Therapeutic Advances in Respiratory Disease最新文献

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.

Background: The modified NUTRIC (nutritional risk in the critically ill) score has been reported to predict clinical outcomes in critically ill patients. However, the applicability of this score may differ between patients undergoing short-term mechanical ventilation (STMV, < 96 h) and those undergoing prolonged acute mechanical ventilation (PAMV, ⩾96 h), as PAMV patients typically experience significantly higher morbidity and mortality.

Objective: This study aimed to investigate the predictive ability of modified NUTRIC score for predicting 28-day mortality in patients receiving STMV and PAMV.

Design: Retrospective single-center cohort study.

Methods: We enrolled patients who received mechanical ventilation (MV) on the day of admission to the intensive care unit (ICU) from 1 December 2015 to 30 November 2020. Modified NUTRIC scores were calculated based on the clinical data of each patient at ICU admission.

Results: The study population comprised 464 patients, including 319 (68.8%) men with a mean age of 69.7 years. Among these patients, 132 (28.4%) received STMV and 332 (71.6%) received PAMV. The overall 28-day mortality rate was 26.7%, which was significantly higher in STMV patients than in PAMV patients (37.9% versus 22.3%, p < 0.001). Evaluation of the predictive performance of the modified NUTRIC score for 28-day mortality revealed areas under the receiver operating characteristic curves of 0.672 [95% confidence interval (CI): 0.627-0.714] for total patients, 0.819 (95% CI, 0.742-0.880) for STMV patients, and 0.595 (95% CI, 0.540-0.648) for PAMV patients. The best overall cutoff value was 5 in total, STMV, and PAMV patients. This cutoff value was a significant predictor of 28-day mortality based on the Cox proportional hazard model for total [hazards ratio (HR): 2.681; 95% CI: 1.683-4.269] and STMV (HR: 5.725; 95% CI: 2.057-15.931) patients, but not for PAMV patients.

Conclusion: The modified NUTRIC score is more effective in predicting 28-day mortality in patients undergoing STMV than in those undergoing PAMV.

Background: Balloon pulmonary angioplasty (BPA) is typically performed in a sequential manner.

Objectives: This study aimed to determine the lowest frequency of BPA for patients who could not reach treatment goals in a short period.

Design: Retrospective cohort.

Methods: We retrospectively enrolled 186 BPA-treated patients diagnosed with chronic thromboembolic pulmonary hypertension. According to the accumulative number of performed BPA sessions or treated pulmonary vessels or the ratio of the number of treated pulmonary vessels/the number of baseline lesions (T/P) prior to the initial occurrence of clinical outcome or censored date, we divided patients into different groups. The principal outcome was clinical worsening.

Results: After stratifying patients by the number of performed BPA sessions, most baseline parameters were comparable among groups. During follow-up, 31 (16.7%) of 186 patients experienced clinical worsening. The 6-month cumulative clinical worsening-free survival rates of ⩾2 performed sessions group were significantly higher than that of 1 performed session group. The 12-month cumulative rates of clinical worsening-free survival exhibited a declining pattern in the subsequent sequence: ⩾3, 2, and 1 performed BPA sessions, and this trend persisted when follow-up time exceeded 12 months. The 6-, 12-, and 24-month cumulative clinical worsening-free survival rates were comparable between patients with 3 and ⩾4 performed BPA sessions. Similar results were also observed when stratifying patients by the accumulative number of treated pulmonary vessels (⩽8, 9-16, ⩾17) and T/P (⩽0.789, 0.790-1.263, ⩾1.264).

Conclusion: To achieve optimal short-term outcomes, patients might need to undergo ⩾2 BPA sessions or have ⩾9 pulmonary vessels treated or have T/P ⩾0.790 within 6 months, and undergo ⩾3 BPA sessions or have ⩾17 pulmonary vessels treated or have T/P ⩾1.264 within 12 months.

Background: Some systematic reviews (SRs) on triple therapy (consisting of long-acting β₂-agonist, long-acting muscarinic antagonist, and inhaled corticosteroid, LABA/LAMA/ICS) for chronic obstructive pulmonary disease (COPD) have reported conflicting results. As the number of syntheses increases, the task of identifying and interpreting evidence becomes increasingly complex and demanding.

Objectives: To provide a comprehensive overview of the efficacy and safety of triple therapy for COPD.

Design: Overview of SRs.

Methods: Two independent reviewers conducted comprehensive searches in PubMed, Embase, Web of Science, and the Cochrane Library to identify relevant SRs that compared triple therapy with any non-triple therapy for COPD, from the inception of these databases until 1 June 2023. The AMSTAR 2 and GRADE tools were utilized to assess the quality of the included studies and the evidence for each outcome.

Results: Eighteen SRs encompassing 30 original studies and involving 47,340 participants were analyzed. The overall AMSTAR 2 rating revealed that 3 SRs were of low quality, 13 SRs were of critically low quality, and 2 SRs were of high quality. No high-certainty evidence revealed a significant advantage of triple therapy in improving lung function or reducing acute exacerbations. However, all evidence, including one high certainty, supported the benefits of improving quality of life. Regarding all-cause mortality, no significant difference was found when compared to LAMA or ICS/LABA; however, high-certainty evidence confirmed its effectiveness when compared with LABA/LAMA. Notably, high-certainty evidence indicated that triple therapy was associated with a significant increase in the risk of pneumonia compared to LABA/LAMA.

Conclusion: Triple therapy demonstrated notable benefits in improving lung function, reducing exacerbations, improving quality of life, and reducing all-cause mortality. However, it is important to note that it may also significantly increase the risk of pneumonia.

Trial registration: This overview protocol was prospectively registered with PROSPERO (No. CRD42023431548).

Background: The prognosis of malignant pleural effusion (MPE) is poor. A timely and accurate diagnosis is the prerequisite for managing MPE patients. Carbohydrate antigen 72-4 (CA72-4) is a diagnostic tool for MPE.

Objective: We aimed to evaluate the diagnostic accuracy of pleural fluid CA72-4 for MPE.

Design: A prospective, preregistered, and double-blind diagnostic test accuracy study.

Methods: We prospectively enrolled participants with undiagnosed pleural effusions from two centers in China (Hohhot and Changshu). CA72-4 concentration in pleural fluid was measured by electrochemiluminescence. Its diagnostic accuracy for MPE was evaluated by a receiver operating characteristic (ROC) curve. The net benefit of CA72-4 was determined by a decision curve analysis (DCA).

Results: In all, 153 participants were enrolled in the Hohhot cohort, and 58 were enrolled in the Changshu cohort. In both cohorts, MPE patients had significantly higher CA72-4 levels than benign pleural effusion (BPE) patients. At a cutoff value of 8 U/mL, pleural fluid CA72-4 had a sensitivity, specificity, and area under the ROC curve (AUC) of 0.46, 1.00, and 0.79, respectively, in the Hohhot cohort. In the Changshu cohort, CA72-4 had a sensitivity, specificity, and AUC of 0.27, 0.94, and 0.86, respectively. DCA revealed the relatively high net benefit of CA72-4 determination. In patients with negative cytology, the AUC of CA72-4 was 0.67.

Conclusion: Pleural fluid CA72-4 helps differentiate MPE and BPE in patients with undiagnosed pleural effusions.

Background: Chronic cough, defined as a cough lasting 8 or more weeks, affects up to 10% of adults. Refractory chronic cough (RCC) is a cough that is uncontrolled despite comprehensive investigation and treatment of comorbid conditions while unexplained chronic cough (UCC) is a cough with no identifiable cause despite extensive evaluation of comorbid conditions. RCC and UCC are often poorly controlled. Understanding individuals' lived experience of the symptoms and impacts of these conditions may guide therapeutic strategies.

Objectives: The primary objectives of this study were to assess respondents' perceptions of the key symptoms of RCC and UCC and the impacts of RCC and UCC and their symptoms on well-being, health-related quality of life, work productivity, and social relationships.

Design: Qualitative study.

Methods: This study enrolled 30 adults with physician-diagnosed RCC or UCC. Two trained qualitative researchers conducted individual, in-depth telephone interviews using a semi-structured interview guide. Interviews were audio-recorded, transcribed, coded, and systematically analyzed to identify content themes.

Results: A total of 15 respondents with RCC and 15 with UCC were included in the study. Many respondents had RCC or UCC for a long duration (median 9 years, range: 0-24). Half of the respondents reported having a coughing episode at least once daily. Only 40% of respondents reported that medication had improved their symptoms. In over half of the respondents, RCC or UCC hindered communication, caused embarrassment, frustration, and worry, and lowered quality of life. Perceptions of meaningful treatment benefits in RCC or UCC varied widely across respondents.

Conclusion: RCC and UCC remained poorly managed in many individuals and were associated with a wide range of symptoms and cough triggers that hindered daily activities and reduced emotional well-being. Understanding individuals' lived experiences may inform the development of RCC and UCC therapeutic strategies.

During the COVID-19 pandemic, the number of patients with hypoxemic acute respiratory failure (ARF) due to SARS-CoV-2 pneumonia threatened to overwhelm intensive care units. To reduce the need for invasive mechanical ventilation (IMV), clinicians tried noninvasive strategies to manage ARF, including the use of awake prone positioning (PP) with continuous positive airway pressure (CPAP). In this article, we review the patho-physiologic rationale, clinical effectiveness and practical issues of the use of PP during CPAP in non-intubated, spontaneously breathing patients affected by SARS-CoV-2 pneumonia with ARF. Use of PP during CPAP appears to be safe and feasible and may have a lower rate of adverse events compared to IMV. A better response to PP is observed among patients in early phases of acute respiratory distress syndrome. While PP during CPAP may improve oxygenation, the impact on the need for intubation and mortality remains unclear. It is possible to speculate on the role of PP during CPAP in terms of improvement of ventilation mechanics and reduction of strain stress.

Background: Gut microbiota assumes an essential role in the development and progression of pulmonary arterial hypertension (PAH). Trimethylamine N-oxide (TMAO), a gut microbiota-dependent metabolite, is correlated with the prognosis of patients with PAH. However, the correlation between changes in TMAO (ΔTMAO) and the prognosis of PAH remains elusive.

Objectives: To investigate the association between ΔTMAO and prognosis of PAH, and explore whether dynamic assessment of TMAO level was superior to measurement at a single time point in predicting prognosis.

Design: Single-center cohort study.

Methods: Consecutive patients diagnosed with PAH and had at least two TMAO measurements taken from May 2019 to June 2020 were eligible. The outcome events of this study were defined as adverse clinical events.

Results: A total of 117 patients with PAH who had two TMAO measurements and follow-up were included in this study. Patients with ΔTMAO ⩾1.082 μmol/L had over four times increased risk of adverse clinical events than their counterparts after adjusting for confounders [hazard ratio (HR) 4.050, 95% confidence interval (CI): 1.468-11.174; p = 0.007]. Patients with constant high TMAO levels at both time points had the highest risk of adverse clinical events compared with patients with constant low TMAO levels (HR 3.717, 95% CI: 1.627-8.492; p = 0.002). ΔTMAO was also associated with changes in parameters reflecting PAH severity (p < 0.05).

Conclusion: Changes in TMAO were independently correlated with prognosis in patients with PAH, irrespective of baseline level of TMAO. ΔTMAO also correlated with alteration in disease severity. Repeated assessment of TMAO level contributes to better identification of patients with increased risk of adverse clinical events.

Background: Sex-related disparities in the prevalence of chronic cough have been consistently reported globally, with varying male-to-female ratios.

Objectives: This study aimed to evaluate sex-related differences by comparing correlations between cough-related symptoms in males and females of different age groups.

Design: Adult patients with chronic cough who completed the Leicester Cough Questionnaire (LCQ) were recruited from 16 respiratory centers.

Methods: Correlation networks were constructed based on Spearman's correlation coefficients in males and females of various age groups. The distinct relationships of cough-related symptoms between subgroups were validated by an independent cohort.

Results: A total of 255 patients were enrolled in this study (male-to-female ratio, 1:1.71). The following LCQ items were highly correlated: embarrassment and interference with daily work, anxiety, and interference with overall life enjoyment/feeling of being fed up, interference with daily work and overall life enjoyment, interference with overall life enjoyment and feeling of being fed up, and feeling of being fed up and annoyance to partner/family/friends. The patterns of these correlations between LCQ items varied in males and females of different ages. The strongest interrelationship was observed in male patients aged >50 years old, which was similar to those in the validation cohort.

Conclusion: The correlation patterns between cough-related symptoms vary significantly according to age and sex. Understanding the mechanisms underlying the development of cough-related symptoms may facilitate sex- and age-specific strategies for chronic cough.