Climate change, air quality, and respiratory health: a focus on particle deposition in the lungs.

This review article delves into the multifaceted relationship between climate change, air quality, and respiratory health, placing a special focus on the process of particle deposition in the lungs. We discuss the capability of climate change to intensify air pollution and alter particulate matter physicochemical properties such as size, dispersion, and chemical composition. These alterations play a significant role in influencing the deposition of particles in the lungs, leading to consequential respiratory health effects. The review paper provides a broad exploration of climate change's direct and indirect role in modifying particulate air pollution features and its interaction with other air pollutants, which may change the ability of particle deposition in the lungs. In conclusion, climate change may play an important role in regulating particle deposition in the lungs by changing physicochemistry of particulate air pollution, therefore, increasing the risk of respiratory disease development.

Climate change influences particle deposition in the lungs by modifying the physicochemical properties of particulate air pollution, thereby escalating the risk of respiratory disease development.It is crucial for healthcare providers to educate patients about the relationship between climate change and respiratory health.People with conditions such as asthma, COPD, and allergies must understand how changes in weather, air pollution, and allergens can exacerbate their symptoms.Instruction on understanding air quality indices and pollen predictions, along with recommendations on adapting everyday activities and medication regimens in response, is essential.

Airway epithelium IgE-FcεRI cross-link induces epithelial barrier disruption in severe T2-high asthma.

Although high-affinity immunoglobulin (Ig)E receptor (FcεRI) expression is upregulated in type 2 (T2)-high asthmatic airway epithelium, its functional role in airway epithelial dysfunction has not been elucidated. Here we report the upregulated expression of FcεRI and p-EGFR (Epidermal Growth Factor Receptor), associated with decreased expression of E-cadherin and claudin-18 in bronchial biopsies of severe T2-high asthmatics compared to mild allergic asthmatics and non-T2 asthmatics. Monomeric IgE (mIgE) decreased the expression of junction proteins, E-cadherin, claudin-18, and ZO-1, and increased alarmin messenger RNA and protein expression in cultured primary bronchial epithelial cells from T2-high asthmatics. Epithelial FcεRI ligation with mIgE decreased transepithelial electric resistance in air-liquid interface cultured epithelial cells. FcεRI ligation with mIgE or IgE- Dinitrophenyl or serum of high-level allergen-specific IgE activated EGFR and Akt via activation of Src family kinases, mediating alarmin expression, junctional protein loss, and increased epithelial permeability. Furthermore, tracheal instillation of mIgE in house dust mite-sensitized mice induced airway hyper-responsiveness, junction protein loss, epithelial cell shedding, and increased epithelial permeability. Thus, our results suggest that IgE-FcεRI cross-linking in the airway epithelium is a potential and unnoticed mechanism for impaired barrier function, increased mucosal permeability, and EGFR-mediated alarmin production in T2-high asthma.

The impact of air pollution on respiratory diseases in an era of climate change: A review of the current evidence.

The impacts of climate change and air pollution on respiratory diseases present significant global health challenges. This review aims to investigate the effects of the interactions between these challenges focusing on respiratory diseases. Climate change is predicted to increase the frequency and intensity of extreme weather events amplifying air pollution levels and exacerbating respiratory diseases. Air pollution levels are projected to rise due to ongoing economic growth and population expansion in many areas worldwide, resulting in a greater burden of respiratory diseases. This is especially true among vulnerable populations like children, older adults, and those with pre-existing respiratory disorders. These challenges induce inflammation, create oxidative stress, and impair the immune system function of the lungs. Consequently, public health measures are required to mitigate the effects of climate change and air pollution on respiratory health. The review proposes that reducing greenhouse gas emissions contribute to slowing down climate change and lessening the severity of extreme weather events. Enhancing air quality through regulatory and technological innovations also helps reduce the morbidity of respiratory diseases. Moreover, policies and interventions aimed at improving healthcare access and social support can assist in decreasing the vulnerability of populations to the adverse health effects of air pollution and climate change. In conclusion, there is an urgent need for continuous research, establishment of policies, and public health efforts to tackle the complex and multi-dimensional challenges of climate change, air pollution, and respiratory health. Practical and comprehensive interventions can protect respiratory health and enhance public health outcomes for all.

Endothelin-1 induces connective tissue growth factor expression in human lung fibroblasts by disrupting HDAC2/Sin3A/MeCP2 corepressor complex.

BACKGROUND: Reduction of histone deacetylase (HDAC) 2 expression and activity may contribute to amplified inflammation in patients with severe asthma. Connective tissue growth factor (CTGF) is a key mediator of airway fibrosis in severe asthma. However, the role of the HDAC2/Sin3A/methyl-CpG-binding protein (MeCP) 2 corepressor complex in the regulation of CTGF expression in lung fibroblasts remains unclear. METHODS: The role of the HDAC2/Sin3A/MeCP2 corepressor complex in endothelin (ET)-1-stimulated CTGF production in human lung fibroblasts (WI-38) was investigated. We also evaluated the expression of HDAC2, Sin3A and MeCP2 in the lung of ovalbumin-induced airway fibrosis model. RESULTS: HDAC2 suppressed ET-1-induced CTGF expression in WI-38 cells. ET-1 treatment reduced HDAC2 activity and increased H3 acetylation in a time-dependent manner. Furthermore, overexpression of HDAC2 inhibited ET-1-induced H3 acetylation. Inhibition of c-Jun N-terminal kinase, extracellular signal-regulated kinase, or p38 attenuated ET-1-induced H3 acetylation by suppressing HDAC2 phosphorylation and reducing HDAC2 activity. Overexpression of both Sin3A and MeCP2 attenuated ET-1-induced CTGF expression and H3 acetylation. ET-1 induced the disruption of the HDAC2/Sin3A/MeCP2 corepressor complex and then prompted the dissociation of HDAC2, Sin3A, and MeCP2 from the CTGF promoter region. Overexpression of HDAC2, Sin3A, or MeCP2 attenuated ET-1-stimulated AP-1-luciferase activity. Moreover, Sin3A- or MeCP2-suppressed ET-1-induced H3 acetylation and AP-1-luciferase activity were reversed by transfection of HDAC2 siRNA. In an ovalbumin-induced airway fibrosis model, the protein levels of HDAC2 and Sin3A were lower than in the control group; however, no significant difference in MeCP2 expression was observed. The ratio of phospho-HDAC2/HDAC2 and H3 acetylation in the lung tissue were higher in this model than in the control group. Overall, without stimulation, the HDAC2/Sin3A/MeCP2 corepressor complex inhibits CTGF expression by regulating H3 deacetylation in the CTGF promoter region in human lung fibroblasts. With ET-1 stimulation, the HDAC2/Sin3A/MeCP2 corepressor complex is disrupted and dissociated from the CTGF promoter region; this is followed by AP-1 activation and the eventual initiation of CTGF production. CONCLUSIONS: The HDAC2/Sin3A/MeCP2 corepressor complex is an endogenous inhibitor of CTGF in lung fibroblasts. Additionally, HDAC2 and Sin3A may be of greater importance than MeCP2 in the pathogenesis of airway fibrosis.

Importance of surface charge of soot nanoparticles in determining inhalation toxicity in mice.

Physicochemical properties of nanoparticles are important in regulating nanoparticle toxicity; however, the contribution of nanoparticle charge remains unclear. The objective of this study was to investigate the pulmonary effects of inhalation of charged soot nanoparticles. We established a stably charged nanoparticle generation system for whole-body exposure in BALB/c mice, which produced positively charged, negatively charged, and neutral soot nanoparticles in a wide range of concentrations. After a 7-day exposure, pulmonary toxicity was assessed, together with proteomics analysis. The charged soot nanoparticles on average carried 1.17-1.35 electric charges, and the sizes for nanoparticles under different charging conditions were all fixed at 69 ~ 72 nm. We observed that charged soot nanoparticles induced cytotoxic LDH and increased lung permeability, with the release of 8-isoprostane and caspase-3 and systemic IL-6 in mice, especially for positively charged soot nanoparticles. Next, we observed that positive-charged soot nanoparticles upregulated Eif2, Eif4, sirtuin, mammalian target of rapamycin (mTOR), peroxisome proliferator-activated receptors (PPAR), and HIPPO-related signaling pathways in the lungs compared with negatively charged soot nanoparticles. HIF1α, sirt1, E-cadherin, and Yap were increased in mice's lungs by positively charged soot nanoparticle exposure. In conclusion, carbonaceous nanoparticles carrying electric ions, especially positive-charged, are particularly toxic when inhaled and should be of concern in terms of pulmonary health protection.

Platelet Activation in High D-Dimer Plasma Plays a Role in Acquired Resistance to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Patients with Mutant Lung Adenocarcinoma.

Objective: Platelet activation and adhesion to cancer cells increase the release of multiple factors that contribute to EMT and chemoresistance. Elevated levels of D-dimer have been associated with poor clinical outcomes in lung cancer. Platelets in high D-dimer plasma may be activated and implicated in acquired resistance to EGFR TKI in advanced lung adenocarcinoma with mutant EGFR. Materials and Methods: Clinical responsive rate (RR), progression-free survival (PFS), and overall survival (OS) were prospectively measured in treatment-naïve lung adenocarcinoma patients with activation mutation. Plasma or platelets from patients with high or low D-dimer level were obtained to investigate the cytotoxic effects of TKIs on mutant cancer cells, and the mechanistic pathways were also explored. Results: Patients with high D-dimer had worse RR, PFS, and OS. High D-dimer plasma induced resistance to gefitinib, erlotinib, afatinib, or osimertinib in EGFR mutant lung cancer cells. Depletion of platelets in high D-dimer plasma reversed the resistance to TKI. Platelets of high D-dimer plasma had higher adherence capacity to cancer cells, and induced EGFR and Akt activation as well as EMT through Src activation. Inhibition of platelet adherence or activation of Src or Akt conquered the resistance to TKI. The acquired resistance to TKI by high D-dimer plasma was less attributed to secondary gene mutation. Conclusion: Increased platelet activation in the high D-dimer plasma may contribute to first-line acquired EGFR TKI resistance. Thus, therapeutic strategy against platelet activation in patients with high D-dimer levels may improve the efficacy of first-line treatment with EGFR TKI.

Climate-mediated air pollution associated with COPD severity.

Air pollution has been reported to be associated with chronic obstructive pulmonary disease (COPD). Our study aim was to examine the mediating effects of air pollution on climate-associated health outcomes of COPD patients. A cross-sectional study of 117 COPD patients was conducted in a hospital in Taiwan. We measured the lung function, 6-min walking distance, oxygen desaturation, white blood cell count, and percent emphysema (low attenuation area, LAA) and linked these to 0-1-, 0-3-, and 0-5-year lags of individual-level exposure to relative humidity (RH), temperature, and air pollution. Linear regression models were conducted to examine associations of temperature, RH, and air pollution with severity of health outcomes. A mediation analysis was conducted to examine the mediating effects of air pollution on the associations of RH and temperature with health outcomes. We observed that a 1 % increase in the RH was associated with increases in forced expiratory volume in 1 s (FEV1), eosinophils, and lymphocytes, and a decrease in the total-lobe LAA. A 1 °C increase in temperature was associated with decreases in oxygen desaturation, and right-, left-, and upper-lobe LAA values. Also, a 1 µg/m3 increase in PM2.5 was associated with a decrease in the FEV1 and an increase in oxygen desaturation. A 1 µg/m3 increases in PM10 and PM2.5 was associated with increases in the total-, right-, left, upper-, and lower-lobe (PM2.5 only) LAA. A one part per billion increase in NO2 was associated with a decrease in the FEV1 and an increase in the upper-lobe LAA. Next, we found that NO2 fully mediated the association between RH and FEV1. We found PM2.5 fully mediated associations of temperature with oxygen saturation and total-, right-, left-, and upper-lobe LAA. In conclusion, climate-mediated air pollution increased the risk of decreasing FEV1 and oxygen saturation and increasing emphysema severity among COPD patients. Climate change-related air pollution is an important public health issue, especially with regards to respiratory disease.

Oxygen Desaturation Is Associated With Fibrocyte Activation via Epidermal Growth Factor Receptor/Hypoxia-Inducible Factor-1α Axis in Chronic Obstructive Pulmonary Disease.

Fibrocytes are bloodborne mesenchymal progenitors which accumulate and differentiate at the disease site. We investigated whether hypoxemia activates fibrocytes, accelerating airflow limitation and exercise intolerance in chronic obstructive pulmonary disease (COPD) patients. Flow cytometry was used to determine collagen I+/CD45+ fibrocytes and α-smooth muscle actin+ differentiating fibrocytes within peripheral blood and cultured cells, as well as the expression of CXC chemokine receptor 4 (CXCR4), epidermal growth factor receptor (EGFR), connective tissue growth factor (CTGF) and hypoxia-inducible factor (HIF)-1α. Fibrocytes in lung specimens were identified by confocal microscopy. Compared to non-desaturators, COPD desaturators (peripheral blood oxygen saturation ≤88% during exercise) had greater number of fibrocytes in peripheral blood and lung specimens, paralleled with faster yearly lung function decline and a 6-minute walk distance. Fibrocytes from desaturators expressed more EGFR, CXCR4, CTGF, and HIF-1α, with a higher capacity of proliferation and myofibroblastic differentiation. Hypoxia (5% oxygen) increased the expression of EGFR, CXCR4, CTGF, and HIF-1α, the number and differentiation in fibrocytes. These effects were attenuated by EGFR inhibitor gefitinib, HIF-1α gene silencing, and anti-CTGF antibody. These data elucidate that hypoxemia triggers fibrocyte activation through the EGFR/HIF-1α axis, aggravating airflow obstruction in COPD.

pcMSC Modulates Immune Dysregulation in Patients With COVID-19-Induced Refractory Acute Lung Injury.

Background and Objectives: The novel coronavirus disease 2019 (COVID-19) has been a pandemic health issue in 30 January 2020. The mortality rate is as high as 50% in critically ill patients. Stem cell therapy is effective for those who are refractory to standard treatments. However, the immune responses that underlie stem cell therapy have not been well reported, particularly, in patients associated with moderate to severe acute respiratory distress syndrome (ARDS). Methods: On Days 0 and 4, an intravenous infusion of 2 × 107 placenta-derived mesenchymal stem cells (pcMSCs) (MatriPlax) were administered to five severe COVID-19 patients refractory to current standard therapies. Peripheral blood inflammatory markers and immune profiles were determined by multi-parameter flow cytometry and studied at Days 0, 4, and 8. Clinical outcomes were also observed. Results: None of the pc-MSC treated patients experienced 28-day mortality compared with the control group and showed a significant improvement in the PaO2/FiO2 ratio, Murray's lung injury scores, reduction in serum ferritin, lactate dehydrogenase (LDH), and C-reactive protein (CRP) levels. The cytokine profiles also showed a reduction in IL-1ß, IFN-γ, IL-2, and IL-6, and an increase in IL-13 and IL-5 type 2 cytokines within 7 days of therapy. Lymphopenia was also significantly improved after 7 days of treatment. Immune cell profiles showed an increase in the proportions of CD4+ T cells (namely, CD4+ naïve T cells and CD4+ memory T cell subtypes), Treg cells, CD19+ B cells (namely, CD19+ naïve B cells, CD27+ switched B cell subtypes) and dendritic cells, and a significant decrease in the proportion of CD14+ monocytes (namely, CD16- classical and CD16+ non-classical subtypes), and plasma/plasmablast cells. No adverse effects were seen at the serial follow-up visits for 2 months after initial therapy. Conclusion: pc-MSCs therapy suppressed hyper-inflammatory states of the innate immune response to COVID-19 infection by increasing Treg cells, decreasing monocytes and plasma/plasmablast cells, and promoting CD4+ T cells and CD19+ B cells toward adaptive immune responses in severely critically ill COVID-19 patients with moderate to severe ARDS, especially those who were refractory to current standard care and immunosuppressive therapies.

Interactions of chemical components in ambient PM2.5 with influenza viruses.

The significance of this work is that ambient PM2.5 is a direct transmission mode for influenza virus infection to the human alveolar epithelium. The concentration of PM2.5 was 11.7 ± 5.5 µg/m3 in Taipei during 24 December 2019-13 January 2020. Approximately 79% of inhaled PM2.5 is able to reach the upper-to-lower airway, and 47% of PM2.5 is able to reach the alveolar epithelium for influenza virus infection. Influenza A and B viruses were detected in PM2.5 on 9 days, and the influenza A/H5 virus was detected on 15 days during the study period. FL and Pyr were negatively correlated with the influenza A virus. D(ah)P and Acp were positively correlated with the influenza B and A/H5 viruses, respectively. Cd, V, and Zn were positively correlated with the influenza A, B, and A/H5 viruses, respectively. Next, influenza A, B, and A/H5 viral plasmids interacted with carbon black, H2O2, DEPs, and UD. We observed that H2O2 significantly decreased levels of complementary DNA of the three influenza viruses. DEPs and UD significantly decreased influenza A and A/H5 viral levels. In conclusion, chemicals in PM2.5 may play vital roles in terms of viable influenza virus in the atmosphere.

Air pollution-regulated E-cadherin mediates contact inhibition of proliferation via the hippo signaling pathways in emphysema.

Air pollution has been linked to emphysema in chronic obstruction pulmonary disease (COPD). However, the underlying mechanisms in the development of emphysema due to air pollution remain unclear. The objective of this study was to investigate the role of components of the Hippo signaling pathway for E-cadherin-mediated contact inhibition of proliferation in the lungs after air pollution exposure. E-Cadherin-mediated contact inhibition of proliferation via the Hippo signaling pathway was investigated in Sprague-Dawley (SD) rats whole-body exposed to air pollution, and in alveolar epithelial A549 cells exposed to diesel exhaust particles (DEPs), E-cadherin-knockdown, and high-mobility group box 1 (HMGB1) treatment. Underlying epithelial differentiation, apoptosis, and senescence were also examined, and the interaction network among these proteins was examined. COPD lung sections were used to confirm the observations in rats. Expressions of HMGB1 and E-cadherin were negatively regulated in the lungs and A549 cells by air pollution, and this was confirmed by knockdown of E-cadherin and by treating A549 cells with HMGB1. Depletion of phosphorylated (p)-Yap occurred after exposure to air pollution and E-cadherin-knockdown, which resulted in decreases of SPC and T1α. Exposure to air pollution and E-cadherin-knockdown respectively downregulated p-Sirt1 and increased p53 levels in the lungs and in A549 cells. Moreover, the protein interaction network suggested that E-cadherin is a key activator in regulating Sirt1 and p53, as well as alveolar epithelial cell differentiation by SPC and T1α. Consistently, downregulation of E-cadherin, p-Yap, SPC, and T1α was observed in COPD alveolar regions with particulate matter (PM) deposition. In conclusion, our results indicated that E-cadherin-mediated cell-cell contact directly regulates the Hippo signaling pathway to control differentiation, cell proliferation, and senescence due to air pollution. Exposure to air pollution may initiate emphysema in COPD patients.

Association Between Air Pollution and Lung Lobar Emphysema in COPD.

The development of emphysema has been linked to air pollution; however, the association of air pollution with the extent of lobar emphysema remains unclear. This study examined the association of particulate matter <2.5 µm in aerodynamic diameters (PM2.5) (≤2.5 µm), nitrogen dioxide (NO2), and ozone (O3) level of exposure with the presence of emphysema in 86 patients with chronic obstructive pulmonary disease (COPD). Exposure to the air pollution estimated using the land-use regression model was associated with lung function, BODE (a body mass index, degree of obstruction, dyspnea severity, and exercise capacity index) quartiles, and emphysema measured as low-attenuation areas on high-resolution CT (HR-CT) lung scans. Using paraseptal emphysema as the reference group, we observed that a 1 ppb increase in O3 was associated with a 1.798-fold increased crude odds ratio of panlobular emphysema (p < 0.05). We observed that PM2.5 was associated with BODE quartiles, modified Medical Research Council (mMRC) dyspnea score, and exercise capacity (all p < 0.05). We found that PM2.5, NO2, and O3 were associated with an increased degree of upper lobe emphysema and lower lobe emphysema (all p < 0.05). Furthermore, we observed that an increase in PM2.5, NO2, and O3 was associated with greater increases in upper lobe emphysema than in lower lobe emphysema. In conclusion, exposure to O3 can be associated with a higher risk of panlobular emphysema than paraseptal emphysema in patients with COPD. Emphysema severity in lung lobes, especially the upper lobes, may be linked to air pollution exposure in COPD.

Higher alveolar deposition of particulate matter in emphysematous lobes of COPD.

The novelty of this study is that it identified the associations between PM2.5 deposition in the lung and the degree of emphysema in different lung lobes of COPD patients, especially in the right middle lobe and both upper lobes https://bit.ly/3k21ri0.

Effects of obesity on pulmonary function considering the transition from obstructive to restrictive pattern from childhood to young adulthood.

Adults with obesity exhibit a restrictive pattern, whereas children with obesity exhibit an obstructive pattern. However, the transition process remains unclear. We performed a systematic search for studies reporting on body mass index and pulmonary function in children. The main outcomes were forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC), and their ratio (FEV1 /FVC). We compared individuals with overweight or with obesity with individuals with normal weight. Random-effects models were used to calculate pooled estimates. A total of 17 studies were included. Individuals with obesity had a lower FEV1 /FVC ratio (mean difference [MD] = -3.61%; 95% confidence interval [CI] = -4.58%, -2.64%) and a higher percent-predicted FVC (MD = 3.33%; 95% CI = 0.79%, 5.88%) than those with normal weight. Obesity impaired pulmonary function in the obstructive pattern during childhood to young adulthood, and the maximum obstruction was observed at the age of 16 years in boys and 20 years in girls. The effects attenuated at approximately 30 years and then shifted to the restrictive pattern after 35 years of age in men and 40 years in women. The effects of obesity on pulmonary function change from the obstructive pattern in childhood to the restrictive pattern in adulthood.

Anti-IgE therapy inhibits chemotaxis, proliferation and transformation of circulating fibrocytes in patients with severe allergic asthma.

BACKGROUND AND OBJECTIVE: Circulating fibrocytes act as precursors of myofibroblasts, contribute to airway remodelling in chronic asthma and migrate to injured tissues by expressing CXCR4 and CCR7. Anti-IgE therapy improves severe allergic asthma (SAA) control and airway remodelling in T2-high SAA. The effects of anti-IgE therapy on fibrocyte activities were investigated in this study. METHODS: The expression of CCR7, CXCR4, ST2 and α-SMA (α-smooth muscle actin) in both circulating and cultured fibrocytes from all patients with asthma was measured, and was repeated after omalizumab treatment in SAA. Fibrocytes recruitment, proliferation and transformation were also measured in response to anti-IgE therapy. RESULTS: Omalizumab effectively improved asthma control and pulmonary function in T2-high SAA, associated with a decline in serum levels of IL-33 and IL-13. Omalizumab down-regulates CXCR4 and CCR7 expression of fibrocytes, which could suppress fibrocyte recruitment into the lungs. Omalizumab also suppressed the increased number of fibrocytes and α-SMA+ fibrocytes within the cultured non-adherent non-T (NANT) cells after 3-7 days of culture. The decrease in serum levels of IL-33 by omalizumab contributed to the effectiveness in inhibiting fibrocyte recruitment, proliferation and myofibroblast transformation through IL-33/ST2 axis. The elevated IL-13 expression in SAA patients potentiated the effects of IL-33 by increasing ST2 expression. CONCLUSION: Omalizumab reduced the number of circulating fibrocytes, cell and number of fibrocytes as well as α-SMA+ fibrocytes after 3-7 days of culture in SAA patients. IL-33 and IL-13 may be implicated in the effectiveness of omalizumab in inhibiting fibrocyte activation contributing partly to the clinical benefits in reducing lamina propria and basement membrane thickening.

Abnormal ADAM17 expression causes airway fibrosis in chronic obstructive asthma.

Patients with chronic obstructive asthma (COA) develop airflow obstruction caused by subepithelial fibrosis. Although a disintegrin and metalloproteinase 17 (ADAM17) has been implicated in lung inflammation and tissue fibrosis, its role in airway fibrosis in COA has not been explored. Here, we found marked overexpression of ADAM17, phosphorylated ADAM17, and connective tissue growth factor (CTGF) in human airway fibroblasts from COA patients, compared with those of normal subjects. Similarly, levels of ADAM17, CTGF, α-smooth muscle actin (α-SMA), and collagen were increased in endobronchial biopsies from COA patients, but not in controls. In an ovalbumin-challenge asthma model, airway fibrosis was inhibited in ADAM17f/f/Cre+ mice compared to control mice. TGF-ß- and thrombin-induced fibrotic protein expression was reduced by ADAM17 small interfering (si)RNA, TAPI-0 (an ADAM17 inhibitor), and EGFR siRNA. In addition, exogenous HB-EGF reversed fibrotic response in ADAM17 knockdown human lung fibroblasts. ADAM17 causes subepithelial fibrosis through regulation of enhanced extracellular matrix production and fibroblast differentiation and is the common pathway for airway fibrosis mediated by TGF-ß and thrombin through an aberrant ADAM17/EGFR signalling pathway.

Profiles of Peripheral Immune Cells of Uncomplicated COVID-19 Cases with Distinct Viral RNA Shedding Periods.

The heterogeneity of immune response to COVID-19 has been reported to correlate with disease severity and prognosis. While so, how the immune response progress along the period of viral RNA-shedding (VRS), which determines the infectiousness of disease, is yet to be elucidated. We aim to exhaustively evaluate the peripheral immune cells to expose the interplay of the immune system in uncomplicated COVID-19 cases with different VRS periods and dynamic changes of the immune cell profile in the prolonged cases. We prospectively recruited four uncomplicated COVID-19 patients and four healthy controls (HCs) and evaluated the immune cell profile throughout the disease course. Peripheral blood mononuclear cells (PBMCs) were collected and submitted to a multi-panel flowcytometric assay. CD19+-B cells were upregulated, while CD4, CD8, and NK cells were downregulated in prolonged VRS patients. Additionally, the pro-inflammatory-Th1 population showed downregulation, followed by improvement along the disease course, while the immunoregulatory cells showed upregulation with subsequent decline. COVID-19 patients with longer VRS expressed an immune profile comparable to those with severe disease, although they remained clinically stable. Further studies of immune signature in a larger cohort are warranted.