Respiratory investigation最新文献

Background

The INCREASE trial, conducted in the United States, showed that inhaled treprostinil improved exercise capacity in pulmonary hypertension associated with interstitial lung disease (PH-ILD). However, hemodynamic and pharmacokinetic measurements were not performed in the trial. The objective of this trial was to evaluate the efficacy on hemodynamics and exercise capacity, safety, and pharmacokinetics (PK) of inhaled treprostinil in Japanese patients with PH-ILD.

Methods

This trial was a multicenter, non-randomized, open-label, single-arm trial of patients with PH-ILD. Inhaled treprostinil was administered at 3 breaths (18 μg)/session four times daily, and the dose was gradually increased to a maximum of 12 breaths (72 μg)/session. The primary endpoints were the change of pulmonary vascular resistance index (PVRI) and peak 6-min walking distance (6MWD) from baseline to week 16. Endpoints also included other efficacy parameters, safety, and PK.

Results

Twenty patients received inhaled treprostinil. At week 16, PVRI decreased from baseline by −40.1% (95% CI, −53.1 to −27.2) and peak 6MWD increased by 13.0 m (95% CI, −15.0 to 49.0). The most frequently reported adverse events related with treprostinil were cough, malaise and blood pressure decreased. PK was similar to those in pulmonary arterial hypertension (PAH) patients.

Conclusions

Treatment with inhaled treprostinil using the same dosing regimen as in the INCREASE trial resulted in improvements in hemodynamics and exercise capacity with a favorable tolerability and safety profile in Japanese patients with PH-ILD.

Background

Presbyphagia, an age-related decline in swallowing function, is considered a precursor stage of dysphagia and a risk state that can lead to aspiration pneumonia and malnutrition. We examined factors associated with presbyphagia in patients with community-acquired pneumonia (CAP).

Methods

A cross-sectional study was conducted with 80 patients with CAP aged ≥65 years admitted to an acute care hospital between June 2021 and April 2024. Presbyphagia was assessed using the 10-item Eating Assessment Tool. The survey items included grip strength, body mass index, the Mini-Cog©, repetitive saliva swallowing test, tongue pressure, and evaluations for sarcopenia and frailty. Logistic regression analysis was performed to examine the factors associated with presbyphagia after adjusting for age and sex.

Results

Of 80 patients, 44 (55%) had presbyphagia. The presbyphagia group was older, had lower Barthel Index scores, and had a higher proportion of history of cerebrovascular accident, sarcopenia and frailty than the non-presbyphagia group. Logistic regression analysis revealed frailty (adjusted odds ratio: 3.106, 95% confidence interval: 1.161–8.313, p = 0.024) was significantly associated with presbyphagia.

Conclusions

Our results revealed a significant association between presbyphagia and frailty in patients with CAP. The relationship between presbyphagia and frailty suggests that these conditions are not caused by a single functional decline or structural change but by a combination of factors. Therefore, it is crucial to comprehensively evaluate presbyphagia in patients with CAP to provide appropriate interventions.

Background

Although radiologic honeycombing is generally associated with progressive fibrosis and a dismal prognosis, some patients display an unexpectedly indolent clinical course. We aimed to assess for variants of honeycombing associated with a more favorable prognosis.

Methods

A computer-assisted search was conducted to identify patients encountered at Mayo Clinic from 1998 to 2022 who had undergone chest CT that manifested exuberant honeycombing. Medical records and chest imaging studies were reviewed to identify clinical, pulmonary function and radiologic features.

Results

Among 136 patients with exuberant honeycombing, 23 patients were identified with CT features of what we termed “bubbly lung” characterized by extensive macrocystic fibrosis; 17 (74%) were female with a median age of 71 years (range, 32–88) at baseline. Underlying diagnoses were ANCA associated vasculitis (22%), overlap CTD (22%), rheumatoid arthritis (17%), IPF (17%), IPAF (9%), systemic sclerosis (4%), undifferentiated CTD (4%), and dermatomyositis (4%). Median FVC was 78% predicted (range 35–112), median DLco was 41% predicted (range 10–92), and median TLC was 73% predicted (range 57–116). Serial FVC measurements were available for 19 (83%) patients with a median interval of 4.7 years (range: 0.4–20); median FVC change per year was 23 ml (range −279 to +232) and median FVC % predicted change per year was 0.00% (range −3.20 to +6.79%). The median survival was 7.1 years, 5-year survival was 76% (95% CI: 58%–100%) and 10-year survival was 48%.

Conclusions

“Bubbly lung” is a variant of exuberant honeycombing that is associated with better-than-expected outcome and FVC decline per year.

Background

Proton pump inhibitors (PPIs) are reported to decrease the efficacy of immune checkpoint inhibitors (ICIs), but there are few reports on the association between ICI efficacy and antacids other than PPIs, and simultaneous examination of the effects of antacids, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) on ICI therapy.

Methods

We conducted a retrospective study of 381 patients with non-small cell lung cancer who received ICI therapy from January 1, 2016 to December 31, 2022. The primary endpoint was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). Antacids included histamine type 2 receptor antagonists (H2RAs), PPIs, and potassium-competitive acid blockers (P-CABs).

Results

Antacids were administered to 218 patients, including 168 with PPIs, 37 with P-CABs, and 13 with H2RAs. Patients with antacids had worse median PFS and OS than those without antacids (PFS, 2.9 vs. 6.2 months; OS, 12.3 vs. 24.0 months), and those with PPIs, P-CABs, or H2RAs had similar results. However, there were no significant differences between patients with and without antacids when stratified by corticosteroid and NSAID use. Multivariate analyses showed that corticosteroids and NSAIDs administered for cancer-associated symptoms were related to poor prognosis, but antacids including PPIs, P-CABs, or H2RAs were not related.

Conclusions

Antacids were not related to ICI efficacy when NSAIDs or corticosteroids were taken into consideration. This may be because the most frequent reason for administering NSAIDs and corticosteroids was cancer-associated symptoms, which are a poor prognostic factor, and most of the patients treated with these medications also received antacids.

Introduction

Adenosine deaminase (ADA) in pleural fluid is a useful marker for diagnosing tuberculous pleurisy. However, recent studies have reported a lower specificity of pleural fluid ADA levels. We previously developed a diagnostic flowchart for patients with pleural fluid ADA ≥40 U/L, incorporating variables such as pleural fluid lactate dehydrogenase <825 U/L, predominant pleural fluid neutrophils or cell degeneration, and a pleural fluid ADA/total protein ratio <14. This flowchart was effective in distinguishing between tuberculous pleurisy and other diseases. Here, we conducted a validation analysis of this flowchart.

Materials and methods

We retrospectively collected data from 458 patients with pleural fluid ADA concentrations ≥40 U/L across eight institutions from January 2019 to December 2023. The diagnostic accuracy rate, sensitivity, and specificity of the diagnostic flowchart were analysed and compared to those in the original study.

Results

Eighty-seven patients were diagnosed with tuberculous pleurisy, and 371 patients were diagnosed with other diseases. The diagnostic accuracy, sensitivity, and specificity for diagnosing tuberculous pleurisy were 77.7%, 86.2%, and 75.7%, respectively. Compared with that in the original study, the rate of tuberculous pleurisy was lower (19.0% vs. 44.5%, p < 0.001), but the diagnostic accuracy rates were not significantly different (p = 0.253). On the basis of the findings from this validation study, we have revised the flowchart to enhance its utility.

Conclusion

The diagnostic flowchart exhibited high diagnostic accuracy in this validation study, comparable to that in the original study. This validation confirms the effectiveness of the flowchart, even in settings with a low incidence of tuberculosis.

Background

Weaning outcomes of patients receiving mechanical ventilation (MV) are affected by multiple factors. A clinical feature of critically ill patients is the presence of lymphopenia, however the clinical significance of lymphopenia in patients receiving prolonged MV remains unclear.

Methods

We enrolled patients who received at least 21 consecutive days of MV in a medical center in Taiwan between 2007 and 2016. Patients with and without lymphopenia (mean count <1000/μL) were compared after propensity score matching.

Results

Of the 3460 patients included in the analysis, 1625 (47.0%) were liberated from MV within 100 days. Lymphopenia and severe lymphopenia (mean count <500/μL) during the first 21 days of MV were common (52.9% and 14.5%, respectively), and restricted cubic spline analysis showed a significant reduction in weaning success when the lymphocyte count dropped below 1000/μL. After propensity score matching, the patients with lymphopenia during the third week had a lower rate of weaning success within 100 days (p = 0.005) and a higher in-hospital mortality rate (p = 0.001) than those without lymphopenia. The lymphopenia group also had significantly reduced platelet (p < 0.001) and albumin (p < 0.001) levels.

Conclusions

Our findings suggest that lymphopenia during the first 3 weeks may be a marker of poor weaning outcomes in patients with prolonged MV.

Background

Refractory chronic cough (RCC) causes significant impairments in the life quality of patients. Further research into the identification of etiologies and development of the treatment schedules for RCC is needed.

Patients and methods

We established an multidisciplinary team (MDT) clinic, by integrating respiratory medicine, otorhinolaryngology, and gastroenterology departments, to investigate cough etiologies and the effectiveness of treatment. The therapeutic effect was assessed quantitatively using the Cough Visual Analog Scales (VAS), Leicester Cough Questionnaire (LCQ), and Reflux Symptoms Index (RSI) scores.

Results

In total, 213 patients attending the MDT outpatient clinic were examined, and 115 patients with RCC were included for analysis. The RCC diagnosis rate among the outpatient was 88.7%. Common causes of RCC included gastroesophageal reflux cough (63.5%), upper airway cough syndrome (UACS) (43.5%), and cough variant asthma (CVA) (14.8%). After an average treatment period of 2.17 ± 1.06 weeks (wk), 73.9% of the patients had partial cough remission, and 6.1% had complete cough remission. The cough VAS score before and after treatment was 6.11 ± 2.02 vs. 3.66 ± 2.22 (P < 0.05), respectively; LCQ total score before and after treatment was 10.24 ± 3.11 vs. 13.16 ± 3.59 (P < 0.05), respectively; and RSI score before and after treatment was 15.82 ± 7.01 vs. 10.71 ± 6.64 (P < 0.05), respectively.

Conclusion

The etiologies of most patients with RCC could be identified in the MDT clinic, and the cough-related symptoms of a significant number of patients with RCC improved in a short period.

Asthma is a chronic inflammatory airway disease characterized by bronchial hyperresponsiveness and reversibility. Despite considerable advances in asthma treatment based on our understanding of its pathophysiology, asthma exacerbations remain challenging. To reduce asthma exacerbations, it is essential to identify triggers, patients’ risk factors, and underlying mechanisms. While exposure to viruses and environmental stimuli are known common triggers for asthma exacerbations, the key factors involved in asthma exacerbations have been identified as type 2 inflammation. Type 2 inflammatory biomarkers have been demonstrated to be useful in predicting individuals at risk of exacerbations. Furthermore, recent clinical trials of targeted biological therapy, which blocks the type 2 pathway, have supported the critical role of type 2 inflammation in asthma exacerbations. Although the specific mechanisms linking type 2 inflammation to asthma exacerbations have not yet been fully elucidated, increasing evidence shows that reduction/oxidation (redox) imbalance likely plays an important role in this association. Under type 2 inflammatory conditions, human airway epithelial cells activate 15-lipoxygenase-1 in complex with phosphatidylethanolamine binding protein-1, leading to the generation of electrophilic hydroperoxyl-phospholipids. When the accumulation of reactive lipid peroxidation surpasses a specific glutathione-dependent activity, these electrophilic compounds are not neutralized, leading to programmed cell death, ferroptosis. Reduced glutathione levels, caused by type 2 inflammation, may impair its ability to neutralize reactive lipid peroxidation. The accumulation of lipid peroxidation with intracellular redox imbalance may contribute to asthma exacerbations in individuals with type 2 inflammation. Inhibiting the ferroptotic pathway holds promise as a therapeutic strategy to alleviate asthma exacerbations.

Randomized controlled trials (RCTs) and studies using real-world data (RWD) each have their strengths and weaknesses, and can effectively complement each other. When RCTs are not feasible, RWD studies offer a valuable alternative. In this narrative review, we examine several types of RWD studies, focusing on studies utilizing administrative claims databases. These include the Diagnosis Procedure Combination databases, commercially available health checkups and healthcare claims databases (such as the JDMC and DeSC databases), and the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). Given that these claims databases cover different populations, patient settings, variables, and levels of accessibility, it is crucial for researchers to select the most appropriate data source to effectively address their research questions. Additionally, it is desirable for readers of studies using these databases to be aware of their characteristics in order to fully understand the context and limitations of the research findings.