Pulmonary Therapy最新文献

Introduction: Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare, progressive pulmonary hypertension characterized by chronic fibrotic thrombi. Treatment includes surgical, endovascular, and pharmaceutical options. With varied treatments, it is essential to understand how they are deployed across real-world settings. We aimed to describe clinical characteristics, treatment patterns, and quality of life across real-world settings in the USA.

Methods: Data were drawn from the Adelphi Real World CTEPH Disease Specific Program™, a cross-sectional survey of US physicians and patients, conducted September 2023-May 2024. Physicians recruited by local fieldwork agents using a short screening questionnaire provided demographics, clinical characteristics, and treatment patterns for 1-6 consecutively consulting patients with right heart catheterization confirmed CTEPH. These patients self-completed a form containing the EQ-5D-5L, visual analog scale (EQ-VAS), workplace and activity impairment scale (WPAI), pulmonary arterial hypertension symptom and impact scale. Data were stratified by treatment setting (accredited or nonaccredited pulmonary hypertension center). Analyses were descriptive.

Results: In total, 98 physicians provided data on 153 patients, of whom 53 completed the patient self-complete form. Mean (standard deviation) patient age was 59.2 years, 59.5% female, and 73.2% considered operable. Of those who had undergone a surgery/procedure (n = 68), 82.1% had undergone pulmonary thromboendarterectomy (PTE), and 19.1% balloon pulmonary angioplasty (BPA). Overall, 82.4% were prescribed any pharmaceutical medication for their CTEPH; of those treated, 81.0% were prescribed anticoagulants. Monotherapy (45.7%) was the most reported regimen in nonaccredited settings; for accredited settings, this was dual therapy (45.5%). EQ-5D-5L scores were low with nearly a quarter of patients reporting problems with usual activities and mobility, and 26.4% needing to change work patterns.

Conclusions: Though treatment patterns generally followed guidelines, BPA was potentially underutilized. Dyspnea was common, despite treatment, with patients experiencing reduced quality of life, highlighting an unmet need.

Introduction: Fractional exhaled nitric oxide (FeNO) is an important type 2 (T2) asthma biomarker. Home-based FeNO monitoring can provide longitudinal data better reflecting the variable nature of T2 inflammation versus single-point data. We sought to compare longitudinal mean FeNO and variability (CV) in relation to asthma control, and to compare detection rate of T2_FeNO inflammation at diagnostic (≥ 40 ppb in GINA 1) and on-treatment (≥ 25 ppb in GINA 2-5) cutoffs during home versus clinic measurements.

Methods: This was an observational study with once-daily home-based FeNO (Vivatmo me) and symptom diary in patients with asthma of different GINA steps performed over 3 months. Clinic FeNO, forced expiratory volume in 1 s (FEV₁), and 5-item asthma control questionnaire (ACQ-5) scores were also collected at two visits (enrolment/study end).

Results: We enrolled 85 patients (n = 23 step 1, n = 37 steps 2-3, and n = 25 steps 4-5). Mean FeNO over 3 months was highest in uncontrolled steps 4-5 (p = 0.006), and FeNO variability in steps 2-3 (p = 0.046). Subjects with optimal control (ACQ < 0.75 both visits) had comparable mean FeNO values, but fewer patients with CV above the median vs. suboptimally controlled patients (39.1% vs. 54.1%; p = 0.03). In GINA 1, FeNO CV was lower in optimally controlled patients (p = 0.10). Mean FeNO was higher on symptomatic asthma days, particularly in step 1 (p = 0.002), with similar trends during loss of asthma control phases. Home FeNO increased the detection rate of T2_FeNO inflammation at a diagnostic cutoff (≥ 40 ppb, step 1) from 8.7% (clinic FeNO) to 47.8% of subjects, and of on-treatment T2_FeNO inflammation in GINA steps 2-3 and 4-5 from 58.3% to 83.3%, and 64% to 96%, respectively.

Conclusion: Home-based FeNO provides important information about airway inflammation, distinct and complementary to symptom control. Detection of T2_FeNO inflammation is facilitated at all GINA steps at diagnostic and predictive/prognostic cutoffs, with important implications for management and diagnosis.

Trial registration: German Clinical Trial Register (DRKS) DRKS00029118, registered July 1, 2022.

Introduction: In Italy, elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) in combination with ivacaftor was reimbursed starting July 2021 for use in people with cystic fibrosis (CF) aged ≥ 12 years homozygous for F508del mutation or heterozygous with at least one F508del allele and with a minimal function mutation. This study assessed the impact of ELX/TEZ/IVA on real-world outcomes among this population in Italy.

Methods: This observational study used data from Verona CF Center from October 2018 to December 2022 to describe the impact of ELX/TEZ/IVA on individuals aged ≥ 12 years with ≥ 1 F508del allele on lung function and healthcare resource utilization (HCRU). Lung function (percent predicted forced expiratory volume in 1 s [ppFEV₁]), hospitalizations, outpatient visits, pulmonary exacerbations (PEx), and prescribed medications were analyzed during baseline and follow-up periods (12 months pre- and post-ELX/TEZ/IVA initiation, respectively) and reported as change from baseline.

Results: A total of 149 individuals were included (mean [standard deviation, SD] age: 32.6 [12.25] years). A mean improvement in ppFEV₁ of +14.38 percentage points (95% confidence interval [CI] 12.65; 16.10) was observed during the follow-up period. An 87.2% reduction in the annualized PEx rate (rate ratio: 0.128 [95% CI 0.085; 0.187]) and an 85.4% reduction in the annualized hospitalization rate (rate ratio: 0.146 [95% CI 0.096; 0.213]) were observed during follow-up compared to baseline. Reductions in the proportion of individuals requiring prescription medications, including intravenous antibiotics, mucolytic agents, and bronchodilators, were observed.

Conclusion: Substantial improvements in lung function and reductions in HCRU were observed after treatment with ELX/TEZ/IVA in the Verona CF Center. Results contribute to the growing evidence of country-specific real-world data on the positive impact of ELX/TEZ/IVA.

Introduction: Dry powder inhalers (DPIs) have a 20-40-fold lower carbon footprint compared to pressurized metered-dose inhalers (pMDIs). Switching from pMDI to DPI is therefore beneficial from an environmental perspective, but many health care professionals are concerned that this may worsen treatment outcomes in asthma and chronic obstructive pulmonary disease (COPD).

Methods: We analyzed patient outcomes and carbon footprints of switching inhaler treatment from pMDI to DPI. We performed a post hoc analysis on clinical outcomes data from a 12-week real-world, non-interventional study of adult patients with asthma or COPD who switched treatment from pMDI to the budesonide-formoterol Easyhaler DPI. Clinical end points included asthma control test (ACT), Mini-Asthma Quality of Life Questionnaire (Mini-AQLQ), lung function tests, and reliever use (asthma), and COPD assessment test (CAT), and modified Medical Research Council dyspnea scale (mMRC) (COPD). In the carbon footprint calculation, we used estimates from the Montreal Protocol for pMDI and for DPI the estimate as reported.

Results: Among all 237 patients (142 asthma, 95 COPD) by switching their treatment clinical improvements were observed in all the outcome measures (p < 0.001). Furthermore, the need for reliever medication decreased among patients with asthma (p < 0.001). The amount of estimated kg CO₂e emissions per year for maintenance treatment was 97.0% lower for the DPI than for pMDI. For reliever medication among patients with asthma, it was 99.6% lower. Among them, the emission savings could amount to approximately 131 kg CO₂e annually. This is of similar magnitude, as individual high-impact environmental actions such as eating a plant-based diet or purchasing green energy.

Conclusions: Our results show that disease control was maintained among patients with asthma or COPD when they switched from pMDI to DPI, while the carbon footprint of inhaler treatment was reduced.

Introduction: Pulmonary arterial hypertension (PAH) is a rare, progressive disease resulting from elevated pulmonary arterial pressure leading to right ventricular failure and death. Optimal adherence and persistence to medical therapy are necessary to improve outcomes. The objective of this study was to characterize adherence and persistence to first-line PAH therapies in patients newly initiating treatment.

Methods: This retrospective cohort study utilized Komodo Research Database claims data. Adults initiating therapy were identified based on ≥ 1 claim for a phosphodiesterase 5 inhibitor (PDE5i) and/or an endothelin receptor antagonist (ERA) from January 1, 2017, to June 30, 2022 (index date), continuous medical and pharmacy health plan enrollment for ≥ 12 months before and including index, ≥ 1 inpatient or ≥ 2 outpatient claims for pulmonary hypertension/PAH, and ≥ 1 claim for right heart catheterization. Adherence was measured by proportion of days covered (PDC); nonadherence was defined as PDC < 80%. Persistence was defined as time from index to treatment discontinuation (gap in therapy > 60 days). Propensity score matching was utilized 1:1:1 across groups.

Results: A total of 9176 patients met the study criteria (6989 PDE5i, 1006 ERA, 1181 dual combination). After matching, each cohort included 714 patients. Median (95% confidence interval) persistence was highest for ERA monotherapy (26.5 [19.0-33.0] months), followed by dual combination therapy (19.8 [16.6-23.4] months) and PDE5i monotherapy (12.9 [10.8-17.4] months)-P = 0.019, dual combination versus ERA; P = 0.026, dual combination versus PDE5i. Nonadherence was highest with dual combination therapy (35.4%), followed by PDE5i monotherapy (17.1%) and ERA monotherapy (11.9%)-P < 0.001, dual combination versus each monotherapy.

Conclusions: Adherence to initial PAH therapy is suboptimal, especially with upfront dual combination therapy. Persistence was highest for ERA monotherapy, followed by dual combination therapy and PDE5i monotherapy. Strategies to improve adherence and persistence are crucial to optimizing outcomes.

The "treatable traits" approach to asthma management has helped revolutionize severe asthma treatment with biologic therapy and includes using biomarkers to identify patients most likely to benefit from a specific treatment. The ability to understand which characteristics predict response to inhaled corticosteroid (ICS) or bronchodilator therapy in mild and moderate-to-severe asthma is also vital for physicians to provide treatment tailored to an individual's phenotype/endotype. Here, we identified studies of inhaled treatments in asthma exploring treatment outcomes based upon subgroups of baseline characteristics, including type 2 biomarkers, asthma attack history, baseline lung function, bronchodilator reversibility, patient age and age at asthma onset, body mass index, smoking status, sex, and ethnicity. We assessed the available evidence regarding the influence of each characteristic on lung function, asthma attacks or asthma control in patients with asthma following treatment with either ICS, ICS/long-acting β₂-agonist (LABA) therapy, or ICS/LABA/long-acting muscarinic antagonist therapy. Of all the characteristics examined, only type 2 biomarkers (blood eosinophil levels and fractional exhaled nitric oxide) appear to consistently predict treatment response, particularly regarding ICS. For all other characteristics, we found either evidence that baseline values are not predictive of response to inhaled treatment or mixed and inconclusive evidence requiring further investigation.

Introduction: The modification of an inhaler's air flow resistance influences a patient's inhalation flow profile, thereby affecting the exit velocity of an aerosol leaving the Respimat® mouthpiece. A slower inhalation maneuver results in reduced plume velocity and thus a decreased oropharyngeal deposition due to reduced impaction. This could not only lead to fewer unwanted side effects associated with inhaled therapies, but also enhance lung deposition.

Methods: Device prototypes with different air flow resistances were designed using custom-made inserts that can be clipped into the Respimat mouthpiece. The consequences on aerosol characteristics, as well as on in vitro deposition, were analyzed. Computational fluid dynamics simulations contributed to a better understanding of the modified aerodynamic conditions.

Results: Different insert geometries resulted in modified device resistances. However, an increased flow resistance does not necessarily result in an improved in vitro performance. The flow restrictors critically determine aerosol characteristics such as plume velocity and spray pattern, thereby altering in vitro deposition patterns. Quantitative data on mouth-throat deposition and aerosol characteristics are reported.

Conclusions: Integrating flow restrictors into the Respimat mouthpiece offers a promising approach to enhance patient centricity by promoting slower inhalation, thereby reducing the likelihood of suboptimal use. The use of a porous insert acting as a diffuser demonstrated minimal impact on internal airflow dynamics and in vitro deposition, suggesting that such designs can support correct inhalation technique without compromising aerosol performance. By minimizing the influence of patient-dependent factors, this strategy may help standardize the inhalation process and improve therapeutic outcomes. Video Abstract available for this article. Video Abstract (MP4 85313 KB).

Introduction: Despite fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI) being available for asthma treatment in the US (United states) since 2020, real-world evidence on its clinical and economic benefits in patients with asthma is lacking. This study aimed to assess the effectiveness of FF/UMEC/VI (100/62.5/25 µg and 200/62.5/25 µg) in US patients with asthma previously on inhaled corticosteroid/long-acting β₂-agonists (ICS/LABA) using administrative claims data.

Methods: Retrospective, longitudinal, pre-post study utilizing data from the Komodo Health database between 09/09/2019 and 12/31/2023. Eligible adults with asthma had been treated with ICS/LABA prior to FF/UMEC/VI initiation (index date: first FF/UMEC/VI prescription). Rates of moderate-severe exacerbations, asthma-related healthcare resource utilization, oral corticosteroid (OCS) and short-acting β₂-agonist (SABA) use, and asthma-related medical costs were evaluated pre- (12 months pre-index) and post-FF/UMEC/VI initiation (12 months post-index). Statistical analyses involved rate ratios (RRs) from a Poisson regression model, odds ratios (ORs) from logistic regression models, and mean differences from linear regression models. Exploratory analyses stratified these results by pre-index ICS/LABA combination and FF/UMEC/VI index dose.

Results: In total, 17,959 patients were included. Following FF/UMEC/VI initiation, odds of having ≥ 1 exacerbation were reduced by 52% (OR [95% confidence interval (CI)] 0.48 [0.46, 0.50]; P < 0.001), rate of moderate-severe exacerbations reduced by 38% (RR [95% CI] 0.62 [0.61, 0.64]; P < 0.001) and asthma-related hospitalizations by 25% (RR [95% CI] 0.75 [0.68, 0.83]; P < 0.001). Odds of ≥ 1 OCS dispensing were reduced by 36% (OR [95% CI] 0.64 [0.62, 0.67]; P < 0.001) and ≥ 1 SABA canister use by 54% (OR [95% CI]: 0.46 [0.44, 0.48]; P < 0.001) post initiation; mean annualized asthma-related medical costs were reduced by $1115 ([95% CI] [$ -1771, $ -459]; P < 0.001). Both FF/UMEC/VI dosage groups had similar results.

Conclusions: In patients who remain uncontrolled despite ICS/LABA treatment, escalating to FF/UMEC/VI is associated with reductions in asthma exacerbations, asthma-related hospitalizations, OCS use, SABA use, and asthma-related medical costs.

Introduction: Neutropenia is a common clinical condition in critically ill patients and may be associated with poor outcomes, particularly in the context of acute respiratory failure (ARF). However, evidence on its prognostic impact remains inconsistent, and there are a lack of data, particularly in noncancer and immunocompetent populations. This study evaluates the association between neutropenia and mortality in critically ill patients with ARF and identifies risk factors for mortality among patients with neutropenia.

Methods: In this retrospective cohort study, 2412 adult patients with ARF admitted to the intensive care unit (ICU) of a tertiary center between January 2019 and December 2023 were analyzed. Neutropenia was defined as an absolute neutrophil count < 1.5 × 10⁹/L at ICU admission. The primary outcome was hospital mortality; secondary outcomes included ICU mortality. Multivariable Cox proportional hazards models were used to assess the association between neutropenia and outcomes. Subgroup analyses and risk factor assessments were conducted among patients with neutropenia.

Results: Among the 2412 patients, 411 (17.0%) had neutropenia at ICU admission. Compared with their counterparts without neutropenia, patients with neutropenia had higher ICU mortality (48.0% versus 18.9%, P < 0.001) and hospital mortality (60.1% versus 28.3%, P = 0.007). Neutropenia remained independently associated with increased ICU (adjusted hazard ratio [HR] 1.48; 95% confidence interval [CI], 1.20-1.83) and hospital mortality (adjusted HR 1.27; 95% CI 1.07-1.52). The association was more pronounced in patients without cancer (adjusted HR 3.08) than in patients with cancer (adjusted HR 1.48; P for interaction < 0.001). Among patients with neutropenia, sequential organ failure assessment (SOFA) score was an independent predictor of hospital mortality (adjusted HR 1.15; 95% CI 1.11-1.20; P < 0.001).

Conclusions: Neutropenia at ICU admission is independently associated with increased mortality in patients with ARF, particularly among those without cancer. SOFA score is a strong prognostic indicator among patients with neutropenia. These findings highlight the need for improved risk stratification, and suggest that patients with neutropenia may benefit from specific management strategies, which should be investigated in future studies.

Introduction: It is important that treatment recommendations reflect real-world data when available, as randomised controlled trials have stringent eligibility criteria and do not represent the entire asthma population or their usual ecosystem of care. Limited real-world evidence has compared the effectiveness of fluticasone furoate/vilanterol (FF/VI) and budesonide/formoterol (BUD/FOR) to date in asthma; we explored this in England using patients from general practice.

Methodology: We retrospectively compared new FF/VI users and new BUD/FOR users from 1 December 2015 to 28 February 2019, based on de-identified data from the Clinical Practice Research Datalink. The baseline period pre-index was ≥ 1 year; the follow-up period was 1 year. At index, eligible adults (≥ 18 years) with diagnosed asthma had ≥ 1 prescription for FF/VI or BUD/FOR, ≥ 1 years' general practitioner registration and records eligible for linkage to Hospital Episode Statistics. Chronic obstructive pulmonary disease was an exclusion criterion. The primary study outcome assessed the overall asthma exacerbation rate in new FF/VI or BUD/FOR users. Secondary outcomes included oral corticosteroid (OCS) use and medication persistence (analysed using Kaplan-Meier curves). For each treatment comparison, propensity scores were generated and confounding between baseline group characteristics was adjusted via inverse probability of treatment weighting, separately carried out for each study outcome. Intercurrent events (ICEs) were considered for analyses, such as death, loss to follow-up, rescue-medication use, treatment discontinuation or switching.

Results: Between groups, baseline attributes were well balanced. Annual per-person rates of exacerbation were numerically similar in the while on-treatment population (measuring outcome until ICE; FF/VI, 0.1356; BUD/FOR, 0.1583 [P = 0.3023]). Patients who continued initiation treatment for 1 year without interruption had significantly lower annual per-person exacerbation rates with FF/VI (0.0722 [n = 425]) versus BUD/FOR (0.2258 [n = 546]) (rate ratio 0.3197 [P = 0.0003]). Patients indexed on FF/VI had significantly fewer OCS prescriptions and lower OCS dosage versus BUD/FOR (respective coefficients: - 0.29 [P = 0.0352]; 0.41 [P = 0.0004]) and improved treatment persistence (hazard ratio: 0.62 [P < 0.0001]).

Conclusions: Patients who continued initiation treatment for a year without interruption had reduced exacerbation rates with FF/VI versus BUD/FOR. The FF/VI group also had reduced treatment discontinuation and OCS use.