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.

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.

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.

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.

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.

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.

Decline in lung function is associated with elevated lipoprotein (a) in individuals without clinically apparent disease: A cross-sectional study.

BACKGROUND AND OBJECTIVE: Reduced lung function and high lipoprotein (a) (Lp(a)) levels are both recognized risk factors for cardiovascular disease. Few studies have investigated the association between serum Lp(a) and lung function in the general population. We evaluated the association between reduced lung function and high Lp(a) levels in healthy individuals without known medical disease diagnoses. METHODS: We performed a cross-sectional study on 64 082 Korean health screening examinees (33 049 males, 38 ± 7 years) who underwent a health examination in 2015. RESULTS: The median Lp(a) level was 12 (6-25)mg/dL. The prevalence of high Lp(a) (defined as >30 mg/dL) was 19.5%. Subjects with a high Lp(a) had both lower values of measured forced expiratory volume in 1 s (FEV1 ) and forced vital capacity (FVC; L) than those with a low Lp(a) (P < 0.001). However, FEV1 /FVC ratio was not significantly different between groups (P = 0.112). Comparison of the second, third and fourth measured FVC (L) quartiles with that of the lowest quartile (1Q) group (reference) on regression analysis revealed adjusted odd ratios (OR) for a high Lp(a) of 0.928 (95% CI: 0.876-0.982), 0.860 (0.808-0.916) and 0.895 (0.839-0.954), respectively (P for trend < 0.001). In addition, adjusted OR for high Lp(a) compared with reference was 0.894 (0.844-0.947), 0.857 (0.806-0.912) and 0.882 (0.8727-0.940) across the measured FEV1 (L) quartiles in increasing order (P for trend < 0.001). CONCLUSION: High Lp(a) levels were associated with reduced lung function in this cross-sectional population study. Longitudinal follow-up studies will be required to validate our findings.

Impact of dosage timing of once-daily inhaled corticosteroids in asthma: A systematic review and meta-analysis.

BACKGROUND: Once-daily inhaled corticosteroids (ICSs) are widely used as first-line therapy in patients with asthma. OBJECTIVE: To compare the efficacy of ICSs administered once daily in the morning or evening as determined by lung function. METHODS: Medline, Embase, and the Cochrane Central Register were searched for relevant clinical trials. The primary outcome was lung function assessed as trough forced expiratory volume in 1 second and peak expiratory flow at end point. RESULTS: Eight randomized clinical trials involving 1,234 patients were analyzed. The total number of patients treated with once-daily ICS in the morning and evening was 628 and 606, respectively. Pooled estimates showed that ICS administered once daily in the evening resulted in mild improvements in trough forced expiratory volume in 1 second (mean difference 0.05 L; 95% confidence interval 0.01-0.09; P = .026; I2 = 22.5%) and morning peak expiratory flow (mean difference 13.92 L/min; 95% confidence interval 5.77-22.06; P = .001; I2 = 13%) at end point compared with morning dosing. The change in use of rescue medicine and the incidence of adverse events with once-daily ICS were not significantly different between the 2 dosing times. CONCLUSION: Compared with morning dosing, ICSs administered once daily in the evening seemed to provide some benefits in lung function for patients with asthma. However, because of methodologic limitations, further large-scale randomized clinical trials for dosing time of once-daily ICSs are needed.

Incidence of hypotension according to the discontinuation order of vasopressors in the management of septic shock: a prospective randomized trial (DOVSS).

BACKGROUND: Vasopressin (AVP) is commonly added to norepinephrine (NE) to reverse shock in patients with sepsis. However, there are no data to support the appropriate strategy of vasopressor tapering in patients on concomitant NE and AVP who are recovering from septic shock. Therefore, the objective of this study was to evaluate the incidence of hypotension while tapering vasopressors in patients on concomitant NE and AVP recovering from septic shock. METHODS: Patients with septic shock receiving concomitant NE and AVP were randomly assigned to taper NE first (NE group) or AVP first (AVP group). The primary end point was the incidence of hypotension within one hour of tapering of the first vasopressor. We also evaluated the association between serum copeptin levels and the occurrence of hypotension. RESULTS: The study was stopped early due to a significant difference in the incidence of hypotension after 38 and 40 patients were enrolled in the NE group and the AVP group, respectively. There were 26 patients (68.4%) in the NE group versus 9 patients (22.5%) in the AVP group who developed hypotension after tapering the first vasopressor (p < 0.001). There was a similar finding during the subsequent tapering of the second vasopressor (64.5% in the NE vs 25.0% in the AVP group, p = 0.020). Finally, NE tapering was significantly associated with hypotension during the study period (hazard ratio, 2.221; 95% confidence interval, 1.106-4.460; p = 0.025). The serum copeptin level was lower in patients in whom hypotension developed during tapering of AVP than it was in those without hypotension. CONCLUSIONS: Tapering NE rather than AVP may be associated with a higher incidence of hypotension in patients recovering from septic shock who are on concomitant NE and AVP. However, further studies with larger sample sizes are required to better determine the appropriate strategy for vasopressor tapering. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01493102 . Registered on 15 December 2011.

Performance of the quick Sequential (sepsis-related) Organ Failure Assessment score as a prognostic tool in infected patients outside the intensive care unit: a systematic review and meta-analysis.

BACKGROUND: The usefulness of the quick Sequential (Sepsis-related) Organ Failure Assessment (qSOFA) score in providing bedside criteria for early prediction of poor outcomes in patients with suspected infection remains controversial. We investigated the prognostic performance of a positive qSOFA score outside the intensive care unit (ICU) compared with positive systemic inflammatory response syndrome (SIRS) criteria. METHODS: A systematic literature search was performed using MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials. Data were pooled on the basis of sensitivity, specificity, and diagnostic OR. Overall test performance was summarized using a hierarchical summary ROC and the AUC. Meta-regression analysis was used to identify potential sources of bias. RESULTS: We identified 23 studies with a total of 146,551 patients. When predicting in-hospital mortality in our meta-analysis, we identified pooled sensitivities of 0.51 for a positive qSOFA score and 0.86 for positive SIRS criteria, as well as pooled specificities of 0.83 for a positive qSOFA score and 0.29 for positive SIRS criteria. Discrimination for in-hospital mortality had similar AUCs between the two tools (0.74 vs. 0.71; P = 0.816). Using meta-regression analysis, an overall mortality rate ≥ 10% and timing of qSOFA score measurement could be significant sources of heterogeneity. For predicting acute organ dysfunction, although the AUC for a positive qSOFA score was higher than that for positive SIRS criteria (0.87 vs. 0.76; P < 0.001), the pooled sensitivity of positive qSOFA score was very low (0.47). In addition, a positive qSOFA score tended to be inferior to positive SIRS criteria in predicting ICU admission (0.63 vs. 0.78; P = 0.121). CONCLUSIONS: A positive qSOFA score had high specificity outside the ICU in early detection of in-hospital mortality, acute organ dysfunction, and ICU admission, but low sensitivity may have limitations as a predictive tool for adverse outcomes. Because between-study heterogeneity was highly represented among the studies, our results should be interpreted with caution.

Proposed risk factors for infection with multidrug-resistant pathogens in hemodialysis patients hospitalized with pneumonia.

BACKGROUND: In patients with hemodialysis-associated pneumonia (HDAP), information on both microbiologic features and antimicrobial strategies is limited. The aim of this study is to investigate predictive factors of infection with multidrug-resistant (MDR) pathogens in HDAP patients. METHODS: This was a multicenter, retrospective, and observational study. Enrolled patients were classified into MDR or non-MDR pathogens groups according to culture results. We examined risk factors of infection with MDR pathogens and created a decision support tool using these risk factors. RESULTS: MDR pathogens were identified in 24 (22.8%) out of a total of 105 HDAP patients. The most common MDR pathogens were methicillin-resistant Staphylococcus aureus (10 patients, 9.5%) and the isolation rate of Pseudomonas aeruginosa was 6.6%. Logistic regression showed two variables were associated with the isolation of MDR pathogens: recent hospitalization (adjusted odds ratio [OR]: 2.951, 95% confidence interval [CI]: 1.022-8.518) and PSI (Pneumonia Severity Index) score (adjusted OR: 1.023, 95% CI: 1.005-1.041). The optimal cut-off value for PSI score using a receiver operating characteristic curve analysis was 147. According to the presence of 0, 1, or 2 of the identified risk factors, the prevalence of MDR pathogens was 7.6, 28.2 and 64.2%, respectively (p < 0.001 for trend). The area under the curve of the prediction tool was 0.764 (95% CI: 0.652-0.875). CONCLUSIONS: We demonstrated that recent hospitalization and PSI > 147 are risk factors of infection with MDR pathogens in HDAP patients. This simple proposed tool would facilitate more accurate identification of MDR pathogens in these patients.

Serum uric acid is positively associated with pulmonary function in Korean health screening examinees.

OBJECTIVES: To determine whether level of serum uric acid (SUA) is linked to pulmonary function in health screening examinees without overt medical conditions. METHODS: We performed a cross-sectional study on 69,928 Koreans that participated in an annual health check. RESULTS: Percent predicted forced vital capacity (FVC%) and forced expiratory volume in 1 s (FEV1%) were positively correlated with SUA in both genders (FVC%: r = .361; FEV1%: r = .314 in males and FVC%: r = .413; FEV1%: r = .382 in females, all p < .001). When the 2nd, 3rd and lowest FEV1% quartile were compared to the highest quartile group (the reference) by regression analysis, the adjusted ORs for hyperuricemia in males were 0.876 (95% CI, 0.809-0.949), 0.631 (0.574-0.695), and 0.311 (0.278-0.349), respectively. The adjusted ORs for hyperuricemia when the 2nd, 3rd and lowest FEV1% quartile were compared to the highest quartile in males were 0.791 (95% CI, 0.729-0.859), 0.565 (0.513-0.623), and 0.302 (0.270-0.337), respectively (p for trend <.001). Similarly, the adjusted OR of having hyperuricemia in females decreased significantly across FEV1% and FVC% quartile groups compared to the reference. CONCLUSIONS: Hyperuricemia may have a positive effect on pulmonary function in middle aged healthy population.

Risk factors for death during pulmonary tuberculosis treatment in Korea: a multicenter retrospective cohort study.

The data regarding risk factors for death during tuberculosis (TB) treatment are inconsistent, and few studies examined this issue in Korea. The purpose of this study was to evaluate baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea. A multicenter retrospective cohort study of 2,481 patients who received TB treatment at eight hospitals from January 2009 to December 2010 was performed. Successful treatment included cure (1,129, 45.5%) and treatment completion (1,204, 48.5%) in 2,333 patients (94.0%). Unsuccessful treatment included death (85, 3.4%) and treatment failure (63, 2.5%) occurred in 148 patients (6.0%). In multivariate analysis, male sex, anemia, dyspnea, chronic heart disease, malignancy, and intensive care unit (ICU) admission were significant risk factors for death during TB treatment. Therefore, male sex, anemia, dyspnea, chronic heart disease, malignancy, and ICU admission could be baseline prognostic factors for death during treatment of adult patients with pulmonary TB in Korea.

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.

Additional role of second washing specimen obtained during single bronchoscopy session in diagnosis of pulmonary tuberculosis.

BACKGROUND: Flexible bronchoscopy with bronchial washing is a useful procedure for diagnosis of pulmonary tuberculosis (TB), when a patient cannot produce sputum spontaneously or when sputum smears are negative. However, the benefit of gaining serial bronchial washing specimens for diagnosis of TB has not yet been studied. Therefore, we conducted a retrospective study to determine the diagnostic utility of additional bronchial washing specimens for the diagnosis of pulmonary TB in suspected patients. METHODS: A retrospective analysis was performed on 174 patients [sputum smear-negative, n = 95 (55%); lack of sputum specimen, n = 79 (45%)] who received flexible bronchoscopy with two bronchial washing specimens with microbiological confirmation of pulmonary TB in Samsung Medical Center, between January, 2010 and December, 2011. RESULTS: Pulmonary TB was diagnosed by first bronchial washing specimen in 141 patients (81%) out of 174 enrolled patients, and an additional bronchial washing specimen established diagnosis exclusively in 22 (13%) patients. Smear for acid-fast bacilli (AFB) was positive in 46 patients (26%) for the first bronchial washing specimen. Thirteen patients (7%) were positive only on smear of an additional bronchial washing specimen. Combined smear positivity of the first and second bronchial washing specimens was significantly higher compared to first bronchial washing specimen alone [Total cases: 59 (34%) vs. 46 (26%), p < 0.001; cases for smear negative sputum: 25 (26%) vs. 18 (19%), p = 0.016; cases for poor expectoration: 34 (43%) vs. 28 (35%), p = 0.031]. The diagnostic yield determined by culture was also significantly higher in combination of the first and second bronchial washing specimens compared to the first bronchial washing. [Total cases: 163 (94%) vs. 141 (81%), p < 0.001; cases for smear negative sputum: 86 (91%) vs. 73 (77%), p < 0.001; cases for poor expectoration: 77 (98%) vs. 68 (86%), p = 0.004]. CONCLUSIONS: Obtaining an additional bronchial washing specimen could be a beneficial and considerable option for diagnosis of TB in patients with smear-negative sputum or who cannot produce sputum samples.

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 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.

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.