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Frontiers in Medicine 2024Sulfur mustard (SM) exposure causes acute and chronic respiratory diseases. The extent of small airway dysfunction (SAD) in individuals exposed to SM is unclear. This...
BACKGROUND
Sulfur mustard (SM) exposure causes acute and chronic respiratory diseases. The extent of small airway dysfunction (SAD) in individuals exposed to SM is unclear. This study evaluated and compared SAD in SM-exposed and SM-unexposed participants using noninvasive lung function tests assessing small airway function.
METHODS
This retrospective cohort study involved SM-exposed ( = 15, mean age: 53 ± 8 years) and SM-unexposed ( = 15, mean age: 53 ± 7 years) Kurdish-Swedish individuals in Sweden. Small airway resistance and reactance were assessed using impulse oscillometry (IOS). Nitrogen (N) multiple breath washout (MBW) was employed to assess lung ventilation heterogeneity. The gas-exchanging capacity of the lungs was assessed using the diffusing capacity of the lungs for the carbon monoxide (DLCO) test. Lung function outcomes were reported as absolute values and -scores. Group comparisons were performed using the Mann-Whitney U test.
RESULTS
No statistically significant differences in age, height, or body mass index were observed between the two groups. IOS showed significantly increased small airway resistance, while NMBW exhibited significantly increased global and acinar ventilation heterogeneity in SM-exposed individuals compared to that in unexposed individuals. SAD was identified in 14 of 15 SM-exposed individuals, defined as at least one abnormal IOS difference between resistance at 5 and 20 Hz (R5-R20) and/or area of reactance (AX) or NMBW lung's acinar zone (S), and DLCO adjusted to the alveolar volume (DLCO/VA) outcome. Of these 14 individuals, only 5 demonstrated concordant findings across the IOS and NMBW tests.
CONCLUSION
Exposure to SM was positively associated with long-term impairment of respiratory tract function in the small airways in the majority of the previously SM-exposed individuals in the present study. Furthermore, both IOS and NMBW should be employed to detect SAD in SM-exposed survivors as they provide complementary information. Identifying and characterizing the remaining pathology of the small airways in survivors of SM exposure is a first step toward improved treatment and follow-up.
PubMed: 38500955
DOI: 10.3389/fmed.2024.1251500 -
Translational Lung Cancer Research Feb 2024A versatile biomarker, survivin, is highly expressed in proliferating cells of multiple cancers in humans and animals. It is an apoptosis-regulating protein, engaging in... (Review)
Review
BACKGROUND AND OBJECTIVE
A versatile biomarker, survivin, is highly expressed in proliferating cells of multiple cancers in humans and animals. It is an apoptosis-regulating protein, engaging in a cascade of reactions that involve several other genes and protein interactions. Currently, researchers are investigating its therapeutic potential due to the evidence linking its overexpression to advanced-stage lung cancer. This review is centered around examining survivin-related molecular mechanisms and its therapeutic role specifically in lung cancer. Our objective is to discuss the role of survivin in prognosis and treatment response, shedding light on immune-targeted therapies, as well as outlining future directions for survivin-based vaccines in lung cancer.
METHODS
The PubMed database and the United States National Library of Medicine search engine at the National Institutes of Health were searched on 24 August 2023 to identify published research studies. Searching "((((((airway [Title/Abstract]) OR (lung [Title/Abstract])) OR (pulm[Title/Abstract])) OR (bronch[Title/Abstract])) OR (nslc[Title/Abstract])) AND (((cancer[Title/Abstract]) OR (carcino[Title/Abstract])) OR (oncol[Title/Abstract]))) AND (survivin[Title/Abstract])" gave 728 results. After screening the title and abstracts and excluding the review articles 168 titles were shortlisted and full text studied. The discussions are added to relevant sections.
KEY CONTENT AND FINDINGS
Survivin is a cell cycle-dependent, inhibitor of apoptosis protein that contributes to carcinogenesis, tumor vascularization, metastasis, and treatment resistance. Several treatments that impact survivin either directly or indirectly have been reported as effective in treating lung cancer. Immunity-based therapy, a novel approach known for its targeted nature and minimal side effects, is currently under investigation for lung cancer treatment. Emerging survivin-centered vaccines exhibit promising attributes in terms of safety, effectiveness, and ability to stimulate an immune response. These factors point towards a significant potential for advancing the future of lung cancer prevention and enhancing overall survival rates.
CONCLUSIONS
Nuclear survivin is a potential biomarker for advanced non-small cell lung cancer. It plays a role in determining drug responsiveness and is found to be significantly elevated in cases of resistance to chemotherapy. Multiple compounds and immunization strategies have been identified to impact lung cancer cells; however, they are currently in the early stages of phase I or phase II clinical trials. The substantial promise of survivin-based immunogenicity-focused treatments warrants in-depth investigation and exploration.
PubMed: 38496694
DOI: 10.21037/tlcr-23-621 -
Scientific Reports Mar 2024Concerns are repeatedly raised about possible adverse respiratory effects of wearing filtering face pieces (FFP) during physical activity. This study compared the impact... (Randomized Controlled Trial)
Randomized Controlled Trial
Concerns are repeatedly raised about possible adverse respiratory effects of wearing filtering face pieces (FFP) during physical activity. This study compared the impact of FFP type 2 (NF95) on pulmonary function, blood gas values, metabolism and discomfort during light, moderate and vigorous physical activity. Healthy adults (n = 13; 6 females, 7 males; mean 31.3, SD 5.5 years) participated in this randomized two-armed (Ergometer cycling with a FFP type 2 vs. no mask) crossover trial. Baseline cardiopulmonary exercise testing and two interventions (masked and unmasked ergometer cycling 40%, 50% and 70% VO2max, 10 min each) were separated by 48 h washout periods. Spiroergometric data (End tidal carbon dioxide partial pressure PetCO; breathing frequency; inspiration time), blood gas analysis outcomes (capillary carbon dioxide partial pressure, pCO) and subjective response (Breathing effort and perceived exertion) were contrasted between conditions using ANOVAs. All participants completed the crossover trial, seven started with the FFP2 condition (No adverse events or side effects). FFP2 decreased breathing frequency, prolonged inspiration time, increased perceived breathing effort and PetCO (p < .05). Blood pCO in millimetres mercury increased during exercise with 50%VO2max (mean 36.67, SD 3.19 vs. mean 38.46, SD 2.57; p < .05) and 70%VO2max (35.04, 2.84 vs. 38.17, 3.43; p < .05) but not during exercise with 40%VO2max (36.55, 2.73 vs. 38.70). Perceived exertion was not affected (p > 0.05) by mask wearing. Conclusion: Mask-induced breathing resistance decreased respiratory performance and limited pulmonary gas exchange. While FFP2 affected subjective breathing effort per se, invasive diagnostics showed that statistically significant metabolic effects are induced from moderate intensity upwards. Trial registration: DRKS-ID: DRKS00030181, Date of registration: 05/09/2022 (German Register for Clinical Trials).
Topics: Male; Adult; Female; Humans; Carbon Dioxide; Exercise; Respiration; Lung; Oxygen Consumption
PubMed: 38491110
DOI: 10.1038/s41598-024-56560-x -
Translational Research : the Journal of... Mar 2024Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and...
Lung cancer has been shown to be targetable by novel immunotherapies which reactivate the immune system and enable tumor cell killing. However, treatment failure and resistance to these therapies is common. Consideration of sex as a factor influencing therapy resistance is still rare. We hypothesize that the success of the treatment is impaired by the presence of the immunosuppressive pregnancy-associated glycoprotein glycodelin that is expressed in patients with non-small-cell lung cancer (NSCLC). We demonstrate that the glycan pattern of NSCLC-derived glycodelin detected by a lectin-based enrichment assay highly resembles amniotic fluid-derived glycodelin A, which is known to have immunosuppressive properties. NSCLC-derived glycodelin interacts with immune cells in vitro and regulates the expression of genes associated with inflammatory and tumor microenvironment pathways. In tumor microarray samples of patients, high glycodelin staining in tumor areas results in an impaired overall survival of female patients. Moreover, glycodelin colocalizes to tumor infiltrating CD8+ T cells and pro-tumorigenic M2 macrophages. High serum concentrations of glycodelin prior to immunotherapy are associated with a poor progression-free survival (p < 0.001) of female patients receiving PD-(L)1 inhibitors. In summary, our findings suggest that glycodelin not only is a promising immunological biomarker for early identification of female patients that do not benefit from the costly immunotherapy, but also represents a promising immunotherapeutic target in NSCLC to improve therapeutic options in lung cancer.
PubMed: 38490536
DOI: 10.1016/j.trsl.2024.02.007 -
Clinics (Sao Paulo, Brazil) 2024Studies suggest peripheral airway abnormalities in Pulmonary Arterial Hypertension (PAH). Impulse Oscillometry (IOS) is a noninvasive and sensitive technique for...
INTRODUCTION
Studies suggest peripheral airway abnormalities in Pulmonary Arterial Hypertension (PAH). Impulse Oscillometry (IOS) is a noninvasive and sensitive technique for assessing the small airways. It evaluates the impedance of the respiratory system ‒ Resistance (R) and reactance (X) ‒ to a pulse of sound waves sent to the lungs, in a range of frequencies (5‒20 Hz).
METHOD
Resistance variables: R5, R20, R5-R20 and reactance variables: AX (reactance area) and Fres (resonance frequency). The aim is to evaluate R and X in patients with idiopathic PAH (IPAH) and to investigate whether there is a correlation between IOS and spirometry.
RESULTS
Thirteen IPAH patients and 11 healthy subjects matched for sex and age underwent IOS and spirometry. IPAH patients had lower FVC and FEV values (p < 0.001), VEF/CVF (p = 0.049) and FEF 25-75 (p = 0.006) than healthy patients. At IOS, IPAH patients showed lower tidal volumes and higher AX (p < 0.05) compared to healthy individuals, and 53.8 of patients had R5-R20 values ≥ 0.07 kPa/L/s. Correlation analysis: X5, AX, R5-R20 and Fres showed moderate correlation with FVC (p = 0.036 r = 0.585, p = 0.001 r = -0.687, p = 0.005 r = -0.726 and p = 0.027 r = -0.610); Fres (p = 0.012 r = -0.669) and AX (p = 0.006 r = -0.711) correlated with FEV; [R5 and R20, (R5-R20)] also correlated with FEV (p < 0.001 r = -0.573, p = 0.020 r = -0.634 and p = 0.010 r = -0.683, respectively) in the IPAH group. There were also moderate correlations of FEF 25-75 % with Z5 (p = 0.041), R5 (p = 0.018), Fres (p = 0.043) and AX (p = 0.023).
DISCUSSION
Patients showed changes suggestive of increased resistance and reactance in the IOS compared to healthy individuals, and the IOS findings showed a good correlation with spirometry variables.
Topics: Humans; Pulmonary Arterial Hypertension; Oscillometry; Forced Expiratory Volume; Respiratory Function Tests; Lung; Spirometry
PubMed: 38490138
DOI: 10.1016/j.clinsp.2023.100313 -
Sleep & Breathing = Schlaf & Atmung Jun 2024Recent studies have highlighted the potential role of a short lingual frenulum as a risk factor for pediatric obstructive sleep apnea syndrome. A shortened frenulum may... (Meta-Analysis)
Meta-Analysis
PURPOSE
Recent studies have highlighted the potential role of a short lingual frenulum as a risk factor for pediatric obstructive sleep apnea syndrome. A shortened frenulum may contribute to abnormal orofacial development, leading to increased upper airway resistance and susceptibility to upper airway collapsibility during sleep. Recognizing early indicators, such as a short lingual frenulum, is crucial for prompt intervention. This systematic review aims to evaluate the association between a short lingual frenulum and the risk of obstructive sleep apnea syndrome in children.
METHODS
This systematic review adheres to PRISMA criteria for a quantitative analysis. A comprehensive search was conducted on five databases until January 2024 to identify relevant studies. The selected articles underwent rigorous analysis, considering study design, sample characteristics, lingual frenulum characterization, sleep assessment methods, and key findings.
RESULTS
A total of 239 references were initially identified. Finally, six studies were included in the qualitative synthesis, with four studies eligible for the quantitative synthesis. The Newcastle-Ottawa scale was employed to assess study quality. Meta-analysis, supported by a moderate evidence profile according to the GRADE scale, revealed statistically significant differences, with odds ratios of 3.051 (confidence interval: 1.939 to 4.801) for a short frenulum and 12.304 (confidence interval: 6.141 to 24.653) for a high-arched palate.
CONCLUSION
This systematic review and meta-analysis provide evidence supporting the association between ankyloglossia and obstructive sleep apnea in children. Nevertheless, it is crucial to consider additional factors such as tongue mobility and the presence of a high-arched palate in further evaluations.
Topics: Child; Humans; Ankyloglossia; Sleep Apnea, Obstructive
PubMed: 38478208
DOI: 10.1007/s11325-024-03021-4 -
Frontiers in Microbiology 2024Metaorganism research contributes substantially to our understanding of the interaction between microbes and their hosts, as well as their co-evolution. Most research is...
Metaorganism research contributes substantially to our understanding of the interaction between microbes and their hosts, as well as their co-evolution. Most research is currently focused on the bacterial community, while archaea often remain at the sidelines of metaorganism-related research. Here, we describe the archaeome of a total of eleven classical and emerging multicellular model organisms across the phylogenetic tree of life. To determine the microbial community composition of each host, we utilized a combination of archaea and bacteria-specific 16S rRNA gene amplicons. Members of the two prokaryotic domains were described regarding their community composition, diversity, and richness in each multicellular host. Moreover, association with specific hosts and possible interaction partners between the bacterial and archaeal communities were determined for the marine models. Our data show that the archaeome in marine hosts predominantly consists of and , which represent keystone taxa among the porifera. The presence of an archaeome in the terrestrial hosts varies substantially. With respect to abundant archaeal taxa, they harbor a higher proportion of methanoarchaea over the aquatic environment. We find that the archaeal community is much less diverse than its bacterial counterpart. Archaeal amplicon sequence variants are usually host-specific, suggesting adaptation through co-evolution with the host. While bacterial richness was higher in the aquatic than the terrestrial hosts, a significant difference in diversity and richness between these groups could not be observed in the archaeal dataset. Our data show a large proportion of unclassifiable archaeal taxa, highlighting the need for improved cultivation efforts and expanded databases.
PubMed: 38476944
DOI: 10.3389/fmicb.2024.1347422 -
Cureus Feb 2024Persistent pulmonary hypertension of the newborn (PPHN) is a condition that can be fatal, marked by increased pulmonary vascular resistance that causes blood to shunt...
Persistent pulmonary hypertension of the newborn (PPHN) is a condition that can be fatal, marked by increased pulmonary vascular resistance that causes blood to shunt from the right to the left. Six infants that present with PPHN due to labile hypoxemia and related cyanosis are examined in this case series. Clinical manifestations, such as premature deliveries, maternal problems, and different reactions to early therapies, are revealed by perinatal and postnatal histories. The newborns' respiratory distress prompted the use of oxygen supplementation and continuous positive airway pressure (CPAP), but intubation was required due to continued hypoxemia. The series aims to establish a way for further study in this crucial area while offering insightful contributions to the clinical subtleties of PPHN and illustrating the importance of specific therapeutic approaches.
PubMed: 38476788
DOI: 10.7759/cureus.54016 -
Respiratory Research Mar 2024Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced...
BACKGROUND
Airway basal cells (BC) from patients with chronic obstructive pulmonary disease (COPD) regenerate abnormal airway epithelium and this was associated with reduced expression of several genes involved in epithelial repair. Quercetin reduces airway epithelial remodeling and inflammation in COPD models, therefore we examined whether quercetin promotes normal epithelial regeneration from COPD BC by altering gene expression.
METHODS
COPD BC treated with DMSO or 1 µM quercetin for three days were cultured at air/liquid interface (ALI) for up to 4 weeks. BC from healthy donors cultured at ALI were used as controls. Polarization of cells was determined at 8 days of ALI. The cell types and IL-8 expression in differentiated cell cultures were quantified by flow cytometry and ELISA respectively. Microarray analysis was conducted on DMSO or 1 µM quercetin-treated COPD BC for 3 days to identify differentially regulated genes (DEG). Bronchial brushings obtained from COPD patients with similar age and disease status treated with either placebo (4 subjects) or 2000 mg/day quercetin (7 subjects) for 6 months were used to confirm the effects of quercetin on gene expression.
RESULTS
Compared to placebo-, quercetin-treated COPD BC showed significantly increased transepithelial resistance, more ciliated cells, fewer goblet cells, and lower IL-8. Quercetin upregulated genes associated with tissue and epithelial development and differentiation in COPD BC. COPD patients treated with quercetin, but not placebo showed increased expression of two developmental genes HOXB2 and ELF3, which were also increased in quercetin-treated COPD BC with FDR < 0.001. Active smokers showed increased mRNA expression of TGF-β (0.067) and IL-8 (22.0), which was reduced by 3.6 and 4.14 fold respectively after quercetin treatment.
CONCLUSIONS
These results indicate that quercetin may improve airway epithelial regeneration by increasing the expression of genes involved in epithelial development/differentiation in COPD.
TRIAL REGISTRATION
This study was registered at ClinicalTrials.gov on 6-18-2019. The study number is NCT03989271.
Topics: Humans; Quercetin; Interleukin-8; Dimethyl Sulfoxide; Pulmonary Disease, Chronic Obstructive; Bronchi; Epithelial Cells; Cells, Cultured; Transcription Factors; Homeodomain Proteins
PubMed: 38468259
DOI: 10.1186/s12931-024-02742-0