Surfactant Protein Research Articles

A Study Into Systemic and Oral Levels of Proinflammatory Biomarkers Associated With Endpoints After Active Non‐Surgical Periodontal Therapy

ABSTRACTAimTo analyse whether some selected inflammatory biomarkers collected from venous blood and gingival crevicular fluid (GCF) were associated with the outcome of non‐surgical periodontal therapy.Materials and MethodsTwo‐hundred and nine patients affected by periodontitis were enrolled in the study, who had undergone steps I and II therapy as well as a non‐surgical re‐instrumentation (NSRI) of periodontal pockets after 6 months. Serum (SE), plasma (PL) and GCF samples were quantitatively analysed for the following inflammatory biomarkers: active matrix metalloproteinase‐8 (aMMP‐8), prostaglandin E2 (PGE2) and surfactant protein D (SP‐D). Therapy outcomes were evaluated using a ‘treat‐to‐target’ endpoint (T2T) at the patient level, defined as ≤ 4 sites with pocket depth ≥ 5 mm.ResultsPatients presented with 23 ± 6 teeth (mean ± SD) at baseline. After steps I and II therapy, 41.6% of the patients reached T2T and after NSRI 47.4%. Univariate analysis identified a potential association between high levels of PL‐SP‐D and more favourable treatment outcomes. Multivariate binary logistic regression adjusted for sex, mean baseline probing depth, diabetes and current smoking status confirmed an independent relationship between baseline PL‐SP‐D and the T2T after steps I and II therapy (aOR 0.432, p = 0.011), implying that a higher level PL‐SP‐D at baseline is associated with a > 50% reduced risk of failing T2T. However, no such association was found for PL‐SP‐D and NSRI.ConclusionHigher baseline PL‐SP‐D levels might be associated with more favourable treatment outcomes after steps I and II therapy. This may be due to its role in the regulation of neutrophil function. However, further investigation is required to confirm this hypothesis. If proven, PL‐SP‐D could play a role as a biomarker for identifying individuals who respond differentially to primary therapy.

Analysis of serum phase proteins and emulsifiers on the whipping capabilities of aerated emulsions: From the perspective of air-liquid interface rheology

In aerated emulsions, the serum phase plays a crucial role in determining whipping capabilities. However, the effects of serum phase components on emulsion properties remain largely unexplored and continue to be a mystery. This study takes a micro-level approach, focusing on the air-liquid interfacial rheology by incorporating different types of surfactants (proteins and emulsifiers) into the serum phase. It systematically explores the effects on the serum phase interface, emulsion properties, whipping capabilities, and foam stability in a stepwise manner. Proteins only slightly affect the strength of the air-liquid interface, primarily improving the capacity to trap bubbles at the initial whipping stage, thereby boosting the overrun of the aerated emulsion. The high viscoelastic modulus of the interface membrane is greatly influenced by the presence of solid lipid nanoparticles of glycerol monostearate (GMS SLN), leading to a reduction in whipping time and improved surface-mediated partial coalescence. This ultimately enhances the quality and stability of the foam system. Tween 80, due to its hydrophilic properties, is able to quickly adsorb at the air-liquid interface using the Gibbs-Marangoni mechanism. This helps to expedite the end of the whipping process and ultimately improves the foam quality. On the contrary, glycerol monooleate (GMO), a lipophilic emulsifier for liquids, struggles to effectively adsorb at the interface, leading to decreased stability of the air-liquid interface in the system and resulting in poor whipping capabilities. This paper delves into the mechanism by which different surfactants affect the whipping capabilities of aerated emulsions through an analysis of serum phase composition, laying the groundwork for enhancing formulation design.

SPA Promotes Atherosclerosis Through Mediating Macrophage Foam Cell Formation-Brief Report.

Atherosclerosis is a progressive inflammatory disease in which macrophage foam cells play a central role in disease pathogenesis. SPA (surfactant protein A) is a lipid-associating protein involved with regulating macrophage function in various inflammatory diseases. However, the role of SPA in atherosclerosis and macrophage foam cell formation has not been investigated. SPA expression was assessed in healthy and atherosclerotic human coronary arteries and the brachiocephalic arteries of wild-type or ApoE-deficient mice fed high-fat diets for 4 weeks. Hypercholesteremic wild-type and SPA-deficient mice fed a high-fat diet for 6 weeks were investigated for atherosclerotic lesions in vivo. In vitro experiments using RAW264.7 macrophages, primary resident peritoneal macrophages extracted from wild-type or SPA-deficient mice, and human monocyte-derived macrophages from the peripheral blood of healthy donors determined the functional effects of SPA in macrophage foam cell formation. SPA expression was increased in atherosclerotic lesions in humans and ApoE-deficient mice and in response to a proatherosclerotic stimulus in vitro. SPA deficiency reduced the lipid profiles induced by hypercholesterolemia, attenuated atherosclerosis, and reduced the number of lesion-associated macrophage foam cells. In vitro studies revealed that SPA deficiency reduced intracellular cholesterol accumulation and macrophage foam cell formation. Mechanistically, SPA deficiency dramatically downregulated the expression of scavenger receptor CD36 (cluster of differentiation antigen 36) cellular and lesional expression. Importantly, SPA also increased CD36 expression in human monocyte-derived macrophages. Our results elucidate that SPA is a novel factor promoting atherosclerosis development. SPA enhances macrophage foam cell formation and atherosclerosis by increasing scavenger receptor CD36 expression, leading to increasing cellular OxLDL influx.

Serum biomarkers in neuroendocrine cell hyperplasia of infancy.

Neuroendocrine cell hyperplasia of infancy (NEHI) is a form of childhood interstitial lung disease of unknown origin associated with hyperplasia of pulmonary neuroendocrine cells (PNECs). Diagnosis is based on the characteristic clinical picture and typical radiological imaging, and, in some cases, on lung biopsies. To date, no biochemical indicators of the disease have been identified. We aimed to determine biomarkers that could be useful in the management of children diagnosed with NEHI. Patients with NEHI and healthy children were enrolled. Concentrations of serum biomarkers secreted by PNECs (calcitonin gene-related peptide and gastrin-releasing peptide) and biomarkers of the destruction of alveolar capillary membrane (surfactant proteins A and D [SP-A and SP-D]; glycoprotein Krebs von den Lungen-6 [KL-6]; metalloproteinases 7 and 9 [MMP-7 and MMP-9]; tissue inhibitor of metalloprotease 1) were measured. Fifty-two children with NEHI and 23 healthy children were included in the study. The median age of children with NEHI was 3.9 years. There were no differences in serum levels of biomarkers secreted by PNECs between groups. KL-6 levels were significantly higher in children with NEHI than in healthy ones (median 119.6 vs. 92.1 U/mL, p = 0.003); however, concentrations of KL-6 were low in both groups. No significant differences existed between groups for the remaining biomarkers associated with the destruction of the alveolar-capillary membrane. Measurement of serum biomarkers released by PNECs and those associated with the destruction of the alveolar-capillary membrane does not appear to be useful in the management of children with NEHI.

Biomarkers of rheumatoid arthritis-associated interstitial lung disease: a systematic review and meta-analysis

BackgroundInterstitial Lung Disease (ILD) represents the most common extra-articular manifestation of Rheumatoid Arthritis (RA) and is a major cause of mortality. This study aims to identify and evaluate biomarkers associated with Rheumatoid Arthritis-Associated Interstitial Lung Disease (RA-ILD).MethodsWe searched PubMed, Cochrane Library, EMBASE, and Web of Science databases for studies related to biomarkers of RA-ILD up until October 7, 2023. The Newcastle-Ottawa Scale (NOS) and standards recommended by the Agency for Healthcare Research and Quality (AHRQ) were used for quality assessment, and meta-analysis was conducted using Stata18.0 software.ResultsA total of 98 articles were assessed for quality, 48 of which were included in the meta-analysis. 83 studies were of high quality, and 15 were of moderate quality. The meta-analysis showed significant differences in biomarkers such as C-Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Anti-Cyclic Citrullinated Peptide (anti-CCP) antibody, Rheumatoid Factor (RF), Krebs von den Lungen-6 (KL-6), Surfactant Protein D (SP-D), Carcinoembryonic Antigen (CEA), Carbohydrate Antigen 19-9 (CA19-9), Matrix Metalloproteinase-7 (MMP-7), C-X-C Motif Chemokine Ligand 10 (CXCL-10), and Neutrophil-to-Lymphocyte Ratio (NLR) between RA-ILD patients and RA patients. However, Platelet-to-Lymphocyte Ratio [Platelet-to-Lymphocyte Ratio (PLR)], Cancer Antigen 125 [Cancer Antigen 125 (CA-125)], and Cancer Antigen 153 [Cancer Antigen 153 (CA-153)] did not show significant differences between the two groups. KL-6, MMP-7, and Human Epididymis Protein 4 (HE4) are negatively correlated with lung function, and KL-6 is associated with the prognosis of RA-ILD.ConclusionsBiomarkers hold promising clinical value for prediction, diagnosis, severity assessment, and prognosis evaluation in RA-ILD. However, these findings need to be validated through multicenter, large-sample, prospective cohort studies.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023448372.

Loss of Surfactant Protein A Alters Perinatal Lung Morphology and Susceptibility to Hyperoxia-Induced Bronchopulmonary Dysplasia

Bronchopulmonary dysplasia (BPD) is a condition of poor alveolar formation that causes chronic breathing impairment in infants born prematurely. Preterm lungs lack surfactant and are vulnerable to oxidative injuries driving the development of BPD. Our recent studies reported that surfactant protein A (SP-A) genetic variants influence susceptibility to neonatal lung disease. SP-A modulates activation of alveolar macrophages and parturition onset in late gestation. We asked whether a lack of SP-A alters alveolarization in a mouse model of hyperoxia-induced BPD. SP-A-deficient and control newborn mice were exposed to either clinically relevant 60% O2 hyperoxia or normoxia for 5–7 days. Alveolar formation was then assessed by mean linear intercept (MLI) and radial alveolar count (RAC) measurements in lung tissue sections. We report that the combination of SP-A deficiency and hyperoxia reduces alveolar growth compared to WT mice. The morphometric analysis of normoxic SP-A-deficient lungs showed lower RAC compared to controls, indicating reduced alveolar number. In the presence of hyperoxia, MLI was higher in SP-A-deficient lungs compared to controls. Differences were statistically significant for female pups. Spatial proteomic profiling of lung tissue sections showed that hyperoxia caused a 4-fold increase in the DNA damage marker γH2Ax in macrophages of SP-A-deficient lungs compared to normoxia. Our short report suggests an important role for SP-A in perinatal lung development and the protection of lung macrophages from oxidant injury. These studies warrant future investigation to discern the temporal interaction of SP-A, gender, oxidant injury, and lung macrophages in perinatal alveolar formation and development of BPD.

Generation of SFTPC-mCherry knock-in reporter human embryonic stem cell line, WAe001-A-2H, using CRISPR/Cas9-based gene targeting

The SFTPC gene is responsible for the production of the pulmonary surfactant protein C (SPC), a highly hydrophobic molecule that plays a crucial role in maintaining lung integrity through its influence on the synthesis of alveolar surfactant proteins. In this study, we harnessed the CRISPR/Cas9 system for precise genome editing to create a modified H1 human embryonic stem cell (hESC) line, incorporating the SFTPC-mCherry reporter construct. Therefore, the engineered SFTPC-mCherry knock-in (KI) hESC line can serve as an effective tool for tracking the expression patterns of the SFTPC gene as alveolar type 2 cells differentiate from hESCs.

Cohort study of serological biomarkers for interstitial lung disease in patients with rheumatoid arthritis

Objective Interstitial lung disease (ILD) is an important cause of mortality in patients with rheumatoid arthritis (RA). Early RA-ILD detection is essential to improve prognosis. Here, we investigated eight serological biomarkers that may contribute to RA-ILD detection. Method Fifty-five patients from the Early Rheumatoid Arthritis Program were evaluated for ILD with high-resolution computed tomography (HRCT) and pulmonary function tests (PFTs) using the SCAPIS protocol. Blood samples were obtained for biomarker analysis, and patients’ clinical records were reviewed. We defined ILD using five different models based on the measurements used to confirm ILD: Model A = HRCT; B = PFTs; C = A plus B; D = C plus symptoms; and E = D plus inhalations. Results Among 55 patients, two had an ILD diagnosis before the study, but over one-third fulfilled the ILD criteria. Cancer antigen 15-3 (CA15-3) and matrix metalloproteinase-7 (MMP-7) differentiated between RA with and without ILD (all p < 0.05). Surfactant protein D (SP-D) showed similar trends, as did macrophage inflammatory protein-1β (MIP-1β) and chitinase 3-like protein-1 (YKL-40). Based on Pearson’s correlation coefficients, MIP-1β and YKL-40 were significantly correlated with DAS28 (MIP-1β: 0.3; YKL-40: 0.4), ESR (MIP-1β: 0.3; YKL-40: 0.4), and CRP (only MIP-1β: 0.4) (all p < 0.05). CA15-3 was correlated with rheumatoid factor and anti-citrullinated peptide antibodies (Pearson’s correlation 0.3; both p = 0.03). Conclusions CA15-3 was the most significant biomarker for ILD detection in RA patients with stable low disease activity, closely followed by MMP-7. SP-D, MIP-1β, and YKL-40 may also contribute to RA-ILD diagnosis.

Contemporary Concise Review 2023: Interstitial lung disease.

In this review, we have discussed several important developments in 2023 in Interstitial Lung Disease (ILD). The association of pollution with genetic predispositions increased the risk of Idiopathic Pulmonary Fibrosis (IPF). An interesting comorbidity of malnutrition was not adequately recognized in ILD. Novel genes have been identified in IPF involving predominantly short telomere length and surfactant protein production leading to alveolar epithelial cell dysfunction. Genetics also predicted progression in IPF. Crosstalk between vascular endothelial cells and fibroblasts in IPF mediated by bone morphogenic protein signalling may be important for remodelling of the lung. A novel modality for monitoring of disease included the 4-min gait speed. New treatment modalities include inhaled pirfenidone, efzofitimod, for sarcoidosis, and earlier use of immunosuppression in connective tissue disease-ILD.

Betamethasone improved near-term neonatal lamb lung maturation in experimental maternal asthma.

Maternal asthma is associated with increased rates of neonatal lung disease, and fetuses from asthmatic ewes have fewer surfactant-producing cells and lower surfactant-protein B gene (SFTPB) expression than controls. Antenatal betamethasone increases lung surfactant production in preterm babies, and we therefore tested this therapy in experimental maternal asthma. Ewes were sensitised to house dust mite allergen, and an asthmatic phenotype induced by fortnightly allergen lung challenges; controls received saline. Pregnant asthmatic ewes were randomised to receive antenatal saline (asthma) or 12mg intramuscular betamethasone (asthma+beta) at 138 and 139 days of gestation (term=150 days). Lambs were delivered by Caesarean section at 140 days of gestation and ventilated for 45min before tissue collection. Lung function and structure were similar in control lambs (n=16, 11 ewes) and lambs from asthma ewes (n=14, 9 ewes). Dynamic lung compliance was higher in lambs from asthma+beta ewes (n=12, 8 ewes) compared to those from controls (P=0.003) or asthma ewes (P=0.008). Lung expression of surfactant protein genes SFTPA (P=0.048) and SFTPB (P<0.001), but not SFTPC (P=0.177) or SFTPD (P=0.285), was higher in lambs from asthma+beta than those from asthma ewes. Female lambs had higher tidal volume (P=0.007), dynamic lung compliance (P<0.001), and SFTPA (P=0.037) and SFTPB gene expression (P=0.030) than males. These data suggest that betamethasone stimulates lung maturation and function of near-term neonates, even in the absence of impairment by maternal asthma.

Moving on from clinical animal-derived surfactants to peptide-based synthetic pulmonary surfactant.

Research on lung surfactant has exerted a great impact on newborn respiratory care and significantly improved survival and outcome of preterm infants with respiratory distress syndrome (RDS) due to surfactant deficiency because of lung immaturity. Current clinical, animal-derived, surfactants are among the most widely tested compounds in neonatology However, limited availability, high production costs, and ethical concerns about using animal-derived products constitute important limitations in their universal application. Synthetic lung surfactant offers a promising alternative to animal-derived surfactant by providing improved consistency, quality and purity, availability and scalability, ease of production and lower costs, acceptance, and safety for the treatment of neonatal RDS and other lung conditions. Third-generation synthetic surfactants built around surfactant protein B (SP-B) and C (SP-C) peptide mimics stand at the forefront of innovation in neonatal pulmonary medicine, while nasal continuous positive airway pressure (nCPAP) has become the standard non-invasive respiratory support for preterm infants. nCPAP can prevent the risk of chronic lung disease (bronchopulmonary dysplasia) and reduce lung injury by avoiding intubation and mechanical ventilation, is a relatively simple technique and can be initiated safely and effectively in the delivery room. Combining nCPAP with noninvasive, preferably aerosol, delivery of synthetic lung surfactant promises to improve respiratory outcomes for preterm infants, especially in low-and-middle income countries.

EMC3 regulates trafficking and pulmonary toxicity of the SFTPCI73T mutation associated with interstitial lung disease.

The most common mutation in surfactant protein C gene (SFTPC), SFTPCI73T, causes interstitial lung disease with few therapeutic options. We previously demonstrated that EMC3, an important component of the multiprotein endoplasmic reticulum membrane complex (EMC), is required for surfactant homeostasis in alveolar type 2 epithelial (AT2) cells at birth. In the present study, we investigated the role of EMC3 in the control of SFTPCI73T metabolism and its associated alveolar dysfunction. Using a knock-in mouse model phenocopying the I73T mutation, we demonstrated that conditional deletion of Emc3 in AT2 cells rescued alveolar remodeling/simplification defects in neonatal and adult mice. Proteomic analysis revealed that Emc3 depletion reversed the disruption of vesicle trafficking pathways and rescued the mitochondrial dysfunction associated with I73T mutation. Affinity purification-mass spectrometry analysis identified potential EMC3 interacting proteins in lung AT2 cells, including Valosin Containing Protein (VCP) and its interactors. Treatment of SftpcI73T knock-in mice and SFTPCI73T expressing iAT2 cells derived from SFTPCI73T patient-specific iPSCs with the specific VCP inhibitor CB5083 restored alveolar structure and SFTPCI73T trafficking respectively. Taken together, the present work identifies the EMC complex and VCP in the metabolism of the disease-associated SFTPCI73T mutant, providing novel therapeutical targets for SFTPCI73T-associated interstitial lung disease.

The bronchoalveolar lavage dilution conundrum: an updated view on a long-standing problem.

Bronchoalveolar lavage (BAL) is used by researchers to study molecular interactions within healthy and diseased human lungs. However, the utility of BAL fluid measurements may be limited by difficulties accounting for dilution of the epithelial lining fluid (ELF) sampled and inconsistent collection techniques. The use of endogenous markers to estimate ELF dilution has been proposed as a potential method to normalize acellular molecule measurements in BAL fluid, but these markers are also imperfect and prone to inaccuracy. The focus of this report is to review factors that affect the interpretation of acellular molecule measurements in lung ELF and present original data comparing the performance of several BAL dilution markers during health and in a human endobronchial endotoxin challenge model of acute inflammation. Our findings suggest that incomplete ELF and lavage fluid mixing, flux of markers across the alveolar barrier, and lung inflammation are all possible factors that can affect marker performance. Accounting for these factors, we show that commonly used markers including urea, total protein, albumin, and immunoglobulin M are likely unreliable BAL dilution markers. In contrast, surfactant protein D appears to be less affected by these factors and may be a more accurate and biologically plausible marker to improve the reproducibility of acellular BAL component measurements across individuals during health and inflammatory states.NEW & NOTEWORTHY In this report, mathematical prediction models and real-world measurements are used to compare the performance of molecular markers of dilution in bronchoalveolar lavage fluid samples. Effects of acute inflammation within individual subjects are highlighted. These findings inform recommendations for normalizing measurements across bronchoalveolar lavage samples and highlight the need for additional markers to improve the rigor of translational studies utilizing bronchoalveolar lavage measurements.

Peanut de-oiling at room temperature by micro-aqueous hydration: Co-destabilization driven by oleosome coalescence and protein aggregation

The peanut de-oiling industry currently lacks efficient processing technologies for de-oiling at low or room temperatures. A novel method, micro-aqueous extraction (MAE), offers over 93 % de-oiling efficiency at room temperature and is also effective for other oilseeds like sesame, camellia, and rapeseed. Despite its effectiveness, the exact mechanism behind oleosomes destabilization at a critical hydration level or oil volume fraction (φ ∼ 0.75) is not fully understood. This study investigates how MAE affects peanut oleosome size, paste stability, and the interfacial properties of surfactant proteins. Results showed that micro-aqueous hydration and agitation caused small droplets (85.6 vol% < 10 μm) to coalesce into larger droplets (90.0 vol% > 30 μm) due to press-induced rupture of the liquid film. Simultaneously, agitation decreased water mobility and protein intrinsic fluorescence, while increasing paste viscosity, leading to protein aggregation. This aggregation further promoted oleosome coalescence. Additionally, hydration and agitation weakened the ability of membrane proteins to stabilize oleosomes by increasing interfacial tension and decreasing dilatational storage modulus. The insights into the peanut oleosome destabilization mechanism for MAE provide a foundation for scaling up the process, with the potential to replace current hot and cold pressing techniques.

The surfactant protein B polymorphisms (rs7316 and rs1130866) and their correlation with disease progression of COVID-19

BackgroundIt is critical to examine the pathogenic pathways in coronavirus disease 2019 (COVID-19) that resulted in the development of severe lung injury. Surfactant protein B (SFTPB) is a vital component for sustaining life and serves pivotal functions in the host’s defensive mechanisms and alveolar surface tension reduction. Our study aimed to determine the effect of SFTPB rs7316 and rs1130866 variants on the course of disease in COVID-19 patients. MethodsThe study cohort comprised 3,184 individuals diagnosed with COVID-19. We employed the RFLP approach to determine the variations of the SFTPB genes. ResultsSFTPB rs7316 did not exhibit a statistically significant correlation with COVID-19 mortality across different inheritance models. But, after making more changes for SARS-CoV-2 variants, it was found that there was a strong link between the TT and TC genotypes of SFTPB rs7316 and death rates, especially for the Delta variant. Furthermore, our study’s findings indicate a significant association between the SFTPB rs1130866 G allele and an elevated risk of mortality in COVID-19 across all variants of SARS-CoV-2. ConclusionsThe use of the SFTPB rs1130866 marker has the potential to facilitate the prediction of COVID-19 severity. On the other hand, for SFTPB rs7316, this kind of prediction seems to depend on the particular SARS-CoV-2 variants.

Efficacy and safety of oral versus intravenous cyclophosphamide in treatment of connective tissue disease-related interstitial lung disease.

Interstitial lung disease (ILD) resulting from connective tissue disease (CTD) greatly undermines people's health. Cyclophosphamide (CYC) is a widely used agent in treating CTD-ILD. We compared the efficacy and safety of oral and intravenous CYC in CTD-ILD treatment. The retrospectively enrolled CTD-ILD patients were divided into the oral and intravenous CYC groups. The chest high-resolution computed tomography examination, forced vital capacity (FVC), lung carbon monoxide diffusion capacity (Dlco) determinations, and 6 min walk test (6MWT) were performed pre-treatment and at the 3rd, 6th, and 12th months posttreatment. Radiographic ILD severity was assessed using the Warrick score. Krebs Von den Lungen-6, surfactant protein A (SP-A), SP-D, and erythrocyte sedimentation rate (ESR) before and at the 12th month post-treatment were determined. CYC cumulative dose and occurrence of adverse reactions during treatment were recorded. CYC cumulative dose in the intravenous CYC group was reduced. Compared with oral CYC treatment, intravenous CYC caused decreased Warrick score and increased FVC and 6MWT at the 6th month, and elevated DLco at the 3rd and 6th months posttreatment. SP-A, SP-D and ESR levels in both groups were reduced 12 months posttreatment, with a more evident decrease in the intravenous CYC group. Intravenous CYC had lower total adverse reaction incidence. Compared with oral CYC, intravenous CYC decreases Warrick score and increases FVC and 6MWT at 6 months posttreatment, and reduces SP-A, SP-D, and ESR levels after 12 months of treatment, which shows low CYC cumulative dose and adverse reaction incidence in treating CTD-ILD.

Liquid Biopsy in Lung Cancer: Nano–Flow Cytometry Detection of Non–Small Cell Lung Cancer in Blood

Non–small cell lung cancer (NSCLC) remains a leading cause of global mortality, with current screening and diagnostic methods often lacking in sensitivity and specificity. In our endeavor to develop precise, objective, and easily accessible diagnostic biomarkers for NSCLC, this study aimed to leverage rapidly evolving liquid biopsy techniques in the field of pathology to differentiate NSCLC patients from healthy controls by isolating peripheral blood samples and enriching extracellular vesicles (EVs) containing lung-derived proteins (thyroid transcription factor-1 [TTF-1] and surfactant protein B [SFTPB]), along with the cancer-associated protein CD151+ EVs. Additionally, for practical applications, we established a nano–flow cytometry assay to detect plasma EVs readily. NSCLC patients demonstrated significantly reduced counts of TTF-1+ EVs and CD151+ EVs in plasma compared with healthy controls (P < .0001), whereas SFTPB+ EVs showed no significant difference (P > .05). Integrated analysis of TTF-1+, CD151+, and SFTPB+ EVs yielded an area under the curve values of 0.913 and 0.854 in the discovery and validation cohorts, respectively. Thus, although further validation is essential, the newly developed technologies are of great significance for the robust detection of NSCLC biomarkers.

Lung antimicrobial proteins and peptides: from host defense to therapeutic strategies.

Representing severe morbidity and mortality globally, respiratory infections associated with chronic respiratory diseases, including complicated pneumonia, asthma, interstitial lung disease, and chronic obstructive pulmonary disease, are a major public health concern. Lung health and the prevention of pulmonary disease rely on the mechanisms of airway surface fluid secretion, mucociliary clearance, and adequate immune response to eradicate inhaled pathogens and particulate matter from the environment. The antimicrobial proteins and peptides contribute to maintaining an antimicrobial milieu in human lungs to eliminate pathogens and prevent them from causing pulmonary diseases. The predominant antimicrobial molecules of the lung environment include human α- and β-defensins and cathelicidins, among numerous other host defense molecules with antimicrobial and antibiofilm activity such as PLUNC (palate, lung, and nasal epithelium clone) family proteins, elafin, collectins, lactoferrin, lysozymes, mucins, secretory leukocyte proteinase inhibitor, surfactant proteins SP-A and SP-D, and RNases. It has been demonstrated that changes in antimicrobial molecule expression levels are associated with regulating inflammation, potentiating exacerbations, pathological changes, and modifications in chronic lung disease severity. Antimicrobial molecules also display roles in both anticancer and tumorigenic effects. Lung antimicrobial proteins and peptides are promising alternative therapeutics for treating and preventing multidrug-resistant bacterial infections and anticancer therapies.

Biomarker trajectory for earlier detection of lung cancer

To determine whether an algorithm based on repeated measurements of a panel of four circulating protein biomarkers (4MP) for lung cancer risk assessment results in improved performance over a single time measurement. We conducted data analysis of the 4MP consisting of the precursor form of surfactant protein B, cancer antigen 125, carcinoembryonic antigen, and cytokeratin-19 fragment in pre-diagnostic sera from 2483 ever-smoker participants (389 cases and 2094 randomly selected non-cases) in the Prostate, Lung, Colorectal, Ovarian (PLCO) Study who had at least two sequential blood collections over 6 years. A parametric empirical Bayes (PEB) algorithm, which incorporates participant biomarker history at each time point, was compared to a single-threshold (ST) method. Among ever-smoker participants, the PEB approach yielded an additional 4% improvement in the AUC compared to the ST approach (P-value: 0.009). When considering an ≥10 PY smoking history and at a fixing the specificity corresponding to 1% 6-year lung cancer risk, PEB resulted in significant improvement in the sensitivity (SenPEB:96.3% vs SenST:91.0%; P-value: 6.7e-3). The PEB algorithm identified 17 of the 35 cases that remained ST negative, at an average of 1.26 years before diagnosis. Ten case individuals who were positive based on ST at an average of 1.03 years prior to diagnosis were identified earlier by PEB, at an average of 2.70 years. An algorithm based on repeated measurements of the 4MP improves sensitivity and results in an earlier detection of lung cancer compared to a single-threshold method. This study was supported by NIH Grant Nos. U01CA271888, U01CA194733, U01CA213285, NCI EDRN U01 CA200468, P30CA016672, and U24CA086368; the Cancer Prevention & Research Institute of Texas RP180505 and RP160693; the SPORE P50CA140388; the CCTS TR000371; and the generous philanthropic contributions to The University of Texas MD Anderson Cancer Center Moon Shots Program and the Lyda Hill Foundation.

The value of surfactant protein a in evaluating the severity and prognosis in community-acquired pneumonia patients

BackgroundPrevious research has discovered that surfactant protein A (SP-A) is involved in the pathophysiology processes of certain lung illnesses. However, no definitive clinical studies have delved into the function of SP-A in individuals afflicted with community-acquired pneumonia (CAP). A prospective cohort study was used to investigate the relationships between blood SP-A levels and the severity and prognosis among CAP patients.Materials and methodsThis study included 260 patients with CAP. Clinical traits and demographic data were examined during hospitalization. The concentrations of serum SP-A and serum interleukin-6 (IL-6) were determined by enzyme-linked immunosorbent assay (ELISA). In addition, to evaluate the severity of CAP, a variety of scores, including the CURB-65, PSI, SMART-COP, and APACHE II, were employed.ResultsThe serum levels of SP-A at admission exhibited a gradual decline as the severity scores of CAP increased. Through Spearman correlation analysis, we observed an association between serum SP-A and some clinical indicators among CAP patients. Furthermore, results from a multiple linear regression model suggested changes in PSI scores (-17.868 scores, 95% CI: -32.743, -2.993) affect serum SP-A more than CURB-65 (-0.547 scores, 95% CI: -0.964, -0.131), SMART-COP (-1.097 scores, 95% CI: -1.889, -0.304) and APACHE II (-3.475 scores, 95% CI: -5.874, -1.075) with age, hypertension, diabetes mellitus, cerebral infarction, coronary heart disease, and bronchitis adjusted. In addition, the prognosis in CAP patients was monitored. Throughout their hospital stay, higher serum levels of SP-A decreased the risks of mechanical ventilation (RR: 0.315; 95% CI: 0.106, 0.937), vasoactive agents (RR: 0.165; 95% CI: 0.034, 0.790), intensive care unit (ICU) admissions (RR: 0.218; 95% CI: 0.066, 0.717) and longer hospital stays (RR: 0.397; 95% CI: 0.167, 0.945).ConclusionIn CAP patients, inverse dose-response correlations exist between serum SP-A levels with severity scores as well as prognosis at admission, suggesting that SP-A may take part in the CAP pathophysiological processes. Moreover, lower serum SP-A on admission is associated with an elevated prognostic risk of mechanical ventilation, the use of vasoactive agents, longer hospital stays, ICU admission, and mortality. Therefore, as a biomarker, SP-A may have the potential to predict the severity and poor prognosis of CAP patients.