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Acute inflammation is the body's first defense in response to pathogens or injury that is partially governed by a novel genus of endogenous lipid mediators that orchestrate the resolution of inflammation, coined specialized pro-resolving mediators (SPMs). SPMs, derived from omega-3-polyunstaturated fatty acids (PUFAs), include the eicosapentaenoic acid-derived and docosahexaenoic acid-derived Resolvins, Protectins, and Maresins. Herein, we review their biosynthesis, structural characteristics, and therapeutic effectiveness in various diseases such as ischemia, viral infections, periodontitis, neuroinflammatory diseases, cystic fibrosis, lung inflammation, herpes virus, and cancer, especially focusing on therapeutic effectiveness in respiratory inflammation and ischemia-related injuries. Resolvins are sub-nanomolar potent agonists that accelerate the resolution of inflammation by reducing excessive neutrophil infiltration, stimulating macrophage functions including phagocytosis, efferocytosis, and tissue repair. In addition to regulating neutrophils and macrophages, Resolvins control dendritic cell migration and T cell responses, and they also reduce the pro-inflammatory cytokines, proliferation, and metastasis of cancer cells. Importantly, several lines of evidence have demonstrated that Resolvins reduce tumor progression in melanoma, oral squamous cell carcinoma, lung cancer, and liver cancer. In addition, Resolvins enhance tumor cell debris clearance by macrophages in the tumor's microenvironment. Resolvins, with their unique stereochemical structure, receptors, and biosynthetic pathways, provide a novel therapeutical approach to activating resolution mechanisms during cancer progression.

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BACKGROUND: Adenoid hypertrophy (AH) is a common pediatric disease that significantly impacts the growth and quality of life of children. However, there is no replicable and valid model for AH. METHODS: An AH rat model was developed via comprehensive allergic sensitization, chronic inflammation induction, and chronic intermittent hypoxia (CIH). The modeling process involved three steps: female Sprague-Dawley rats (aged 4-5 weeks) were used for modeling. Allergen sensitization was induced via intraperitoneal administration and intranasal provocation using ovalbumin (OVA); chronic nasal inflammation was induced through intranasal lipopolysaccharide (LPS) administration for sustained nasal irritation; CIH akin to obstructive sleep apnea/hypopnea syndrome was induced using an animal hypoxia chamber. Postmodel establishment, behaviors, and histological changes in nasopharynx-associated lymphoid tissue (NALT) and nasal mucosa were assessed. Arterial blood gas analysis and quantification of serum and tissue levels of (interleukin) IL-4 and IL-13, OVA-specific immunoglobulin E (sIgE), eosinophil cationic protein (ECP), tumor necrosis factor (TNF-α), IL-17, and transforming growth factor (TGF)-ß were conducted for assessment. The treatment group received a combination of mometasone furoate and montelukast sodium for a week and then was evaluated. RESULTS: Rats exhibited notable nasal symptoms and hypoxia after modeling. Histopathological analysis revealed NALT follicle hypertrophy and nasal mucosa inflammatory cell infiltration. Elevated IL-4, IL-13, IL-17, OVA-sIgE, ECP, and TNF-α levels and reduced TGF-ß levels were observed in the serum and tissue of model-group rats. After a week of treatment, the treatment group exhibited symptom and inflammatory factor improvement. CONCLUSION: The model effectively simulates AH symptoms and pathological changes. But it should be further validated for genetic, immunological, and hormonal backgrounds in the currently used and other strains and species.

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The coronavirus disease 2019 (COVID-19) is a respiratory disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), but whether the asthmatic patients are at increased risk for severe COVID-19 illness than non-asthmatic patients has remained unclear. This scoping review aimed to assess the available evidence to determine if asthmatic patients are at a higher risk for severe COVID-19 illness. Searching several electronic databases and adhering to the PRISMA guidelines, we conducted a scoping review of 70 articles and using defined inclusion-exclusion criteria, 21 articles were analyzed in-depth and included in this scoping review. The findings of this scoping review point to a lack of relationship between asthma and severe COVID-19 illness. While a limited number of studies (n = 4) identified asthma as a risk factor, most studies (n = 17) found no independent association between asthma and severe COVID-19 illness. We, thus, conclude that asthma may not be a potential risk factor for severe COVID-19 illness. Owing to limited evidence, we recommend large-scale prospective cohort studies with standardized methodologies to decipher potential role of asthma in COVID-19 severity. Further, understanding the impact of specific asthma medications, genetic factors, and other comorbidities on COVID-19 outcomes may help inform clinical practice guidelines for effective patient health management.

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Background: Childhood Asthma Control Test (C-ACT) is a well-validated questionnaire for asthma controls among 4-11 years old children. This study aims to examine if longitudinal C-ACT score changes could also reflect lung pathophysiologic changes. Methods: Thirty-seven children (43% female) aged 5 to 10 years old with mild or moderate asthma were followed up for 6 weeks with bi-weekly assessments of C-ACT, airway mechanics, lung function and respiratory inflammation. Associations of longitudinal changes in C-ACT score with lung pathophysiologic indicators were evaluated using linear mixed-effects models. Results: A two-point worsening of total C-ACT score (sum of child and caregiver-reported) was associated with significant decreases in forced expiratory volume during the 1st second (FEV1) by 1.7% (P=0.04) and forced vital capacity (FVC) by 1.6% (P=0.01) and increased total airway resistance [airway resistance at 5 Hz (R5)] by 3.8% (P=0.05). A two-point worsening in child-reported score was significantly associated with 3.1% and 2.5% reductions in FEV1 and FVC, respectively, and with increases in R5 by 6.5% and large airway resistance [airway resistance at 20 Hz (R20)] by 5.5%. In contrast, a two-point worsening of caregiver-reported score was associated with none of the concurrent lung pathophysiologic measurements. Worsening of total C-ACT score was significantly associated with increased respiratory inflammation [fractional exhaled nitric oxide (FeNO)] in a subset (n=23) of children without eosinophilic airway inflammation. C-ACT scores were associated with none of the small airway measures. Conclusions: In children with mild or moderate asthma, longitudinal C-ACT score changes could reflect acute changes in large airway resistance and lung function. Measures of small airway physiology would provide valuable complementary information for asthma control. Asthma phenotype may affect whether C-ACT score could reflect respiratory inflammation.

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BACKGROUND: Human beings are widespread exposed to organophosphate esters (OPEs), but little is known about their effects on respiratory health. OBJECTIVES: To investigate the associations of exposure to OPEs with lung function and airway inflammation among U.S. participants from NHANES, 2011-2012. METHODS: A total of 1636 participants aged 6-79 years were included. Concentrations of OPE metabolites were measured in urine and lung function was assessed with spirometry. Fractional exhaled nitric oxide (FeNO) and blood eosinophils (B-Eos), two important inflammatory biomarkers, were also measured. Linear regression was performed to examine the relationships of OPEs with FeNO, B-Eos and lung function. Bayesian kernel machine regression (BKMR) was used to evaluate the joint associations between OPEs mixtures and lung function. RESULTS: Three of seven OPE metabolites had detection frequencies > 80 %, including diphenyl phosphate (DPHP), bis (1,3-dichloro-2-propyl) phosphate (BDCPP), bis-2-chloroethyl phosphate (BCEP). A 10-fold increase in DPHP concentrations were associated with 1.02 mL decreases in FEV1 (ß = -0.01, 95 % CIs = -0.02, -0.003) and FVC (ß = -0.01, 95 % CIs = -0.02, -0.003), respectively, and the similar, modest decreases were seen for BDCPP. For each 10-fold increase in BCEP concentration, FVC was also reduced by 1.02 mL (ß = -0.01, 95 % CIs = -0.02, -0.002). Moreover, the negative associations were only found in non-smokers aged >35 years. The aforementioned associations were confirmed by BKMR, but we cannot definitively identify a constituent driving this association. B-Eos was negatively associated with FEV1 and FEV1/FVC, but not with OPEs. No associations were found of FeNO with OPEs and lung function. CONCLUSIONS: Exposure to OPEs was associated with modest decrements in lung function, although the observed decrease in FVC and FEV1 is unlikely to be of real clinical relevance for the majority of subjects in this series. Moreover, those associations presented age and smoking status-dependent pattern. Unexpectedly, the adverse effect was not mediated by FeNO/B-Eos.

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Cooking Oil Fumes (COFs) contain carcinogenic organic substances such as polycyclic aromatic hydrocarbons (PAHs) and heterocyclic amines (HCAs), of which 2-Amino-1-methyl-6-phenylimidazo(4,5-b)pyridine (PhIP) is known as mainly meat-borne carcinogens. In this work, to identify the mechanisms to induce the inflammation response in human lung cells (A549) exposed to COFs, we investigated the physicochemical and biological characteristics of COFs generated with PhIP precursors (L-phenylalanine, creatinine, and glucose) at high cooking temperatures (300 °C and 600 °C). Interestingly, we found that PhIP was not formed both at 300 °C and 600 °C, while a large number of carbon nanoparticles were generated from soybean oil containing the PhIP precursors at 600 °C. From the biological analysis, COFs generated with the PhIP precursors at 600 °C induced the most significant pro-inflammatory cytokine (IL-6). This result indicates that the particulate matter in COFs generated with the PhIP precursors above the smoke temperature is the primary factor directly affecting the lung inflammatory response rather than PhIP. This study demonstrates for the first time a novel principle of the inflammatory response that the PhIP precursors can aggravate lung injury by affecting the physical properties of COFs depending on cooking temperature. Therefore, our finding is a significant result of overcoming the bias in previous studies focusing only on the chemical toxicity of PhIP in the inflammatory response of COFs.

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Emerging antimicrobial resistance in respiratory infections requires novel intervention strategies. Non-digestible oligosaccharides (NDOs) are a diverse group of carbohydrates with broad protective effects. In addition to promoting the colonization of beneficial gut microbiota and maintaining the intestinal homeostasis, NDOs act as decoy receptors, effectively blocking the attachment of pathogens on host cells. NDOs also function as a bacteriostatic agent, inhibiting the growth of specific pathogenic bacteria. Based on this fact, NDOs potentiate the actions of antimicrobial drugs. Therefore, there is an increasing interest in characterizing the anti-infective properties of NDOs. This focused review provides insights into the mechanisms by which representative NDOs may suppress respiratory infections by targeting pathogens and host cells. We summarized the most interesting mechanisms of NDOs, including maintenance of gut microbiota homeostasis, interference with TLR-mediated signaling, anti-oxidative effects and bacterial toxin neutralization, bacteriostatic and bactericidal effects, and anti-adhesion or anti-invasive properties. A detailed understanding of anti-infective mechanisms of NDOs against respiratory pathogens may contribute to the development of add-on therapy or alternatives to antimicrobials.

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McIntyre Powder (MP) is a fine aluminum powder that was developed to prevent silicosis in gold and uranium mine workers in Ontario, Canada, and was administered to miners there from 1943 to 1979. Mine workers were exposed to high concentrations (35.6 mg/m3 ) of MP for approximately 10 min before every work shift. Contemporary physical and chemical characterizations of this powder have revealed that 12% of the powder is in the ultrafine particle size-range (nanoparticles); and the remaining 88%, in the fine particulate size range (below 2.5 µm in diameter). The confluence of ultrafine particulate (UFP) composition and high airborne concentration of MP would be expected to overwhelm the defense mechanisms of the lung and increase the lung dust burden of the mine worker exposed to respirable dust in the mine. Published studies revealing associations between air pollution particulates and increased risk for cardiovascular disease (CVD) shown a dose-response relationship with ambient PM2.5 and UFP and suggest that miners exposed to MP may also be at increased risk of CVD. The historical perspective of the use of MP in northern Ontario hard-rock mines and its potential implications for CVD in exposed mine workers are discussed.

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Vaccination through the upper respiratory tract (URT) is highly effective for the prevention of respiratory infectious diseases. Toll-like receptor (TLR)-based adjuvants are immunostimulatory and considered potential adjuvant candidates. However, the patterns of immune response to different TLRs at the URT have not been revealed. In this study, SPF mice were preexposed to TLR agonists intranasally to simulate the status of humans. Inflammatory response to TLR agonists and TLR signal-mediated adaptive immune responses were analyzed. The results revealed that similar to human tonsils, inflammatory response to stimulation with TLR4 or TLR2 agonist was attenuated in agonist-exposed mice but not in mice without this exposure. In contrast, TLR9 or TLR3 agonist preexposure did not affect the inflammatory response to restimulation by matching agonists. For the adaptive immune response, after agonist preexposure the antibody response to antigens adjuvanted with TLR4 or TLR2 agonist was substantially restricted, whereas, both antibody and T cell responses to antigens adjuvanted with TLR9 or TLR3 agonist were activated as robustly as in mice without agonist exposure. Moreover, we demonstrate that the mechanisms underlying the differential activation of TLRs are regulated at the level of TLR expression in innate and adaptive immune cells. These results indicate that TLRs on the cell surface (TLR4 and 2) and in the endolysosomal compartments (TLR9 and 3) display distinct immune response patterns. The findings provide important information for the use of TLR agonists as mucosal adjuvants and enhance our understanding of immune responses to bacterial and viral infections in the respiratory mucosa. IMPORTANCE Agonists of TLRs are potential adjuvant candidates for mucosal vaccination. We demonstrated that the TLR-mediated inflammatory and antibody responses in the URT of SPF mice exposed to extracellular TLR agonists were substantially restricted. In contrast, inflammatory and adaptive immune responses, including B and T cell activation, were not desensitized in mice exposed to intracellular TLR agonists. The distinct responsive patterns of extra and intracellular TLRs regulated at TLR expression in immune cells. The results indicated that TLRs differentially impact the innate and adaptive immune response in the URT, which contributes to the selection of TLR-based mucosal adjuvants and helps understand the difference between the immune response in bacterial and viral infections.

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Asthma, a chronic illness, is characterized by inflammation and airway constriction. Uncontrolled severe asthma is related to poor quality of life and increased utilization of health resources. Conventional treatments are associated with a significant amount of adverse effects. Recent years have seen the identification of various molecular effectors and signaling pathways as interesting targets for the biological therapy of severe asthma that is resistant to current therapies. Because they only target some downstream components of the inflammatory response in asthma, leaving other components unaffected, current biologic treatments only lower the exacerbation rate by 50%. If we focus on the upstream mediators of the inflammatory response in asthma, it might have a greater effect and be more efficient. Tezepelumab is a human monoclonal IgG2 antibody that specifically binds to thymic stromal lymphopoietin (TSLP) at the level of its TSLPR (thymic stromal lymphopoietin receptor) binding site, inhibiting the interaction between human TSLP and TSLPR. It is being used to treat the cytokines on the respiratory epithelial layer known as "alarmins." It is the only biologic drug available for treating severe uncontrolled asthma, despite limitations in biomarker and phenotype. In light of recent developments, the lack of knowledge on tezepelumab prompts us to publish a comprehensive systematic review. We discovered that regardless of blood eosinophil level and fractional exhaled nitric oxide levels, tezepelumab dramatically lowers asthma exacerbation in patients with severe uncontrolled asthma when compared to placebo. Tezepelumab also lessens patients' demand for healthcare resources while improving clinical indicators of lung function, health-related quality of life, and asthma management in patients. Tezepelumab plays a role in enhancing pre-bronchodilator FEV1 and lowering blood eosinophil count and fractional exhaled nitric oxide in patients with or without chronic allergies (FeNO). There have been no reports of fatalities or severe adverse events connected to tezepelumab.

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BACKGROUND: Fine particle pollution, specifically pollution by fine particulate matter (PM2.5), remains a significant concern in developing countries and plays an important role in the development and progression of respiratory diseases. Increasing evidences have demonstrated that long non-coding RNAs (lncRNAs) may act as vital molecules by binding to specific RNA-binding protein (RBP); however, their relationship with PM2.5 pollution is largely unexplored. OBJECTIVE: We investigated the association between lncRNA and respiratory system inflammation caused by PM2.5. METHODS: PM2.5 components were detected by gas chromatography-mass spectrometry (GC-MS), inductively coupled plasma-mass spectrometry (ICP-MS), and ionic chromatography. We established an inflammation model of PM2.5-induced toxicity in vivo (male and female SD rats, 0, 25, 50 and 100 mg/k PM2.5, 1, 7 and 14 days, single non-invasive tracheal instillation) and in vitro (rat alveolar macrophage cell line (NR8383), 0, 50, 100, 200, 400 µM PM2.5 for 24, 48, and 72 h). lncRNA high-throughput sequencing (lncRNA-seq) was used to investigate lncRNA profiles in PM2.5-treated NR8383 cells, and RNA interference (RNAi) was applied to explore the function of the target lncRNA. The mechanisms associated with specific lncRNAs were explored using comprehensive identification of RNA-binding proteins by mass spectrometry (ChIRP-MS) and western blot. RESULTS: PM2.5-treated NR8383 cells and SD rats exhibited respiratory inflammation. lncRNA AABR07005593.1 was a pro-inflammatory factor that regulated IL-6 levels. Mechanistically, ChIRP-MS and western blot analyses revealed that highly expressed lncRNA AABR07005593.1 interacted with MCCC1 to involve in the activation of NF-κB pathway, and ultimately promoted the expression of IL-6. CONCLUSION: This study demonstrated that PM2.5 induced inflammation in vivo and in vitro. Furthermore, lncRNA AABR07005593.1 bound to MCCC1 to potentiated IL-6 expression. Therefore, lncRNA AABR07005593.1 may act as a potential biomarker for PM2.5 inflammation.

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Lactobacillus (L.) rhamnosus CRL1505 accumulates inorganic polyphosphate (polyP) in its cytoplasm in response to environmental stress. The aim of this study was to evaluate the potential effects of polyP from the immunobiotic CRL1505 on an acute respiratory inflammation murine animal model induced by lipopolysaccharide (LPS). First, the presence of polyP granules in the cytoplasm of CRL1505 strain was evidenced by specific staining. Then, it was demonstrated in the intracellular extracts (ICE) of CRL1505 that polyP chain length is greater than 45 phosphate residues. In addition, the functionality of the genes involved in the polyP metabolism (ppk, ppx1 and ppx2) was corroborated by RT-PCR. Finally, the possible effect of the ICE of CRL1505 strain containing polyP and a synthetic polyP was evaluated in vivo using a murine model of acute lung inflammation. It was observed that the level of cytokines pro-inflammatory (IL-17, IL-6, IL-2, IL-4, INF-γ) in serum was normalized in mice treated with ICE, which would indicate that polyP prevents the local inflammatory response in the respiratory tract. The potential application of ICE from L. rhamnosus CRL1505 as a novel bioproduct for the treatment of respiratory diseases is one of the projections of this work.

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BACKGROUND: Facemask had increasingly been utilized as a personal protective measure to reduce exposure to ambient particulate matter (PM) during heavily-polluted days and routine life. However, evidence on the potential effects on cardiovascular system by wearing particulate-filtering facemask was limited. METHODS: We conducted a double-blinded randomized crossover trial (RCT) to evaluate the effects of wearing N95 facemasks on the molecular responses of cardiopulmonary system among 52 healthy college students in Beijing, China. We measured cardiopulmonary health indicators and collected biological samples before and after (up to 5 h at multiple time points) a 2-h walk to examine the changes in lung function, biomarkers of respiratory and systemic oxidative stress/inflammation. We applied linear mixed-effect models to evaluate the effect of the facemask-intervention on the health of cardio-pulmonary system. RESULTS: In the trial wearing real facemasks, FEV1 increased by 2.05% (95% CI: 0.27%-3.87%), 2.80% (95% CI: 1.00%-4.63%), and 2.87% (95% CI: 1.07%-4.70%) at V1 (30-min), V2 (3-h), and V3 (5-h) after the 2-h walk outsides, respectively. Compared with participants wearing the sham mask, the percentage change of nitrate in EBC was lower among those wearing the real mask. After the 2-h exposure, urinary MDA levels increased compared to the baseline in both trials. Real trial was lower than sham trial for 6 cytokines (i.e., IL-6, IL-10, IL-13, IL-17A, IFN-γ and TNF-α) in serum at 5-h post-exposure. Wearing facemasks on polluted days produced better improvement, however, on cleaner days, the improvement was weaker. CONCLUSIONS: Short-term use of N95 facemasks appeared to effectively reduce the levels of lung function declines, the respiratory oxidative stress, and the systemic inflammation/oxidative stress which may be induced by short-term exposure to PM. Wearing facemasks on polluted days (PM2.5 > 75 µg/m3) presented larger beneficial effects on the cardiopulmonary health than in clean days (PM2.5 < 75 µg/m3).

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Endoplasmic reticulum (ER) stress is an important reaction of airway epithelial cells in response to various stimuli, and may also be involved in the mucin secretion process. In the present study, the effect of ER stress on neutrophil elastase (NE)­induced mucin (MUC)5AC production in human airway epithelial cells was explored. 16HBE14o­airway epithelial cells were cultured and pre­treated with the reactive oxygen species (ROS) inhibitor, N­acetylcysteine (NAC), or the ER stress chemical inhibitor, 4­phenylbutyric acid (4­PBA), or the cells were transfected with inositol­requiring kinase 1α (IRE1α) small interfering RNA (siRNA) or X­box­binding protein 1 (XBP1) siRNA, respectively, and subsequently incubated with NE. The results obtained revealed that NE increased ROS production in the 16HBE14o­cells, with marked increases in the levels of ER stress­associated proteins, such as glucose­regulated protein 78 (GRP78), activating transcription factor 6 (ATF6), phosphorylated protein kinase R­like endoplasmic reticulum kinase (pPERK) and phosphorylated (p)IRE1α. The protein and mRNA levels of spliced XBP1 were also increased, and the level of MUC5AC protein was notably increased. The ROS scavenger NAC and ER stress inhibitor 4­PBA were found to reduce ER stress­associated protein expression and MUC5AC production and secretion. Further analyses revealed that MUC5AC secretion was also attenuated by IRE1α and XBP1 siRNAs, accompanied by a decreased mRNA expression of spliced XBP1. Taken together, these results demonstrate that NE induces ER stress by promoting ROS production in 16HBE14o­airway epithelial cells, leading to increases in MUC5AC protein production and secretion via the IRE1α and XBP1 signaling pathways.

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PURPOSE: We aimed to critically review the available information on the potential contribution of excessive kallikrein-kinin systems (KKSs) activation to severe respiratory inflammation in SARS-CoV-2 infection, and the likely consequence of ACE inhibition in seriously affected patients. METHODS: The literature related to the above topic was reviewed including papers that analysed the connections, actions, interactions, consequences and occasionally suggestions for rational interventions. RESULTS/CONCLUSION: Severe broncho-alveolar inflammation seems to be caused, at least in part, by upregulation of the KKS that increases plasma and/or local tissue concentrations of bradykinin (BK) in patients with COVID-19 infection. Besides KKS activation, suppression of ACE activity results in decreased bradykinin degradation, and these changes in concert can lead to excessive BK B1 and B2 receptor (BKB1R/BKB2R) activation. Aminopeptidase P (APP), and carboxypeptidase N also degrade bradykinin, but their protein expression and activity are unclear in COVID-19 infection. On the other hand, ACE2 expression is upregulated in patients with COVID-19 infection, so ACE2 activity is unlikely to be decreased despite blockade of part of ACE2 by the virus for entry into the cells. ACE2 cleaves lys-des-arginine9BK and arg-des-arginine9BK, the active metabolites of bradykinin, which stimulate the BKB1R receptor. Stimulation of BKB1R/BKB2R can exacerbate the pulmonary inflammatory response by causing vascular leakage and edema, vasodilation, smooth muscle spasm and stimulation of pain afferent nerves. Despite all uncertainties, it seems rational to treat comorbid COVID patients with serious respiratory distress syndrome with ARBs instead of high-dose ACE inhibitor (ACEi) that will further decrease bradykinin degradation and enhance BKB1R/BKB2R activation, but ACEi may not be contraindicated in patients with mild pulmonary symptoms.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel member of the genus of betacoronavirus, which caused a pandemic of coronavirus disease 2019 (COVID-19) worldwide. The innate immune system plays a critical role in eliminating the virus, which induces inflammatory cytokine and chemokine secretion, produces different interferons, and activates the adaptive immune system. Interactions between the autonomic nervous system and innate immunity release neurotransmitters or neuropeptides to balance the excess secretion of inflammatory cytokines, control the inflammation, and restore the host homeostasis. However, more neuro-immune mechanisms to defend against viral infection should be elucidated. Here, we mainly review and provide our understanding and viewpoint on the interaction between respiratory viral proteins and host cell receptors, innate immune responses to respiratory viral infection, and the autonomic neural regulation of the innate immune system to control respiratory viruses caused by lungs and airways inflammation.

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BACKGROUND: PM2.5 pollution waves (PPWs) are severe air pollution events with extremely high-level concentration of ambient PM2.5. PPWs, such as haze days, were suggested to be associated with increased cardiopulmonary mortality and morbidity. However, the biological mechanism response to ambient PM2.5 during PPWs is still unclear. METHODS: A randomized crossover trial was conducted on 29 healthy young adults. Repeated health measurements were performed before, during and after two typical PPWs under filtered and sham indoor air purification, with a washout interval of at least 2 weeks. Health parameters including blood pressure (BP), pulmonary function, fractional exhaled nitric oxide (FeNO) and circulating biomarkers which reflect platelet activation, blood coagulation and systematic oxidative stress were measured. RESULTS: Ambient PM2.5 levels elevated apparently during PPWs. Under sham purification, significant increase in FeNO and soluble P-selectin (sP-selectin) and decreases in pulmonary function were observed from pre-PPWs period to during-PPWs period. The changes in health biomarkers as mentioned above became attenuated and insignificant under filtered condition. For instance, sP-selectin increased by 12.0% (95% CI: 3.8%, 20.8%) during-PPWs periods compared with pre-PPWs periods under sham purification, while non-significant change was observed under filtered condition. Significant associations between time-weighted personal PM2.5 exposure and increased levels of health biomarkers including FeNO, sP-selectin, oxidized low-density lipoprotein (ox-LDL) and 8-isoprostane (8-isoPGF2α) were found. CONCLUSION: PPWs could affect cardiopulmonary health through systematic oxidative stress, platelet activation and respiratory inflammation in healthy adults, and short-term indoor air purification could alleviate the adverse cardiopulmonary effects.

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Catalase (CAT) and myeloperoxiase (MPO) are heme-containing enzymes that have attracted attention for their role in the etiology of numerous respiratory disorders such as cystic fibrosis, bronchial asthma, and acute hypoxemic respiratory failure. However, information regarding the interrelationship and competition between the two enzymes, free iron accumulation, and decreased levels of non-enzymatic antioxidants at sites of inflammation is still lacking. Myeloperoxidase catalyzes the generation of hypochlorous acid (HOCl) from the reaction of hydrogen peroxide (H2O2) and chloride (Cl-). Self-generated HOCl has recently been proposed to auto-inhibit MPO through a mechanism that involves MPO heme destruction. Here, we investigate the interplay of MPO, HOCl, and CAT during catalysis, and explore the crucial role of MPO inhibitors and HOCl scavengers in protecting the catalytic site from protein modification of both enzymes against oxidative damage mediated by HOCl. We showed that CAT not only competes with MPO for H2O2 but also scavenges HOCl. The protective role provided by CAT versus the damaging effect provided by HOCl depends in part on the ratio between MPO/CAT and the affinity of the enzymes towards H2O2 versus HOCl. The severity of such damaging effects mainly depends on the ratio of HOCl to enzyme heme content. In addition to its effect in mediating protein modification and aggregation, HOCl oxidatively destroys the catalytic sites of the enzymes, which contain porphyrin rings and iron. Thus, modulation of MPO/CAT activities may be a fundamental feature of catalysis, and functions to down-regulate HOCl synthesis and prevent hemoprotein heme destruction and/or protein modification.

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