Therapeutic Advances in Respiratory Disease最新文献

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.

Primary lung cancer in childhood is extremely rare, with an incidence rate of less than 2/100,0000, and pulmonary mucoepidermoid carcinoma (PMEC), is even rarer. Their symptoms are usually not specific, and there are no guidelines for their management, which makes their clinical management a challenge for pediatricians. The purpose of this report is to discuss the clinical presentation, positive signs, examinations, pathological characteristics, surgical modalities, chemotherapy regimens, and prognosis in children. The clinical data of four patients diagnosed with PMEC at the Children's Hospital of Chongqing Medical University from June 2021 to November 2022 were retrospectively analyzed, and their clinical features, treatment, and prognosis were summarized. Among them, two were male and two were female; their ages ranged from 3 years and 10 months to 10 years and 11 months, and all were staged according to tumor node metastasis classification (TNM). Immunohistochemical tests were performed in all children, among which four cases were positive for cytokeratin (CK), two cases were positive for CK7, four cases were positive for p63, about 5-10% of tumor cells were positive for Ki67. Among the four children, three had surgery alone and one had surgery + chemotherapy. All four children are presently living, with no evidence of tumor recurrence or metastasis. PMEC in children is very rare, and its age of onset and symptoms are not specific, and there is no obvious correlation with gender. Its diagnosis mainly relies on pathomorphological diagnosis, and immunohistochemical detection has no specific performance. The prognosis of children with PMEC is related to the clinical stage and whether surgery is performed. Whether further chemotherapy or radiotherapy is needed for patients who cannot undergo surgical resection and for those who have a combination of distant metastases requires further clinical studies.

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: The role of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) validated with video-assisted mediastinoscopic lymphadenectomy (VAMLA) for mediastinal restaging of patients with non-small cell lung cancer (NSCLC) after induction therapy has never been described.

Objective: To report on our experience in this clinical setting.

Design: Retrospective analysis of a prospectively built database.

Methods: Patients with stage IIIA (N2) NSCLC who underwent EBUS-TBNA for mediastinal restaging after induction therapy were included. The sensitivity, specificity, negative predictive value (NPV), positive predictive value (PPV), and diagnostic accuracy of EBUS-TBNA and VAMLA for mediastinal restaging were calculated. The number of patients needed to undergo confirmatory VAMLA (NNT) after a negative EBUS-TBNA for mediastinal restaging to avoid a case of pathologic (p) N2 disease after resection was also calculated.

Results: Forty-six patients underwent EBUS-TBNA which was positive in 12 patients and negative in 34. Patients with a negative EBUS-TBNA underwent VAMLA which was positive in seven cases. Of the other 27 patients with a negative VAMLA, 26 underwent resection that did not show N2 disease. The sensitivity, specificity, NPV, PPV, and diagnostic accuracy of EBUS-TBNA for restaging were 63.1%, 100%, 79.4%, 100%, and 84.7%, respectively. The sensitivity, specificity, NPV, PPV, and diagnostic accuracy of confirmatory VAMLA after EBUS-TBNA was 100%. The NNT confirmatory VAMLA after a negative EBUS-TBNA to avoid a case of pN2 disease at resection was five patients.

Conclusion: EBUS-TBNA must remain as the first-choice test for invasive mediastinal restaging. However, the results of our study in terms of sensitivity and NPV, even considering the small size of our population, suggest that negative results of EBUS-TBNA should be interpreted with caution and surgical exploration of the mediastinum (specially VAMLA, if available) should be considered in these patients.

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: 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: 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: Muscular atrophy often can be seen at the end of stage in many chronic diseases. It will also negatively influence patients' outcomes. Different studies showed that the association between muscular atrophy and mortality in patients with chronic obstructive pulmonary disease (COPD) was unclear. This study will continue to assess the influence of muscular atrophy on mortality in patients with COPD.

Objectives: To systematically evaluate the association between muscular atrophy and death in patients with COPD.

Design: Systematic review.

Methods and data sources: A systematic review and meta-analysis was conducted. Databases including PubMed, Web of Science, Embase, the Cochrane Library, the China Biomedical Literature Service System, China Biomedical Literature Service System (CINAHL), China National Knowledge Infrastructure, the Wanfang database, and the WeiPu (VIP) were systematically searched for cohort studies on muscular atrophy and COPD from inception to July 1st, 2023. Two reviewers independently review, assess, and extract data from the included studies. Meta-analysis was performed using RevMan 5.4 software.

Results: Thirteen cohort studies were ultimately included, involving 10,528 patients with COPD. There were seven cohort studies included in the meta-analysis, including 3,458 COPD patients. The meta-analysis showed that patients with COPD combined with muscular atrophy had a higher mortality risk (HR = 2.20, 95%CI (1.74, 2.79), p < 0.00001). At the same time, patients with COPD who had muscular atrophy may had longer hospital stays.

Conclusion: Muscular atrophy is associated with the mortality and disease prognosis of patients with COPD. The conclusion needs to be supported and validated by more high-quality studies given the limitation of the number of articles included in this study.

Trial registration: This systematic review protocol was prospectively registered with PROSPERO (No. CRD42024589435).