.

Introduction: Escalation to single- or multiple-inhaler triple therapy (SITT; MITT) is a recommended option for patients with asthma who remain uncontrolled by medium-dose inhaled corticosteroid/long-acting β₂-agonist; however, characterization of elderly users of triple therapy is limited. This real-world cohort study describes demographics and clinical characteristics of elderly patients with asthma with and without comorbid chronic obstructive pulmonary disease (COPD) who are new users of triple therapy, and asthma treatment patterns preceding triple therapy initiation.

Methods: This retrospective cohort study used administrative claims data from the Optum Clinformatics Data Mart database. Eligible patients were ≥ 65 years of age with asthma or with asthma and comorbid COPD who initiated either triple therapy with single-inhaler fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI; 100/62.5/25 μg) or MITT between September 18, 2017 and September 30, 2020. Demographics, clinical characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns were described in the 12-month period before triple therapy initiation (baseline period).

Results: In total, 15,557 patients were included. Among FF/UMEC/VI initiators with asthma (N = 635) mean age was 73.3 years and 66.6% were female. During the baseline period, > 75% of patients used controller therapy, > 92% used rescue medications, 27.9% experienced ≥ 1 asthma-related exacerbation, with mean annual exacerbation rate of 0.42, and mean all-cause healthcare costs were $23,407. Patients with asthma initiating MITT and patients with asthma and comorbid COPD initiating FF/UMEC/VI or MITT had similar characteristics, healthcare resource utilization, healthcare costs, and asthma treatment patterns to FF/UMEC/VI initiators with asthma.

Conclusions: Triple therapy is often initiated following use of other asthma controller medications in real-world practice. Substantial rescue medication use and high disease and economic burden among this elderly patient population suggest that their asthma was not adequately controlled prior to triple therapy initiation. This retrospective study provides an early profile of elderly patients with asthma in the USA.

Introduction: Evidence for use of pulmonary arterial hypertension targeted-therapies in patients with chronic thromboembolic pulmonary hypertension (CTEPH) is limited. In MERIT-1, the endothelin receptor antagonist macitentan improved hemodynamic and functional parameters versus placebo in patients with inoperable CTEPH over a 24-week double-blind (DB) period. Its open-label (OL) extension study (MERIT-2) provides long-term safety/efficacy data.

Methods: MERIT-2 (NCT02060721) was a multicenter, single-arm, OL, phase 2 extension study of MERIT-1. Patients completing MERIT-1 were eligible to receive 10 mg macitentan once-daily in MERIT-2. Safety and efficacy (6-min walk distance [6MWD] and change in World Health Organization functional class [WHO FC]) were assessed in all patients in MERIT-2 regardless of treatment received in DB (All patients MERIT-2 OL macitentan 10 mg group) and the subgroup of patients receiving DB macitentan in MERIT-1 (Long-term [DB/OL] macitentan 10 mg subgroup).

Results: Of the 80 patients randomized in MERIT-1, 76 entered MERIT-2 (All patients MERIT-2 OL macitentan 10 mg group): 40 who received DB macitentan (DB-macitentan patients) and 36 DB placebo (DB-placebo patients). Median (interquartile range) macitentan exposure in the All patients MERIT-2 OL macitentan 10 mg group was 45.5 (26.0, 66.1) months. During the OL period, treatment-emergent adverse events (AE) were reported in 72 (94.7%) patients; most frequent were worsening of pulmonary hypertension (19.7%), decreased hemoglobin (18.4%) and upper respiratory tract infection (15.8%). Fourteen (18.4%) patients died; none were assessed as macitentan-related. At Month 6 post-OL baseline, mean (standard deviation) change in 6MWD was - 0.4 m (43.62) for DB-macitentan patients and 10.7 m (45.63) for DB-placebo patients; the majority had unchanged (83.3%) or improved (12.5%) WHO FC. Safety/efficacy analyses were consistent in the Long-term (DB/OL) macitentan 10 mg subgroup.

Conclusion: These analyses provide long-term safety/efficacy data in patients with inoperable CTEPH treated with macitentan. No unexpected safety findings occurred; reported AEs were consistent with the known safety profile of macitentan. At 6 months post-OL baseline, DB-placebo patients modestly improved 6MWD; DB-macitentan patients maintained improvements observed in MERIT-1. WHO FC was largely unchanged.

Trial registration: ClinicalTrials.gov Identifiers: NCT02021292; NCT02060721.

Introduction: This real-world study assessed the effectiveness of bebtelovimab (BEB) versus nirmatrelvir/ritonavir (NR) among outpatients with COVID-19 during the Omicron variant era.

Methods: We conducted a cohort study evaluating patients treated with BEB or NR from February to August 2022 (study period). Follow-up began the day after treatment and continued for 30 days. Cohorts were constructed using de-identified electronic health record data from TriNetX Dataworks USA. The study assessed 30-day all-cause hospitalization or death (composite) using the risk difference (RD) and 95% confidence interval (95% CI).

Results: Unmatched cohorts included 12,920 BEB- and 70,741 NR-treated patients. After exact matching on key baseline covariates (age > 65 years, immunocompromised, recent emergency department [ED] visit, and COVID-19 vaccination) and high-dimensional propensity score matching (1:1) on a broader set of covariates, 5827 patients were included in each cohort. BEB-treated patients were older and had more comorbidities compared to NR-treated patients prior to matching. After matching, baseline characteristics were well balanced. The cumulative incidence of the primary outcome (hospitalization or death) was 2.0% and 1.8% for BEB and NR, respectively (RD 0.2%; 95% CI - 0.3%, 0.7%). The upper bound of the RD 95% CI (0.7%) excluded the noninferiority margin (1.795%), demonstrating that BEB was not inferior to NR. The RDs of the secondary outcomes were (BEB vs NR): hospitalization (RD 0.1%; 95% CI - 0.4%, 0.6%); ED visit (RD 0.5%; 95% CI - 0.3%, 1.3%); and death (RD 0.09%; 95% CI - 0.003%, 0.2%). Results from subgroup, sensitivity, and linked analyses (EHR + claims + mortality data) were consistent with the main results.

Conclusion: Treatment with BEB was not inferior to NR with respect to 30-day all-cause hospitalization or death. The risk of secondary outcomes was not different for patients treated with BEB compared to NR.

Introduction: Asthma is a complex condition characterized by airway inflammation. Interleukin-6 (IL-6) plays a significant role in asthma pathogenesis through its effects on T cells and its association with pro-inflammatory responses. Both lung and circulating IL-6 levels are elevated in asthma. IL-6 is positively associated with disease severity, frequent exacerbations, and impaired lung function, all of which can be observed clinically. We developed an IL-6 cut-off model to examine the association between high IL-6, race, high body mass index (BMI), metabolic disease, and asthma severity as assessed by reduced lung function.

Methods: This study utilized the Coronary Artery Risk Development in Young Adults (CARDIA) database, comprised of 5115 adults, to investigate the relationship between IL-6 levels, asthma, race, and metabolic dysfunction. A "healthy" subset of 427 patients was used to compute the IL-6 cut-off. IL-6 levels within detection limits (0.15-12 pg/mL) were analyzed. The IL-6 cut-off was determined using the 95th percentile of log-transformed IL-6 values for lean (BMI < 25) and healthy individuals. Specific cut-offs were established for racial groups. Statistical analyses involved comparing patient characteristics between high and low IL-6 groups, regression analyses, and assessment of factors influencing lung function changes.

Results: Using an IL-6 cut-off of 4.979 pg/mL, the cohort was divided into high and low IL-6 groups. High IL-6 correlated with Black race, higher BMI, hypertension, and markers of metabolic dysfunction, e.g., elevated HbA1c, C-reactive protein (CRP), and reduced lung function. Multivariable analysis linked high IL-6 with male gender, high BMI, Black race, HbA1c, CRP, and inversely with lung function and total cholesterol. Obesity showed a consistent positive association with elevated IL-6, regardless of the presence or absence of asthma. Patients with asthma and high IL-6 were more likely to be Black and showed increased CRP. Lung function was lowest in non-lean, high IL-6 patients with asthma, with similar trends in non-lean (BMI ≥ 25) patients without asthma.

Conclusion: This study underscores the significant association between IL-6, asthma, obesity, and metabolic dysfunction. Elevated IL-6 correlates with asthma severity, particularly in individuals with obesity. Future research should explore anti-IL-6 therapies for specific phenotypes, such as obesity-related asthma. These findings advance our understanding of asthma and the role of IL-6 in its pathogenesis.

The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) in the same patient is referred to as overlap syndrome (OS). Patients with OS suffer more frequently from cardiovascular disease (CVD) and carry a higher risk of COPD-related exacerbations than patients with COPD alone, especially when OSA is left untreated. Based on recent evidence, triple therapy, namely inhaled corticosteroid/long-acting muscarinic antagonist/long-acting beta-agonist (ICS-LABA-LAMA), is a treatment strategy in COPD patients with a history of exacerbations and/or CVD comorbidity. While several studies have previously focused on the role of triple therapy in patients with COPD, none of these has examined the potential benefits of this treatment in patients with COPD and concomitant OSA. Moreover, it is unknown whether patients with OS should be treated with triple therapy starting from their initial assessment, since they represent a population at risk for future exacerbations, in comparison to patients with COPD alone. In this commentary, we discuss these issues and highlight the need for further studies regarding the role of triple therapy in outcomes for patients with OS.

Introduction: Obstructive sleep apnea (OSA) is a common sleep-related breathing disorder among children with attention deficit hyperactivity disorder (ADHD). This study aims to determine the prevalence of OSA in children with ADHD, compare the differences in clinical characteristics between children with ADHD-OSA and those without OSA (ADHD-nonOSA), and to identify the correlation between OSA and ADHD in children.

Methods: This cross-sectional descriptive study was conducted on 524 children with ADHD, aged 6-12 years, at the Vietnam National Children's Hospital from October 2022 to September 2023. Respiratory polygraphy was used to determine the prevalence of OSA in this study population; clinical data of children with ADHD-OSA and ADHD-nonOSA were collected and analyzed in each group. The severity of ADHD symptoms was measured by the Vanderbilt ADHD Parent Diagnosis Rating Scale (VADPRS questionnaire), and the severity of OSA was defined by Apnea-Hypopnea Index (AHI).

Results: The prevalence of OSA in children with ADHD was 23.3%, with the majority of moderate-to-severe OSA. Significant differences were observed in sleep onset time, total sleep duration, and various sleep-related behaviors, such as bedtime resistance and difficulty waking up in the morning, between children with ADHD-OSA and ADHD-nonOSA (p < 0.001, p < 0.001, p < 0.05, and p < 0.005, respectively). The severity levels of inattention, hyperactivity, and behavioral disorders were significantly higher in children with moderate-to-severe OSA compared to those with mild OSA (p < 0.005, p < 0.005, and p < 0.001, respectively). There were significant correlations between AHI with inattention scores (r = 0.677; p < 0.0001), hyperactivity scores (r = 0.438; p = 0.05), behavioral disorder scores (r = 0.342; p < 0.05), and anxiety/depression scores (r = 0.357; p < 0.05) measured by VADPRS questionnaire.

Conclusions: OSA is a common sleep-related breathing disorder in children with ADHD, which might exacerbate ADHD symptoms. Thus, screening of OSA in children with ADHD is essential during the management of ADHD in this population.

Introduction: Elexacaftor/tezacaftor/ivacaftor (ETI) has been shown to substantially improve clinical outcomes among people living with cystic fibrosis (pwCF). The impact of ETI on health care resource utilization in the context of universal health care is largely unknown. We aimed to assess the impact of ETI on hospital and non-hospital health care resource utilization in a national cohort of pwCF up to 2 years after ETI initiation.

Methods: We included all pwCF aged 12 years or older in the Danish Cystic Fibrosis Cohort initiating ETI therapy between 1 September 2020 and 31 December 2022. The following health care contacts were reported: acute and elective hospitalizations, acute and elective outpatient contacts, general practitioner (GP) visits, other specialist visits, physiotherapist/chiropractor visits, pharmacy visits, and blood sampling appointments. Pre- and post-ETI data were analyzed using logistic and linear regression models estimating number of visits, days in hospital, and odds ratios (ORs) for one monthly contact.

Results: A total of 283 pwCF initiated ETI in the study period. At 24 months post-ETI, utilization of the following health care resources was reduced: elective hospitalizations [OR 0.20 (95% CI: 0.08; 0.50)], elective outpatient hospital contacts [0.70 (0.57; 0.86)], pharmacy visits [0.56 (0.45; 0.71)], and blood sampling appointments [0.61 (0.49; 0.77)]. Number of contacts per month was reduced for the aforementioned outcomes, as well as number of days in hospital for elective hospitalizations. A downward but not statistically significant trend was observed for acute hospitalizations. No significant change was observed for acute outpatient visits, GP visits, other specialist visits, or visits to a physiotherapist/chiropractor.

Conclusion: In a national cohort of pwCF, ETI was associated with substantial reductions in elective hospitalizations, elective outpatient contacts, duration of elective hospitalizations, pharmacy visits, and blood sampling appointments, sustained 2 years post-ETI initiation. These findings highlight the real-world effectiveness of ETI in the context of a universal health care system.