Hai-Wen Lu

Evaluation of PCR in Bronchoalveolar Lavage Fluid for Diagnosis of Pneumocystis jirovecii Pneumonia: A Bivariate Meta-Analysis and Systematic Review

Background As a promising tool, PCR in bronchoalveolar lavage fluid (BALF) has not been accepted as a diagnostic criterion for PJP. Objective We undertook a systematic review of published studies to evaluate the diagnostic accuracy of PCR assays in BALF for PJP. Methods Eligible studies from PubMed, Embase and Web of Science reporting PCR assays in BALF for diagnosing PJP were identified. A bivariate meta-analysis of the method’s sensitivity, specificity, and positive and negative likelihood ratios with a 95% confidence interval (CI) were analyzed. The post-test probability was performed to evaluate clinical usefulness. A summary receiver operating characteristics (SROC) curve was used to evaluate overall performance. Subgroup analyses were carried out to analysis the potential heterogeneity. Results Sixteen studies published between 1994 and 2012 were included. The summary sensitivity and specificity values (95% CI) of PCR in BALF for diagnosis of PJP were 98.3% (91.3%–99.7%) and 91.0% (82.7%–95.5%), respectively. The positive and negative likelihood ratios were 10.894 (5.569–21.309) and 0.018 (0.003–0.099), respectively. In a setting of 20% prevalence of PJP, the probability of PJP would be over 3-fold if the BALF-PCR test was positive, and the probability of PJP would be less than 0.5% if it was negative. The area under the SROC curve was 0.98 (0.97–0.99). Conclusions The method of PCR in BALF shows high sensitivity and good specificity for the diagnosis of PJP. However, clinical practice for the diagnosis of PJP should consider the consistent respiratory symptoms, radiographic changes and laboratory findings of the suspected patients.

Effects of long-term use of macrolides in patients with non-cystic fibrosis bronchiectasis: a meta-analysis of randomized controlled trials

BackgroundThe purpose of this study was to evaluate the clinical benefits and safety of the long-term use of macrolides in patients with non-cystic fibrosis (non-CF) bronchiectasis.MethodsEmbase, Pubmed, the Cochrane Library and Web of Science databases were searched from inception up to March 2014. The primary outcome was the improvement of exacerbations of bronchiectasis. Secondary endpoints included changes of microbiology, lung function, quality of life, sputum volume, adverse events and macrolide resistance.ResultsThe literature search yielded 139 studies, ten of which containing 601 patients were included in this meta-analysis. Macrolides showed a statistically-significant improvement in reducing acute exacerbations per patient during follow-up treatment (RR = 0.55, 95% CI: 0.47, 0.64, P < 0.001), increasing the number of patients free from exacerbations (OR = 2.81, 95% CI: 1.85, 4.26, P < 0.001), and prolonging time to a first exacerbation (HR = 0.38, 95% CI: 0.28, 0.53, P < 0.001). Macrolides maintenance treatment was superior to control with respect to attenuating FEV1 decline (p = 0.02), improving sputum volume (p = 0.009) and SGRQ total scores (p = 0.02), but showed a higher risk of adverse events, especially diarrhea (OR = 5.36; 95% CI: 2.06, 13.98, P = 0.0006). Eradication of pathogens was improved in the macrolide group (OR = 1.76, 95% CI: 0.91, 3.41, P = 0.09), while pathogen resistance caused by macrolides dramatically increased (OR = 16.83, 95% CI: 7.26, 38.99, P < 0.001). The new appearance of a microbiologic profile or participant withdrawal due to adverse events showed no significant differences between the two groups.ConclusionIn patients with non-CF bronchiectasis, macrolide maintenance treatment can effectively reduce frequency of exacerbations, attenuate lung function decline, decrease sputum volume, improve quality of life, but may be accompanied with increased adverse events (especially diarrhea) and pathogen resistance.

Asthma and bronchiectasis exacerbation

Bronchiectasis and asthma are common respiratory diseases worldwide. However, the influence of asthma on bronchiectasis remains unclear. The objective of this study is to analyse the effects of asthma on bronchiectasis exacerbation. Data from inpatients diagnosed with bronchiectasis with or without asthma at Shanghai Pulmonary Hospital (Shanghai, China) between January 2013 and December 2014 were retrospectively collected and analysed. 249 patients with only bronchiectasis and 214 patients with both bronchiectasis and asthma were included in the study. Follow-up records were used to evaluate the effect of asthma on bronchiectasis exacerbation. The variables found to be independently associated with bronchiectasis exacerbations were age (OR 1.07, 95% CI 1.03–1.11; p<0.001), duration of symptoms (OR 1.06, 95% CI 1.03–1.09; p<0.001), the presence of asthma (OR 2.6, 95% CI 1.15–5.88; p=0.021), forced expiratory volume in 1 s <50% predicted (OR 4.03, 95% CI 1.75–9.26; p=0.001), isolation of Pseudomonas aeruginosa in sputum (OR 2.41, 95% CI 1.00–5.79; p=0.05) and lung lesion extension to more than two lobes (OR 2.73, 95% CI 1.16–6.45; p=0.022). The existence of asthma was associated with an independent increase in risk of bronchiectasis exacerbation. The existence of asthma was associated with an independent increase in risk of bronchiectasis exacerbation http://ow.ly/XFSWS

The existence of bronchiectasis predicts worse prognosis in patients with COPD

Bronchiectasis is prevalent in patients with COPD. The objective of this study was to assess the clinical characteristics and prognostic value of bronchiectasis in patients with COPD in China. Data from patients diagnosed with COPD at the Shanghai Pulmonary Hospital between January 2009 and December 2013 were retrospectively collected and analyzed. SPSS statistical software was used to analyze the data. Data from 896 patients with COPD were analyzed. Bronchiectasis was present in 311 patients. The isolation of pseudomonas aeruginosa (PA) from sputum was the variable most significantly associated with the presence of bronchiectasis in patients with COPD (hazard ratio (HR), 2.93; 95% confidence interval (CI), 1.35–6.37; P = 0.007). During follow-up (median of 21 months; interquartile range: 10-39 months), there were 75 deaths, of which 39 were in the bronchiectasis group. The presence of bronchiectasis (HR, 1.77; 95% CI, 1.02–3.08; P = 0.043) was associated with an increase in all-cause mortality in patients with COPD. These results suggest that bronchiectasis in patients with COPD was associated with the isolation of PA from the sputum. Bronchiectasis was an independent risk factor for all-cause mortality in patients with COPD.

Efficacy and safety of long-term inhaled antibiotic for patients with noncystic fibrosis bronchiectasis: a meta-analysis.

The evidence supported the use of nebulized antibiotics in non‐cystic fibrosis (non‐CF) bronchiectasis is indefinite. A meta‐analysis was performed to determine the efficacy and safety of long‐term inhaled antibiotics for patients with non‐CF bronchiectasis.

Efficiency and safety of surgical intervention to patients with Non-Cystic Fibrosis bronchiectasis: a meta-analysis

No quantitative systematic review was found to report the efficiency and safety of surgical resection in the management of non-cystic fibrosis (non-CF) bronchiectasis. We therefore conducted a meta-analysis to assess the effects of operative intervention to patients with non-CF bronchiectasis. PubMed, the Cochrane library and Web of Science databases were searched up to July 8th, 2015. The pooled mortality from 34 studies recruiting 4788 patients was 1.5% (95% CI, 0.9–2.5%). The pooled morbidity from 33 studies consisting of 4583 patients was 16.7% (95% CI, 14.8–18.6%). The pooled proportion of patients from 35 studies, consisting of 4614 patients who were free of symptoms was 66.5% (95% CI, 61.3–71.7%) after surgery. The summary proportion of patients from 35 articles including 4279 participants who were improved was 27.5% (95% CI, 22.5–32.5%), and 9.1% (95% CI, 7.3–11.5%) showed no clinical improvement. In conclusion, our analysis indicated that lung resection in the management of non-CF bronchiectasis is associated with significant improvements in symptoms, low risk of mortality and acceptable morbidity.

Pulmonary Vein Stenosis Complicating Radiofrequency Catheter Ablation: Five Case Reports and Literature Review.

AbstractThe aim of this study is to characterize the clinical manifestations and features of pulmonary vein stenosis (PVS) by retrospectively analyzing clinical data of patients in addition to reviewing the literature simultaneously to improve the understanding of PVS complicating radiofrequency catheter ablation and to provide evidence for early diagnosis and timely treatment.Clinical, imaging, and follow-up data of 5 patients with PVS-complicating radiofrequency catheter ablation were retrospectively analyzed between January 2012 and December 2014 in Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China. Relevant studies previously reported were also reviewed.Three out of 5 patients received pulmonary angiography. The initial symptoms were not specific, presenting chest pain in 3 cases, hemoptysis in 2 cases. The average duration between radiofrequency ablation to the onset of symptoms was 5.8 months. The chest image results were consolidation and pleural effusion mainly. Veins distributed in the left lungs were mostly influenced in 4 patients, and the inferior veins in 3 patients. Cardiac ultrasound examinations showed pulmonary arterial hypertension in 2 patients. Two patients received selective bronchial artery embolization after bronchial artery radiography because of hemoptysis. One patient underwent video-assisted thoracoscopic biopsy because of the suspicion of tumor.PVS is a condition mostly undetected because of its silent manifestations and inconsistent follow-up. The accurate clinical diagnosis is very difficult. A careful review of medical history and follow-up observation may be useful for all the patients who received the radiofrequency catheter ablation to recognize PVS in the early stage.

Distribution of Major Pathogens from Sputum and Bronchoalveolar Lavage Fluid in Patients with Noncystic Fibrosis Bronchiectasis: A Systematic Review

Objective: Noncystic fibrosis (non-CF) bronchiectasis remains as a common health problem in Asia. Pathogens’ distribution in airways of patients with non-CF bronchiectasis is important for doctors to make right decision. Data Sources: We performed this systematic review on the English language literatures from 1966 to July 2014, using various search terms included “pathogens” or “bacteria” or “microbiology” and “bronchiectasis” or “non-cystic fibrosis bronchiectasis” or “non-CF bronchiectasis” or “NCFB.” Study Selection: We included studies of patients with the confirmed non-CF bronchiectasis for which culture methods were required to sputum or bronchoalveolar lavage fluid (BALF). Weighted mean isolation rates for Haemophilus influenzae, Pseudomonas aeruginosa, Streptococcus pneumoniae, Stapylococcus aureus, Moxarella catarrhails were compared according to different methodology. Results: The total mean bacterial culture positive rates were 63%. For studies using sputum samples, the mean positive culture rates were 74%. For studies using BALF alone or BALF and sputum, it was 48%. The distributions of main bacterial strains were 29% for H. influenzae, 28% for P. aeruginosa, 11% for S. pneumoniae, 12% for S. aureus, and 8% for M. catarrhails with methodology of sputum. Meanwhile, the bacterial distributions were 37% for H. influenzae, 8% for P. aeruginosa, 14% for S. pneumoniae, 5% for S. aureus, and 10% for M. catarrhails with methodology of BALF alone or BALF and sputum. Analysis of the effect of different methodology on the isolation rates revealed some statistically significant differences. Conclusions: H. influenzae accounted for the highest percentage in different methodology. Our results suggested that the total positive culture rates and the proportion of P. aeruginosa from sputum and BALF specimens had significant differences, which can be used in further appropriate recommendations for the treatment of non-CF bronchiectasis.

CARD9S12N facilitates the production of IL-5 by alveolar macrophages for the induction of type 2 immune responses

The adaptor CARD9 functions downstream of C-type lectin receptors (CLRs) for the sensing of microbial infection, which leads to responses by the TH1 and TH17 subsets of helper T cells. The single-nucleotide polymorphism rs4077515 at CARD9 in the human genome, which results in the substitution S12N (CARD9S12N), is associated with several autoimmune diseases. However, the function of CARD9S12N has remained unknown. Here we generated CARD9S12N knock-in mice and found that CARD9S12N facilitated the induction of type 2 immune responses after engagement of CLRs. Mechanistically, CARD9S12N mediated CLR-induced activation of the non-canonical transcription factor NF-κB subunit RelB, which initiated production of the cytokine IL-5 in alveolar macrophages for the recruitment of eosinophils to drive TH2 cell–mediated allergic responses. We identified the homozygous CARD9 mutation encoding S12N in patients with allergic bronchopulmonary aspergillosis and revealed activation of RelB and production of IL-5 in peripheral blood mononuclear cells from these patients. Our study provides genetic and functional evidence demonstrating that CARD9S12N can turn alveolar macrophages into IL-5-producing cells and facilitates TH2 cell–mediated pathologic responses.CARD9 serves as an adaptor for C-type lectin receptor signaling. Xin Lin and colleagues show that CARD9 inhibits RelB-mediated IL-5 expression. The CARD9S12N mutant, prevalent in humans, cannot interact with RelB and promotes enhanced allergic responses to fungal pathogens.

Asthma–COPD overlap syndrome showed more exacerbations however lower mortality than COPD

Background Asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) is a new determinate syndrome whose exact characteristics remain unclear. Aim The objective of this study is to find more difference between ACOS and COPD. Design A retrospective study of ACOS and COPD in Chinese. Methods Data from 65 patients with ACOS and 65 patients with COPD were retrospectively collected and analyzed. The basis of this study was to compare the two groups while ruling out differences in age, sex and smoking history. Results Patients with ACOS tended to have earlier ages of onset, longer durations of symptoms, better nutritional status, higher single-breath diffusing capacity of carbon monoxide (DLCO) %predicted and airway resistance %predicted, more exacerbations in the preceding 12 months and shorter lengths of hospitalization. DLCO %predicted, airway resistance %predicted, and length of hospitalization were the variables most significantly associated with the presence of ACOS in patients with COPD. ROC correlating airway resistance %predicted value and current ACOS showed an optimal cutoff of airway resistance %predicted of over 296.6. During follow-up (median: 45 months; interquartile range: 6-82 months), 16 patient deaths were recorded (3 patients with ACOS). The risk remained significantly higher in patients with COPD alone than in patients with ACOS (HR 3.932; 95% CI 1.083-19.755; P  = 0.046). Conclusion Patients with ACOS were more likely to have better prognoses and lower mortality than those with COPD alone, though with greater exacerbation frequency.