Respiratory medicine最新文献

Background

Pulmonary hypertension (PH) is the abnormal elevation of pressure in the pulmonary vascular system, with various underlying causes. A specific type of PH is pulmonary arterial hypertension (PAH), a severe condition characterized by high pulmonary arterial pressure resulting from structural changes in distal pulmonary vessels, altered arterial tone, and inflammation. This leads to right ventricular hypertrophy and heart failure. The molecular mechanisms behind PAH are not well understood. This manuscript aims to elucidate these mechanisms using the genetic tool, aiding in diagnosis and treatment selection.

Method

In our present study, we have obtained blood samples from both patients with pulmonary arterial hypertension (PAH) and healthy individuals. We conducted a comparative transcriptome analysis to identify genes that are either upregulated or downregulated in PAH patients when compared to the control group. Subsequently, we carried out a validation study focusing on the log2-fold downregulated genes in PAH, employing Quantitative Real-Time PCR for confirmation. Additionally, we quantified the proteins encoded by the validated genes using the ELISA technique.

Results

The results of the transcriptome analysis revealed that 97 genes were significantly upregulated, and 6 genes were significantly downregulated. Among these, we chose to focus on and validate only four of the downregulated genes, as they were directly or indirectly associated with the hypertension pathway. We also conducted validation studies for the proteins encoded by these genes, and the results were consistent with those obtained in the transcriptome analysis.

Conclusion

In conclusion, the findings of this study indicate that the four validated genes identified in the context of PAH can be further explored as potential targets for both diagnostic and therapeutic applications.

Introduction

Enhancing lung function can significantly improve daily life functionality for children with cerebral palsy, leading to increased interest in respiratory physiotherapy training devices in clinical practice. This study aims to evaluate the efficacy of devices (inspiratory muscle training and feedback devices) for improving pulmonary function through various respiratory parameters.

Methods

A systematic review with meta-analysis of randomized clinical trials was conducted in seven databases up until May 2023. The included studies focused on training inspiratory muscle function using specific devices (inspiratory muscle training and feedback devices) in children with cerebral palsy. The main outcomes were maximum expiratory pressure and maximum inspiratory pressure. Secondary outcomes included forced vital capacity, forced expiratory volume in 1 s, peak expiratory flow, and the Tiffenau index. The effects of respiratory treatment were calculated through the estimation of the effect size and its 95% confidence intervals. The risk of bias in the included studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias (RoB2).

Results

Nine studies were included in the systematic review with meta-analysis, involving a total of 321 children aged between 6 and 18 years after secondary analyses were conducted. Feedback devices were found to be more effective in improving maximum expiratory pressure (effect size −0.604; confidence interval −1.368 to 0.161), peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity. Inspiratory muscle training devices yielded better effectiveness in improving maximum inspiratory pressure (effect size −0.500; confidence interval −1.259 to 0.259), the Tiffeneau index, and quality of life.

Conclusion

Both devices showed potential in improving pulmonary function in children with cerebral palsy. Further high-quality clinical trials are needed to determine the optimal dosage and the most beneficial device type for each pulmonary function parameter.

Background

Clofazimine (CFZ) has shown promising effects against Mycobacterium avium-intracellulare complex pulmonary disease (MAC-PD) and Mycobacterium abscessus species pulmonary disease (MABS-PD). However, the optimal CFZ dose remains unknown. We aimed to explore the relationship between steady-state CFZ concentration and its safety and efficacy in MAC-PD and MABS-PD.

Methods

This prospective observational study focused on patients with MAC-PD and MABS-PD treated with CFZ (UMIN 000041053). To understand the safety and efficacy profile of CFZ and elucidate its optimal concentration, we analyzed CFZ-induced pigmentation grade, QTc interval, and culture conversion outcomes in relation to serum CFZ concentration using Student's t-test, a concentration-QTc model, and multivariable logistic regression analysis, respectively. In total, 64 patients (34 with MAC-PD; 30 with MABS-PD) were included.

Results

The steady-state concentration of CFZ was higher in the moderate-to-severe pigmentation group than in the none-to-light pigmentation group (P < 0.001). At a CFZ concentration of 1 mg/L, the QTc interval was prolonged by 17.3 ms (95 % confidence interval [CI], 3.9–25.4) from baseline. Culture conversion was achieved in 33 (51.6 %) patients. The only significant predictor of culture conversion was surgery (adjusted odds ratio, 5.4; 95 % CI, 1.3–38.0). CFZ concentration and MIC of CFZ less than 0.25 mg/L were not associated with culture conversion in this study.

Conclusion

CFZ-induced pigmentation and QT interval prolongation are associated with serum CFZ concentrations. CFZ dosage may be optimized by monitoring serum CFZ concentration.

Background

Patients with uncontrolled asthma should be evaluated for medication adherence. This study aimed to identify characteristics associated with poor adherence to inhaled corticosteroids (ICS) and to explore adherence prior to treatment escalation.

Methods

This nationwide longitudinal cohort study included adult asthma patients (n = 30880) with a healthcare visit including Asthma Control Test (ACT) and registered in the Swedish National Airway Register between 1 July 2017 and 28 February 2019 (index date). Patient data was crosslinked to other national registers. Treatment steps two years pre- and one year post-index, were identified by prescribed drugs. Poor adherence was defined as Medication Possession Ratio <80 %.

Results

Poor adherence was identified in 73 % of patients in treatment steps 2–5, where of 35 % had uncontrolled asthma (ACT≤19). In adjusted models, poor adherence was associated with better disease control; ACT≤19 (OR 0.78, 95 % CI 0.71–0.84), short-acting β2-agonist (SABA) overuse (0.69, 0.61–0.79) and exacerbations (0.79, 0.70–0.89) in steps 2–3. Among patients with uncontrolled asthma, poor adherence was associated with SABA overuse (1.71, 1.50–1.95), exacerbations (1.29, 1.15–1.46), current smoking (1.38, 1.21–1.57) and inversely associated with asthma management education (0.85, 0.78–0.93. Similar results were observed in steps 4–5. When investigating post-index treatment, 53 % remained stationary, 30 % stepped down and 17 % escalated treatment. Prior to escalation, 49 % had poor adherence.

Conclusions

Poor ICS adherence was associated with better asthma control. Among uncontrolled patients, poor adherence was associated with SABA overuse and exacerbations. Our result highlights the importance of asthma management education to improve adherence in uncontrolled patients.

Objective

To assess antibiotics impact on outcomes in COVID-19 pneumonia patients with varying procalcitonin (PCT) levels.

Methods

This retrospective cohort study included 3665 COVID-19 pneumonia patients hospitalized at five Mayo Clinic sites (March 2020 to June 2022). PCT levels were measured at admission. Patients’ antibiotics use and outcomes were collected via the Society of Critical Care Medicine (SCCM) Viral Infection and Respiratory Illness Universal Study (VIRUS) registry. Patients were stratified into high and low PCT groups based on the first available PCT result. The distinction between high and low PCT was demarcated at both 0.25 ng/ml and 0.50 ng/ml.

Results

Our cohort consisted of 3665 patients admitted with COVID-19 pneumonia. The population was predominantly male, Caucasian and non-Hispanic. With the PCT cut-off of 0.25 ng/ml, 2375 (64.8 %) patients had a PCT level <0.25 ng/mL, and 1290 (35.2 %) had PCT ≥0.25 ng/ml. While when the PCT cut off of 0.50 ng/ml was used we observed 2934 (80.05 %) patients with a PCT <0.50 ng/ml while 731(19.94 %) patients had a PCT ≥0.50 ng/ml. Patients with higher PCT levels exhibited significantly higher rates of bacterial infections (0.25 ng/ml cut-off: 4.2 % vs 7.9 %; 0.50 ng/ml cut-off: 4.6 % vs 9.2 %).

Antibiotics were used in 66.0 % of the cohort. Regardless of the PCT cutoffs, the antibiotics group showed increased hospital length of stay (LOS), intensive care unit (ICU) admission rate, and mortality. However, early de-escalation (<24 h) of antibiotics correlated with reduced hospital LOS, ICU LOS, and mortality. These results were consistent even after adjusting for confounders.

Conclusion

Our study shows a substantial number of COVID-19 pneumonia patients received antibiotics despite a low incidence of bacterial infections. Therefore, antibiotics use in COVID pneumonia patients with PCT <0.5 in the absence of clinical evidence of bacterial infection has no beneficial effect.

Background

Pulmonary rehabilitation (PR) is an effective treatment method for chronic obstructive pulmonary disease (COPD). However, individuals with chronic diseases that require lifelong treatment and experience exacerbations need motivational methods.

Objectives

The aim of this study was to examine the effects of virtual reality on symptoms, daily living activity, functional capacity, anxiety and depression levels in COPD exacerbation.

Methods

Fifty patients hospitalized for COPD exacerbation were included in the study. They were randomly assigned to two groups. Twenty-five patients participated in a traditional PR (once-daily until discharge), including pedaling exercises. The second/25 patients followed the same protocol but experienced cycling simulation in the forest via virtual reality (VR + PR). All patients were evaluated using 1-minute/Sit-to-Stand test (STST), modified-Medical Research Council (mMRC) scale, COPD Assessment test (CAT), Hospital Anxiety and Depression Scale (HADS), and London Chest Activities of Daily Living (LCADL) before and after the treatment.

Results

The STST showed an increase in both groups post-treatment, notably higher in the VR + PR (p = 0.037). Dyspnea levels and CAT scores decreased in all patients, but the decrease was greater in the PR + VR group for both parameters (p = 0.062, p = 0.003; respectively). Both groups experienced a reduction in the HADS scores compared to the pre-treatment, with a more significant decrease in depression and the total score in the VR + PR (p < 0.05). LCADL's sub-parameters and total score, excluding household, decreased in both groups after treatment (p < 0.05). The improvement was more substantial in the VR + PR.

Conclusions

Virtual reality provides benefits in the management of COPD exacerbations and can be used safely.

Clinical trial registiration

Registered at clinicaltrials.gov, registration ID: NCT05687396, URL: www.clinicaltrials.gov.

Background

Exacerbations are implicated in bronchiectasis and COPD, which frequently co-exist [COPD-Bronchiectasis association (CBA)]. We aimed to determine the bacterial and viral spectrum at stable-state and exacerbation onset of CBA, and their association with exacerbations and clinical outcomes of CBA as compared with bronchiectasis.

Methods

We prospectively collected spontaneous sputum from adults with CBA, bronchiectasis with (BO) and without airflow obstruction (BNO) for bacterial culture and viral detection at stable-state and exacerbations.

Results

We enrolled 76 patients with CBA, 58 with BO, and 138 with BNO (711 stable and 207 exacerbation visits). Bacterial detection rate increased from BNO, CBA to BO at steady-state (P = 0.02), but not at AE onset (P = 0.91). No significant differences in viral detection rate were found among BNO, CBA and BO. Compared with steady-state, viral isolations occurred more frequently at exacerbation in BNO (15.8 % vs 32.1 %, P = 0.001) and CBA (19.5 % vs 30.6 %, P = 0.036) only. In CBA, isolation of viruses, human metapneumovirus and bacteria plus viruses was associated with exacerbation. Repeated detection of Pseudomonas aeruginosa (PA) correlated with higher modified Reiff score (P = 0.032) in CBA but not in BO (P = 0.178). Repeated detection of PA yielded a shorter time to the first exacerbation in CBA [median: 4.3 vs 11.1 months, P = 0.006] but not in BO (median: 8.4 vs 7.6 months, P = 0.47).

Conclusions

Isolation of any viruses, human metapneumovirus and bacterialplus viruses was associated with CBA exacerbations. Repeated detection of PA confers greater impact of future exacerbations on CBA than on BO.

Background

Salbutamol is a cornerstone for relieving acute asthma symptoms, typically administered through a pressurized metered-dose inhaler (pMDI). Dry powder inhalers (DPIs) offer an alternative, but concerns exist whether DPIs provide an effective relief during an obstructive event.

Objective

We aimed to show non-inferiority of Salbutamol Easyhaler DPI compared to pMDI with spacer in treating methacholine-induced bronchoconstriction. Applicability of Budesonide-formoterol Easyhaler DPI as a reliever was also assessed.

Methods

This was a randomized, parallel-group trial in subjects sent to methacholine challenge (MC) test for asthma diagnostics. Participants with at least 20 % decrease in forced expiratory volume in 1 s (FEV₁) were randomized to receive Salbutamol Easyhaler (2 × 200 μg), Ventoline Evohaler with spacer (4 × 100 μg) or Budesonide-formoterol Easyhaler (2 × 160/4.5 μg) as a reliever. The treatment was repeated if FEV₁ did not recover to at least −10 % of baseline.

Results

180 participants (69 % females, mean age 46 yrs [range 18–80], FEV₁%pred 89.5 [62–142] %) completed the trial. Salbutamol Easyhaler was non-inferior to pMDI with spacer in acute relief of bronchoconstriction showing a −0.083 (95 % LCL -0.146) L FEV₁ difference after the first dose and −0.032 (−0.071) L after the last dose. The differences in FEV₁ between Budesonide-formoterol Easyhaler and Salbutamol pMDI with spacer were −0.163 (−0.225) L after the first and −0.092 (−0.131) L after the last dose.

Conclusion

The study confirms non-inferiority of Salbutamol Easyhaler to Ventoline Evohaler with spacer in relieving acute bronchoconstriction, making Easyhaler a sustainable and safe reliever for MC test and supports its use during asthma attacks.