Pulmonary Therapy最新文献

Introduction: This study estimated the potential public health impact of alternative COVID-19 vaccination strategies in Singapore.

Methods: The outcomes of alternative vaccination strategies using a Pfizer-BioNTech COVID-19 vaccine updated to the latest circulating strain were estimated using a combined decision tree-Markov cohort model. The model was previously used to estimate the impact of vaccination based on epidemiological data from 2021/22 and vaccine coverage data from 2022/23. It has now been updated with epidemiology data from 2023/24 and an assumed vaccine coverage of 20%. Age-specific inputs were derived from local epidemiological data and published sources. The model projected health outcomes (cases, hospitalizations, and deaths) and economic outcomes (direct medical costs and productivity losses) across different age and risk subgroups.

Results: Vaccinating individuals aged 60 and above, as well as individuals aged 6 months to 59 years with comorbidities, making them at high risk for severe COVID-19 outcomes, with a vaccine coverage of 20%, is projected to result in 14,099 fewer infections, 2668 fewer hospitalizations, and 21 fewer deaths in 1 year. This leads to a total estimated savings of SGD 21.3 million in direct medical costs and SGD 24.8 million in indirect costs. Increasing coverage to 50% has the potential to further increase deaths, hospitalizations, infections, and costs averted by 150%.

Conclusions: Although vaccination has a smaller impact on public health compared to the previous evaluation because of the updated epidemiology and lower estimated coverage, an updated vaccine can still have a public health and economic impact in Singapore.

Drug-induced interstitial lung disease (DI-ILD) has emerged as a clinically significant complication associated with a broadening spectrum of therapeutic agents. DI-ILD can result in significant morbidity and mortality if not promptly diagnosed and treated. In this review, we synthesize current evidence concerning the epidemiology, risk factors, pathophysiological mechanisms, clinical manifestations, diagnostic approaches, and management strategies of DI-ILD, with focused emphasis on three major therapeutic groups: immune checkpoint inhibitors (ICIs), chimeric antigen receptor T-cell (CAR-T) therapies, and biological agents; adding other commonly used drugs known for causing DI-ILD as well, such as: amiodarone, methotrexate, and nitrofurantoin. Early recognition, drug discontinuation, tailored immunosuppression, and supportive care are pivotal to improving outcomes. Enhanced medical awareness and a multidisciplinary care approach are essential to mitigate morbidity and mortality. By synthesizing current knowledge, this review aims to enhance awareness and understanding of DI-ILD, thereby facilitating earlier diagnosis and more effective management strategies for this potentially severe adverse drug event.

Emerging evidence demonstrates the evolving role of fungi in the pathophysiology and disease progression observed in bronchiectasis. Fungal-associated traits are linked to disease severity, exacerbation frequency and airway inflammation. Structural abnormalities and impaired mucociliary clearance, characteristic of bronchiectasis, predispose to fungal colonisation, with subsequent immunopathogenic responses dependent on underlying host immunity. The diagnosis of fungal infection remains challenging in clinical settings, owing to the limitations of existing diagnostic modalities; however, the development of culture-independent molecular techniques shows promise. The use of next-generation sequencing has significantly advanced our understanding of the fungal microbiome in bronchiectasis, identifying fungi that are challenging to culture. Integrative microbiomics further elucidates the intricate and dynamic role of fungi in relation to other microbial kingdoms, and across distant organs such as the gut, revealing important relationships with bacterial pathogens including Pseudomonas aeruginosa. Airway inflammatory profiling has shown fungal-associated inflammatory endotypes which may serve as treatable traits. Environmental influences on fungi and bronchiectasis-exacerbated by air pollution and climate change-underscore the key role of the exposome in fungal-associated endotypes in bronchiectasis. This review outlines the clinical significance of fungi in bronchiectasis, the current diagnostic and treatment challenges, and emerging fungal-associated endotypes in the context of environmental influence on disease.

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).