Pulmonary Therapy最新文献

Introduction: Real-world data on the comparative effectiveness of endothelin receptor antagonists (ERAs; macitentan, bosentan, ambrisentan) for pulmonary arterial hypertension (PAH), particularly in Asian countries, are scarce. We evaluated the persistence of these ERAs before and after macitentan approval in Japan (2015).

Methods: We used real-world data from the Japanese Medical Data Vision administrative claims database between April 2008 and November 2020. Patients with PAH were identified from the dataset. Persistence to ERA treatment before and after approval of macitentan in Japan was defined as the time between start of the index ERA and treatment discontinuation or death. Propensity score adjustment was applied to minimize confounding effects among treatment groups.

Results: In the pre-macitentan approval cohort, 153 and 51 patients received bosentan and ambrisentan, respectively. In the post-macitentan approval cohort, 331, 284, and 91 patients received macitentan, bosentan, and ambrisentan, respectively. Unadjusted median persistence for ambrisentan- and bosentan-treated patients was 19 and 10 months, respectively (adjusted HR 0.87 [95% CI 0.61-1.24]; P = 0.434 [bosentan as reference]). In the post-macitentan approval cohort, unadjusted median persistence was 18 months for macitentan-treated patients versus 6 and 8 months for ambrisentan- and bosentan-treated patients, respectively. Adjusted HRs for ambrisentan and bosentan were 1.48 (95% CI 1.12-1.95; P = 0.006) and 1.63 (95% CI 1.30-2.04; P < 0.001 [macitentan as reference]), respectively.

Conclusions: Real-world data for Japanese patients with PAH showed that persistence was significantly higher for macitentan, versus ambrisentan and bosentan, since its approval.

Introduction: Awake prone positioning has the potential to improve oxygenation and decrease respiratory rate, potentially reducing the need for intubation in patients with acute hypoxemic respiratory failure. We investigated awake prone positioning-induced changes in oxygenation and respiratory rate, and the prognostic capacity for intubation in patients with COVID-19 pneumonia.

Methods: International multicenter prospective observation study in critically ill adult patients with COVID-19 receiving supplemental oxygen. We collected data on oxygenation and respiratory rate at baseline, and at 1 h after being placed in prone positioning. The combined primary outcome was oxygenation and respiratory rate at 1 h. The secondary endpoint was treatment failure, defined as need for intubation within 24 h of start of awake prone positioning.

Results: Between March 27th and November 2020, 101 patients were enrolled of which 99 were fully analyzable. Awake prone positioning lasted mean of 3 [2-4] h. In 77 patients (77.7%), awake prone positioning improved oxygenation, and in 37 patients (54.4%) it decreased respiratory rate. Twenty-nine patients (29.3%) were intubated within 24 h. An increase in SpO₂/FiO₂ of < 10 (OR 5.1, 95% CI 1.4-18.5, P = 0.01), a failure to increase PaO₂/FiO₂ to > 116 mmHg (OR 3.6, 95% CI 1.2-10.8, P = 0.02), and a decrease in respiratory rate of < 2 breaths/min (OR 3.6, 95% CI 1.3-9.5, P = 0.01) were independent variables associated with need for intubation. The AUC-ROC curve for intubation using a multivariable model was 0.73 (95% CI 0.62-0.84).

Conclusions: Awake prone positioning improves oxygenation in the majority of patients, and decreases respiratory rate in more than half of patients with acute hypoxemic respiratory failure caused by COVID-19. One in three patients need intubation within 24 h. Awake prone position-induced changes in oxygenation and respiratory rate have prognostic capacity for intubation within 24 h.

Introduction: There is increasing pressure to prefer propellant-free inhaler devices over pressurized metered-dose inhalers (pMDI) due to environmental considerations. In this work, we present results from three life cycle assessments (LCAs) on Easyhaler dry powder inhaler product portfolio and assess the changes in environmental impact and carbon footprint (CF) of the products over time.

Methods: Three cradle-to-grave LCAs were conducted in 2019, 2021, and 2023. The 2019 assessment covered four products while 2021 and 2023 assessments included all six products in the portfolio. LCA for the protective cover sometimes used with Easyhaler was conducted in 2023. In addition to CF, nine other environmental impact categories were assessed to ensure that no burden shifting occurs.

Results: During the study period, the non-weighted average CF of the Easyhaler decreased by 11.2%. For individual products, the decrease varied from 5.0 to 6.8% between the assessments. In the latest assessment, the average CF of Easyhaler was 547 gCO₂e with a range of 452-617 gCO₂e. The LCA of the protective cover was assessed for the first time in 2023 and had a CF of 66 gCO₂e.

Conclusions: Our results show that the climate impact of pharmaceutical products can be reduced without making changes to the product itself. The CF of Easyhaler products is in agreement with the lower end of the CF range previously reported for dry powder inhalers. Climate impact from the protective cover was one-tenth compared to the climate impact from the product itself.

This review provides an overview of menopausal hormone therapy and pulmonary disease risk, with a focus on the effect of hormone replacement therapy (HRT) on pulmonary function and its relation to lung diseases. This summary is based on authors' knowledge in the field of HRT and supplemented by a PubMed search using the terms "menopause hormone therapy," "asthma", "lung cancer", "chronic obstructive pulmonary disease", "lung function", and "pulmonary hypertension". Available evidence indicates that there is limited research on the role of sex hormones in the susceptibility, severity, and progression of chronic respiratory diseases. However, some studies suggest that the hormonal changes that occur during the menopausal transition may have an impact on pulmonary function and respiratory diseases. Women are in need of convenient access to a safe and effective modality for personalized HRT based on an artificial intelligence (AI)-driven platform that will enable them to receive personalized hormonal treatment through frequent, convenient, and accurate measurements of hormone levels in peripheral blood.

Introduction: Cystic fibrosis (CF) is a life-limiting genetic disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Elexacaftor/tezacaftor/ivacaftor (ELX/TEZ/IVA) is a CFTR modulator (CFTRm) that targets the underlying cause of CF. Based on safety and efficacy demonstrated in clinical trials, ELX/TEZ/IVA is approved in the US for the treatment of CF in people aged ≥ 2 years who have ≥ 1 F508del-CFTR mutation or a CFTR mutation that is responsive to ELX/TEZ/IVA based on in vitro data. While ELX/TEZ/IVA demonstrated unprecedented improvements in lung function and dramatic reductions in pulmonary exacerbations (PEx) and associated hospitalizations in clinical trials, a limited number of studies have examined the impact of ELX/TEZ/IVA on healthcare resource utilization (HCRU) and associated costs in a real-world setting. The aim of this retrospective study was to evaluate changes in PEx, HCRU, and associated non-CFTRm healthcare costs following initiation of ELX/TEZ/IVA among people with CF aged ≥ 12 years in the US.

Methods: We evaluated the rates of PEx, HCRU, and associated costs before and after initiation of ELX/TEZ/IVA in people with CF aged ≥ 12 years using data from the Merative MarketScan® Commercial Claims and Encounters Database and the Merative Multi-State Medicaid Database from April 21, 2019 to December 31, 2020. Because the study period included time following the onset of the COVID-19 pandemic, we limited our primary analysis to the period prior to the pandemic (October 21, 2019 to March 12, 2020). Outcomes following the onset of the pandemic (March 13 to December 31, 2020) were examined in an exploratory analysis.

Results: In both commercially insured and Medicaid-insured people with CF, ELX/TEZ/IVA was associated with reductions in PEx, hospitalizations, and associated costs prior to the COVID-19 pandemic, and these reductions were maintained following the onset of the pandemic.

Conclusions: These findings suggest that ELX/TEZ/IVA reduces the burden and costs associated with PEx and hospitalizations in people with CF.

Introduction: The fourth outbreak of COVID-19 with the delta variant in Vietnam was very fierce due to the limited availability of vaccines and the lack of healthcare resources. During that period, the high mortality of patients with severe and critical COVID-19 caused many concerns for the health system, especially the intensive care units. This study aimed to analyze the predictive factors of death and survival in patients with severe and critical COVID-19.

Methods: We conducted a cross-sectional and descriptive study on 151 patients with severe and critical COVID-19 hospitalized in the Intensive Care Unit of Binh Duong General Hospital.

Results: Common clinical symptoms of severe and critical COVID-19 included shortness of breath (97.4%), fatigue (89.4%), cough (76.8%), chest pain (47.7%), loss of smell (48.3%), loss of taste (39.1%), and headache (21.2%). The abnormal biochemical features were leukopenia (2.1%), anemia, thrombocytopenia (18%), hypoxia with low PaO₂ (34.6%), hypocapnia with reduced PaCO₂ (29.6%), and blood acidosis (18.4%). Common complications during hospitalization were septic shock (15.2%), cardiogenic shock (5.3%), and embolism (2.6%). The predictive factors of death were being female, age > 65 years, cardiovascular comorbidity, thrombocytopenia (< 137.10⁹/l), and hypoxia at inclusion or after the first week or blood acidosis (pH < 7.28). The use of a high dose of corticosteroids reduced the mortality during the first 3 weeks of hospitalization but significantly increased risk of death after 3 and 4 weeks.

Conclusions: Common clinical symptoms, laboratory features, and death-related complications of critical and severe COVID-19 patients were found in Vietnamese patients during the fourth wave of the COVID-19 pandemic. The results of this study provide new insight into the predictive factors of mortality for patients with severe and critical COVID-19.

Introduction: The incidence of malignant pleural effusion (MPE) in patients with small cell lung cancer (SCLC) in an American population is approximately 11%, and overall survival in that group is 3 months (compared to 7 months without an effusion. To our knowledge, no study has been done in the United Kindgom and we thus sought to determine the characteristics of the local population.

Method: All patients coded as having small cell lung cancer from Somerset register from January 2012-September 2021 were reviewed. We excluded those with indeterminate pathology reports, carcinoid or large cell neuroendocrine cancers. Basic demographics, presence of an MPE and any interventions and outcomes were collected for descriptive analysis. Continuous variables are presented as mean (±) range, median (± IQR) when outliers were present and categorical variables as percentages where appropriate. Caldicott reference C3905.

Results: Four hundred one patients with SCLC were identified (11% of all patients, median time to death from presentation 208 days, IQR 304 [many outliers); 224 (55.9%) were female, 177 male [median age 75 years, IQR 13]. One hundred seven (27%) presented with an effusion: 23 were sampled, 10 had positive cytology, all were exudates, 8 required chest drainage, the mean performance status (PS) was 2 (range 1-4) and the median time to death 142 days, IQR 45. Of the 294 with no initial effusions, 70 (24%) developed a pleural effusion with progressive disease (mean PS 1, median age 71.5 years, IQR 14, median to death 327 days, IQR 395, 1 outlier); 224 patients never had a MPE with a median time to death of 212 days, IQR 305, multiple outliers and, when compared to those with a MPE at any point, median time to death was 211 days, IQR 295.5 (multiple outliers).

Conclusion: Meaningful analysis was difficult because of the presence of multiple outliers in values collected and not correcting for stage at presentation or treatment modalities and previous studies did not correct for those either. Those presenting with an MPE had a poorer prognosis, probably signifying advanced disease and the presence of MPE in our SCLC cohort seems higher. Large prospective databases for this are required.

Introduction: The objective of the present study was to evaluate the efficacy and safety of MP-AzeFlu nasal spray in comparison to commercially available azelastine hydrochloride and fluticasone propionate sprays in Chinese patients with moderate-to-severe allergic rhinitis (AR).

Methods: We conducted a 14-day multicenter, randomized, double-blind, active controlled prospective clinical study in adult and adolescent patients with AR, who had moderate-to-severe symptoms. The primary efficacy endpoint was the change from baseline in combined 12-h reflective total nasal symptom score (rTNSS) (morning [AM] + afternoon [PM]). The safety profile of the study medications was assessed through the recording, reporting, and analysis of baseline medical conditions, adverse events (AEs), vital signs, and focused nasal examination. Three hundred patients per treatment group were randomized, which led to a total sample size estimation of 900 patients.

Results: MP-AzeFlu group showed significantly higher symptom reduction for the entire 2-week treatment period in rTNSS when compared with the AZE group (LS mean difference: - 1.96; 95% CI: - 2.53, - 1.39; p < 0.0001), or the FLU group (LS mean difference: - 0.98; 95% CI: - 1.55, - 0.41; p = 0.0007). The results of adult RQLQ showed improvement in QoL in all treatment groups. Except for dysgeusia (bitter taste) that was reported by more patients (13 [4.3%]) in the MP-AzeFlu group, the incidence of all other TEAEs in the MP-AzeFlu group was comparable or even lower than in other treatment groups.

Conclusions: MP-AzeFlu, when administered as one spray per nostril twice daily for 14 days, alleviated AR symptoms in Chinese patients with moderate-to-severe AR.

Trial registration: Clinicaltrials.gov; NCT03599791, Registered June 29, 2018, retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03599791 .