An increased risk of pulmonary hypertension in patients with combined pulmonary fibrosis and emphysema: a meta-analysis.

BACKGROUND AND AIM: Pulmonary hypertension (PH) is a common complication of combined pulmonary fibrosis and emphysema (CPFE). Whether the incidence of PH is increased in CPFE compared with pure pulmonary fibrosis or emphysema remains unclear. This meta-analysis aimed to evaluate the risk of PH in patients with CPFE compared to those with IPF or COPD/emphysema. METHODS: We searched the PubMed, Embase, Cochrane Library, and CNKI databases for relevant studies focusing on the incidence of PH in patients with CPFE and IPF or emphysema. Pooled odds ratios (ORs) and standard mean differences (SMD) with 95% confidence intervals (95% CIs) were used to evaluate the differences in the clinical characteristics presence and severity of PH between patients with CPFE, IPF, or emphysema. The survival impact of PH in patients with CPFE was assessed using hazard ratios (HRs). RESULTS: A total of 13 eligible studies were included in the meta-analysis, involving 560, 720, and 316 patients with CPFE, IPF, and emphysema, respectively. Patients with CPFE had an increased PH risk with a higher frequency of pulmonary hypertension and higher estimated systolic pulmonary artery pressure (esPAP), compared with those with IPF (OR: 2.66; 95% CI: 1.55-4.57; P < 0.01; SMD: 0.86; 95% CI: 0.52-1.19; P < 0.01) or emphysema (OR: 3.19; 95% CI: 1.42-7.14; P < 0.01; SMD: 0.73; 95% CI: 0.50-0.96; P < 0.01). In addition, the patients with CPFE combined with PH had a poor prognosis than patients with CPFE without PH (HR: 6.16; 95% CI: 2.53-15.03; P < 0.01). CONCLUSIONS: Our meta-analysis showed that patients with CPFE were associated with a significantly higher risk of PH compared with those with IPF or emphysema alone. The presence of PH was a poor predictor of mortality.

Neutrophil activation and NETosis are the predominant drivers of airway inflammation in an OVA/CFA/LPS induced murine model.

BACKGROUND: Asthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment. METHODS: We established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot. RESULTS: We found that the ovalbumin (OVA)/complete Freund's adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness. CONCLUSION: Our findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.