Therapeutic Advances in Respiratory Disease最新文献

Background: Liver injury is the hallmark adverse reaction of endothelin receptor antagonist (ERA). Since the first drug, bosentan has been widely used in clinical practice, hepatotoxicity has been accompanied by the history of ERA. The new ERA has been proven to have a lower liver risk but the current research findings are inconsistent. ERA-based targeted drug combinations are commonly used in the treatment of pulmonary arterial hypertension, where the risk of liver injury is difficult to estimate.

Objectives: This study aimed to compare the correlation between ERA and different ERA combination regimens with liver injury in the real world.

Design: This is a retrospective study using data from the Adverse Event Reporting System (Food and Drug Administration AERS, FAERS).

Methods: The study used proportional imbalance and Bayesian analysis to mine FAERS data from January 2004 to December 2022 to determine the association of three ERAs with liver injury and to further mine the risk of liver injury due to the combination of ERAs with other targeted drugs. In addition, we analyzed the onset time, mortality, and hospitalization rate of liver injury caused by different ERA combination regimens.

Results: We screened out 3581 ERA-related liver injury events, of which bosentan (59.82%) had the largest number of cases. The patients with liver injury were mainly female (60.63%), and the age was concentrated between 61 and 75 years (26.75%). According to different signal mining methods, reporting odds ratio (ROR; 3.38, 95% confidence interval = 3.23-3.53), proportional reporting ratio (PRR; 3.22, χ² = 37.84), Bayesian confidence propagation neural network (BCPNN; 1.68, 95% confidence interval = 1.61), multi-item gamma Poisson shrinker (MGPS; 3.21, 95% confidence interval = 3.09), bosentan had the strongest association with liver injury compared to ambrisentan and macitentan. Furthermore, bosentan + sildenafil [ROR (2.52, 95% confidence interval = 2.23-2.84), PRR (2.44, χ² = 15.92), BCPNN (1.29, 95% confidence interval = 1.14), MGPS (2.44, 95% confidence interval = 2.21)], bosentan + epoprostenol [ROR (5.39, 95% confidence interval = 4.29-6.77), PRR (4.94, χ² = 65.18), BCPNN (2.30, 95% confidence interval = 1.83), MGPS (4.94, 95% confidence interval = 4.08)], bosentan + iloprost [ROR (2.70, 95% confidence interval = 2.11-3.45), PRR (2.61, χ² = 31.03), BCPNN (1.38, 95% confidence interval = 1.08), MGPS (2.61, 95% confidence interval = 2.12)] had a higher risk of liver injury caused by the three ERA combination regimens. The median time to onset of hepatotoxicity associated with all ERA combination regimens was 259 days (interquartile range: 58-716.5 days). Finally, the hospitalization rate for patients experiencing hepatotoxicity with ERA combination regimens was 47.86% and the mo

Background: Interstitial lung diseases (ILD) unresponsive to medical therapy often require lung transplantation (LTx), which prolongs quality of life and survival. Ideal timing for referral for LTx remains challenging, with late referral associated with significant morbidity and mortality. Among other criteria, patients with ILD should be considered for LTx if forced vital capacity (FVC) is less than 80% or diffusion capacity for carbon monoxide (DLCO) is less than 40%. However, data on referral rates are lacking.

Objectives: To evaluate referral rates for LTx based on pulmonary function tests (PFTs) and identify barriers associated with non-referral.

Design: A single-center retrospective cohort study.

Methods: The study consisted of ILD patients who performed PFT between 2014 and 2020. Patients with FVC < 80% or a DLCO < 40% were included in the study. Patients with absolute contraindications to LTx were excluded. Referral rates were computed, and a comparison was made between referred and non-referred subjects.

Results: Out of 114 ILD patients meeting criteria for referral to LTx, 35 were referred (30.7%), and 7 proceeded to undergo LTx. Median time from PFT to referral for assessment was 255 days [interquartile range (IQR) 35-1077]. Median time from referral to LTx was 89 days (IQR 59-143). Referred patients were younger (p = 0.003), had lower FVC (p < 0.001), DLCO (p < 0.001), and a higher rate of pulmonary hypertension (p = 0.04). Relatively better PFT, and older age, were significantly associated with non-referral of patients.

Conclusion: There is under-referral of ILD patients who are eligible for LTx, which is associated with severe disease and missed opportunities for LTx. Further research is required to validate these findings.

Background: Empiric therapy with multichannel intraluminal impedance-pH monitoring (MII-pH) has been used for the initial treatment of gastroesophageal reflux-induced chronic cough (GERC). However, an algorithm based on the gastroesophageal reflux disease questionnaire (GerdQ) has the potential to achieve a simple, structured, and effective treatment approach for patients with GERC.

Objectives: This study compared the efficacy of anti-reflux therapy based on GerdQ (new structured pathway, NSP) with medical treatment after MII-pH examination (ordinary clinical pathway, OCP) in the management of GERC.

Design: For the NSP, we adapted the GerdQ score to establish the basis for a treatment algorithm. For the OCP, treatment was determined using the MII-pH examination results.

Methods: The non-inferiority (NI) hypothesis was used to evaluate NSP versus OCP.

Results: Overall, the NSP and OCP-based therapeutic algorithms have similar efficacy for GERC [NI analysis: 95% confidence interval (CI), -4.97 to 17.73, p = 0.009; superiority analysis: p = 0.420]. Moreover, the cough symptom scores and cough threshold improved faster in the NSP group than in the OCP group at week 8 (p < 0.05). In the subgroup analyses using the GerdQ and GerdQ impact scale (GIS) scores, patients with low-likelihood GERC (GerdQ < 8) were more likely to benefit from OCP (NI analysis: 95% CI, -19.73 to 18.02, p = 0.213). On the other hand, in patients with high-likelihood and low-reflux impact GERC patients (GerdQ > 8 and GIS < 4), the NSP arm was not inferior to the standard treatment of OCP (NI analysis: 95% CI, -8.85 to 28.21%, p = 0.04; superiority analysis: p = 0.339), indicating that GerdQ- and GIS-guided diagnosis and management of patients with GERC could be an alternative to MII-pH management, especially in settings with reduced medical resources.

Conclusions: The use of the GerdQ algorithm should be considered when handling patients with GERC in the primary care setting.

Trial registration: This research was registered in the Chinese Clinical Trials Registry (ChiCTR-ODT-12001899).

Background: High-flow nasal cannula (HFNC) and conventional oxygen therapy (COT) are important respiratory support strategies for acute hypoxemic respiratory failure (AHRF) in coronavirus disease 2019 (COVID-19) patients. However, the results are conflicting for the risk of intubation with HFNC as compared to COT.

Objectives: We systematically synthesized the outcomes of HFNC relative to COT in COVID-19 patients with AHRF and evaluated these outcomes in relevant subpopulations.

Design: This study was designed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

Data sources and methods: We searched PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, medRxiv, BioRxiv, and the Cochrane Central Register of Controlled Trials for randomized controlled trials and observational studies that compared the efficacy of HFNC with COT in patients with COVID-19-related AHRF. Primary outcomes were intubation rate and mortality rate. Secondary outcomes were the ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO₂/FiO₂), respiratory rate, hospital length of stay, intensive care unit (ICU) length of stay, and days free from invasive mechanical ventilation.

Results: In total, 20 studies with 5732 patients were included. We found a decreased risk of requiring intubation in HFNC compared to COT [odds ratio (OR) = 0.61, 95% confidence interval (CI): 0.46-0.82, p = 0.0009, I² = 75%]. Similarly, we found HFNC was associated with lower risk of intubation rate compared to COT in the subgroup of patients with baseline PaO₂/FiO₂ < 200 mmHg (OR = 0.69, 95% CI: 0.55-0.86, p = 0.0007, I² = 45%), and who were in ICU settings at enrollment (OR = 0.57, 95% CI: 0.38-0.85, p = 0.005, I² = 80%). HFNC was associated with an improvement of PaO₂/FiO₂ and respiratory rate compared to COT. The use of HFNC compared to COT did not reduce the mortality rate, days free from invasive mechanical ventilation, hospital length of stay, or ICU length of stay.

Conclusion: Compared to COT, HFNC may decrease the need for tracheal intubation in patients with COVID-19-related AHRF, particularly among patients with baseline PaO₂/FiO₂ < 200 mmHg and those in ICU settings.

Trial registration: This systematic review and meta-analysis protocol was prospectively registered with PROSPERO (no. CRD42022339072).

Background: With the rise of targeted treatments for asthma, treatment with omalizumab is a new option.

Objectives: To assess the improvement of pulmonary function with additional omalizumab treatment in patients (⩾6 years old) with moderate-to-severe allergic asthma.

Data sources and methods: Observational studies of randomized controlled trials of add-on omalizumab for the treatment of patients with moderate-to-severe allergic asthma, published from the establishment till August 2022, were retrieved from WAN FANG DATA, PubMed, CNKI, Embase, Cochrane, and Web of Science databases. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria, using RevMan 5.3 to analyze the data.

Results: A total of 11 randomized controlled clinical trials were included, involving a total of 3578 patients with asthma, 1856 patients in the omalizumab group, and 1722 patients in the control group. The improvement in Forced expiratory volume in 1 s as a percentage of predicted normal and Forced expiratory volume in 1 s was more pronounced in the omalizumab-treated group [MD = 3.91, 95% confidence interval (CI): 1.89-5.94, p = 0.0002; MD = 0.09, 95% CI: 0.05-0.13, p < 0.0001], while the improvement in Morning Peak expiratory flow rate was not statistically different between the two groups (MD = 3.64, 95% CI: -22.17-29.45, p = 0.78).

Conclusion: Additional omalizumab treatment showed some improvement in lung function in patients with moderate-to-severe asthma.

Trial registration: PROSPERO ID:CRD42022378498.

Background: To limit the progression of disease, people with cystic fibrosis (pwCF) perform daily respiratory physiotherapy, which is perceived as the most burdensome routine in managing their condition. The elexacaftor-tezacaftor-ivacaftor (ETI) combination has changed respiratory management.

Objective: To investigate how the perceived treatment burden changed in 1 year of treatment with ETI.

Design: Prospective observational study.

Methods: Ad hoc questionnaires for the pwCF and for the caregivers of pwCF < 18 years were administered before the initiation of ETI therapy and then at 6-12 months. The Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the Sinonasal Outcome Test (SNOT-22) were administered to explore disease-related symptoms and social limitations. The International Physical Activity Questionnaire was used to determine levels of physical activity. Mixed-effect models were fitted to explore whether the time engaged in respiratory physiotherapy changed during 1 year.

Results: The study included 47/184 pwCF aged 21.4 (5.7) years, who completed 1 year of ETI therapy. At 6 months, time on aerosol therapy was decreased by 2.5 (95% CI -32.9 to 27.8) min/day, time on airway clearance therapies (ACTs) was decreased by 8.8 (95% CI -25.9 to 8.3) min/day, and time for cleaning and disinfecting respiratory equipment was decreased by 10.6 (95% CI -26.5 to 5.3) min/day. At 1 year, gains in time saved were nearly 15 min/day on average. At 1 year, 5/47 (10.6%) pwCF reported that they had discontinued positive expiratory pressure mask.

Conclusion: PwCF on ETI may note less time engaged in their daily respiratory physiotherapy routine. Nonetheless, aerosol therapy, ACTs and maintaining respiratory equipment were still perceived as time-consuming daily activities.

Background: Although electromagnetic navigation bronchoscopy (ENB) is highly sensitive in the diagnosis of peripheral pulmonary nodules (PPNs), its diagnostic yield for subgroups of smaller PPNs is under evaluation.

Objectives: Diagnostic yield evaluation of biopsy using ENB for PPNs <2 cm.

Design: The diagnostic yield, sensitivity, specificity, positive predictive value, and negative predictive value of the ENB-mediated biopsy for PPNs were evaluated.

Methods: Patients who had PPNs with diameters <2 cm and underwent ENB-mediated biopsy between May 2015 and February 2020 were consecutively enrolled. The final diagnosis was made via pathological examination after surgery.

Results: A total of 82 lesions from 65 patients were analyzed. The median tumor size was 11 mm. All lesions were subjected to ENB-mediated biopsy, of which 29 and 53 were classified as malignant and benign, respectively. Subsequent segmentectomy, lobectomy, or wedge resection, following pathological examinations were performed on 64 nodules from 57 patients. The overall sensitivity, specificity, positive predictive value, and negative predictive value for nodules <2 cm were 53.3%, 91.7%, 92.3%, and 51.2%, respectively. The receiver operating curve showed an area under the curve of 0.721 (p < 0.001). Additionally, the sensitivity, specificity, positive predictive value, and negative predictive value were 62.5%, 100%, 100%, and 42.9%, respectively, for nodules with diameters equal to or larger than 1 cm; and 30.8%, 86.7%, 66.7%, and 59.1%, respectively, for nodules less than 1 cm. In the subgroup analysis, neither the lobar location nor the distance of the PPNs to the pleura affected the accuracy of the ENB diagnosis. However, the spiculated sign had a negative impact on the accuracy of the ENB biopsy (p = 0.010).

Conclusion: ENB has good specificity and positive predictive value for diagnosing PPNs <2 cm; however, the spiculated sign may negatively affect ENB diagnostic accuracy. In addition, the diagnostic reliability may only be limited to PPNs equal to or larger than 1 cm.

Background: It remains unclear whether erythrocyte sedimentation rate (ESR) accurately predicts prognosis during treatment and how ESR changes.

Objectives: We aimed to assess the predictive values of ESR as a prognostic factor of Mycobacterium avium complex pulmonary disease (MAC-PD) while on anti-mycobacterial treatment and its changes according to the treatment responses.

Design: This study is a retrospective cohort study.

Methods: This study included patients aged 18 years or older who initiated anti-mycobacterial treatment for MAC-PD at Seoul National University Hospital between January 1, 2009 and March 31, 2022. ESR should be measured at least twice, with a minimum interval of 3 months, during the initial 12 months from the commencement of antibiotic treatment. A mixed linear regression and Cox proportional-hazards models were used to analyze repeated ESR data and the association with patient survival.

Results: Of a total of 825 patients who initiated antibiotic treatment for MAC-PD, 369 patients were included in the analysis. Increased levels of ESR during the treatment process were associated with a higher risk of mortality (adjusted hazard ratio 1.03; 95% confidence interval, 1.02-1.03) after adjusting age, sex, comorbidities, presence of cavity, acid-fast bacilli smear positivity, and culture conversion at 12 months. During the treatment, ESR at 12 months of treatment significantly decreased compared to baseline ESR in both the culture-converted and not-converted groups, which was categorized based on whether the culture conversion was achieved within the 12 months after treatment initiation.

Conclusion: ESR predicted mortality during treatment and decreased over time, regardless of treatment outcomes. Our results underscore the importance of administering anti-mycobacterial treatment even in patients who did not achieve a microbiological cure.

Nanoparticles have attracted extensive attention due to their high degree of cell targeting, biocompatibility, controllable biological activity, and outstanding pharmacokinetics. Changing the size, morphology, and surface chemical groups of nanoparticles can increase the biological distribution of agents to achieve precise tissue targeting and optimize therapeutic effects. Examples of their use include nanoparticles designed for increasing antigen-specific immune responses, developing vaccines, and treating inflammatory diseases. Nanoparticles show the potential to become a new generation of therapeutic agents for regulating inflammation. Recently, many nanomaterials with targeted properties have been developed to treat acute lung injury/acute respiratory distress syndrome (ALI/ARDS). In this review, we provide a brief explanation of the pathological mechanism underlying ALI/ARDS and a systematic overview of the latest technology and research progress in nanomedicine treatments of ALI, including improved nanocarriers, nanozymes, and nanovaccines for the targeted treatment of lung injury. Ultimately, these nanomedicines will be used for the clinical treatment of ALI/ARDS.

Background: Invasive lung adenocarcinoma with MPP/SOL components has a poor prognosis and often shows a tendency to recurrence and metastasis. This poor prognosis may require adjustment of treatment strategies. Preoperative identification is essential for decision-making for subsequent treatment.

Objective: This study aimed to preoperatively predict the probability of MPP/SOL components in lung adenocarcinomas by a comprehensive model that includes radiomics features, clinical characteristics, and serum tumor biomarkers.

Design: A retrospective case control, diagnostic accuracy study.

Methods: This study retrospectively recruited 273 patients (males: females, 130: 143; mean age ± standard deviation, 63.29 ± 10.03 years; range 21-83 years) who underwent resection of invasive lung adenocarcinoma. Sixty-one patients (22.3%) were diagnosed with lung adenocarcinoma with MPP/SOL components. Radiomic features were extracted from CT before surgery. Clinical, radiomic, and combined models were developed using the logistic regression algorithm. The clinical and radiomic signatures were integrated into a nomogram. The diagnostic performance of the models was evaluated using the area under the curve (AUC). Studies were scored according to the Radiomics Quality Score and Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis guidelines.

Results: The radiomics model achieved the best AUC values of 0.858 and 0.822 in the training and test cohort, respectively. Tumor size (T_size), solid tumor size (ST_size), consolidation-to-tumor ratio (CTR), years of smoking, CYFRA 21-1, and squamous cell carcinoma antigen were used to construct the clinical model. The clinical model achieved AUC values of 0.741 and 0.705 in the training and test cohort, respectively. The nomogram showed higher AUCs of 0.894 and 0.843 in the training and test cohort, respectively.

Conclusion: This study has developed and validated a combined nomogram, a visual tool that integrates CT radiomics features with clinical indicators and serum tumor biomarkers. This innovative model facilitates the differentiation of micropapillary or solid components within lung adenocarcinoma and achieves a higher AUC, indicating superior predictive accuracy.