Association of air pollution exposure with exercise-induced oxygen desaturation in COPD.

BACKGROUND: There is a link between exposure to air pollution and the increased prevalence of chronic obstructive pulmonary disease (COPD) and declining pulmonary function, but the association with O2 desaturation during exercise in COPD patients with emphysema is unclear. Our aims were to estimate the prevalence of O2 desaturation during exercise in patients with COPD, and determine the association of exposure to air pollution with exercise-induced desaturation (EID), the degree of emphysema, and dynamic hyperinflation (DH). METHODS: We assessed the effects of 10-year prior to the HRCT assessment and 7 days prior to the six-minute walking test exposure to particulate matter with an aerodynamic diameter of < 10 µm (PM10) or of < 2.5 µM (PM2.5), nitrogen dioxide (NO2), and ozone (O3) in patients with emphysema in this retrospective cohort study. EID was defined as a nadir standard pulse oximetry (SpO2) level of < 90% or a delta (△)SpO2 level of ≥ 4%. Ambient air pollutant (PM2.5, PM10, O3, and NO2) data were obtained from Taiwan Environmental Protection Administration (EPA) air-monitoring stations, usually within 10 km to each participant's home address. RESULTS: We recruited 141 subjects with emphysema. 41.1% of patients with emphysema exhibited EID, and patients with EID had more dyspnea, worse lung function, more severe emphysema, more frequent acute exacerbations, managed a shorter walking distance, had DH, and greater long-term exposure to air pollution than those without EID. We observed that levels of 10-year concentrations of PM10, PM2.5, and NO2 were significantly associated with EID, PM10 and PM2.5 were associated with the severity of emphysema, and associated with DH in patients with emphysema. In contrast, short-term exposure did not have any effect on patients. CONCLUSION: Long-term exposure to ambient PM10, PM2.5 and NO2, but not O3, was associated with EID.

Lnc-IL7R alleviates PM2.5-mediated cellular senescence and apoptosis through EZH2 recruitment in chronic obstructive pulmonary disease.

BACKGROUND: Long-term exposure to PM2.5 (particulate matter with an aerodynamic diameter of ≤ 2.5 µm) is associated with pulmonary injury and emphysema in patients with chronic obstructive pulmonary disease (COPD). We investigated mechanisms through which the long noncoding RNA lnc-IL7R contributes to cellular damage by inducing oxidative stress in COPD patients exposed to PM2.5. METHODS: Associations of serum lnc-IL7R levels with lung function, emphysema, and previous PM2.5 exposure in COPD patients were analyzed. Reactive oxygen species and lnc-IL7R levels were measured in PM2.5-treated cells. The levels of lnc-IL7R and cellular senescence-associated genes, namely p16INK4a and p21CIP1/WAF1, were determined through lung tissue section staining. The effects of p16INK4a or p21CIP1/WAF1 regulation were examined by performing lnc-IL7R overexpression and knockdown assays. The functions of lnc-IL7R-mediated cell proliferation, cell cycle, senescence, colony formation, and apoptosis were examined in cells treated with PM2.5. Chromatin immunoprecipitation assays were conducted to investigate the epigenetic regulation of p21CIP1/WAF1. RESULTS: Lnc-IL7R levels decreased in COPD patients and were negatively correlated with emphysema or PM2.5 exposure. Lnc-IL7R levels were upregulated in normal lung epithelial cells but not in COPD cells exposed to PM2.5. Lower lnc-IL7R expression in PM2.5-treated cells induced p16INK4a and p21CIP1/WAF1 expression by increasing oxidative stress. Higher lnc-IL7R expression protected against cellular senescence and apoptosis, whereas lower lnc-IL7R expression augmented injury in PM2.5-treated cells. Lnc-IL7R and the enhancer of zeste homolog 2 (EZH2) synergistically suppressed p21CIP1/WAF1 expression through epigenetic modulation. CONCLUSION: Lnc-IL7R attenuates PM2.5-mediated p21CIP1/WAF1 expression through EZH2 recruitment, and its dysfunction may augment cellular injury in COPD.

3-Nitrobenzanthrone promotes malignant transformation in human lung epithelial cells through the epiregulin-signaling pathway.

Exposure to environmental and occupational contaminants leads to lung cancer. 3-Nitrobenzanthrone (3-nitro-7H-benz[de]anthracen-7-one, 3-NBA) is a potential carcinogen in ambient air or diesel particulate matter. Studies have revealed that short-term exposure to 3-NBA induces cell death, reactive oxygen species activation, and DNA adduct formation and damage. However, details of the mechanism by which chronic exposure to 3-NBA influences lung carcinogenesis remain largely unknown. In this study, human lung epithelial BEAS-2B cells were continuously exposed to 0-10-µM 3-NBA for 6 months. NanoString analysis was conducted to evaluate gene expression in the cells, revealing that 3-NBA-mediated transformation results in a distinct gene expression signature including carbon cancer metabolism, metastasis, and angiogenesis. Alterations in tumor-promoting genes such as EREG (epiregulin), SOX9, E-cadherin, TWIST, and IL-6 were involved in epithelial cell aggressiveness. Kaplan-Meier plotter analyses indicated that increased EREG and IL-6 expressions in early-stage lung cancer cells are correlated with poor survival. In vivo xenografts on 3-NBA-transformed cells exhibited prominent tumor formation and metastasis. EREG knockout cells exposed to 3-NBA for a short period exhibited high apoptosis and low colony formation. By contrast, overexpression of EREG in 3-NBA-transformed cells markedly activated the PI3K/AKT and MEK/ERK signaling pathways, resulting in tumorigenicity. Furthermore, elevated IL-6 and EREG expressions synergistically led to STAT3 signaling activation, resulting in clonogenic cell survival and migration. Taken together, chronic exposure of human lung epithelial cells to 3-NBA leads to malignant transformation, in which the EREG signaling pathway plays a pivotal mediating role. • Short-term exposure of lung epithelial cells to 3-NBA can lead to ROS production and cell apoptosis. • Long-term chronic exposure to 3-NBA upregulates the levels of tumor-promoting genes such as EREG and IL-6. • Increased EREG expression in 3-NBA-transformed cells markedly contributes to tumorigenesis through PI3K/AKT and MEK/ERK activation and synergistically enhances the IL-6/STAT3 signaling pathway, which promotes tumorigenicity.

Addressing the ACGME Competency of Communicating with the Public through the Use of TEDx Talks.

OBJECTIVES: Competency-based public communication skills are not systematically taught in most medical curricula, reflecting a gap between medical knowledge and holistic patient care as trainees transition into clinicians. We sought to investigate the efficacy of technology, entertainment, and design (TED) talks in postgraduate year (PGY) training programs. METHODS: The authors organized an official internal TEDx event in which six PGY trainees volunteered as speakers. Two experienced physicians and two administrators also participated as speakers to provide trainees a didactic shadow learning experience. The remaining PGY trainees, along with clerks, physicians, nurses, pharmacists, and administrators, attended the conference. Before the event, speakers undertook individual training sessions and learned the principles of the presentation structure and storytelling mode. At the end of the event, a survey evaluating overall satisfaction in communication skills and professionalism was administered to all of the attendees. RESULTS: Survey participants totaled 104, with a response rate of 97.2%. TEDx talks improved trainees' levels of patient care, communication, and professionalism. Speakers reported the high level of satisfaction with the event (mean 4.96 on a 5-point Likert scale; standard deviation 0.20). Participants agreed that the shadowing experience was useful and that the event encouraged them to pursue interests outside the medical field. CONCLUSIONS: This study highlights that TED is successful in terms of participant satisfaction and training in communication and professionalism. Engaging and training PGY trainees through TED-style events could bridge the gap between acquired knowledge and professional competencies. The authors recommend the implementation of TED-style events in medical training programs.

Impaired lnc-IL7R modulatory mechanism of Toll-like receptors is associated with an exacerbator phenotype of chronic obstructive pulmonary disease.

Patients with chronic obstructive pulmonary disease (COPD) are susceptible to bacterial infections, which worsen lung inflammation and contribute to lung function decline and acute exacerbation. Long noncoding (lnc) RNAs are emerging regulators of inflammation with unknown clinical relevance. Herein, we report that levels of the Toll-like receptor (TLR)-related lnc interleukin (IL) 7 receptor (IL7R) were significantly reduced in peripheral blood mononuclear cells from patients with COPD compared with those from normal controls, and the levels were correlated with pulmonary function. Moreover lnc-IL7R levels were reduced in lavaged alveolar macrophages and primary human small airway epithelial cells (HSAEpCs) from patients with COPD. Lnc-IL7R knockdown in primary human macrophages, HSAEpCs, and human pulmonary microvascular endothelial cells (HPMECs) significantly augmented the induction of proinflammatory mediators after TLR2/4 activation. By contrast, lnc-IL7R overexpression attenuated inflammation after TLR2/4 activation. Similar results with lnc-IL7R-mediated inflammation were observed in COPD HSAEpCs. Mechanistically, lnc-IL7R mediated a repressive chromatin state of the proinflammatory gene promoter as a result of decreased acetylation (H3K9ac) and increased methylation (H3K9me3 and H3K27me3). Plasma lnc-IL7R levels were reduced in patients with COPD who experienced more acute exacerbation in the previous year. Notably, patients with lower lnc-IL7R levels in the subsequent year had increased exacerbation risk. Low lnc-IL7R expression in COPD may augment TLR2/4-mediated inflammation and be associated with acute exacerbation.

Suppressor of variegation 3-9 homologue 1 impairment and neutrophil-skewed systemic inflammation are associated with comorbidities in COPD.

BACKGROUND: Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD. Here, we aimed to determine whether impaired SUV39H1 expression in COPD patients associated with neutrophilic/eosinophilic inflammation responses and comorbidities. METHODS: A total of 213 COPD patients and 13 healthy controls were recruited from the Shuang Ho Hospital, Taipei Medical University. SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy and 30 COPD participants were measured by immunoblotting. We classified the patients into two groups based on low (fold change, FC < 0.5) and high SUV39H1 expression (FC ≥ 0.5) compared to normal controls. Clinical outcomes including neutrophil or eosinophil counts associated with SUV39H1-related inflammation were evaluated by Chi square analyses or Mann-Whitney U test. The correlations between the percentage of neutrophils and number of COPD comorbidities or Charlson Comorbidity Index (CCI) scores were performed by Spearman's rank analysis. RESULTS: Low SUV39H1 expression group had high neutrophil counts relative to high SUV39H1expression group. In the COPD cohort, the high comorbidity group (≥ 2 comorbidities) had higher counts of whole white blood cell (WBC) and neutrophil, and lower proportion of eosinophil and eosinophil/neutrophil, as compared with low comorbidity group (0 and 1 comorbidities). The quantity of neutrophils was associated with COPD comorbidities (Spearman's r = 0.388, p < 0.001), but not with CCI scores. We also found that the high comorbidity group had more exacerbations per year compared with low comorbidity group (1.5 vs. 0.9 average exacerbations, p = 0.005). However, there were no significant differences between groups with these non-frequent (0-1 exacerbation) and frequent exacerbations per year (> 1 exacerbation) in numbers of WBC and proportion of neutrophils, eosinophils or eosinophil/neutrophil. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities. CONCLUSION: Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.

Exposure to PM2.5 is associated with malignant pleural effusion in lung cancer patients.

Air pollution has been recognized to be a risk factor for lung cancer. The objective of this study was to investigate the effects of air pollution on heavy metal alterations in the pleural effusion of lung cancer patients. Pleural effusion was collected from patients with lung cancer and congestive heart failure (CHF). One-year average levels of particulate matter with an aerodynamic diameter of < 10 µm (PM10), PM2.5, NO2, and SO2 were linked to the exposure of these subjects. Traffic-related metals, included Al, Fe, Cu, Zn, and Pb, were determined in the pleural effusion. Logistic regression models were used to examine their associations. There were 63 lung cancer patients and 31 CHF patients enrolled in the current study. We found that PM10, PM2.5, and NO2 were negatively correlated with Al in the pleural effusion, whereas PM2.5 was positively correlated with Zn in the pleural effusion. Increases in 1 µg/m3 of PM2.5 and 1 ng/mL of Zn were associated with lung cancer (adjusted OR=2.394, 95% CI= 1.446-3.964 for PM2.5; adjusted OR=1.003, 95% CI=1.000-1.005 for Zn). Increases in PM2.5 and Zn in the pleural effusion increased the risk of malignant pleural effusion in lung cancer patients (adjusted OR=1.517; 95% CI=1.082-2.127 for PM2.5; adjusted OR=1.002, 95% CI=1.000-1.005 for Zn). Furthermore, we observed that adenocarcinomas increased in association with a 1-µg/m3 increase in PM2.5 (crude OR=1.683; 95% CI=1.006-2.817) in lung cancer patients. In conclusion, PM2.5 exposure and the possible resultant Zn in the pleural effusion associated with the development of malignant pleural effusion in lung cancer.

Resuscitation fluid types in sepsis, surgical, and trauma patients: a systematic review and sequential network meta-analyses.

BACKGROUND: Crystalloids and different component colloids, used for volume resuscitation, are sometimes associated with various adverse effects. Clinical trial findings for such fluid types in different patients' conditions are conflicting. Whether the mortality benefit of balanced crystalloid than saline can be inferred from sepsis to other patient group is uncertain, and adverse effect profile is not comprehensive. This study aims to compare the survival benefits and adverse effects of seven fluid types with network meta-analysis in sepsis, surgical, trauma, and traumatic brain injury patients. METHODS: Searched databases (PubMed, EMBASE, and Cochrane CENTRAL) and reference lists of relevant articles occurred from inception until January 2020. Studies on critically ill adults requiring fluid resuscitation were included. Intervention studies reported on balanced crystalloid, saline, iso-oncotic albumin, hyperoncotic albumin, low molecular weight hydroxyethyl starch (L-HES), high molecular weight HES, and gelatin. Network meta-analyses were conducted using random-effects model to calculate odds ratio (OR) and mean difference. Risk of Bias tool 2.0 was used to assess bias. Confidence in Network Meta-Analysis (CINeMA) web application was used to rate confidence in synthetic evidence. RESULTS: Fifty-eight trials (n = 26,351 patients) were identified. Seven fluid types were evaluated. Among patients with sepsis and surgery, balanced crystalloids and albumin achieved better survival, fewer acute kidney injury, and smaller blood transfusion volumes than saline and L-HES. In those with sepsis, balanced crystalloids significantly reduced mortality more than saline (OR 0.84; 95% CI 0.74-0.95) and L-HES (OR 0.81; 95% CI 0.69-0.95) and reduced acute kidney injury more than L-HES (OR 0.80; 95% CI 0.65-0.99). However, they required the greatest resuscitation volume among all fluid types, especially in trauma patients. In patients with traumatic brain injury, saline and L-HES achieved lower mortality than albumin and balanced crystalloids; especially saline was significantly superior to iso-oncotic albumin (OR 0.55; 95% CI 0.35-0.87). CONCLUSIONS: Our network meta-analysis found that balanced crystalloids and albumin decreased mortality more than L-HES and saline in sepsis patients; however, saline or L-HES was better than iso-oncotic albumin or balanced crystalloids in traumatic brain injury patients. TRIAL REGISTRATION: PROSPERO website, registration number: CRD42018115641).

Correlation between early clinical exposure environment, attitudes toward basic medicine, and medical students' basic science learning performance.

BACKGROUND: Early clinical exposure (ECE) is viewed as a way to provide contexts of basic science and highlight its relevance to medical practice. However, very few studies have specifically looked into how the ECE experience contributes to students' academic performance. The purpose of this study was to investigate whether ECE experiences (external cause) or students' learning attitudes (internal cause) more closely correlated with medical students' academic performance. METHODS: Subjects who participated in the study comprised 109 s-year students at Taipei Medical University. Fifty of the 109 study participants were enrolled in an elective ECE program. The dependent variable in this study was the test score of a systems-based basic sciences (SBBS) course. Independent variables of the study included students' attitudes and test anxiety towards the SBBS course, engagement/length of time spent in ECE, and the ECE learning environment. Data of students' engagement in ECE, levels of their motivational beliefs and test anxiety, differences in the ECE learning environment, and the SBBS final test scores of these 109 respondents were collected for hierarchical multiple regression (HMR) analyses. RESULTS: Results of the HMR analyses revealed that students' test anxiety towards basic science and also the learning environment of the ECE had significant positive predictive power on their SBBS test scores. CONCULSION: This study discovers that medical students' academic performance in basic science correlates not only with their anxiety to testing, but even more so with the clinical environment they are exposed to. Hence we suggest including further investigations about different learning environments on ECE experiences in future studies.

Nocturnal Pressure Controlled Ventilation Improves Sleep Efficiency in Patients Receiving Mechanical Ventilation.

BACKGROUND: Patients receiving mechanical ventilation commonly experience sleep fragmentation. The present meta-analysis compared the effects of pressure controlled ventilation (PCV) and pressure support ventilation (PSV) on sleep quality. METHODS: We conducted a search of the PubMed, Embase, and Cochrane Library databases for studies published before November 2023. In this meta-analysis, individual effect sizes were standardized, and the pooled effect size was determined by using random-effects models. The primary outcome was sleep efficiency. The secondary outcomes were wakefulness, percentages of REM (rapid eye movement) sleep and stages 3 and 4 non-REM sleep, the fragmentation index, and the incidence of apneic events. RESULTS: This meta-analysis examined 4 trials that involved 67 subjects. Sleep efficiency was significantly higher in the PCV group than in the PSV group (mean difference 15.57%, 95% CI 8.54%-22.59%). Wakefulness was significantly lower in the PCV group than in the PSV group (mean difference -18.67%, 95% CI -30.29% to -7.04%). The percentage of REM sleep was significantly higher in the PCV group than in the PSV group (mean difference 2.32%, 95% CI 0.20%-4.45%). Among the subjects with a tendency to develop sleep apnea, the fragmentation index was significantly lower in those receiving PCV than PSV (mean difference -40.00%, 95% CI -51.12% to -28.88%). The incidence of apneic events was significantly lower in the PCV group than in the PSV group (risk ratio 0.06, 95% CI 0.01-0.45). CONCLUSIONS: Compared with PSV, PCV may improve sleep quality in patients receiving nocturnal mechanical ventilation.

Reduced Tolerogenic Program Death-Ligand 1-Expressing Conventional Type 1 Dendritic Cells Are Associated with Rapid Decline in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized, at least in part, by autoimmunity through amplified T helper 1 and 17 (Th1 and Th17) immune responses. The loss of immune tolerance controlled by programmed death-ligand 1 (PD-L1) may contribute to this. OBJECTIVES: We studied the tolerogenic role of PD-L1+ dendritic cells (DCs) and their subtypes in relation to specific T cell immunity and the clinical phenotypes of COPD. METHODS: We used flow cytometry to analyze PD-L1 expression by the DCs and their subtypes in the peripheral blood mononuclear cells (PBMCs) from normal participants and those with COPD. T cell proliferation and the signature cytokines of T cell subtypes stimulated with elastin as autoantigens were measured using flow cytometry and enzyme-linked immunosorbent assays (ELISA), respectively. MEASUREMENT AND MAIN RESULTS: A total of 83 participants were enrolled (normal, n = 29; COPD, n = 54). A reduced PD-L1+ conventional dendritic cell 1 (cDC1) ratio in the PBMCs of the patients with COPD was shown (13.7 ± 13.7%, p = 0.03). The decrease in the PD-L1+ cDC1 ratio was associated with a rapid decline in COPD (p = 0.02) and correlated with the CD4+ T cells (r = -0.33, p = 0.02). This is supported by the NCBI GEO database accession number GSE56766, the researchers of which found that the gene expressions of PD-L1 and CD4, but not CD8 were negatively correlated from PBMC in COPD patients (r = -0.43, p = 0.002). Functionally, the PD-L1 blockade enhanced CD4+ T cell proliferation stimulated by CD3/elastin (31.2 ± 22.3%, p = 0.04) and interleukin (IL)-17A production stimulated by both CD3 (156.3 ± 54.7, p = 0.03) and CD3/elastin (148 ± 64.9, p = 0.03) from the normal PBMCs. The PD-L1 blockade failed to increase IL-17A production in the cDC1-depleted PBMCs. By contrast, there was no significant change in interferon (IFN)-γ, IL-4, or IL-10 after the PD-L1 blockade. Again, these findings were supported by the NCBI GEO database accession number GSE56766, the researchers of which found that only the expression of RORC, a master transcription factor driving the Th17 cells, was significantly negatively correlated to PD-L1 (r = -0.33, p = 0.02). CONCLUSIONS: Circulating PD-L1+ cDC1 was reduced in the patients with COPD, and the tolerogenic role was suppressed with susceptibility to self-antigens and linked to rapid decline caused by Th17-skewed chronic inflammation.

Interstitial lung disease related to occupational hard metal exposure: two case reports.

BACKGROUND: Hard metal lung disease (HMLD) is a relatively less known occupational interstitial lung disease, and instances of HMLD resulting from para-occupational exposure are rarely reported. CASE PRESENTATION: This paper presents two cases of interstitial lung disease caused by exposure to hard metal. The first case involves a 37-year-old Taiwanese man who had worked at a grinder station for hard metal materials for 12 years without respiratory protective equipment. He experienced a dry cough and exertional dyspnea, and his chest imaging and pathology findings were consistent with the features of usual interstitial pneumonia. Analysis of his lung tissue revealed the presence of tungsten and cobalt. The second case involves a 68-year-old Taiwanese woman, the mother of the first patient, who had hand-washed her son's workwear. She experienced a dry cough and had similar imaging findings to her son. After her son left his job, they both exhibited improved symptoms and lung functions with nintedanib treatment. These findings suggest a diagnosis of HMLD and interstitial lung disease resulting from para-occupational exposure to hard metal dust. CONCLUSIONS: The diagnosis of HMLD relies on obtaining a detailed occupational exposure history. If HMLD is diagnosed, discontinuing exposing to hard metal dusts can lead to improved lung function.

Prediction value of neutrophil and eosinophil count at risk of COPD exacerbation.

INTRODUCTION: Predicting acute exacerbations (AEs) in chronic obstructive pulmonary disease (COPD) is crucial. This study aimed to identify blood biomarkers for predicting COPD exacerbations by inflammatory phenotypes. MATERIALS AND METHODS: We analyzed blood cell counts and clinical outcomes in 340 COPD patients aged 20-90 years. Patients were categorized into eosinophilic inflammation (EOCOPD) and non-eosinophilic inflammation (N-EOCOPD) groups. Blood cell counts, eosinophil-to-lymphocyte ratio (ELR), neutrophil-to-lymphocyte ratio (NLR) and neutrophil-to-eosinophil ratio (NER) were calculated. Linear and logistic regression models assessed relationships between health outcomes and blood cell counts. RESULTS: EOCOPD patients had distinct characteristics compared to N-EOCOPD patients. Increased neutrophil % and decreased lymphocyte % were associated with reduced pulmonary function, worse quality of life and more exacerbations, but they did not show statistical significance after adjusting by age, sex, BMI, smoking status, FEV1% and patient's medication. Subgroup analysis revealed a 1.372-fold increase in the OR of AE for every 1 unit increase in NLR in EOCOPD patients (p < .05). In N-EOCOPD patients, every 1% increase in blood eosinophil decreased the risk of exacerbation by 59.6%. CONCLUSIONS: Our study indicates that distinct white blood cell profiles in COPD patients, with or without eosinophilic inflammation, can help assess the risk of AE in clinical settings.

Recruitment maneuvers to reduce pulmonary atelectasis after cardiac surgery: A meta-analysis of randomized trials.

BACKGROUND: Pulmonary atelectasis is a common postoperative complication that may lead to intrapulmonary shunt, refractory hypoxemia, and respiratory distress. Recruitment maneuvers may relieve pulmonary atelectasis in patients undergoing cardiac surgery. We conducted a meta-analysis of randomized controlled trials to evaluate the effectiveness of recruitment maneuvers in these patients. METHODS: We conducted a search in PubMed, Embase, Cochrane Library, and the ClinicalTrials.gov registry for trials published before March 2020. Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size by using random-effects models. Pulmonary atelectasis was assessed postoperatively. Secondary outcomes included hypoxic events, arterial oxygen tension (Pao2)/inspired oxygen fraction (Fio2) ratio, cardiac index, mean arterial pressure, and postoperative complications including pneumothorax and pneumonia. RESULTS: We reviewed 16 trials involving 1455 patients. Patients receiving recruitment maneuvers had a reduced incidence of pulmonary atelectasis (group with recruited pressure >40 cmH2O: risk ratio [RR], 0.20; 95% confidence interval [CI], 0.07-0.57; group with recruited pressure <40 cmH2O: RR, 0.54; 95% CI, 0.33-0.89), reduced incidence of hypoxic events (RR, 0.23; 95% CI, 0.14-0.37), reduced incidence of pneumonia (RR, 0.42; 95% CI, 0.18-0.95), and improved Pao2/Fio2 ratio (weighted mean difference [WMD]; 58.87, 95% CI, 31.24-86.50) without disturbing the cardiac index (WMD, 0.22; 95% CI, -0.18 to 0.61) or mean arterial pressure (WMD, -0.30, 95% CI, -3.19 to 2.59) as compared with those who received conventional mechanical ventilation. The incidence of pneumothorax was nonsignificant between the groups. CONCLUSIONS: Recruitment maneuvers may reduce postoperative pulmonary atelectasis, hypoxic events, and pneumonia and improve Pao2/Fio2 ratios without hemodynamic disturbance in patients undergoing cardiac surgery.

lnc-IL7R Expression Reflects Physiological Pulmonary Function and Its Aberration Is a Putative Indicator of COPD.

Despite rapidly evolving pathobiological mechanistic demystification, coupled with advances in diagnostic and therapeutic modalities, chronic obstructive pulmonary disease (COPD) remains a major healthcare and clinical challenge, globally. Further compounded by the dearth of available curative anti-COPD therapy, it is posited that this challenge may not be dissociated from the current lack of actionable COPD pathognomonic molecular biomarkers. There is accruing evidence of the involvement of protracted 'smoldering' inflammation, repeated lung injury, and accelerated lung aging in enhanced predisposition to or progression of COPD. The relatively novel uncharacterized human long noncoding RNA lnc-IL7R (otherwise called LOC100506406) is increasingly designated a negative modulator of inflammation and regulator of cellular stress responses; however, its role in pulmonary physiology and COPD pathogenesis remains largely unclear and underexplored. Our previous work suggested that upregulated lnc-IL7R expression attenuates inflammation following the activation of the toll-like receptor (TLR)-dependent innate immune system, and that the upregulated lnc-IL7R is anti-correlated with concomitant high PM2.5, PM10, and SO2 levels, which is pathognomonic for exacerbated/aggravated COPD in Taiwan. In the present study, our quantitative analysis of lnc-IL7R expression in our COPD cohort (n = 125) showed that the lnc-IL7R level was significantly correlated with physiological pulmonary function and exhibited COPD-based stratification implications (area under the curve, AUC = 0.86, p < 0.001). We found that the lnc-IL7R level correctly identified patients with COPD (sensitivity = 0.83, specificity = 0.83), precisely discriminated those without emphysematous phenotype (sensitivity = 0.48, specificity = 0.89), and its differential expression reflected disease course based on its correlation with the COPD GOLD stage (r = −0.59, p < 0.001), %LAA-950insp (r = −0.30, p = 0.002), total LAA (r = −0.35, p < 0.001), FEV1(%) (r = 0.52, p < 0.001), FVC (%) (r = 0.45, p < 0.001), and post-bronchodilator FEV1/FVC (r = 0.41, p < 0.001). Consistent with other data, our bioinformatics-aided dose−response plot showed that the probability of COPD decreased as lnc-IL7R expression increased, thus, corroborating our posited anti-COPD therapeutic potential of lnc-IL7R. In conclusion, reduced lnc-IL7R expression not only is associated with inflammation in the airway epithelial cells but is indicative of impaired pulmonary function, pathognomonic of COPD, and predictive of an exacerbated/ aggravated COPD phenotype. These data provide new mechanistic insights into the ailing lung and COPD progression, as well as suggest a novel actionable molecular factor that may be exploited as an efficacious therapeutic strategy in patients with COPD.

Climate-mediated air pollution associated with COPD severity.

Air pollution has been reported to be associated with chronic obstructive pulmonary disease (COPD). Our study aim was to examine the mediating effects of air pollution on climate-associated health outcomes of COPD patients. A cross-sectional study of 117 COPD patients was conducted in a hospital in Taiwan. We measured the lung function, 6-min walking distance, oxygen desaturation, white blood cell count, and percent emphysema (low attenuation area, LAA) and linked these to 0-1-, 0-3-, and 0-5-year lags of individual-level exposure to relative humidity (RH), temperature, and air pollution. Linear regression models were conducted to examine associations of temperature, RH, and air pollution with severity of health outcomes. A mediation analysis was conducted to examine the mediating effects of air pollution on the associations of RH and temperature with health outcomes. We observed that a 1 % increase in the RH was associated with increases in forced expiratory volume in 1 s (FEV1), eosinophils, and lymphocytes, and a decrease in the total-lobe LAA. A 1 °C increase in temperature was associated with decreases in oxygen desaturation, and right-, left-, and upper-lobe LAA values. Also, a 1 µg/m3 increase in PM2.5 was associated with a decrease in the FEV1 and an increase in oxygen desaturation. A 1 µg/m3 increases in PM10 and PM2.5 was associated with increases in the total-, right-, left, upper-, and lower-lobe (PM2.5 only) LAA. A one part per billion increase in NO2 was associated with a decrease in the FEV1 and an increase in the upper-lobe LAA. Next, we found that NO2 fully mediated the association between RH and FEV1. We found PM2.5 fully mediated associations of temperature with oxygen saturation and total-, right-, left-, and upper-lobe LAA. In conclusion, climate-mediated air pollution increased the risk of decreasing FEV1 and oxygen saturation and increasing emphysema severity among COPD patients. Climate change-related air pollution is an important public health issue, especially with regards to respiratory disease.

Associations of the distance-saturation product and low-attenuation area percentage in pulmonary computed tomography with acute exacerbation in patients with chronic obstructive pulmonary disease.

Background: Chronic obstructive pulmonary disease (COPD) has high global health concerns, and previous research proposed various indicators to predict mortality, such as the distance-saturation product (DSP), derived from the 6-min walk test (6MWT), and the low-attenuation area percentage (LAA%) in pulmonary computed tomographic images. However, the feasibility of using these indicators to evaluate the stability of COPD still remains to be investigated. Associations of the DSP and LAA% with other COPD-related clinical parameters are also unknown. This study, thus, aimed to explore these associations. Methods: This retrospective study enrolled 111 patients with COPD from northern Taiwan. Individuals' data we collected included results of a pulmonary function test (PFT), 6MWT, life quality survey [i.e., the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT)], history of acute exacerbation of COPD (AECOPD), and LAA%. Next, the DSP was derived by the distance walked and the lowest oxygen saturation recorded during the 6MWT. In addition, the DSP and clinical phenotype grouping based on clinically significant outcomes by previous study approaches were employed for further investigation (i.e., DSP of 290 m%, LAA% of 20%, and AECOPD frequency of ≥1). Mean comparisons and linear and logistic regression models were utilized to explore associations among the assessed variables. Results: The low-DSP group (<290 m%) had significantly higher values for the mMRC, CAT, AECOPD frequency, and LAA% at different lung volume scales (total, right, and left), whereas it had lower values of the PFT and 6MWT parameters compared to the high-DSP group. Significant associations (with high odds ratios) were observed of the mMRC, CAT, AECOPD frequency, and PFT with low- and high-DSP groupings. Next, the risk of having AECOPD was associated with the mMRC, CAT, DSP, and LAA% (for the total, right, and left lungs). Conclusion: A lower value of the DSP was related to a greater worsening of symptoms, more-frequent exacerbations, poorer pulmonary function, and more-severe emphysema (higher LAA%). These readily determined parameters, including the DSP and LAA%, can serve as indicators for assessing the COPD clinical course and may can serve as a guide to corresponding treatments.

Associations between lung-deposited dose of particulate matter and culture-positive pulmonary tuberculosis pleurisy.

Epidemiological studies identified the relationship between air pollution and pulmonary tuberculosis. Effects of lung-deposited dose of particulate matter (PM) on culture-positive pulmonary tuberculosis remain unclear. This study investigates the association between lung-deposited dose of PM and pulmonary tuberculosis pleurisy. A case-control study of subjects undergoing pleural effusion drainage of pulmonary tuberculosis (case) and chronic heart failure (control) was conducted. Metals and biomarkers were quantified in the pleural effusion. The air pollution exposure was measured and PM deposition in the head, tracheobronchial, alveolar region, and total lung region was estimated by Multiple-path Particle Dosimetry (MPPD) Model. We performed multiple logistic regression to examine the associations of these factors with the risk of tuberculosis. We observed that 1-µg/m3 increase in PM10 was associated with 1.226-fold increased crude odds ratio (OR) of tuberculosis (95% confidence interval (CI): 1.023-1.469, p<0.05), 1-µg/m3 increase in PM2.5-10 was associated with 1.482-fold increased crude OR of tuberculosis (95% CI: 1.048-2.097, p < 0.05), 1-ppb increase in NO2 was associated with 1.218-fold increased crude OR of tuberculosis (95% CI: 1.025-1.447, p < 0.05), and 1-ppb increase in O3 was associated with 0.735-fold decreased crude OR of tuberculosis (95% CI: 0.542 0.995). We observed 1-µg/m3 increase in PM deposition in head and nasal region was associated with 1.699-fold increased crude OR of tuberculosis (95% CI: 1.065-2.711, p < 0.05), 1-µg/m3 increase in PM deposition in tracheobronchial region was associated with 1.592-fold increased crude OR of tuberculosis (95% CI: 1.095-2.313, p < 0.05), 1-µg/m3 increase in PM deposition in alveolar region was associated with 3.981-fold increased crude OR of tuberculosis (95% CI: 1.280-12.386, p < 0.05), and 1-µg/m3 increase in PM deposition in total lung was associated with 1.511-fold increased crude OR of tuberculosis (95% CI: 1.050-2.173, p < 0.05). The results indicate that particle deposition in alveolar region could cause higher risk of pulmonary tuberculosis pleurisy than deposition in other lung regions.

High-flow nasal cannula for reducing hypoxemic events in patients undergoing bronchoscopy: A systematic review and meta-analysis of randomized trials.

BACKGROUND: Patients undergoing bronchoscopic procedures may develop hypoxemia and severe complications. High-flow nasal cannula (HFNC) may prevent hypoxemic events during bronchoscopy. We conducted a systematic review of randomized controlled trials (RCTs) to evaluate the effectiveness of HFNC in these patients. METHODS: We conducted a search in PubMed, Embase, and the Cochrane Library for RCTs published before November 2021. Individual effect sizes were standardized, and a meta-analysis was performed to calculate the pooled effect size using random-effects models. The primary outcome was the incidence of hypoxemic events (oxygen saturation [SpO2] < 90%) during bronchoscopy. Secondary outcomes included the incidence of interrupted bronchoscopy due to desaturation, lowest SpO2 during bronchoscopy, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2), end-tidal CO2 (EtCO2) at the end of bronchoscopy, and the incidence of intubation after the procedure. RESULTS: Five trials involving 257 patients were reviewed. The incidence of hypoxemic events was lower in the HFNC group than in the conventional oxygen therapy group (risk ratio, 0.25; 95% confidence interval [CI], 0.14-0.42). The lowest SpO2 during the procedure was significantly higher in the HFNC group than in the conventional oxygen therapy group (weighted mean difference [WMD], 7.12; 95% CI, 5.39-8.84). PaO2 at the end of the procedure was significantly higher in the HFNC group than in the conventional oxygen therapy group (WMD, 20.36; 95% CI, 0.30-40.42). The incidence of interrupted bronchoscopy due to desaturation, PaCO2 and EtCO2 at the end of the procedure, and the incidence of intubation after the procedure were not significantly different between groups. CONCLUSIONS: HFNC may reduce the incidence of hypoxemic events and improve oxygenation in patients undergoing bronchoscopy.

Recruitment maneuvers in patients undergoing thoracic surgery: a meta-analysis.

OBJECTIVE: Pulmonary atelectasis is a common postoperative complication that may lead to intrapulmonary shunt, refractory hypoxemia, and respiratory distress. Recruitment maneuvers may relieve pulmonary atelectasis in patients undergoing thoracic surgery. This meta-analysis of randomized controlled trials (RCTs) is to evaluate the effectiveness and safety of recruitment maneuvers in patients undergoing thoracic surgery. METHODS: We performed a literature search on the PubMed, Embase, and Cochrane Library databases and the ClinicalTrials.gov registry for trials published before April 2021. We investigated postoperative pulmonary atelectasis incidence, intrapulmonary shunt fraction, static lung compliance, and mean arterial pressure. RESULTS: Six RCTs involving 526 patients were reviewed. Patients receiving a recruitment maneuver exhibited a significant decrease in intrapulmonary shunt fraction [weighted mean difference (WMD) - 0.02, 95% CI - 0.03 to - 0.01], improved static lung compliance (WMD 2.16; 95% CI 1.14-3.18), and PaO2/FIO2 ratio (WMD 31.31; 95% CI 12.11-50.52) without a significant difference in mean arterial pressure (WMD - 0.64; 95% CI - 4.92 to 3.64). The incidence pulmonary atelectasis favored recruitment maneuver group, but was not statistically significant (RR 0.55; 95% CI 0.27-1.12). CONCLUSIONS: Recruitment maneuvers may be a viable treatment for reducing intra-pulmonary shunt and improving static lung compliance and PaO2/FIO2 ratio without the disturbance of hemodynamics in patients undergoing thoracic surgery.