Mitochondrial damage leading to oxidant stress may play an important role in the pathogenesis of airflow obstruction and emphysema. NLPR3 inflammasome can be activated by mitochondrial ROS (mtROS) and other stimuli. We examined the importance of mtROS and NLRP3 inflammasome and their interactions in multiple ozone-induced lung inflammation and emphysema. C57/BL6 mice were exposed to ozone (2.5 ppm, 3 h) or filtered air twice a week over 6 weeks. MitoTEMPO (20 mg/kg), an inhibitor of mtROS, and VX765 (100 mg/kg), an inhibitor of caspase-1 activity, were administered by intraperitoneal or intragastric injection respectively 1 h prior to each ozone exposure for 6 weeks. Ozone-exposed mice had increased bronchoalveolar lavage (BAL) total cells and levels of IL-1β, KC and IL-6, augmented lung tissue inflammation scores, enhanced oxidative stress with higher serum 8-OHdG concentrations, emphysema with greater mean linear intercept (Lm), airway remodeling with increased airway smooth muscle mass and airflow limitation as indicated by a reduction in the ratio of forced expiratory volume at 25 and 50 milliseconds to forced vital capacity (FEV25/FVC, FEV50/FVC). Both MitoTEMPO and VX765 reduced lung inflammation scores, cytokine levels, oxidative stress and increased mitochondrial fission proteins. VX765 also attenuated emphysema, airway remodeling and airflow limitation. MitoTEMPO inhibited the increased expression of mitochondrial complex II and IV and of NLPR3 while VX765 inhibited the expression and activity of NLRP3 and caspase-1 pathway in the lung. Both mtROS and NLRP3 inflammasome play a role in ozone-induced lung inflammation while only NLRP3 is involved in ozone-induced emphysema.

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Knowledge of predominant microbial patterns in community-acquired pneumonia (CAP) constitutes the basis for initial decisions about empirical antimicrobial treatment, so a prospective study was performed during 2003–2004 among CAP of adult Chinese urban populations. Qualified patients were enrolled and screened for bacterial, atypical, and viral pathogens by sputum and/or blood culturing, and by antibody seroconversion test. Antibiotic treatment and patient outcome were also assessed. Non-viral pathogens were found in 324/610 (53.1%) patients among whom M. pneumoniae was the most prevalent (126/610, 20.7%). Atypical pathogens were identified in 62/195 (31.8%) patients carrying bacterial pathogens. Respiratory viruses were identified in 35 (19%) of 184 randomly selected patients with adenovirus being the most common (16/184, 8.7%). The nonsusceptibility of S. pneumoniae to penicillin and azithromycin was 22.2% (Resistance (R): 3.2%, Intermediate (I): 19.0%) and 79.4% (R: 79.4%, I: 0%), respectively. Of patients (312) from whom causative pathogens were identified and antibiotic treatments were recorded, clinical cure rate with β-lactam antibiotics alone and with combination of a β-lactam plus a macrolide or with fluoroquinolones was 63.7% (79/124) and 67%(126/188), respectively. For patients having mixed M. pneumoniae and/or C. pneumoniae infections, a better cure rate was observed with regimens that are active against atypical pathogens (e.g. a β-lactam plus a macrolide, or a fluoroquinolone) than with β-lactam alone (75.8% vs. 42.9%, p = 0.045). In Chinese adult CAP patients, M. pneumoniae was the most prevalent with mixed infections containing atypical pathogens being frequently observed. With S. pneumoniae, the prevalence of macrolide resistance was high and penicillin resistance low compared with data reported in other regions.

Importance: Heart injury can be easily induced by viral infection such as adenovirus and enterovirus. However, whether coronavirus disease 2019 (COVID-19) causes heart injury and hereby impacts mortality has not yet been fully evaluated. Objective: To explore whether heart injury occurs in COVID-19 on admission and hereby aggravates mortality later. Design, Setting, and Participants: A single-center retrospective cohort study including 188 COVID-19 patients admitted from December 25, 2019 to January 27, 2020 in Wuhan Jinyintan Hospital, China; follow up was completed on February 11, 2020. Exposures: High levels of heart injury indicators on admission (hs-TNI; CK; CK-MB; LDH; α-HBDH). Main Outcomes and Measures: Mortality in hospital and days from admission to mortality (survival days). Results: Of 188 patients with COVID-19, the mean age was 51.9 years (standard deviation: 14.26; range: 21∼83 years) and 119 (63.3%) were male. Increased hs-TnI levels on admission tended to occur in older patients and patients with comorbidity (especially hypertension). High hs-TnI on admission (≥ 6.126 pg/mL), even within the clinical normal range (0∼28 pg/mL), already can be associated with higher mortality. High hs-TnI was associated with increased inflammatory levels (neutrophils, IL-6, CRP, and PCT) and decreased immune levels (lymphocytes, monocytes, and CD4 ⁺ and CD8 ⁺ T cells). CK was not associated with mortality. Increased CK-MB levels tended to occur in male patients and patients with current smoking. High CK-MB on admission was associated with higher mortality. High CK-MB was associated with increased inflammatory levels and decreased lymphocytes. Increased LDH and α-HBDH levels tended to occur in older patients and patients with hypertension. Both high LDH and α-HBDH on admission were associated with higher mortality. Both high LDH and α-HBDH were associated with increased inflammatory levels and decreased immune levels. hs-TNI level on admission was negatively correlated with survival days ( r = -0.42, 95% CI= -0.64∼-0.12, P=0.005). LDH level on admission was negatively correlated with survival days ( r = -0.35, 95% CI= -0.59∼-0.05, P=0.022). Conclusions and Relevance: Heart injury signs arise in COVID-19, especially in older patients, patients with hypertension and male patients with current smoking. COVID-19 virus might attack heart via inducing inflammatory storm. High levels of heart injury indicators on admission are associated with higher mortality and shorter survival days. COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, because COVID-19 is never just confined to respiratory injury. Key points: Question: Does coronavirus disease 2019 (COVID-19) cause heart injury and hereby impact mortality? Findings: In this retrospective cohort study including 188 patients with COVID-19, patients with high levels of high-sensitivity cardiac troponin I (hs-TNI) on admission had significantly higher mortality (50.0%) than patients with moderate or low levels of hs-TNI (10.0% or 9.1%). hs-TNI level on admission was significantly negatively correlated with survival days ( r = -0.42, 95% CI= -0.64∼-0.12, P=0.005). Meaning: COVID-19 patients with signs of heart injury on admission must be early identified and carefully managed by cardiologists, in order to maximally prevent or rescue heart injury-related mortality in COVID-19.