The Dosing Strategy to Improve Adherence to Roflumilast in Treatment for Chronic Obstructive Lung Disease: A Systemic Review and Meta-Analysis.

Background: The clinical efficacy of roflumilast, an oral phosphodiesterase-4 inhibitor, has been demonstrated in patients with severe chronic obstructive pulmonary disease (COPD). However, roflumilast has shown frequent adverse drug reactions (ADRs). This study was performed to investigate the dosing strategy that will improve adherence to roflumilast in COPD. Methods: We conducted a systematic review and meta-analysis using PubMed, Embase, and Cochrane Central Register. The dosing strategy for roflumilast was classified into a dose-escalation group and a low-dose group. We investigated clinical outcomes according to dosing strategy. Results: Five clinical trials involving 2424 patients were included. Both the dose-escalation and the low-dose groups showed a decrease in discontinuation rate compared to the standard dosing group for roflumilast (risk ratio [RR], 0.81; 95% confidence interval [CI], 0.67-0.97; P = 0.02 and RR, 0.62; 95% CI, 0.48-0.80; P < 0.01, respectively). In the two strategies, the pooled proportions of discontinuation were 27.9% and 11.7%, respectively. Although the pooled proportion of any ADR was not statistically decreased in the two strategies, diarrhea was significantly reduced in the low-dose group compared to the standard group (RR, 0.58; 95% CI, 0.42-0.82; P < 0.01). The pooled incidence of acute exacerbations was similar between the low-dose and the standard groups (22.9% and 20.1%, respectively; P = 0.27). Conclusion: Our findings show that the two alternative dosing strategies might have the benefit of improving adherence to roflumilast in COPD. Further large-scale trials are required to support our findings.

Increased Apolipoprotein B/Apolipoprotein A-I Ratio Is Associated With Decline in Lung Function in Healthy Individuals: The Kangbuk Samsung Health Study.

BACKGROUND: Lung dysfunction and high apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio are both recognized risk factors for cardiovascular disease. However, few studies have examined the association between the apoB/ApoA-I ratio and lung function. Therefore, we investigated whether this ratio is associated with decreased lung function in a large healthy cohort. METHODS: We performed a cohort study on 68,418 healthy Koreans (34,797 males, mean age: 38.1 years) who underwent a health examination in 2019. ApoB/apoA-I ratio was categorized into quartiles. Spirometric values at the fifth percentile in our population were considered the lower limit of normal (LLN), which was used to define lung function impairment. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs), using the lowest quartile as the reference, were estimated to determine lung function impairment. RESULTS: Mean apoB/apoA-I ratio was 0.67 ± 0.21. Subjects with the highest quartile of this ratio had the lowest predicted forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) after controlling for covariates (P < 0.001). However, FEV1/FVC ratio was not significantly different among the four quartiles (P = 0.059). Compared with the lowest quartile (Q1, reference), the aORs (95% CI) for FEV1% < LLN across increasing quartiles (from Q2 to Q4) were 1.216 (1.094-1.351), 1.293 (1.156-1.448), and 1.481 (1.311-1.672) (P for trend < 0.001), respectively. Similarly, the aORs for FVC% < LLN compared with the reference were 1.212 (1.090-1.348), 1.283 (1.147-1.436), and 1.502 (1.331-1.695) with increasing quartiles (P for trend < 0.001). However, the aORs for FEV1/FVC < LLN were not significantly different among groups (P for trend = 0.273). CONCLUSION: High apoB/apoA-I ratio was associated with decreased lung function. However, longitudinal follow-up studies are required to validate our findings.

Safety and tolerability of combination treatment with pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis: a systematic review and meta-analysis.

Background: The role of combination treatments with two antifibrotic agents, pirfenidone and nintedanib, has been not established in idiopathic pulmonary fibrosis (IPF). This study was performed to investigate the safety and tolerability of combination antifibrotic treatment in patients with IPF. Methods: We conducted a proportional meta-analysis and searched PubMed, EMBASE, and the Cochrane Central Register for relevant clinical trials. The primary outcome was the proportion of discontinuation of combination treatment over the treatment period. We also examined the pooled proportions of serious and any adverse drug reactions (ADRs). Results: Four clinical trials involving 191 patients were analyzed. In pooled estimates, 29% of patients discontinued treatment during the study period [95% confidence interval (CI): 17-41%, I2=65.42%]. The pooled proportions of serious and any ADRs were 10% (95% CI: 1-19%; I2=79.13%) and 82% (95% CI: 75-90%; I2=39.20%), respectively. During the follow-up period, gastrointestinal symptoms were the most frequent ADR. Acute exacerbation (AE) of IPF was reported in 7.0% of patients. Conclusions: Our findings showed relatively frequent incidence of discontinuation and ADRs for combination therapy in IPF. Further large-scale, randomized, controlled trials are needed to support our results because of the methodological limitations of the included trials and a scarcity of trials for analysis.

The impact of antimicrobial de-escalation therapy in culture-negative pneumonia: a systematic review and meta-analysis.

BACKGROUND/AIMS: Antimicrobial de-escalation (ADE) remains a challenging strategy in the treatment of pneumonia. We investigated the outcomes of ADE as measured by mortality and duration of the use of antibiotics in patients with culture- negative pneumonia. METHODS: We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. The primary outcome was inpatient mortality. RESULTS: We examined six studies comprising 11,933 subjects, of whom 1,152 received ADE. Overall, the ADE strategy was associated with a statistically lower risk of in-hospital mortality compared with non-ADE (risk ratio [RR] = 0.60, 95% confidence interval [CI] = 0.38 to 0.93). Although substantial heterogeneity was found among the included studies (I2 = 66%), a meta-regression analysis could not reveal plausible sources of heterogeneity. And ADE was associated with a shorter duration of total and initial antibiotic therapies and total length of hospital stay compared with non-ADE. CONCLUSION: Our findings suggest that ADE seems to be significantly associated with better clinical outcomes compared with non-ADE. Caution is demanded when interpreting data of this study because of substantial between-study heterogeneity.

The impact of insulin resistance on the association between metabolic syndrome and lung function: the Kangbuk Samsung Health Study.

BACKGROUND/OBJECTIVE: Metabolic syndrome (MS) is related to lung dysfunction. However, its impact according to insulin resistance (IR) remains unknown. Therefore, we evaluated whether the relation of MS with lung dysfunction differs by IR. SUBJECT/METHODS: This cross-sectional study included 114,143 Korean adults (mean age, 39.6 years) with health examinations who were divided into three groups: metabolically healthy (MH), MS without IR, and MS with IR. MS was defined as presence of any MS component, including IR estimated by HOMA-IR ≥ 2.5. Adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for lung dysfunction were obtained in MS, MS without IR, and MS with IR groups compared with the MH (reference) group. RESULTS: The prevalence of MS was 50.7%. The percent predicted forced expiratory volume in 1 s (FEV1%) and forced vital capacity (FVC%) showed statistically significant differences between MS with IR and MH and between MS with IR and MS without IR (all P < 0.001). However, those measures did not vary between MH and MS without IR (P = 1.000 and P = 0.711, respectively). Compared to MH, MS was not at risk for FEV1% < 80% (1.103 (0.993-1.224), P = 0.067) or FVC% < 80% (1.011 (0.901-1.136), P = 0.849). However, MS with IR was clearly associated with FEV1% < 80% (1.374 (1.205-1.566) and FVC% < 80% (1.428 (1.237-1.647) (all p < 0.001), though there was no evident association for MS without IR (FEV1%: 1.078 (0.975-1.192, P = 0.142) and FVC%: 1.000 (0.896-1.116, p = 0.998)). CONCLUSION: The association of MS with lung function can be affected by IR. However, longitudinal follow-up studies are required to validate our findings.

Metabolically healthy and unhealthy obesity and the development of lung dysfunction.

We investigated the association of metabolically healthy (MH) and unhealthy (MU) obesity with incident lung dysfunction. This cohort study included 253,698 Korean lung disease-free adults (mean age, 37.4 years) at baseline. Spirometry-defined lung dysfunction was classified as a restrictive pattern (RP) or obstructive pattern (OP). We defined obesity as BMI ≥ 25 kg/m2 and MH as the absence of any metabolic syndrome components with a homeostasis model assessment of insulin resistance < 2.5: otherwise, participants were considered MU. During a median follow-up of 4.9 years, 10,775 RP cases and 7140 OP cases develped. Both MH and MU obesity showed a positive association with incident RP, with a stronger association in the MU than in the MH group (Pinteraction = 0.001). Multivariable-adjusted hazard ratios (95% CI) for incident RP comparing obesity to the normal-weight category was 1.15 (1.05-1.25) among the MH group and 1.38 (1.30-1.47) among MU group. Conversely, obesity was inversely associated with OP because of a greater decline in forced vital capacity than forced expiratory volume in 1 s. Both MH and MU obesity were positively associated with RP. However, the associations between obesity, metabolic health, and lung functions might vary depending on the type of lung disease.

Diagnostic yield of radial probe endobronchial ultrasonography-guided transbronchial biopsy without fluoroscopy in peripheral pulmonary lesions: A systematic review and meta-analysis.

PURPOSE: Although radial probe endobronchial ultrasound (R-EBUS) has been used to investigate peripheral pulmonary lesions (PPLs), its diagnostic performance without fluoroscopy remains unclear. We sought to determine the diagnostic yield of R-EBUS-guided transbronchial biopsy (TBB) without fluoroscopy. METHODS: We performed a systematic literature review using Pubmed, Embase, and the Cochrane Central Register. Then, we performed a proportional meta-analysis to determine the diagnostic yield of this modality. Subgroup and meta-regression analyses were used to identify factors affecting the performance of R-EBUS-guided TBB without fluoroscopy. RESULTS: We identified 31 studies consisting of a total of 6491 patients. Pooled overall diagnostic yield of R-EBUS-guided TBB without fluoroscopy was 0.70 (95% confidence interval [CI], 0.67-0.74). There was significant heterogeneity across studies (I2  = 89.45%, p < 0.001). In subgroup and meta-regression analyses, air bronchus sign on chest computed tomography scans, larger size PPLs, probe location within lesions, and heterogeneous echogenicity were associated with significantly higher diagnostic yield. Diagnostic yield from the upper lobe was statistically lower than that from the middle and lower lobes. Pooled pneumothorax rate was 0.01 (95% CI, 0.01-0.01, I2  = 63.51%, p < 0.001). CONCLUSIONS: R-EBUS-guided TBB without fluoroscopy appears to be a relatively useful tool with a low pneumothorax rate for the diagnosis of PPLs. Factors mentioned above may affect the diagnostic yield of this tool. Because of substantial between-study heterogeneity, our results should be interpreted with caution.

The Clinical Efficacy of Type 2 Inflammation-Specific Agents Targeting Interleukins in Reducing Exacerbations in Severe Asthma: A Meta-Analysis.

PURPOSE: Monoclonal antibodies against type 2 inflammatory pathways are currently promising therapeutics for severe asthma. The aim of this study was to determine how well type 2 (T2) inflammation-specific agents targeting interleukins reduce the rate of asthma exacerbations (AE) in patients with severe asthma. MATERIALS AND METHODS: We performed a systematic review and meta-analysis in accordance with PRISMA guidelines. A systematic literature search was conducted in PubMed, Embase, and the Cochrane Central Register. The primary outcome was the reduction rate of annualized AEs. RESULTS: We analyzed 17 studies comprising 11800 subjects. A total of 6197 patients received T2-specific agents (benralizumab, dupilumab, lebrikizumab, mepolizumab, reslizumab, and tralokinumab). Overall, T2-specific agents were significantly associated with a lower risk of AE, compared with placebo [rate ratio (RR) 0.58, 95% confidence interval (CI) 0.51 to 0.66]. Among all studied agents, only tralokinumab did not demonstrate a reduction in AE. The efficacy of T2-specific agents in reducing AE was maintained regardless of the pathway used. A subgroup analysis indicated that T2-specific agents further reduced the risk of AE in patients with eosinophil counts of ≥300 cells/µL (RR 0.41, 95% CI 0.32 to 0.53). CONCLUSION: Our findings suggest that T2-specific agents are significantly associated with a reduced rate of AE, compared with placebo. Their efficacy appears to be enhanced in patients with eosinophil counts of ≥300 cells/µL.

The effect of metabolic health and obesity on lung function: A cross sectional study of 114,143 participants from Kangbuk Samsung Health Study.

OBJECTIVE: Although the role of obesity-induced metabolic abnormalities in impaired lung function is well-established, the risk of impaired lung function among obese individuals without metabolic abnormalities, referred to metabolically-healthy obesity (MHO), is largely unexplored. Therefore, we evaluated the impact of MHO on lung function in a large health-screening cohort. METHODS: 114,143 subjects (65,342 men, mean age and BMI: 39.6 years and 23.6) with health examinations in 2019 were divided into four groups as follows: metabolically healthy non-obese (MHNO), MHO, metabolically unhealthy non-obese (MUHNO), and metabolically unhealthy obese (MUHO). Metabolic health was defined as fewer than two metabolic syndrome components. Obesity was defined as BMI ≥25 kg/m2. Adjusted odds ratios (aORs), using MHNO as a reference, were calculated to determine lung function impairment. RESULTS: Approximately one-third (30.6%) of the study subjects were obese. The prevalence of MHO was 15.1%. Subjects with MHO had the highest FEV1% and FVC% values but the lowest FEV1/FVC ratio (p<0.001). These results persisted after controlling for covariates. Compared with MHNO, the aORs (95% confidence interval) for FEV1% < 80% in MHO, MUHNO and MUHO were 0.871 (0.775-0.978), 1.274 (1.114-1.456), and 1.176 (1.102-1.366), respectively (P for trend = 0.014). Similarly, the aORs in MHO, MUHNO, and MUHO were 0.704 (0.615-0.805), 1.241 (1.075-1.432), and 1.226 (1.043-1.441), respectively, for FVC% < 80% (p for trend = 0.013). However, the aORs for FEV1/FVC<0.7 were not significantly different between groups (p for trend = 0.173). CONCLUSIONS: The MHO group had better lung function than other groups. However, longitudinal follow-up studies are required to validate our findings.

Comparing the diagnostic accuracy of rapid antigen detection tests to real time polymerase chain reaction in the diagnosis of SARS-CoV-2 infection: A systematic review and meta-analysis.

BACKGROUND: Timely and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is crucial to reduce the risk of viral transmission. We investigated the diagnostic accuracy of rapid antigen detection tests (RADTs) in the diagnosis of SARS-CoV-2 infection. METHODS: A systematic literature search was performed using Pubmed, Embase, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary receiver-operating characteristic curve (HSROC) of RADTs were pooled using meta-analysis. We used commercial and laboratory-developed reverse transcriptase-polymerase chain reaction (RT-PCR) as reference standards. RESULTS: We identified 24 studies comprising 14,188 patients. The overall pooled sensitivity, specificity, and DOR of RADTs for diagnosis of SARS-CoV-2 were 0.68 (95%CI, 0.59 - 0.76), 0.99 (95%CI, 0.99 - 1.00), and 426.70 (95% CI, 168.37 - 1081.65), respectively. RADTs and RT-PCR had moderate agreement with an estimated pooled Cohen's kappa statistic of 0.75 (95%CI, 0.74-0.77), and area under the HSROC of 0.98 (95%CI, 0.96 - 0.99). The pooled sensitivity of RADTs was significantly increased in subjects with viral load of Ct-value ≤25 or in those within 5 days after symptom onset than it was in subjects with lower viral loads or longer symptom duration. CONCLUSIONS: The overall sensitivity of RADTs was inferior to that of the RT-PCR assay. The RADTs were more sensitive for samples of Ct-value ≤ 25 and might be suitable for subjects in the community within 5 days of symptom onset.

Diagnostic Accuracy of the Quidel Sofia Rapid Influenza Fluorescent Immunoassay in Patients with Influenza-like Illness: A Systematic Review and Meta-analysis.

BACKGROUND: Although the Quidel Sofia rapid influenza fluorescent immunoassay (FIA) is widely used to identify influenza A and B, the diagnostic accuracy of this test remains unclear. Thus, the objective of this study was to determine the diagnostic performance of this test compared to reverse transcriptase-polymerase chain reaction. METHODS: A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. Pooled sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary receiver-operating characteristic curve (HSROC) of this test for identifying influenza A and B were determined using meta-analysis. A sensitivity subgroup analysis was performed to identify potential sources of heterogeneity within selected studies. RESULTS: We identified 17 studies involving 8,334 patients. Pooled sensitivity, specificity, and DOR of the Quidel Sofia rapid influenza FIA for identifying influenza A were 0.78 (95% confidence interval [CI], 0.71-0.83), 0.99 (95% CI, 0.98-0.99), and 251.26 (95% CI, 139.39-452.89), respectively. Pooled sensitivity, specificity, and DOR of this test for identifying influenza B were 0.72 (95% CI, 0.60-0.82), 0.98 (95% CI, 0.96-0.99), and 140.20 (95% CI, 55.92-351.54), respectively. The area under the HSROC for this test for identifying influenza A was similar to that for identifying influenza B. Age was considered a probable source of heterogeneity. CONCLUSION: Pooled sensitivities of the Quidel Sofia rapid influenza FIA for identifying influenza A and B did not quite meet the target level (≥80%). Thus, caution is needed when interpreting data of this study due to substantial between-study heterogeneity.

Diagnostic accuracy of the Cepheid Xpert Xpress and the Abbott ID NOW assay for rapid detection of SARS-CoV-2: A systematic review and meta-analysis.

Rapid and accurate diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is essential to prevent the spread of the virus. We investigated the diagnostic accuracy of the Xpert Xpress and the ID NOW assays for rapid detection of SARS-CoV-2 using a systemic review and meta-analysis approach. A systematic literature search was performed using PubMed, Embase, and the Cochrane COVID-19 Study Register. The sensitivity and specificity of these tests for detecting viruses in patients with suspected SARS-CoV-2 infection were pooled. We used commercial and laboratory-developed reverse transcription-polymerase chain reactions as reference standards. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the risk of bias. We identified 11 studies involving 1734 subjects for the Xpert Xpress assay and 10 studies involving 1778 subjects for the ID NOW assay. The pooled sensitivity and specificity of the Xpert Xpress assay for detection of SARS-CoV-2 were 0.99 (95% confidence interval [CI], 0.97 to 0.99) and 0.97 (95% CI, 0.95 to 0.98), respectively. The pooled sensitivity and specificity of the ID NOW assay were 0.79 (95% CI, 0.69 to 0.86) and 1.00 (95% CI, 0.98 to 1.00), respectively. The studies included in our analysis seemed to have low methodological quality. The Xpert Xpress assay showed excellent diagnostic accuracy for rapid detection of SARS-CoV-2. However, as the ID NOW assay showed relatively low sensitivity, this test might miss several positive samples.

Decreased lung function is associated with vitamin D deficiency in apparently health, middle aged Koreans: the Kangbuk Samsung Health Study.

BACKGROUND/OBJECTIVES: There has been inconsistent relationships between serum vitamin D levels and lung function in previous studies. However, previous studies included patients with medical diseases, affecting both vitamin D levels and lung function. Considering this view of potential confounders, we investigated if vitamin D deficiency (VDD) is linked to lung function in health screening examinee without overt medical conditions. SUBJECTS/METHODS: We conducted a cohort study on 68,457 healthy Koreans (36,759 males, mean age: 37.7 years) with a health examination in 2015. Measured forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) were categorized in quartiles. To examine the relationships between VDD and lung function, adjusted odds ratios (aORs) for VDD were estimated by logistic regression. RESULTS: Median vitamin D level was 14.9 ng/mL. The prevalence of VDD (defined as <20 ng/ml) was 74.5%. Compared with the highest quartile (Q4, reference), the aORs for VDD across decreasing quartiles (from Q3 to Q1) were 1.05, 1.06, 1.10 for FVC, and 1.07, 1.10, 1.10 for FEV1 (P for trend < 0.01 for both), in all subjects. Similarly, the aOR of having VDD for men also increased with decreasing quartiles of FVC and FEV1 in a dose-response manner (p for trend < 0.01 for both). However, neither FVC nor FEV1 was associated with VDD in women. CONCLUSIONS: VDD was associated with decreased lung function in middle aged Korean men without overt medical conditions. VDD could be a modifiable risk factor for impaired lung function, in men but not in women.

Diagnostic comparison of methacholine and mannitol bronchial challenge tests for identifying bronchial hyperresponsiveness in asthma: a systematic review and meta-analysis.

OBJECTIVE: Bronchial hyperresponsiveness (BHR) is a representative feature of asthma. Although methacholine and mannitol are commonly used for bronchial challenge tests, the optimal roles of the two agents for assessing BHR remain unclear. We compared the diagnostic performance of methacholine and mannitol in bronchial challenge tests. METHODS: A systematic literature search was performed using MEDLINE, EMBASE, and the Cochrane Central Register. The sensitivity, specificity, diagnostic odds ratio (DOR), and a hierarchical summary of the receiver-operating characteristic curve (HSROC) of the two agents for detecting BHR in asthma were pooled using meta-analysis. A meta-regression analysis was used to identify potential sources of heterogeneity within the selected studies. RESULTS: We identified six studies comprising 565 patients. The pooled sensitivity, specificity, and DOR of methacholine were 0.61 (95%CI, 0.44-0.76), 0.93 (95%CI, 0.70-0.99), and 23.47 (95% CI, 2.51-219.89), respectively. The pooled sensitivity, specificity, and diagnostic odds ratio of mannitol were 0.50 (95%CI, 0.28-0.73), 0.97 (95% CI, 0.94-0.99), and 35.22 (95% CI, 8.82-140.62), respectively. The area under the HSROC for mannitol was higher than that for methacholine (0.97 vs. 0.81, p < 0.01). Considerable between-study heterogeneity was present for sensitivity and specificity in studies of both index tests. Univariate meta-regression analysis revealed that age and sex of the study participants were probable sources of heterogeneity for specificity in studies of methacholine. CONCLUSION: Although mannitol showed better diagnostic performance than methacholine for identifying BHR in asthma, substantial between-study heterogeneity necessitates caution when interpreting the data.

Decreased lung function is associated with elevated ferritin but not iron or transferrin saturation in 42,927 healthy Korean men: A cross-sectional study.

OBJECTIVES: Though elevated ferritin level and decreased lung function both predispose people to cardio-metabolic disease, few reports have investigated the association between them. Furthermore, it remains unclear whether the association reflects a change in iron stores or an epiphenomenon reflecting metabolic stress. Therefore, we looked for possible associations between ferritin, iron, and transferrin saturation (TSAT) and lung function to clarify the role of iron-related parameters in healthy men. METHODS: We conducted a cohort study of 42,927 healthy Korean men (mean age: 38.6 years). Percent predicted forced expiratory volume in one second (FEV1%) and forced vital capacity (FVC%) were categorized into quartiles. Adjusted odds ratios (aORs) and 95% confidence intervals (using the highest quartile as reference) were calculated for hyperferritinemia, high iron, and high TSAT after controlling for potential confounders. RESULTS: The median ferritin level was 199.8 (141.5-275.6) ng/mL. The prevalence of hyperferritinemia (defined as >300 ng/mL) was 19.3%. Subjects with hyperferritinemia had lower FEV1% and FVC% than those with normal ferritin level with a slight difference, but those were statistically significant (99.22% vs.99.61% for FEV1%, p = 0.015 and 98.43% vs. 98.87% for FVC, p = 0.001). However, FEV1/FVC ratio was not significantly different between groups (P = 0.797). Compared with the highest quartile, the aORs for hyperferritinemia across decreasing quartiles were 1.081 (1.005-1.163), 1.100 (1.007-1.200), and 1.140 (1.053-1.233) for FEV1% (p for trend = 0.007) and 1.094 (1.018-1.176), 1.101 (1.021-1.188), and 1.150 (1.056-1.252) for FVC% (p for trend = 0.001). However, neither FEV1% nor FVC% was associated with iron or TSAT. CONCLUSIONS: Hyperferritinemia was associated with decreased lung function in healthy Korean men, but iron and TSAT were not. Longitudinal follow-up studies are required to validate our findings.

The Clinical Efficacy of Pulmonary Hypertension-Specific Agents in Idiopathic Pulmonary Fibrosis: Systematic Review and Meta-Analysis of Randomized Controlled Clinical Trials.

BACKGROUND: Pulmonary hypertension (PH) is common in patients with idiopathic pulmonary fibrosis (IPF) and is associated with poor outcomes. This study was performed to determine the clinical efficacy of PH-specific therapeutic agents for IPF patients. METHODS: We performed a systematic review and meta-analysis using MEDLINE, EMBASE, and the Cochrane Central Register. We searched randomized controlled trials (RCTs) without language restriction until November 2018. The primary outcome was all-cause mortality to end of study. RESULTS: We analyzed 10 RCTs involving 2,124 patients, 1,274 of whom received PH-specific agents. In pooled estimates, the use of PH-specific agents was not significantly associated with reduced all-cause mortality to end of study compared with controls (hazard ratio, 0.99; 95% confidence interval [CI], 0.92, 1.06; P = 0.71; I² = 30%). When we performed subgroup analyses according to the type of PH-specific agent, sample size, age, forced vital capacity, diffusion lung capacity, and the extent of honeycombing, PH-specific agents also showed no significant association with a reduction in all-cause mortality. A small but significant improvement in quality of life, measured using the St. George Respiratory Questionnaire total score, was found in the PH-specific agent group (mean difference, -3.16 points; 95% CI, -5.34, -0.97; P = 0.005; I² = 0%). We found no significant changes from baseline in lung function, dyspnea, or exercise capacity. Serious adverse events were similar between the two groups. CONCLUSION: Although PH-specific agents provided small health-related quality-of-life benefits, our meta-analysis provides insufficient evidence to support their use in IPF patients.

Performance of pneumococcal urinary antigen test in patients with community-onset pneumonia: a propensity score-matching study.

BACKGROUND/AIMS: Although pneumococcal urinary antigen tests (PUATs) have universally been used for the diagnosis of pneumococcal pneumonia, data on the efficacy of these exams are limited. The objective of our study was to investigate the clinical impact of the PUAT in patients with community-onset pneumonia (CO-pneumonia). METHODS: We conducted a retrospective cohort study of patients diagnosed with CO-pneumonia. Patients were classified according to their PUAT results and were matched using the propensity score-matching method. The primary outcome was 30-day mortality. RESULTS: A total of 1,257 patients were identified and 163 (13.0%) demonstrated positive PUAT results. The sensitivity and specificity values of PUAT for overall pneumococcal pneumonia were 56.5% and 91.4%, respectively. In the full cohort, there were no significant differences in 30-day mortality between the two groups (6.1% in the positive PUAT group vs. 8.2% in the negative PUAT group, p = 0.357). However, in the propensity-matched cohort, the 30-day mortality rates were lower in the positive PUAT group (5.6% vs. 17.4%, p = 0.001). With respect to secondary outcomes, the proportion of patients with potentially drug-resistant pathogens, changes in antibiotics, and failure rates of initial antibiotic therapy were significantly lower in the positive PUAT group than in the negative PUAT group of the propensity-matched cohort. CONCLUSION: We found that the sensitivity of the index test was low and specificity was high in this clinical setting. And our findings suggest that positive PUAT results may be associated with favorable clinical outcomes in patients with CO-pneumonia.

Incidence of Hypotension after Discontinuation of Norepinephrine or Arginine Vasopressin in Patients with Septic Shock: a Systematic Review and Meta-Analysis.

BACKGROUND: There has been no consensus regarding the discontinuation order of vasopressors in patients recovering from septic shock treated with concomitant norepinephrine (NE) and arginine vasopressin (AVP). The aim of this study was to compare the incidence of hypotension within 24 hours based on whether NE or AVP was discontinued first in order to determine the optimal sequence for discontinuation of vasopressors. METHODS: A systematic literature search was conducted in MEDLINE, Embase, and the Cochrane Central Register. The primary end-point was incidence of hypotension within 24 hours after discontinuation of the first vasopressor. RESULTS: We identified five studies comprising 930 patients, of whom 631 (67.8%) discontinued NE first and 299 (32.2%) discontinued AVP first. In pooled estimates, a random-effect model showed that discontinuation of NE first was associated with a significant reduction of the incidence of hypotension compared to discontinuing AVP first (31.8% vs. 54.8%; risk ratios, 0.35; 95% confidence interval, 0.16 to 0.76; P = 0.008; I² = 90.7%). Although a substantial degree of heterogeneity existed among the trials, we could not identify the significant source of bias. In addition, there were no significant differences in intensive care unit (ICU) mortality, in-hospital mortality, 28-day mortality, or ICU length of stay between the groups. CONCLUSION: Discontinuing NE prior to AVP was associated with a lower incidence of hypotension in patients recovering from septic shock. However, our results should be interpreted with caution, due to the considerable between-study heterogeneity.

Performance of a quick sofa-65 score as a rapid sepsis screening tool during initial emergency department assessment: A propensity score matching study.

PURPOSE: We sought to elucidate the performance of a Quick Sequential Organ Function Assessment-65 (qSOFA-65) score in recognizing sepsis and to compare the qSOFA-65 score to systemic inflammatory response syndrome (SIRS) and qSOFA scores. METHODS: We performed a matched case-control study using propensity score matching. The number of patients meeting qSOFA-65, qSOFA, and SIRS positive criteria were calculated between the sepsis and non-sepsis groups. We compared the diagnostic performance of the three scoring systems in predicting sepsis. RESULTS: A total of 2441 patients were included in the study. In propensity matched cohorts, the percentage of patients who met qSOFA-65, qSOFA, and SIRS positive criteria were 46.7%, 14.3%, and 55.6%, respectively. The sensitivity and specificity scores for the qSOFA-65, qSOFA, and SIRS positive criteria for sepsis were 0.66 and 0.73, 0.28 and 0.97, and 0.66 and 0.55, respectively. The AUC value of qSOFA-65 positive criteria in predicting sepsis was significantly higher than that of qSOFA and SIRS positive criteria (adjusted AUC 0.688 vs. 0.630 vs. 0.596, respectively). CONCLUSIONS: We found that qSOFA-65 was more likely to identify patients with sepsis on the initial ED visit relative to qSOFA or SIRS. This may have quality improvement implications in predicting sepsis.

The association of prior hospitalization with clinical outcomes among patients admitted with pneumonia: a propensity score matching study.

BACKGROUND: Although prior hospitalization (PH) has been considered as a risk factor for infection with potentially drug-resistant (PDR) pathogens in patients admitted with pneumonia, the evidence is limited. We aimed to elucidate the clinical impact of PH on these patients. METHODS: PH was defined as hospitalization for two or more days in the preceding 90 days. Patients with PH-associated pneumonia (PHAP) or community-acquired pneumonia (CAP) were matched using the propensity score matching method, and the clinical outcomes were compared. We also conducted subgroup analyses based on intravenous antibiotic use during PH, duration of PH, and time to re-admission. RESULTS: A total of 704 patients were identified; the PHAP group included 97 patients (13.7%). After matching according to propensity scores, the baseline characteristics of the PHAP group were similar to those of the CAP group. The isolation rate of PDR pathogens as well as the 30-day and total in-hospital mortality did not differ between propensity score-matched PHAP and CAP patients (13.6% vs. 10.2%, P = 0.485; 10.2% vs. 14.8%, P = 0.362; and 13.6% vs. 15.9%, P = 0.671, respectively). In subgroup analyses, only intravenous antibiotic use during PH was associated with the isolation rate of PDR pathogens (adjusted OR: 5.066; 95% CI: 1.231-20.845). CONCLUSIONS: PH itself might not be related with higher isolation rates of PDR pathogens or mortality in patients admitted with pneumonia. Therefore, it seems reasonable that broad spectrum antibiotic therapy for PDR pathogens should be selectively applied to PHAP patients with intravenous antibiotic use during PH.