Respiratory Aspergillus Colonization Was Associated With Relapse of Acute Exacerbation in Patients With Chronic Obstructive Pulmonary Disease: Analysis of Data From A Retrospective Cohort Study.

Background: Patients with chronic obstructive pulmonary disease (COPD) are more susceptible to Aspergillus colonization or infection. Several studies have demonstrated that invasive pulmonary Aspergillosis (IPA) and Aspergillus hypersensitivity (AH) have a detrimental effect on COPD. However, it remains to be clarified whether Aspergillus colonization is associated with acute exacerbation of COPD (AECOPD). This study aimed to explore the impact of Aspergillus colonization in the lower respiratory tract on AECOPD. Method: Patients with Aspergillus colonization were identified from a retrospective cohort of hospitalized AECOPD from 2011 to 2016 in eight centers in Shanghai, China. The demographic information, conditions of the stable stage, clinical characteristics during hospitalization, and 1-year follow-up information after discharge were collected and compared to participants without fungi colonization. Result: Twenty-six hospitalized AECOPD patients with Aspergillus colonization and 72 controls were included in the final analysis after excluding patients with other fungi isolation and matching. The rates of recurrence of acute exacerbation within 90 days and 180 days after discharge in the patients with Aspergillus colonization were both significantly higher than that in the fungi negative patients (90 days: 19.2 vs. 4.2%, p = 0.029; 180 days: 23.1 vs. 4.2%, p = 0.010), and the all-cause mortality within 1 year was also higher (11.5 vs. 0.0%, p = 0.017). Multivariate logistic regression analysis showed that Aspergillus colonization was an independent risk factor for the recurrence of acute exacerbation within 90 days and 180 days (90 days: OR = 8.661, 95% CI: 1.496-50.159, p = 0.016; 180 days: OR =10.723, 95% CI: 1.936-59.394, p = 0.007). Conclusion: Aspergillus colonization may predict poor prognosis of AECOPD while leading to an increased risk of recurrent AECOPD in a short period.

Candida in Lower Respiratory Tract Increases the Frequency of Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Retrospective Case-Control Study.

Objective: To explore impact of Candida on the acute exacerbation of chronic obstructive pulmonary disease (AECOPD) outcome. Methods: A retrospective, multi-center, case-control study was performed. Patients hospitalized for AECOPD in 25 centers during Jan 2011-Dec 2016 were enrolled. Data were collected, including demographic information, conditions during the stable phase of COPD, clinical characteristics of AECOPD, and follow-up information within 1 year after discharge. Univariate analysis and binary logistic regression were applied, and p < 0.05 was regarded as significant. Results: Totally 1,103 patients were analyzed, with 644 lower respiratory airway (LTR) Candida positive cases and 459 Candida negative controls. Long-term prognosis was significantly different between Candida positive and negative group, including the recurrent AECOPD within 180 days (75.5 vs. 6.6%, p < 0.001) and mortality within 1 year (6.9 vs. 0.4%, p < 0.001). Univariate logistic analysis showed that LTR Candida isolation was related to higher recurrence rate of AECOPD within 180 days and mortality within 1 year. Binary logistic regression analysis demonstrated that LTR Candida isolation was independently associated with recurrence of AECOPD within 180 days. Conclusions: LTR Candida isolation was associated with worse long-term prognosis of AECOPD and independently related to higher risks of recurrent AECOPD within 180 days.

Effects of thrombolytic drugs and a selective endothelin-1 receptor antagonist on acute pulmonary thromboembolism in dogs.

BACKGROUND: It has been shown that neurohumoral factors other than mechanical obstruction are involved in the pathophysiology of acute pulmonary thromboembolism (APTE). The aim of this study was to investigate the effects of thrombolytic drugs, a selective endothelin-1 receptor (ET-1R) antagonist alone or their combination on APTE in a canine model. METHODS: Twenty dogs were randomly assigned to five groups: sham, model, urokinase (UK), BQ123, and combination (UK plus BQ123). The dogs in the sham group underwent sham surgery. APTE was induced in the other four groups by intravenous injection of autologous blood clots. Dogs in the UK, BQ123 and combination groups received UK, BQ123 (a selective ET-1R antagonist), or UK plus BQ123, respectively. The dogs in the model group were given saline. Mean pulmonary artery pressure (mPAP), serum concentrations of ET-1, thromboxane (TXB2), and tumor necrosis factor (TNF)-alpha were determined at different time points following the induction of APTE. RESULTS: UK and BQ123 alone markedly decreased mPAP in APTE. By comparison, the reduction was more significant in the combination group. Compared with the sham group ((-0.90 +/- 0.61) mmHg), mPAP increased by (7.44 +/- 1.04), (3.42 +/- 1.12) and (1.14 +/- 0.55) mmHg in the model group, UK alone and BQ123 alone groups, respectively, and decreased by (2.24 +/- 0.67) mmHg in the combination group (P < 0.01). Serum ET-1 concentrations in the BQ123 and combination groups were (52.95 +/- 8.53) and (74.42 +/- 10.27) pg/ml, respectively, and were significantly lower than those in the model and UK groups ((84.56 +/- 7.44) and (97.66 +/- 8.31) pg/ml respectively; P < 0.01). Serum TNF-alpha concentrations were significantly lower in the BQ123 group than in the model, UK and combination groups (P < 0.05). CONCLUSIONS: Our results indicate that the selective ET-1R antagonist BQ123 not only reduces the increase of mPAP and serum ET-1 level, but also inhibits the production of TNF-alpha, and attenuates the local inflammatory response induced by APTE. Selective ET-1R antagonists may be beneficial to the treatment of APTE, particularly when used in combination with a thrombolytic agent.