Canadian respiratory journal最新文献

Background: Pulmonary sarcoidosis predominantly affects the upper lung zones but sometimes affects the lower lung zones. We hypothesised that patients with lower lung zone-dominant sarcoidosis had lower baseline forced vital capacity, progressive restrictive lung function decline, and higher long-term mortality.

Methods: We retrospectively reviewed clinical data including the pulmonary function tests of 108 consecutive patients with pulmonary sarcoidosis pathologically confirmed by lung and/or mediastinal lymph node biopsy from 2004 to 2014 from our database.

Results: Eleven patients (10.2%) with lower lung zone-dominant sarcoidosis were compared with 97 patients with nonlower lung zone-dominant sarcoidosis. The median age of the patients with lower dominance was significantly older (71 vs. 56, p = 0.0005). The patient with lower dominance had a significantly lower baseline percent forced vital capacity (FVC) (96.0% vs. 103%, p = 0.022). The annual change in FVC was -112 mL in those with lower dominance vs. 0 mL in nonlower dominance (p = 0.0033). Fatal acute deterioration was observed in three patients (27%) in the lower dominant group. Overall survival in the lower dominant group was significantly worse.

Conclusions: Patients with lower lung zone-dominant sarcoidosis had an older age and lower baseline FVC with disease progression and acute deterioration associated with higher long-term mortality.

Background: Limited data are available about the clinical outcomes of AECOPD patients with respiratory acidosis treated with HFNC versus NIV.

Methods: We conducted a retrospective study to compare the efficacy of HFNC with NIV as initial ventilation support strategy in AECOPD patients with respiratory acidosis. Propensity score matching (PSM) was implemented to increase between-group comparability. Kaplan-Meier analysis was utilized to evaluate differences between the HFNC success, HFNC failure, and NIV groups. Univariate analysis was performed to identify the features that differed significantly between the HFNC success and HFNC failure groups.

Results: After screening 2219 hospitalization records, 44 patients from the HFNC group and 44 from the NIV group were successfully matched after PSM. The 30-day mortality (4.5% versus 6.8%, p = 0.645) and 90-day mortality (4.5% versus 11.4%, p = 0.237) did not differ between the HFNC and NIV groups. Length of ICU stay (median: 11 versus 18 days, p = 0.001), length of hospital stay (median: 14 versus 20 days, p = 0.001), and hospital cost (median: 4392 versus 8403 $USD, p = 0.001) were significantly lower in the HFNC group compared with NIV group. The treatment failure rate was much higher in the HFNC group than in the NIV group (38.6% versus 11.4%, p = 0.003). However, patients who experienced HFNC failure and switched to NIV showed similar clinical outcomes to those who first received NIV. Univariate analysis showed that log NT-proBNP was an important factor for HFNC failure (p = 0.007).

Conclusions: Compared with NIV, HFNC followed by NIV as rescue therapy may be a viable initial ventilation support strategy for AECOPD patients with respiratory acidosis. NT-proBNP may be an important factor for HFNC failure in these patients. Further well-designed randomized controlled trials are needed for more accurate and reliable results.

Background: Ventilator-associated pneumonia (VAP) is among the most important hospital-acquired infections in an intensive-care unit setting. However, clinical practice lacks effective theoretical tools for preventing VAP in the elderly.

Aim: To describe the independent factors associated with VAP in elderly intensive-care unit (ICU) patients on mechanical ventilation (MV) and to construct a risk prediction model.

Methods: A total of 1851 elderly patients with MV in ICUs from January 2015 to September 2019 were selected from 12 tertiary hospitals. Study subjects were divided into a model group (n = 1219) and a validation group (n = 632). Two groups of patients were divided into a VAP group and a non-VAP group and compared. Univariate and logistic regression analyses were used to explore influencing factors for VAP in elderly ICU patients with MV, establish a risk prediction model, and draw a nomogram. We used the area under the receiver operating characteristic curve (AUROC) and the Hosmer-Lemeshow goodness-of-fit test to evaluate the predictive effect of the model. Findings regarding the length of ICU stay, surgery, C-reactive protein (CRP), and the number of reintubations were independent risk factors for VAP in elderly ICU patients with MV. Predictive-model verification results showed that the area under the curve (AUC) of VAP risk after MV in the modeling and verification groups was 0.859 and 0.813 (P < 0.001), respectively, while P values for the Hosmer-Lemeshow test in these two groups were 0.365 and 0.485, respectively.

Conclusion: The model could effectively predict the occurrence of VAP in elderly patients with MV in ICUs. This study is a retrospective study, so it has not been registered as a clinical study.

Background: There is currently limited evidence for a correlation between the recommended operation and overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC).

Methods: NSCLC patients with stages III and IV, recommended for operation, were identified in the US National Cancer Institute Surveillance, Epidemiology, and End Results database (SEER).We used propensity score matching (PSM) and multivariable Cox proportional hazards regression to ensure the robustness of our findings. The cumulative rates of death were compared between patients with and without recommended operations using the Kaplan-Meier curves.

Results: Operation was recommended for 3331 patients but was not performed in 912 (27.4%) patients (then on-operative group). After PSM, 553 pairs matched. Compared to the nonoperative group, the hazard ratios (HRs) in the operative group were 0.46 (95% CI 0.23-0.95 and p=0.037) in stage IIIA and 0.54 (95% CI 0.42-0.68 and p < 0.001) in stage IVA. However, in stages IIIB, IIIC, and IVB, the recommended operative group was not associated with better OS. The OS was not different in stage IIIA-N2, stage IVA-N1, and stage IVA-N3 patients between groups (p=0.28, p=0.14, and p=0.79, respectively). Moreover, the recommended operative group had better OS than the nonoperative group in stage IIIA-N0 (p=0.00085), stage IIIA-N1 (p=0.009), stage IVA-N0 (p < 0.001), and stage IVA-N2 (p=0.034).

Conclusion: Compared to the nonoperative group, recommended operation improved survival in NSCLC patients with stage IIIA-N0, stage IIIA-N1, stage IVA-N0, and stage IVA-N2. However, in stages IIIA-N2, IIIB, IIIC, IVA-N1, IVA-N3, and IVB, recommended operation did not lead to significantly improved survival time.

Background: Lung squamous cell carcinoma (LUSC) is a common malignancy. And the antitumor effect of bovine pox virus-associated kinase 1 (VRK1) is becoming a hot research topic.

Methods: VRK1 expression and prognosis in LUSC were analyzed using the GEPIA database. The expression of VRK1 mRNA was detected in 25 LUSC clinical tissue samples by RT-PCR. VRK1 shRNA was transfected into LUSC NCI-H520 and SK-MES-1 cell lines to interfere with VRK1 expression, and the efficiency of VRK1 shRNA interference was detected by the western blot. The effects of VRK1 downregulation on LUSC cell viability, migration, cell cycle, and apoptosis were analyzed by the CCK8 assay, scratch assay, transwell assay, and flow cytometry. The effect of VRK1 downregulation on DNA damage response (DDR) was examined by immunofluorescence staining and western blot assays and further validated by in vivo experiments.

Results: VRK1 was highly expressed in both LUSC tissues and cells. Survival analysis showed that the overall survival of LUSC patients with high VRK1 expression was significantly lower than that of LUSC patients with low VRK1 expression (P=0.0026). The expression level of the VRK1 gene was significantly higher in cancer tissues of LUSC patients than in paracancerous tissues. After transfection of VRK1 shRNA in both LUSC cells, cell activity decreased (P < 0.001), migration ability started to be inhibited (P < 0.001), the ratio of G0/G1 phase cells increased (P < 0.001), and apoptosis rate increased (P < 0.001). Immunofluorescence and western blot results showed that shVRK1 increased the level of γ-H2A.X (P < 0.001) and promoted apoptosis of tumor cells (P < 0.001). In addition, the results of animal experiments showed that shVRK1 had antitumor effects (P < 0.001) and a combined effect with DOX (P < 0.001).

Conclusion: The downregulation of VRK1 significantly affected the proliferation, apoptosis, migration, and cell cycle progression of LUSC cells via DDR, suggesting that VRK1 is a suitable target for potential LUSC therapy.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease characterized by excessive deposition of extracellular matrix in the interstitial lung parenchyma, often manifested by dyspnea and progressive loss of lung function. The role of inflammation in the pathogenesis of IPF is not well understood. This study evaluated the histopathological and inflammatory components of bleomycin-induced pulmonary fibrosis in mouse and sheep models, in terms of their ability to translate to the human IPF. Merino sheep (n = 8) were bronchoscopically administered with two bleomycin infusions, two weeks apart, into a caudal lung segment, with a saline (control) administered into a caudal segment in the opposite lung. Balb/c mice were twice intranasally instilled, one week apart, with either bleomycin (n = 7); or saline (control, n = 7). Lung samples were taken for the histopathological assessment 28 days in sheep and 21 days in mice after the first bleomycin administration. We observed tertiary lymphoid aggregates, in the fibrotic lung parenchyma of sheep, but not in mouse lung tissues exposed to bleomycin. B-cell and T-cell infiltration significantly increased in sheep lung tissues compared to mouse lung tissues due to bleomycin injury. Statistical analysis showed that the fibrotic score, fibrotic fraction, and tissue fraction significantly increased in sheep lung tissues compared to murine lung tissues. The presence of tertiary lymphoid aggregates in the lung parenchyma and increased infiltration of T-cells and B-cells, in the sheep model, may be useful for the future study of the underlying inflammatory disease mechanisms in the lung parenchyma of IPF patients.

Background: High-flow nasal cannula (HFNC) is an oxygen delivery method shown to reduce the risk of intubation and mortality in patients with type 1 respiratory failure. The ROX-index score can predict HFNC failure. This study aims to evaluate sequential ROX-index assessments as predictors of HFNC failure and mortality.

Methods: Prospective observational single-center study including all adult patients with positive SARS-CoV-2 PCR placed under HFNC from 1st November 2020 to 31st May 2021, and patients with hemodynamic instability or unable to tolerate HFNC were excluded. The primary endpoint was successful HFNC de-escalation.

Results: In univariate analysis, HFNC de-escalation was associated with younger age (59.2 ± 14 vs. 67.7 ± 10.5 and p < 0.001), lower levels of serum lactate (1.1 vs. 1.5 and p=0.013), and higher ROX-index at 12 hrs (5.09 vs. 4.13 and p < 0.001). ROC curve analysis of ROX-index at 12 hrs yielded a c-statistic of 71.2% (95% CI 61.6-80.9 and p < 0.001). ROX-index at 12 hrs and age retained significance in multivariate analysis. Using an optimal cutoff point of 4.43, we calculated a sensitivity of 64.5% and specificity of 69.6%. In univariate survival analysis, older age (68.8 ± 9.7 vs. 58.9 ± 13.9 and p < 0.001), greater creatinine values (0.96 vs. 0.84 and p=0.022), greater SOFA score (p=0.039), and a lower 12 hrs ROX-index (4.22 vs. 4.95 and p=0.02) were associated with hospital mortality. The SOFA score and age retained significance in multivariate survival analysis.

Conclusion: ROX-index is proven to be a valuable and easy-to-use tool for clinicians in the assessment of COVID-19 patients under HFNC.

Inhalation of nebulized TP has received little attention in the past. Here, we intend to investigate the effect of nebulized inhaled TP on airway inflammation in a mouse model of asthma. 29 SPF BALB/c mice were divided into four groups: blank control (Blk, n = 5), normal saline (NS, n = 8), dexamethasone (Dex, n = 8), and TP (n = 8). During the process of sensitization, mice in the three intervention groups were treated with nebulized NS, an injection of Dex, and nebulized triptolide, respectively. Then bronchoalveolar lavage fluid (BALF), peripheral blood, and lung tissue were collected. Relevant cytokines, transcriptional factors, and CD4+Th17+ T cell proportions were assessed and compared. IL-6, IL-17, IL-23, and TGF-β1 demonstrated a significant difference between groups in the following order: Dex < TP < NS (P ≤ 0.001), while IL-10 changed in the opposite direction (P < 0.001). At the transcriptional level in lung tissue, the Ct value of IL-17 in the Dex group was significantly higher than in the NS and TP groups (P < 0.001). Meanwhile, it was higher in the TP group than in the NS group (P < 0.001). The Ct value of RORγt demonstrated a significant difference among three groups in the following order: Dex > TP > NS (P < 0.001). An opposite trend of FoxP3 Ct value was revealed in the order: NS > TP > Dex. The proportion of CD4+Th17+ cells was 9.53 ± 2.74% in the NS group, 4.23 ± 2.26% in the Dex group, and 6.76 ± 2.99% in the TP group, which shows significant differences between the NS and Dex (P < 0.001) or NS and TP groups (P < 0.05). Inhalation of nebulized triptolide can play a role in suppressing airway inflammation with inflammatory cytokines and transcriptional factors reduced and CD4+Th17+ T cells dampened, also in a manner less than injected dexamethasone.

Background: The ILD-GAP scoring system has been widely used to predict the prognosis of patients with interstitial lung disease (ILD). The ability of the ILD-GAP scoring system combined with the Charlson Comorbidity Index score (CCIS) (ILD-GAPC) to predict ILD prognosis was investigated.

Methods: In ILD patients, including idiopathic pulmonary fibrosis (IPF), idiopathic nonspecific interstitial pneumonia (iNSIP), collagen vascular disease-related interstitial pneumonia (CVD-IP), chronic hypersensitivity pneumonitis (CHP), and unclassifiable ILD (UC-ILD), treated between April 2013 and April 2017, the relationships between baseline clinical parameters, including age, sex, CCIS, ILD diagnosis, pulmonary function test results, and disease outcomes, were retrospectively assessed, and the ability to predict prognosis was compared between the ILD-GAP and ILD-GAPC models, respectively.

Results: A total of 185 patients (mean age, 71.9 years), all of whom underwent pulmonary function testing, including percentage predicted diffusion capacity for carbon monoxide, were assessed. ILD diagnosis consisted of IPF in 57 cases, iNSIP and CVD-IP in 117 cases, CHP in 6 cases, and UC-ILD in 5 cases. The ILD-GAPC provided a greater area under the receiver operating characteristic curve (0.758) for predicting 3-year ILD-related events than the ILD-GAP (0.721). In addition, log-rank tests showed that the Kaplan-Meier curves differed significantly among low, middle, and high ILD-GAPC scores (P < 0.001), unlike ILD-GAP scores (P = 0.083).

Conclusions: The ILD-GAPC model could provide more accurate information for predicting prognosis in patients with ILD than the ILD-GAP model.

Introduction: Nocturnal hypoventilation may occur due to obesity, concomitant chronic obstructive pulmonary disease (COPD), obstructive sleep apnea, and/or the use of narcotic analgesics. The aim of the study was to evaluate the risk and severity of nocturnal hypoventilation as assessed by transcutaneous continuous capnography in the patients submitted to thoracic surgery.

Materials and methods: The material of the study consisted of 45 obese (BMI 34.8 ± 3.7 kg/m²) and 23 nonobese (25.5 ± 3.6 kg/m²) patients, who underwent thoracic surgery because of malignant (57 patients) and nonmalignant tumors. All the patients received routine analgesic treatment after surgery including intravenous morphine sulfate. Overnight transcutaneous measurements of CO₂ partial pressure (tcpCO₂) were performed before and after surgery in search of nocturnal hypoventilation, i.e., the periods lasting at least 10 minutes with tcpCO₂ above 55 mmHg.

Results: Nocturnal hypoventilation during the first night after thoracic surgery was detected in 10 patients (15%), all obese, three of them with COPD, four with high suspicion of moderate-to-severe OSA syndrome, and one with chronic daytime hypercapnia. In the patients with nocturnal hypoventilation, the mean tcpCO₂ was 53.4 ± 6.1 mmHg, maximal tcpCO₂ was 59.9 ± 8.4 mmHg, and minimal tcpCO₂ was 46.4 ± 6.7 mmHg during the first night after surgery. In these patients, there were higher values of minimal, mean, and maximal tcpCO₂ in the preoperative period. Nocturnal hypoventilation in the postoperative period did not influence the duration of hospitalization. Among 12 patients with primary lung cancer who died during the first two years of observation, there were 11 patients without nocturnal hypoventilation in the early postoperative period.

Conclusion: Nocturnal hypoventilation may occur in the patients after thoracic surgery, especially in obese patients with bronchial obstruction, obstructive sleep apnea, or chronic daytime hypercapnia, and does not influence the duration of hospitalization.