Significance and Potential Role of Eosinophils in Non-Cystic Fibrosis Bronchiectasis.

Bronchiectasis is a complex and heterogeneous disease with a myriad of pulmonary and extrapulmonary etiologies. Bronchiectasis has a predominantly neutrophilic inflammatory profile. However, eosinophilic inflammation has also been documented in both the airways and the systemic circulation. Various diseases (eg, asthma, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis with nasal polyps) characterized by heightened type 2 airway inflammatory responses, including blood or sputum eosinophilia, may coexist with bronchiectasis. Apart from those eosinophilic etiologies or comorbidities related to bronchiectasis, around 20% of patients with bronchiectasis have peripheral eosinophilia (at least 3% or 300 eosinophils/µL) with no identified concomitant disease (also termed "eosinophilic bronchiectasis"), whose roles have not been fully understood. The two key points regarding these observations are that eosinophils confer both bactericidal and antiviral properties against common pathogenic microorganisms that are usually detected in bronchiectasis, and that eosinophilic bronchiectasis has been associated with better therapeutic response to inhaled corticosteroids and other anti-TH2 profile treatments. In this review, we summarize the most significant evidence regarding the role of eosinophils in patients with bronchiectasis, including the association of bronchiectasis with eosinophilic diseases (as etiologies or comorbidities), and existing data on eosinophilic bronchiectasis not related to eosinophilic disorders.

The association between prothrombin time-international normalized ratio and long-term mortality in patients with coronary artery disease: a large cohort retrospective study with 44,662 patients.

BACKGROUND: The association between prothrombin time-international normalized ratio (PT-INR) and long-term prognosis among patients with coronary artery disease (CAD) without atrial fibrillation or anticoagulant therapy was still unclear. We analyzed the association of PT-INR levels and long-term mortality in a large cohort of CAD patients without atrial fibrillation or using of anticoagulant drugs. METHODS: We obtained data from 44,662 patients who were diagnosed with CAD and had follow-up information from January 2008 to December 2018. The patients were divided into 4 groups (Quartile 1: PT-INR ≤ 0.96; Quartile2: 0.96 < PT-INR ≤ 1.01; Quartile3: 1.01 < PT-INR ≤ 1.06; Quartile4: PT-INR > 1.06). The main endpoint was long-term all-cause death. Kaplan-Meier curve analysis and Cox proportional hazards models were used to investigate the association between quartiles of PT-INR levels and long-term all-cause mortality. RESULTS: During a median follow-up of 5.25 years, 5613 (12.57%) patients died. We observed a non-linear shaped association between PT-INR levels and long-term all-cause mortality. Patients in high PT-INR level (Quartile4: PT-INR > 1.06) showed a significantly higher long-term mortality than other groups (Quartile2 or 3 or 4), (Compared with Quartile 1, Quartile 2 [0.96 < PT-INR ≤ 1.01], aHR = 1.00, 95% CI 0.91-1.00, P = 0.99; Quartile 3 [1.01 < PT-INR ≤ 1.06], aHR = 1.10, 95% CI 1.01-1.20, P = 0.03; Quartile 4 [PT-INR > 1.06], aHR = 1.33, 95% CI 1.22-1.45, P < 0.05). CONCLUSIONS: Our study demonstrates high levels of PT-INR were associated with an increased risk of all-cause mortality.

Malnutrition in patients with coronary artery disease: Prevalence and mortality in a 46,485 Chinese cohort study.

BACKGROUND AND AIMS: Malnutrition is associated with poor prognosis in a wide range of illnesses. However, its long-term prognostic impact in general coronary artery disease (CAD) patients is not well known. We aim to report the prevalence and long-term mortality of malnutrition in the whole general population. METHODS AND RESULTS: In this retrospective cohort study, the controlling nutritional status (CONUT) score was applied to 46,485 consecutive patients undergoing coronary angiography (CAG) and diagnosed with CAD from January 2007 to July 2018. Patients were stratified as having no malnutrition (n = 19,780), mild (n = 21,092), moderate (n = 5286) and severe malnutrition (n = 327), based on CONUT score. Overall, mean age was 63.1 ± 10.7 years, and 75.8% of patients (n = 35,250) were male. 45.4% of patients were mildly malnourished and 12.1% were moderately or severely malnourished. During a median follow-up of 5.1 years (interquartile range: 3.0-7.7 years), 6093 (17.3%) patients died. After adjusting for confounders, malnutrition risk was associated with significantly increased risk for all-cause death (mild vs. normal, HR = 1.19,95% confidence interval [CI]: 1.12 to 1.28; moderate vs. normal, HR = 1.42,95% CI: 1.30 to 1.55; severe vs. Normal, HR = 1.95, 95% CI: 1.57 to 2.41) (p for trend<0.001). The similar result on all-cause mortality was also found in different subgroups stratified by gender, chronic kidney disease, anemia, percutaneous coronary intervention. CONCLUSIONS: Malnutrition is a common complication among patients with CAD, and is strongly associated with increased mortality. Further studies need to explore the efficacy of nutritional interventions on long-term prognosis among CAD patients. This study was registered at Clinicaltrials.gov as NCT04407936.

Association of Lipoprotein(a)-Associated Mortality and the Estimated Glomerular Filtration Rate Level in Patients Undergoing Coronary Angiography: A 51,500 Cohort Study.

Background: High lipoprotein(a) is associated with poor prognosis in patients at high risk for cardiovascular disease. Renal function based on the estimated glomerular filtration rate (eGFR) is a potential risk factor for the change of lipoprotein(a). However, the regulatory effect of eGFR stratification on lipoprotein(a)-associated mortality has not been adequately addressed. Methods: 51,500 patients who underwent coronary angiography (CAG) or percutaneous coronary intervention (PCI) were included from the Cardiorenal ImprovemeNt (CIN) study (ClinicalTrials.gov NCT04407936). These patients were grouped according to lipoprotein(a) quartiles (Q1-Q4) stratified by eGFR categories (<60 and ≥60 mL/min/1.73m2). Cox regression models were used to estimate hazard ratios (HR) for mortality across combined eGFR and lipoprotein(a) categories. Results: The mean age of the study population was 62.3 ± 10.6 years, 31.3% were female (n = 16,112). During a median follow-up of 5.0 years (interquartile range: 3.0-7.6 years), 13.0% (n = 6,695) of patients died. Compared with lipoprotein(a) Q1, lipoprotein(a) Q2-Q4 was associated with 10% increased adjusted risk of death in all patients (HR: 1.10 [95% CI: 1.03-1.17]), and was strongly associated with about 23% increased adjusted risk of death in patients with eGFR <60 mL/min/1.73m2 (HR: 1.23 [95% CI: 1.08-1.39]), while such association was not significant in patients with eGFR ≥60 mL/min/1.73m2 (HR: 1.05 [95% CI: 0.97-1.13]). P for interaction between lipoprotein(a) (Q1 vs. Q2-Q4) and eGFR (≥60 vs. eGFR <60 mL/min/1.73m2) on all-cause mortality was 0.019. Conclusions: Elevated lipoprotein(a) was associated with increased risk of all-cause mortality and such an association was modified by the baseline eGFR in CAG patients. More attention should be paid to the patients with reduced eGFR and elevated lipoprotein(a), and the appropriate lipoprotein(a) intervention is required.

Coronary Artery Disease: Optimal Lipoprotein(a) for Survival-Lower Is Better? A Large Cohort With 43,647 Patients.

Background: A high level of lipoprotein(a) can lead to a high risk of cardiovascular events or mortality. However, the association of moderately elevated lipoprotein(a) levels (≥15 mg/dL) with long-term prognosis among patients with coronary artery disease (CAD) is still uncertain. Hence, we aim to systematically analyzed the relevance of baseline plasma lipoprotein(a) levels to long-term mortality in a large cohort of CAD patients. Methods: We obtained data from 43,647 patients who were diagnosed with CAD and had follow-up information from January 2007 to December 2018. The patients were divided into two groups (<15 and ≥15 mg/dL). The primary endpoint was long-term all-cause death. Kaplan-Meier curve analysis and Cox proportional hazards models were used to investigate the association between moderately elevated baseline lipoprotein(a) levels (≥15 mg/dL) and long-term all-cause mortality. Results: During a median follow-up of 5.04 years, 3,941 (18.1%) patients died. We observed a linear association between lipoprotein(a) levels and long-term all-cause mortality. Compared with lipoprotein(a) concentrations <15 mg/dL, lipoprotein(a) ≥15 mg/dL was associated with a significantly higher risk of all-cause mortality [adjusted hazard ratio (aHR) 1.10, 95%CI: 1.04-1.16, P-values = 0.001). Similar results were found for the subgroup analysis of non-acute myocardial infarction, non-percutaneous coronary intervention, chronic heart failure, diabetes mellitus, or non-chronic kidney diseases. Conclusion: Moderately elevated baseline plasma lipoprotein(a) levels (≥15 mg/dL) are significantly associated with higher all-cause mortality in patients with CAD. Our finding provides a rationale for testing the lipoprotein(a)-reducing hypothesis with lower targets (even <15 mg/dL) in CAD outcome trials.

Predictive value of creatine kinase MB for contrast-induced acute kidney injury among myocardial infarction patients.

BACKGROUND: Predictive value of creatine kinase MB (CK-MB) for contrast-induced acute kidney injury (CI-AKI) among myocardial infarction (MI) patients has rarely been reported. We aim to evaluate the predictive value of CK-MB for CI-AKI among MI patients. METHODS: Totally, 1131 MI patients were included from the REduction of rIsk for Contrast-Induced Nephropathy (REICIN) study. The peak CK-MB before coronary angiography (CAG) was chosen. The study population was divided into two groups by log-transformed CK-MB cut-off point. The association between CK-MB and CI-AKI was tested by multivariable logistic regression. CK-MB was integrated with Age, creatinine and ejection fraction (ACEF) score and Mehran risk score (MRS) to evaluate the additive value of CK-MB. The integrated models were validated internally by the bootstrap method and externally by the PREdictive Value of COntrast voluMe to creatinine Clearance Ratio (PRECOMIN) study data set. RESULTS: Overall, 62(5.48%) patients developed CI-AKI, patients with CK-MB point > 4.7 displayed a higher incidence of CI-AKI than those without (11.9% vs. 4.0%, p < 0.001). CK-MB point > 4.7 was independently associated with CI-AKI (adjusted OR: 3.40, 95% CI: 1.93-5.98, p < 0.001). The additions of CK-MB to ACEF score, Mehran score A and Mehran score B resulted in increases in C-statistics, which ranged from 0.680 to 0.733 (p = 0.046), 0.694 to 0.727 (p = 0.091), 0.704 to 0.734 (p = 0.102), respectively. Internal validation also showed increases in C-statistics, and external validation performed well in discrimination and calibration. CONCLUSIONS: Preprocedural peak CK-MB was a predictor of CI-AKI among MI patients.

Trends in incidence and long-term prognosis of acute kidney injury following coronary angiography in Chinese cohort with 11,943 patients from 2013 to 2017: an observational study.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication with poor prognosis after coronary angiography (CAG). With the prevention methods widely being implemented, the temporal trends of incidence and mortality of CA-AKI are still unknown over the last five years. The study aims to determine the incidence and prognosis of CA-AKI in China. METHODS: This retrospective cohort study was based on the registry at Guangdong Provincial People's Hospital in China (ClinicalTrials.gov NCT04407936). We analyzed data from hospitalization patients who underwent CAG and with preoperative and postoperative serum creatinine (Scr) values from January 2013 to December 2017. RESULTS: 11,943 patients were included in the study, in which the mean age was 63.01 ± 10.79 years and 8,469 (71.1 %) were male. The overall incidence of CA-AKI was 11.2 %. Compared with 2013, the incidence of CA-AKI in 2017 was significantly increased from 9.7 to 13.0 % (adjusted odds ratios [aOR], 1.38; 95 %CI, 1.13-1.68; P-value < 0.01, P for trend < 0.01). The temporal trends of incidence among patients of different ages and genders yielded similar findings. During a standardized follow-up of 1 year, 178 (13.7 %) CA-AKI patients died in total, which showed no obvious decreased trend in this 5 five years from 21.1 to 16.5 (adjusted hazard ratio [aHR], 0.72; 95 %CI, 0.36-1.45; P-value = 0.35, P for trend = 0.24). CONCLUSIONS: Our Chinese cohort showed that the incidence of CA-AKI increased significantly, while CA-AKI associated mortality showed no obvious decreased trend in the last five years. Our findings support more active measures to prevent CA-AKI and improve the prognosis of CA-AKI patients.

Association between baseline LDL-C and prognosis among patients with coronary artery disease and advanced kidney disease.

BACKGROUND: Lower low-density lipoprotein cholesterol (LDL-C) is significantly associated with improved prognosis in patients with coronary artery disease (CAD). However, LDL-C reduction does not decrease all-cause mortality among CAD patients when renal function impairs. The association between low baseline LDL-C (< 1.8 mmol/L) and mortality is unknown among patients with CAD and advanced kidney disease (AKD). The current study aimed to evaluate prognostic value of low baseline LDL-C level for all-cause death in these patients. METHODS: In this observational study, 803 CAD patients complicated with AKD (eGFR < 30 mL/min/1.73 m2) were enrolled between January 2008 to December 2018. Patients were divided into two groups (LDL-C < 1.8 mmol/L, n = 138; LDL-C ≥ 1.8 mmol/L, n = 665). We used Kaplan-Meier methods and Cox regression analyses to assess the association between baseline low LDL-C levels and long-term all-cause mortality. RESULTS: Among 803 participants (mean age 67.4 years; 68.5% male), there were 315 incidents of all-cause death during a median follow-up of 2.7 years. Kaplan-Meier analysis showed that low LDL-C levels were associated with worse prognosis. After adjusting for full 24 confounders (e.g., age, diabetes, heart failure, and dialysis, etc.), multivariate Cox regression analysis revealed that lower LDL-C level (< 1.8 mmol/L) was significantly associated with higher risk of all-cause death (adjusted HR, 1.38; 95% CI, 1.01-1.89). CONCLUSIONS: Our data demonstrated that among patients with CAD and AKD, a lower baseline LDL-C level (< 1.8 mmol/L) did not present a higher survival rate but was related to a worse prognosis, suggesting a cautiousness of too low LDL-C levels among patients with CAD and AKD.

Association of Early and Late Contrast-Associated Acute Kidney Injury and Long-Term Mortality in Patients Undergoing Coronary Angiography.

BACKGROUND: Contrast-associated acute kidney injury (CA-AKI) is a common complication in patients undergoing coronary angiography (CAG). However, few studies demonstrate the association between the prognosis and developed CA-AKI in the different periods after the operation. METHODS: We retrospectively enrolled 3206 patients with preoperative serum creatinine (Scr) and at least twice SCr measurement after CAG. CA-AKI was defined as an increase ≥50% or ≥0.3 mg/dL from baseline in the 72 hours after the procedure. Early CA-AKI was defined as having the first increase in SCr within the early phase (<24 hours), and late CA-AKI was defined as an increase in SCr that occurred for the first time in the late phase (24-72 hours). The first endpoint of this study was long-term all-cause mortality. Kaplan-Meier analysis was used to count the cumulative mortality, and the log-rank test was used to assess differences between curves. Univariate and multivariate cox regression analyses were performed to assess whether patients who developed different type CA-AKI were at increased risk of long-term mortality. RESULTS: The number of deaths in the 3 groups was 407 for normal (12.7%), 106 for early CA-AKI (32.7%) and 57 for late CA-AKI (17.7%), during a median follow-up period of 3.95 years. After adjusting for important clinical variables, early CA-AKI (HR = 1.33, 95% CI: 1.02-1.74, P=0.038) was significantly associated with mortality, while late CA-AKI (HR = 0.92, 95% CI: 0.65-1.31, P=0.633) was not. The same results were found in patients with coronary artery disease, chronic kidney disease, diabetes mellitus, and percutaneous coronary intervention. CONCLUSIONS: Early increases in Scr, i.e., early CA-AKI, have better predictive value for long-term mortality. Therefore, in clinical practice, physicians should pay more attention to patients with early renal injury related to long-term prognosis and give active treatment.

The U-Shape Relationship Between Glycated Hemoglobin Level and Long-Term All-Cause Mortality Among Patients With Coronary Artery Disease.

Background: Although glycated hemoglobin (HbA1c) was considered as a prognostic factor in some subgroup of coronary artery disease (CAD), the specific relationship between HbA1c and the long-term all-cause death remains controversial in patients with CAD. Methods: The study enrolled 37,596 CAD patients and measured HbAlc at admission in Guangdong Provincial People's Hospital. The patients were divided into 4 groups according to HbAlc level (Quartile 1: HbA1c ≤ 5.7%; Quartile 2: 5.7% < HbA1c ≤ 6.1%; Quartile 3: 6.1% < HbA1c ≤ 6.7%; Quartile 4: HbA1c > 6.7%). The study endpoint was all-cause death. The restricted cubic splines and cox proportional hazards models were used to investigate the association between baseline HbAlc levels and long-term all-cause mortality. Results: The median follow-up was 4 years. The cox proportional hazards models revealed that HbAlc is an independent risk factor in the long-term all-cause mortality. We also found an approximate U-shape association between HbA1c and the risk of mortality, including increased risk of mortality when HbA1c ≤ 5.7% and HbA1c > 6.7% [Compared with Quartile 2, Quartile 1 (HbA1c ≤ 5.7), aHR = 1.13, 95% CI:1.01-1.26, P < 0.05; Quartile 3 (6.1% < HbA1c ≤ 6.7%), aHR = 1.04, 95% CI:0.93-1.17, P =0.49; Quartile 4 (HbA1c > 6.7%), aHR = 1.32, 95% CI:1.19-1.47, P < 0.05]. Conclusions: Our study indicated a U-shape relationship between HbA1c and long-term all-cause mortality in CAD patients.

Facile preparation of biomass lignin-based hydroxyethyl cellulose super-absorbent hydrogel for dye pollutant removal.

The severe preparation process, poor swelling properties and mechanical properties of traditional cellulose and polyvinyl alcohol (PVA) composite hydrogels heavily limited their practical applications. To solve these issues, we use long-chain hydroxyethyl celluloses (HECs) as framework backbones, short-chain PVAs as branched chains, lignin molecules as extended crosslinkers and epichlorohydrin molecules as crosslinkers to prepare the lignin-based hydroxyethyl cellulose-PVA (LCP) super-absorbent hydrogels in the alkaline aqueous solution under mild reaction conditions, demonstrating high swelling ratio of up to 1220 g/g. The LCP hydrogels could take up large amounts of positively charged dyes rhodamine 6G, crystal violet and methylene blue with uptakes of 153, 184 and 196 mg/g, respectively. The LCP super-absorbent hydrogels also present excellent water retention, biodegradability and excellent swelling properties, which are very promising for applications in the fields of commercial diapers, soil water retention and seed cultivation in agriculture, and dye pollutant removal.

Improved enzymatic hydrolysis of hardwood and cellulase stability by biomass kraft lignin-based polyoxyethylene ether.

Water-soluble kraft lignin-based polyoxyethylene ether (KL-PEG), synthesized from the black liquor of kraft pulping and PEG, was used to improve the enzymatic hydrolysis efficiency of dilute acid pretreated (DA-pretreated) Eucalyptus hardwood and cellulase stability. The physicochemical properties of KL-PEG polymer such as solubility, surface tension, charge and aggregation behavior in the solution were first studied. KL-PEG could enhance the enzymatic hydrolysis of Avicel and DA-pretreated Eucalyptus from 63.6% and 58.3% to 78.5% and 93.8%, respectively. The enzymatic activity of cellulase after the enzymatic hydrolysis of Avicel and DA-pretreated Eucalyptus for 72 h remained approximately 84% and 44% in the presence of KL-PEG polymer. KL-PEG could improve the stability and longevity of the cellulase, facilitate the recovery and save the amount of cellulase. The efficient utilization of the pulping black liquor lignin was of great significance to alleviate the pressure brought by the shortage of petrochemical resources, and build an energy-saving and low-carbon society.

Validity of Fractional Exhaled Nitric Oxide in Diagnosis of Corticosteroid-Responsive Cough.

BACKGROUND: Whether fractional exhaled nitric oxide (FeNO) measurement alone or combined with sputum eosinophil and atopy is useful in predicting corticosteroid-responsive cough (CRC) and non-CRC (NCRC) is not clear. METHODS: A total of 244 patients with chronic cough and 59 healthy subjects as control were enrolled. The causes of chronic cough were confirmed according to a well-established diagnostic algorithm. FeNO measurement and induced sputum for differential cell were performed in all subjects. RESULTS: CRC occurred in 139 (57.0%) patients and NCRC occurred in 105. The FeNO level in CRC significantly correlated with sputum eosinophils (rs = 0.583, P < .01). The median (quarter) of FeNO level in CRC was significantly higher than NCRC (32.0 ppb [19.0-65.0 ppb] vs 15.0 ppb [11.0-22.0 ppb], P < .01). FeNO of 31.5 ppb had a sensitivity and specificity of 54.0% and 91.4%, respectively, in predicting CRC from chronic cough, with a positive predictive value of 89.3% and a negative predictive value of 60.0%. If the patients had a combination of low level of FeNO ( < 22.5 ppb), normal sputum eosinophil ( < 2.5%), and absence of atopy, the sensitivity and specificity would be 30.3% and 93.5% for predicting NCRC. CONCLUSIONS: In our cohort, a high level (≥ 31.5 ppb) of FeNO indicates more likelihood of CRC, but the sensitivity is insufficient to rule out a diagnosis of CRC. A combination of low-level FeNO, normal sputum eosinophil, and absence of atopy suggests a lower likelihood of CRC.

Will nonasthmatic eosinophilic bronchitis develop into chronic airway obstruction?: a prospective, observational study.

OBJECTIVE: The long-term prognosis of nonasthmatic eosinophilic bronchitis (NAEB) is still unclear. The aim of this study was to observe the frequency of relapse among patients with NAEB and the likelihood of NAEB developing into chronic airflow obstruction over time. METHODS: Patients with NAEB were followed for at least 1 year between 2003 and 2013. During this period, we evaluated clinical symptoms, sputum eosinophil count, spirometry, and bronchial hyperresponsiveness. A linear mixed model was adopted to determine the relationship between time and lung function. RESULTS: A total of 234 patients with NAEB were identified, of whom 141 were followed for > 1 year (median, 4.1 years). Up to 59.6% of patients had a relapse after treatment. Both allergic rhinitis (OR, 4.37; 95% CI, 1.049-18.203; P = .043) and sputum eosinophilia after 4 weeks of treatment with inhaled corticosteroids (OR, 9.493; 95% CI, 2.381-37.850; P = .001) were risk factors for relapse. Among the 141 patients, mild asthma developed in eight (5.7%). During the follow-up period, no progressive decline in FVC, FEV1, and FEV1/FVC were observed (P > .05). Although the proportion of small airway dysfunction (maximum midexpiratory flow [MMEF] < 65%) significantly increased at the last visit in all groups (all P < .05), only the relapse group showed an MMEF decline at the end of follow-up (P < .05) in the linear mixed model. CONCLUSIONS: More than 50% of patients with NAEB have repeated episodes associated with persistent sputum eosinophilia after treatment and allergic rhinitis. In the current cohort, chronic airway obstruction does not develop despite small airway dysfunction increases over time.