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FEMS Microbes 2024Asthma is a common allergic airway disease that has been associated with the development of the human microbiome early in life. Both the composition and function of the...
Asthma is a common allergic airway disease that has been associated with the development of the human microbiome early in life. Both the composition and function of the infant gut microbiota have been linked to asthma risk, but functional alterations in the gut microbiota of older patients with established asthma remain an important knowledge gap. Here, we performed whole metagenomic shotgun sequencing of 95 stool samples from a cross-sectional cohort of 59 healthy and 36 subjects with moderate-to-severe asthma to characterize the metagenomes of gut microbiota in adults and children 6 years and older. Mapping of functional orthologs revealed that asthma contributes to 2.9% of the variation in metagenomic content even when accounting for other important clinical demographics. Differential abundance analysis showed an enrichment of long-chain fatty acid (LCFA) metabolism pathways, which have been previously implicated in airway smooth muscle and immune responses in asthma. We also observed increased richness of antibiotic resistance genes (ARGs) in people with asthma. Several differentially abundant ARGs in the asthma cohort encode resistance to macrolide antibiotics, which are often prescribed to patients with asthma. Lastly, we found that ARG and virulence factor (VF) richness in the microbiome were correlated in both cohorts. ARG and VF pairs co-occurred in both cohorts suggesting that virulence and antibiotic resistance traits are coselected and maintained in the fecal microbiota of people with asthma. Overall, our results show functional alterations via LCFA biosynthetic genes and increases in antibiotic resistance genes in the gut microbiota of subjects with moderate-to-severe asthma and could have implications for asthma management and treatment.
PubMed: 38560624
DOI: 10.1093/femsmc/xtae010 -
Respiratory Research Mar 2024The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the...
BACKGROUND
The clinical significance of the impulse oscillometry-defined small airway bronchodilator response (IOS-BDR) is not well-known. Accordingly, this study investigated the clinical characteristics of IOS-BDR and explored the association between lung function decline, acute respiratory exacerbations, and IOS-BDR.
METHODS
Participants were recruited from an Early Chronic Obstructive Pulmonary Disease (ECOPD) cohort subset and were followed up for two years with visits at baseline, 12 months, and 24 months. Chronic obstructive pulmonary disease (COPD) was defined as a post-bronchodilator forced expiratory volume in 1 s (FEV)/forced vital capacity (FVC) ratio < 0.70. IOS-BDR was defined as meeting any one of the following criteria: an absolute change in respiratory system resistance at 5 Hz ≤ - 0.137 kPa/L/s, an absolute change in respiratory system reactance at 5 Hz ≥ 0.055 kPa/L/s, or an absolute change in reactance area ≤ - 0.390 kPa/L. The association between IOS-BDR and a decline in lung function was explored with linear mixed-effects model. The association between IOS-BDR and the risk of acute respiratory exacerbations at the two-year follow-up was analyzed with the logistic regression model.
RESULTS
This study involved 466 participants (92 participants with IOS-BDR and 374 participants without IOS-BDR). Participants with IOS-BDR had higher COPD assessment test and modified Medical Research Council dyspnea scale scores, more severe emphysema, air trapping, and rapid decline in FVC than those without IOS-BDR over 2-year follow-up. IOS-BDR was not associated with the risk of acute respiratory exacerbations at the 2-year follow-up.
CONCLUSIONS
The participants with IOS-BDR had more respiratory symptoms, radiographic structural changes, and had an increase in decline in lung function than those without IOS-BDR.
TRIAL REGISTRATION
Chinese Clinical Trial Registry, ChiCTR1900024643. Registered on 19 July, 2019.
Topics: Humans; Asthma; Bronchodilator Agents; Forced Expiratory Volume; Oscillometry; Pulmonary Disease, Chronic Obstructive; Respiratory Function Tests; Spirometry
PubMed: 38555433
DOI: 10.1186/s12931-024-02765-7 -
Journal of Clinical Medicine Mar 2024The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death... (Review)
Review
The phenomenon of antimicrobial resistance (AMR) is a critical global health challenge, with prospects indicating its potential to become the leading cause of death worldwide in the coming years. Individuals with pre-existing conditions, such as neoplastic disease undergoing chemotherapy, those on immunosuppressive therapy, and individuals with rare diseases like cystic fibrosis (CF), face heightened challenges due to AMR. CF is a rare disease caused by a deficiency in the synthesis of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel protein, resulting in multi-organ clinical symptoms, particularly in the respiratory system. PwCF experience recurrent pulmonary exacerbations triggered by bacterial or viral infections, making them particularly vulnerable to the impact of AMR. This review delves into the complex relationship between AMR and climate dynamics, focusing on the unique challenges faced by individuals with CF. It discusses the methods employed to measure AMR, its global impact on antibiotic resistance, and the specific microbial communities present in the CF airway. The review also explores the intricacies of antimicrobial resistance within the context of cystic fibrosis, emphasizing the urgent need for research in this field.
PubMed: 38541936
DOI: 10.3390/jcm13061711 -
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