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Medicina (Kaunas, Lithuania) Mar 2024: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis...
Lower Arginine Bioavailability, Increased FeNO Levels, and Airway Resistance on Impulse Oscillometry Are Characteristics of Asthma in Children and Young Adults with Sickle Cell Disease.
: Data on characteristics of asthma in children with sickle cell disease (SCD) is conflicting. Recently, the L-arginine pathway has gained attention in the pathogenesis of asthma and SCD. This study aimed to determine the distinctive clinical and laboratory features and the role of arginine metabolism in asthmatic children with SCD. : A total of 52 children and adolescents with SCD, including 24 with asthma (SCD-A) and 28 without asthma (SCD-NA), and 40 healthy controls were included. A questionnaire, atopy tests, fractional exhaled nitric oxide (FeNO), and lung function tests were employed. Serum metabolites of the arginine pathway were measured. The results of the three groups were compared. : The demographic characteristics and atopy markers of the three groups were similar. FEV1%, FEV1/FVC, MMEF%, and total lung capacity (TLC%) values of SCD-A patients were not significantly different from the SCD-NA group, but they were significantly lower than the values measured in the controls. FeNO values greater than 35 ppb were present only in the SCD-A group. In impulse oscillometry, median resistance values at 5 Hz (R5)% were higher in both SCD subgroups than in healthy controls ( = 0.001). The (R5-20/R5)% values were higher in the SCD-A group ( = 0.028). Serum arginine levels and arginine bioavailability indices were significantly lower in the SCD-A group than in the SCD-NA group and healthy controls ( = 0.003 and < 0.001). : Asthma in children with SCD was not associated with atopy or low FEV1/FVC levels. However, lower arginine bioavailability and higher FeNO levels differentiated asthma in patients with SCD. High R5% and (R5-20/R5)% values indicated increased airway resistance in SCD, with a predominance of small airway disease in asthmatics.
Topics: Child; Adolescent; Humans; Young Adult; Airway Resistance; Fractional Exhaled Nitric Oxide Testing; Biological Availability; Oscillometry; Spirometry; Nitric Oxide; Asthma; Respiratory Function Tests; Anemia, Sickle Cell
PubMed: 38541172
DOI: 10.3390/medicina60030446 -
Immunity, Inflammation and Disease Mar 2024The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the...
BACKGROUND
The dosage of ovalbumin (OVA) during the sensitization stage is considered a crucial factor in the development of airway hyperresponsiveness (AHR). However, the inconsistent dosages of sensitizing OVA used in current studies and the lack of research on their impact on AHR are notable limitations.
METHODS
We examined the impact of increasing sensitizing doses of OVA in a murine asthma model, which entailed initial sensitization with OVA followed by repeated exposure to OVA aerosols. BALB/c mice were primed with doses of OVA (0, 10, 20, 50, and 100 μg) plus 1 mg Alum on Days 0 and 7, and were challenged with OVA aerosols (10 mg/mL for 30 min) between Days 14 and 17. Antigen-induced AHR to methacholine (MCh), as well as histological changes, eosinophilic infiltration, and epithelial injury were assessed.
RESULTS
The result indicated that there are striking OVA dose-related differences in antigen-induced AHR to MCh. The most intense antigen-induced AHR to MCh was observed with sensitization at 50 μg, while weaker responses were seen at 10, 20, and 100 μg. Meanwhile, there was a significant increase in eosinophil count with sensitization at 50 μg. The changes of AHR were correlated with total cells count, lymphocytes count, eosinophils count, and basophils count in bronchoalveolar lavage fluid; however, it did not correlate with histological changes such as cellular infiltration into bronchovascular bundles and goblet cell hyperplasia of the bronchial epithelium.
CONCLUSION
Overall, this study demonstrated that sensitization with 50 μg of OVA resulted in the most significant AHR compared to other dosages. These findings may offer valuable insights for future research on mouse asthma modeling protocols.
Topics: Animals; Mice; Ovalbumin; Bronchial Hyperreactivity; Respiratory Aerosols and Droplets; Asthma; Respiratory Hypersensitivity; Methacholine Chloride
PubMed: 38533918
DOI: 10.1002/iid3.1225 -
BMC Pulmonary Medicine Mar 2024Aerobic training is the primary method of rehabilitation for improving respiratory function in patients with chronic obstructive pulmonary disease (COPD) in remission....
BACKGROUND
Aerobic training is the primary method of rehabilitation for improving respiratory function in patients with chronic obstructive pulmonary disease (COPD) in remission. However, the mechanism underlying this improvement is not yet fully understood. The use of transcriptomics in rehabilitation medicine offers a promising strategy for uncovering the ways in which exercise training improves respiratory dysfunction in COPD patients. In this study, lung tissue was analyzed using transcriptomics to investigate the relationship between exercise and lung changes.
METHODS
Mice were exposed to cigarette smoke for 24 weeks, followed by nine weeks of moderate-intensity treadmill exercise, with a control group for comparison. Pulmonary function and structure were assessed at the end of the intervention and RNA sequencing was performed on the lung tissue.
RESULTS
Exercise training was found to improve airway resistance and lung ventilation indices in individuals exposed to cigarette smoke. However, the effect of this treatment on damaged alveoli was weak. The pair-to-pair comparison revealed numerous differentially expressed genes, that were closely linked to inflammation and metabolism.
CONCLUSIONS
Further research is necessary to confirm the cause-and-effect relationship between the identified biomarkers and the improvement in pulmonary function, as this was not examined in the present study.
Topics: Humans; Mice; Animals; Lung; Pulmonary Disease, Chronic Obstructive; Pulmonary Alveoli; Respiration; Gene Expression Profiling
PubMed: 38532405
DOI: 10.1186/s12890-024-02967-1 -
Geriatrics (Basel, Switzerland) Mar 2024To assess ventilatory evolution through the Ventilatory Workload Kinetic Index (VWKI) in patients with asthma and chronic obstructive pulmonary disease (COPD) during...
To assess ventilatory evolution through the Ventilatory Workload Kinetic Index (VWKI) in patients with asthma and chronic obstructive pulmonary disease (COPD) during stability and exacerbation. Retrospective analysis. Conducted at the Padre Alberto Hurtado Hospital, Santiago, Chile. Ten patients with asthma and fifty-five with COPD participated. Sixty-five clinical records were reviewed. The VWKI in stability and exacerbation of these patients was extracted. When analyzing the baseline with the peak in both asthma and COPD, there was a significant increase in the VWKI. Similarly, the loads, translations, and supports significantly increased from the baseline to the peak. However, in the loads, there were no changes in airway resistance for asthma or in cough for COPD. Likewise, the supports for asthma and COPD showed no changes in the O. The VWKI determined ventilatory issues in outpatients and made locating the greatest compromise in loads, translations, or supports possible.
PubMed: 38525746
DOI: 10.3390/geriatrics9020029 -
Nature Communications Mar 2024Mutations in mexZ, encoding a negative regulator of the expression of the mexXY efflux pump genes, are frequently acquired by Pseudomonas aeruginosa at early stages of...
Mutations in mexZ, encoding a negative regulator of the expression of the mexXY efflux pump genes, are frequently acquired by Pseudomonas aeruginosa at early stages of lung infection. Although traditionally related to resistance to the first-line drug tobramycin, mexZ mutations are associated with low-level aminoglycoside resistance when determined in the laboratory, suggesting that their selection during infection may not be necessarily, or only, related to tobramycin therapy. Here, we show that mexZ-mutated bacteria tend to accumulate inside the epithelial barrier of a human airway infection model, thus colonising the epithelium while being protected against diverse antibiotics. This phenotype is mediated by overexpression of lecA, a quorum sensing-controlled gene, encoding a lectin involved in P. aeruginosa tissue invasiveness. We find that lecA overexpression is caused by a disrupted equilibrium between the overproduced MexXY and another efflux pump, MexAB, which extrudes quorum sensing signals. Our results indicate that mexZ mutations affect the expression of quorum sensing-regulated pathways, thus promoting tissue invasiveness and protecting bacteria from the action of antibiotics within patients, something unnoticeable using standard laboratory tests.
Topics: Humans; Anti-Bacterial Agents; Pseudomonas aeruginosa; Pseudomonas Infections; Tobramycin; Mutation; Bacterial Proteins; Microbial Sensitivity Tests
PubMed: 38519499
DOI: 10.1038/s41467-024-46938-w -
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