Pulmonary Morphological Changes Research Articles

To Evaluate The Histomorphological Changes Of Postmortem Transthoracic Needle Biopsy/Autopsy Lung In COVID-19 Patients

Objective: To study the histomorphological changes in postmortem needle biopsy/autopsy lung in COVID-19 Patients. Study Design: This was an observational study done at Shri Atal Bihari Vajpayee Medical College & Research Institute, Bengaluru, and Karnataka from March 2021 to May 2021. Methodology: A total of 30 patients who died of Covid-19 were included and all of them were diagnosed to be Covid -19 positive by RT-PCR testing. Post-mortem transthoracic needle biopsy was done to obtain lung tissue by using B-Bard biopsy gun in midaxillary approach. The biopsy samples were grossed and processed after fixing for 48hrs. The slides obtained were stained by routine hematoxylin and eosin stain, studied for morphology of the lung tissue and findings were recorded. Results: We obtained consent for post-mortem transthoracic needle biopsy/autopsy of lung in 30 deceased cases. All these cases were positive for SARS –COV2 on RT-PCR. The age of the cases was ranging from 26-72 years and median age is 53years, males (63.3%) were affected more than females (36.7%). Most deceased had comorbidities, among them diabetes mellitus (26.6%) and hypertension (26.6%) were most common. Lung biopsy samples were taken from 30 deceased patients. Histomorphological feature of diffuse alveolar damage was seen in 90% (27 out of 30) cases. Other findings noted on microscopy were chronic interstitial inflammation in 6.7% cases, pulmonary edema (3.33%), intra alveolar haemorrhage (3.33%) and viral cytopathic changes (3.33%). Conclusion: This study highlighted the pulmonary morphological changes which are most prominent in COVID-19 infections, but it was a difficult to ascertain that the findings are related to viral infection or due to associated coomorbidities

NF-κB affected the serum levels of TNF-α and IL-1β via activation of the MAPK/NF-κB signaling pathway in rat model of acute pulmonary microthromboembolism.

Pulmonary thromboembolism caused by thrombi blocking major pulmonary artery and its branches, is a frequently encountered phenomenon and an important cause of high morbidity and mortality in lung diseases and may develop into persistent pulmonary hypertension (PH). Nuclear factor-κB (NF-κB) signaling pathway had been reported participated in the formation and development of PH by promoting inflammatory response. The aim of this study was to investigate the effects of NF-κB activation on the serum levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) in acute pulmonary microthromboembolism (APMTE) rats. Rats were randomized into five groups. APMTE group received jugular vein injection of autologous thrombus, while control group rats received normal saline injection. Pulmonary hemodynamic parameters were measured through ECHO-guided transthoracic puncture. Pulmonary vascular morphological changes were analyzed by HE. The expression changes of NF-κB and serum TNF-α、IL-1β levels were detected by enzyme-linked immunosorbent assay. Protein expression of the MAPK/NF-κB signaling pathway including p-IκBα, p-p38 MAPK, p-NF-κB p65, IκBα, p38 MAPK, and NF-κB p65 was determined using western blot analysis. Compared with control group, the expression of NF-κB in lung tissue and the levels of serum TNF-α and IL-1β rats were higher, a significant reduction in IκBα and elevation in the phosphorylation of IκBα, p38 MAPK, and NF-κB p65 were found in APMTE group rats. And UK administration reversed the APMTE-induced increase in TNF-α, IL-1β, p-IκBα, p-MAPK, and p-NF-κB protein. Furthermore, the levels of NF-κB, TNF-α, and IL-1β were positively correlated with mean pulmonary artery. And the levels of TNF-α and IL-1β were positively correlated with NF-κB. These findings suggest that the activation of MAPK/NF-κB pathway as a critical driver of increasing TNF-α and IL-1β level in APMTE rats and UK exerted protective effects against APMTE-induced PH may be related to the downregulation of the MAPK/NF-κB signaling pathway.

Dynamic evaluation of acute lung injury using hyperpolarized 129 Xe magnetic resonance.

Prognosticating acute lung injury (ALI) is challenging, in part because of a lack of sensitive biomarkers. Hyperpolarized gas magnetic resonance (MR) has unique advantages in pulmonary function measurement and can provide promising biomarkers for the assessment of lung injuries. Herein, we employ hyperpolarized 129 Xe MRI and generate a number of imaging biomarkers to detect the pulmonary physiological and morphological changes during the progression of ALI in an animal model. We find the measured ratio of 129 Xe in red blood cells to interstitial tissue/plasma (RBC/TP) is significantly lower in the ALI group on the second (0.32 ± 0.03, p = 0.004), seventh (0.23 ± 0.03, p < 0.001), and 14th (0.29 ± 0.04, p = 0.001) day after lipopolysaccharide treatment compared with that in the control group (0.41 ± 0.04). In addition, significant differences are also observed for RBC/TP measurements between the second and seventh day (p = 0.001) and between the seventh and 14th day (p = 0.018) in the ALI group after treatment. Besides RBC/TP, significant differences are also observed in the measured exchange time constant (T) on the second (p = 0.038) and seventh day (p = 0.009) and in the measured apparent diffusion coefficient (ADC) and alveolar surface-to-volume ratio (SVR) on the 14th day (ADC: p = 0.009 and SVR: p = 0.019) after treatment in the ALI group compared with that in the control group. These findings indicate that the parameters measured with 129 Xe MR can detect the dynamic changes in pulmonary structure and function in an ALI animal model.

Correlation between serum GDF-15 level and pulmonary vascular morphological changes and prognosis in patients with pulmonary arterial hypertension.

To investigate how serum GDF-15 concentration affects pulmonary artery hemodynamics and pulmonary vascular morphological changes in patients with pulmonary arterial hypertension. A total of 45 patients admitted to our hospital from December 2017 to December 2019, were selected for the study. Pulmonary vascular hemodynamics and pulmonary vascular morphology were detected by RHC and IVUS. Serum GDF-15 levels were detected by enzyme-linked immunosorbent assay (ELISA). Based on the concentration of GDF-15, the patients were divided into two groups-the normal GDF-15 group (GDF-15 <1,200 pg/ml, 12 cases) and the elevated GDF-15 group (GDF-15 ≥1,200 pg/ml, 33 cases). A statistical analysis was performed to compare the effects of normal blood GDF-15 levels and high serum GDF-15 levels on hemodynamics and pulmonary vascular morphology in each group of patients. The average levels of RVP, sPAP, dPAP, mPAP, and PVR in patients with elevated GDF-15 levels were higher than those in patients with normal GDF-15 levels. The difference between the two groups was statistically significant (P < 0.05). The average levels of Vd, elastic modulus, stiffness index β, lesion length, and PAV in the normal GDF-15 group were lower than those in the elevated GDF-15 group. The average levels of compliance, distensibility, and minimum l umen area were higher than those in the elevated GDF-15 group. The difference between the two groups was statistically significant (P < 0.05). The survival analysis results showed that the 1-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 100% and 87.9%, respectively, and that the 3-year survival rate of patients with normal GDF-15 levels and elevated GDF-15 levels was 91.7% and 78.8%, respectively. The survival rates of the two groups were compared by the Kaplan Meier method, and the difference was not statistically significant (P > 0.05). Patients with pulmonary arterial hypertension with elevated GDF-15 levels have higher pulmonary arterial pressure, higher pulmonary vascular resistance, and more serious pulmonary vascular lesions, which are potentially more harmful. There was no statistically significant difference in survival rates among patients with different serum GDF-15 levels.

Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism

To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH). A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue. The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05). Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.

Effects of panax notoginseng saponins on pulmonary vascular remodeling in rats with pulmonary hypertension and its mechanisms

Objective: To investigate the effects of panax notoginseng saponins (PNS) on pulmonary vascular remodeling and SIRT1/FOXO3a/p27 pathway in pulmonary arterial hypertension (PAH) rats. Methods: Male SD rats weighing 200~250g were randomly divided into control group, monocrotaline group (MCT) and monocrotaline + panax notoginseng saponins group (MCT+PNS), with 10 rats in each group. The rats in control group were injected intraperitoneally with normal saline 3 ml/kg on the first day, then injected intraperitoneally with normal saline 2.5 ml/kg every day. The rats in MCT group were injected intraperitoneally with MCT 60 mg/kg on the first day, followed by daily injection of normal saline 2.5 ml/kg. In MCT+PNS group, 60 mg/kg MCT was injected intraperitoneally on the first day, and 50 mg/kg PNS was injected intraperitoneally every day. The above models were fed conventionally for 4 weeks. After the modeling was completed, the mean pulmonary artery pressure (mPAP) and right ventricular systolic pressure (RVSP) of rats in each group were detected by right heart catheter method, weighed and calculated right ventricular hypertrophy index (RVHI), and the pulmonary vascular structure and morphological changes were observed by HE and Masson staining. The protein and gene expressions of SIRT1, FOXO3a, p27, PCNA and Caspase-3 were detected by qPCR and Western blot. Results: Compared with control group, mPAP, RVSP and RVHI in MCT group were increased significantly (P＜0.01), pulmonary vessels were thickened significantly and collagen fibers were increased, protein and gene expressions of SIRT1, FOXO3a, p27 and Caspase-3 were decreased (P＜0.05 or P＜0.01). The protein and gene expressions of PCNA were increased (P＜0.05). Compared with MCT group, the levels of mPAP, RVSP and RVHI in MCT+PNS group were decreased significantly (P＜0.05 or P＜0.01), pulmonary vascular thickening was alleviated and collagen fibers were reduced. The protein and gene expressions of SIRT1, FOXO3a, p27 and Caspase-3 were increased (P＜0.05 or P＜0.01), while the protein and gene expressions of PCNA were decreased (P＜0.05 or P＜0.01). Conclusion: Panax notoginseng saponins can relieve pulmonary vascular remodeling in rats with pulmonary hypertension by activating SIRT1/FOXO3a/p27 pathway.

Wnt5a regulates autophagy in Bacille Calmette-Guérin (BCG)-Infected pulmonary epithelial cells

Autophagy functions as a critical process that can suppress the proliferation of Mycobacterium tuberculosis (Mtb) within infected host cells. Wnt5a is a secreted protein that plays a range of physiological functions, activating several signaling pathways and thereby controlling cellular responses to particular stimuli. The importance of Wnt5a as a regulator of protection against Mtb infection, however, has yet to be fully characterized. Here, changes in murine pulmonary epithelial-like TC-1 cell morphology, autophagy, the Wnt/Ca2+ signaling pathway, and the mTOR autophagy pathway were analyzed following infection with the Mtb model pathogen Bacille Calmette-Guerin (BCG) in order to understand the regulatory role of Wnt5a in this context. These experiments revealed that Wnt5a was upregulated and autophagy was enhanced in TC-1 cells infected with BCG, and Wnt5a overexpression was found to drive BCG-induced autophagy in these cells upon infection, whereas the inhibition or knockdown of Wnt5a yielded the opposite effect. At the mechanistic level, Wnt5a was found to mediate non-canonical Wnt/Ca2+ signaling and thereby inhibit mTOR-dependent pathway activation, promoting autophagic induction within BCG-infected TC-1 cells. These data offer new insight regarding how Wnt5a influences Mtb-induced autophagy within pulmonary epithelial cells, providing a foundation for further research exploring the immunological control of this infection through the modulation of autophagy.

Srolo Bzhtang reduces inflammation and vascular remodeling via suppression of the MAPK/NF-κB signaling pathway in rats with pulmonary arterial hypertension

Ethnopharmacological relevanceSrolo Bzhtang (SBT), which consists of Solms-laubachia eurycarpa, Bergenia purpurascens, Glycyrrhiza uralensis, and lac secreted by Laccifer lacca Kerr (Lacciferidae Cockerell), is a well-known traditional Tibetan medicinal formula and was documented to cure “lung-heat” syndrome by eliminating “chiba” in the ancient Tibetan medical work Four Medical Tantras (Rgyud bzhi). Clinically, it is a therapy for pulmonary inflammatory disorders, such as pneumonia, chronic bronchitis, and chronic obstructive pulmonary disease. However, whether and how SBT participates in pulmonary arterial hypertension (PAH) is still unclear. Aim of the studyWe aimed to determine the role of SBT in attenuating pulmonary arterial pressure and vascular remodeling caused by monocrotaline (MCT) and hypoxia. To elucidate the potential mechanism underlying SBT-mediated PAH, we investigated the changes in inflammatory cytokines and mitogen-activated protein kinase (MAPK)/nuclear factor-kappa B (NF-κB) signaling pathway. Materials and methodsMCT- and hypoxia-induced PAH rat models were used. After administering SBT for four weeks, the rats were tested for hemodynamic indicators, hematological changes, pulmonary arterial morphological changes, and the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in serum and lung tissues. Protein expression of the MAPK/NF-κB signaling pathway was determined using western blotting. ResultsSBT reduced pulmonary arterial pressure, vascular remodeling, and the levels of inflammatory cytokines induced by MCT and hypoxia in rats. Furthermore, SBT significantly suppressed the MAPK/NF-κB signaling pathway. ConclusionsTo our knowledge, this is the first study to demonstrate that SBT alleviates MCT- and hypoxia-induced PAH in rats, which is related to its anti-inflammatory actions involving inhibition of the MAPK/NF-κB signaling pathway.

Langerhans cell histiocytosis with lung and skin involvement

Langergans cell histiocytosis (LCH) is a rare orphan pa-thology. Even rarer the clinicians see histiocytic lesions of the lungs and skin, the share of cases varies from 20–40% in case of multisystem LCH. Two clinical cases of LCH with lesions of the lungs, skin, pituitary gland and bones which differ in the manifestation and progression speed of the disease, are presented. The most characteristic clinical, radiological and functional features of pulmonary LCH and morphological changes are reviewed in detail. The clinical manifestations of skin histiocytosis are nonspeci-fic, making it difficult to diagnose LCH. Currently, the fre-quency of this pathology is on the grow, which increases the responsibility for its timely diagnosis, based on clear clinical and morphological comparisons. For proper dia-gnosis and timely treatment, a biopsy of the pathological focus is necessary, followed by histological and immu-nohistochemical examination with antibodies to protein S100, CD1a, CD68, CD207 (langerin)

The difference in postoperative pulmonary functional change between upper and lower thoracoscopic lobectomy

OBJECTIVESThrough 3-dimensional lung volumetric and morphological analyses, we aimed to evaluate the difference in postoperative functional changes between upper and lower thoracoscopic lobectomy.METHODSA total of 145 lung cancer patients who underwent thoracoscopic upper lobectomy (UL) were matched with 145 patients with lung cancer who underwent thoracoscopic lower lobectomy (LL) between April 2012 and December 2018, based on their sex, age, smoking history, operation side, and pulmonary function. Spirometry and computed tomography were performed before and 6 months after the operation. In addition, the postoperative pulmonary function, volume and morphological changes between the 2 groups were compared.RESULTSThe rate of postoperative decreased and the ratio of actual to predicted postoperative forced expiratory volume in 1 s were significantly higher after LL than after UL (P < 0.001 for both). The tendency above was similar irrespective of the resected side. The postoperative actual volumes of the ipsilateral residual lobe and contralateral lung were larger than the preoperatively measured volumes in each side lobectomy. Moreover, the increased change was particularly remarkable in the middle lobe after right LL. The change in the D-value, representing the structural complexity of the lung, was better maintained in the left lung after LL than after UL (P = 0.042).CONCLUSIONSPulmonary function after thoracoscopic LL was superior to that after UL because the upward displacement and the pulmonary reserves of the remaining lobe appeared more robust after LL.

Indirect lung injury predictive model in experimental trauma

Background: Trauma remains a medical-social problem, still having high lethality rate. Indirect lung injury (ILI) occurs in trauma due to systemic neutrophils activation and proteases release into primarily intact tissues. There are no data in the literature regarding ILI predictive models in trauma. Material and methods: In the experimental study (19 traumatized male rabbits), the proteases, antiproteases and the pulmonary morphological changes, assessed according to the SAMCRS score (Semiquantitative Reflected Qualitative Changes Assessment Scale) were followed. There were used two statistical instruments – correlational analysis and multivariate linear regression. Results: Initially, a correlational analysis between the values of the SAMCRS score and the proteases/ anti proteases was performed. The null hypothesis was rejected (F = 7.017, p = .002). The correlation coefficient of the predicted results and the real values of SAMCRSlungs was .854, the determination coefficient being .626. The final model included the following parameters: constant (B = 9.427; 95% CI 7.341, 11.513; p &lt;.001); α2-macroglobulin0 (B = -4.053; 95% Cl -6.350, -1.757; p = .002); AEAMP0 (B = .002; 95% CI .000, .004; p = .075); AEAMP24 (B = -. 006; 95% CI -.010, -.002; p = .003); AECG2 (B = .081; 95% CI .040, .122; p = .001); AEE0 (B = -. 026; 95% CI -.040, -.011; p = .002). Conclusions: In this research, a predictive model for indirect lung injury in experimental trauma was developed, the predictors being some elements of the proteases/antiproteases system. This, in turn, allows the hypotheses emission regarding the pathophysiology, prophylaxis and treatment of ILI.

Ninjin'yoeito Ameliorates Skeletal Muscle Complications in COPD Model Mice by Upregulating Peroxisome Proliferator-Activated Receptor γ Coactivator-1α Expression.

PurposeSarcopenia, the loss of skeletal muscle mass and strength, is a common systemic consequence of chronic obstructive pulmonary disease (COPD) and is correlated with higher mortality. Ninjin’yoeito (NYT) is a Japanese herbal medicine used to treat athrepsia and anorexia and is reported to ameliorate weight loss and muscular dysfunction. Recent studies have shown that its crude components upregulate the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-related pathway, which is involved in skeletal muscle functions. Here, we examined whether NYT improves skeletal muscle complications by upregulating PGC-1α in COPD model mice.Materials and MethodsMice were divided into four groups: control, NYT, smoking, and smoking + NYT. The smoking and smoking + NYT groups were exposed to cigarette smoke for 60 min once daily. The mice in the NYT and smoking + NYT groups were fed an NYT-containing diet (3% w/w). We performed cellular analysis of bronchoalveolar lavage fluid, assessed pulmonary morphological changes, examined the expression of PGC-1α mRNA and protein in the gastrocnemius and soleus muscle, measured the hindlimb muscle volume with micro-computed tomography, and determined the myofiber proportion in soleus muscle after 12 weeks.ResultsCigarette smoke exposure resulted in reduced skeletal muscle volume and slow-twitch muscle fibers and development of pulmonary emphysema. NYT feeding induced partial recovery of the damaged alveolar wall; however, NYT did not ameliorate smoke-induced alveolar enlargement. These findings revealed that NYT did not have sufficient efficacy in suppressing pulmonary emphysema. On the other hand, PGC-1α expression in muscle tissue of the NYT-fed mice increased significantly, resulting in suppression of smoke-induced loss of muscle mass and alteration in the muscle fiber distribution.ConclusionNYT increases PGC-1α expression in the muscle of COPD model mice and is involved in suppressing cigarette smoke-induced muscle complications. NYT may be a novel preventive and therapeutic medication for muscular dysfunctions in COPD.

Glycyrrhizic acid ameliorates sodium nitrite-induced lung and salivary gland toxicity: Impact on oxidative stress, inflammation and fibrosis.

Despite wide application of sodium nitrite (SN) as food additive, it exhibits considerable side effects on various body organs at high dose or chronic exposure. The aim of this study was to test whether Glycyrrhizic acid (GA) could ameliorate SN-induced toxicity in lung and submandibular salivary gland (SMG). A sample size of 30 adult male albino rats was randomly allocated into 3 groups. Group 1 served as control group. Rats were treated orally with 80 mg/kg of SN in group 2 or SN preceded by (15 mg/kg) GA in group 3. Lung & SMG tissues were used for oxidative stress assessment, examination of histopathological changes, fibrosis (MTC, TGF-β and α-SMA) and inflammation (TNF-α, IL-1β and CD-68). Concurrent administration of GA ameliorated pulmonary and salivary SN-induced toxicity via restoring the antioxidant defense mechanisms with reduction of MDA levels. GA reduced the key regulators of fibrosis TGF-β and α-SMA and collagen deposition. In addition to reduction of inflammatory cytokine (TNF-α, IL-1β) and macrophages recruitments, GA amended both pulmonary and salivary morphological changes. The present study proposed GA as a promising natural herb with antioxidant, anti-inflammatory and antifibrotic effects against pulmonary and salivary SN-induced toxicity.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

PET in the diagnostic management of infectious/inflammatory pulmonary pathologies: a revisit in the era of COVID-19.

A20 attenuates hypoxia-induced pulmonary arterial hypertension by inhibiting NF-κB activation and pulmonary artery smooth muscle cell proliferation

PAH is a progressive disease characterized by uncontrolled proliferation of PASMCs. Zinc finger protein A20 is a negative feedback regulatory protein of NF-κB activity. The aim of this study was to evaluate zinc finger protein A20 can alleviate PAH in hypoxia exposed mice. C57BL/6 mice received a tail vein injection of adenovirus-mediated ad-A20 and ad-A20 shRNA were exposed to hypoxia. PASMCs isolated from rat pulmonary arteries were cultured in hypoxia, and were transfection of A20 adenovirus. Pulmonary hemodynamic parameters were measured by right heart catheterization. Pulmonary vascular morphological changes were analyzed by HE and α-SMA staining. The expression changes of A20, NF-κB and its downstream protein were detected. The expression of phospho-p65 was increased with the prolongation of hypoxia time. The expression of A20 in lung tissue of chronic hypoxia group decreased with the prolongation of hypoxia time. Adenovirus-mediated A20 (ad-A20) overexpression significantly attenuated the abnormally increased RVSP, RV/(LV + S) ratio, WT%, WA%, α-SMA and the pulmonary vessel muscularization. Ad-A20 treatment markedly attenuated the degradation of phospho-p65 and inhibited the induction of phospho-IκBα induced by hypoxia treatment. Furthermore, silencing A20 abolished the protection by anti-inflammatory activity and the inhibitory effect on cell proliferation. We showed that Zinc finger protein A20 can block NF-κB signaling pathway, alleviates the hypoxia-induced abnormal elevation of pulmonary arterial pressure, hyperproliferation of PASMCs and the pulmonary vascular remodeling.

Herbal Medication, Macmoondong Decoction, Attenuates LPS‐Induced COPD in Small Airways via TGF‐β, CCL‐2, and CXCL1

Chronic obstructive pulmonary disease (COPD) is an incurable disease related to the respiratory system. A 2017 report by the World Health Organization stated that it was the third most common cause of death in 2015. Macmoondong decoction is a prescription that has been used widely in Korea for the treatment of respiratory diseases, but there have been few investigations into the therapeutic mechanism. To investigate the anti-COPD effect of macmoondong decoction, the animals were divided into five treatment groups: control; COPD-induced control; Spiriva; 150 mg/kg macmoondong decoction; and 1500 mg/kg macmoondong decoction. Changes typically observed in COPD, such as the populations of WBC and neutrophils in BALF, the level of IgE in serum, morphological changes, the DNA levels, and the protein expression of cytokines and chemokines (TGF-β, CCL-2, CXCL1, and CXCL11) in the pulmonary system, were evaluated. Macmoondong decoction inhibited the populations of WBC and neutrophils in BALF and the level of IgE in serum. Dose-dependent prevention of the pulmonary morphological changes, such as emphysema and airway fibrosis, was observed. Macmoondong decoction suppressed the expression of DNA and proteins related to the occurrence of COPD, such as TGF-β, CCL-2, CXCL1, and CXCL11. In particular, the expression of TGF-β, CCL-2, and CXCL1 was significantly suppressed by 1500 mg/kg macmoondong decoction treatment compared with Spiriva treatment. Macmoondong decoction exerted an anti-COPD effect, and the mechanism of its action may be the suppression of TGF-β, CCL-2, CXCL1, and CXCL11 expression, which occurred in a dose-dependent manner. The mechanism of action of macmoondong decoction may be the dose-dependent suppression of TGF-β, CCL-2, CXCL1, and CXCL11, with TGF-β, CCL-2, and CXCL1 as the potential key factors involved in COPD suppression.

Interleukin-1 Receptor Antagonist Protects Newborn Mice Against Pulmonary Hypertension.

Pulmonary hypertension secondary to bronchopulmonary dysplasia (BPD-PH) represents a major complication of BPD in extremely preterm infants for which there are currently no safe and effective interventions. The abundance of interleukin-1 (IL-1) is strongly correlated with the severity and long-term outcome of BPD infants and we have previously shown that IL-1 receptor antagonist (IL-1Ra) protects against murine BPD; therefore, we hypothesized that IL-1Ra may also be effective against BPD-PH. We employed daily injections of IL-1Ra in a murine model in which BPD/BPD-PH was induced by antenatal LPS and postnatal hyperoxia of 65% O2. Pups reared in hyperoxia for 28 days exhibited a BPD-PH-like disease accompanied by significant changes in pulmonary vascular morphology: micro-CT revealed an 84% reduction in small vessels (4–5 μm diameter) compared to room air controls; this change was prevented by IL-1Ra. Pulmonary vascular resistance, assessed at day 28 of life by echocardiography using the inversely-related surrogate marker time-to-peak-velocity/right ventricular ejection time (TPV/RVET), increased in hyperoxic mice (0.27 compared to 0.32 in air controls), and fell significantly with daily IL-1Ra treatment (0.31). Importantly, in vivo cine-angiography revealed that this protection afforded by IL-1Ra treatment for 28 days is maintained at day 60 of life. Despite an increased abundance of mediators of pulmonary angiogenesis in day 5 lung lysates, namely vascular endothelial growth factor (VEGF) and endothelin-1 (ET-1), no difference was detected in ex vivo pulmonary vascular reactivity between air and hyperoxia mice as measured in precision cut lung slices, or by immunohistochemistry in alpha-smooth muscle actin (α-SMA) and endothelin receptor type-A (ETA) at day 28. Further, on day 28 of life we observed cardiac fibrosis by Sirius Red staining, which was accompanied by an increase in mRNA expression of galectin-3 and CCL2 (chemokine (C-C motif) ligand 2) in whole hearts of hyperoxic pups, which improved with IL-1Ra. In summary, our findings suggest that daily administration of the anti-inflammatory IL-1Ra prevents the increase in pulmonary vascular resistance and the pulmonary dysangiogenesis of murine BPD-PH, thus pointing to IL-1Ra as a promising candidate for the treatment of both BPD and BPD-PH.

Lung clearance index – useful parameter for assessing lung function in cystic fibrosis children

CF is a polymorphic disease whose evolution is marked by pulmonary pathology. Distal obstruction, demonstrated anatomopathological, can be evidenced by spirometry, which can only be used in certain age groups. Early detection of obstruction with appropriate therapy is essential to prolong the life expectancy of these patients. A promising parameter has been described relatively recently, lung clearance index obtained by the multiple wash-out technique. Several studies have demonstrated its efficacy and correlation with pulmonary morphological changes, pointing out that LCI is a feasible and specific parameter to detect small-age lung changes in the CF patient. In conclusion, lung clearance index is a specific parameter for the detection of cystic fibrosis pneumopathy and is currently the standard way to monitor CF pneumopathy, and in future to be used in the current practice of CF centers.

Experimental Research on the Impact of Alveolar Morphology on Deposition of Inhalable Particles in the Human Pulmonary Acinar Area

Studying the deposition pattern of inhalable particles in the pulmonary acinus has significance in clarifying the predisposing cause, progression, clinical treatment and prevention of common respiratory system diseases such as emphysema. In this study, we established an in vitro experimental model capable of simulating pulmonary acinar morphological lesions, such as emphysema and pulmonary atrophy. In addition, the deposition efficiencies of inhalable particles with various diameters in the pulmonary acinus were investigated under an unsteady state respiratory mode. The changes in pulmonary acinar morphology significantly affected the deposition rates of particles. Moreover, alveolar atrophy increased the deposition rate of particles, while pulmonary alveolar dilatation decreased the deposition rate. The results of this study may provide experimental evidence for the development of a disease course by pulmonary acinus morphologic changes. The established model also provides a feasible in vitro experimental model for studying the deposition pattern of inhalable particles in the pulmonary acinus.

1,25(OH)2D3 attenuates pulmonary arterial hypertension via microRNA-204 mediated Tgfbr2/Smad signaling

Pulmonary arterial hypertension (PAH) is a devastating disease characterized by high pulmonary artery pressure. It is reported that microRNA-204 (miR-204) plays an important role in the development of PAH. Calcitriol [1,25-dihydroxyvitamin D3, 1,25(OH)2D3] mediates multiple pathophysiological processes. The aim of the current study was to explore the role of 1,25(OH)2D3 in PAH. PAH was induced in rats and rat pulmonary arterial endothelial cells (PAECs) were isolated as in vitro PAH model. The mean pulmonary artery pressure, morphologic changes, and expressions of transforming growth factor-beta1 (Tgfbr2), Smad2/7, alpha smooth muscle actin (α-SMA), and p21 were then measured. Furthermore, the effect of 1,25(OH)2D3 on rat PAECs with or without hypoxia treatment was also assessed by measuring the proliferation, migration, and cell cycle distribution of PAECs. The potential targets of miR-204 were also predicted and validated with a dual-luciferase reporter system. Then the role of miR-204 and Tgfbr2 in the anti-PAH effect of 1,25(OH)2D3 was further explored by modulating the expression of the two genes. The overall pulmonary hypertension and hypoxia-induced proliferation and migration of PAECs were attenuated by administration of 1,25(OH)2D3, which was associated with the suppressed expressions of Tgfbr2, α-SMA, and Smad7 and induced expressions of miR-204, p21 and Smad2 both in vitro and in vivo. Moreover, the luciferase reporter assay identified Tgfbr2 as a novel direct target of miR-204. Both overexpression of miR-204 and inhibition of Tgfbr2 would strengthen the effect of 1,25(OH)2D3 administration. Findings outlined in the current study demonstrated that 1,25(OH)2D3 was a promising therapeutic modality for treatment of PAH, function of which was exerted through miR-204 mediated Tgfbr2 signaling.