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Frontiers in Immunology 2023Chronic obstructive pulmonary disease (COPD) is a complex disease involving inflammation, cell senescence, and autoimmunity. Dialectical treatment for COPD with...
INTRODUCTION
Chronic obstructive pulmonary disease (COPD) is a complex disease involving inflammation, cell senescence, and autoimmunity. Dialectical treatment for COPD with traditional Chinese medicine (TCM) has the advantage of fewer side effects, more effective suppression of inflammation, and improved immune function. However, the biological base of TCM pattern differentiation in COPD remains unclear.
METHODS
Liquid Chromatography-Quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap MS/MS) based metabolomics and lipidomics were used to analyze the serum samples from COPD patients of three TCM patterns in Lung Qi Deficiency (n=65), Lung-Kidney Qi Deficiency (n=54), Lung-Spleen Qi Deficiency (n=52), and healthy subjects (n=41). Three cross-comparisons were performed to characterize metabolic markers for different TCM patterns of COPD vs healthy subjects.
RESULTS
We identified 28, 8, and 16 metabolites with differential abundance between three TCM patterns of COPD vs healthy subjects, respectively, the metabolic markers included cortisol, hypoxanthine, fatty acids, alkyl-/alkenyl-substituted phosphatidylethanolamine, and phosphatidylcholine, etc. Three panels of metabolic biomarkers specific to the above three TCM patterns yielded areas under the receiver operating characteristic curve of 0.992, 0.881, and 0.928, respectively, with sensitivity of 97.1%, 88.6%, and 91.4%, respectively, and specificity of 96.4%, 81.8%, and 83.9%, respectively.
DISCUSSION
Combining metabolomics and lipidomics can more comprehensively and accurately trace metabolic markers. As a result, the differences in metabolism were proven to underlie different TCM patterns of COPD, which provided evidence to aid our understanding of the biological basis of dialectical treatment, and can also serve as biomarkers for more accurate diagnosis.
Topics: Humans; Medicine, Chinese Traditional; Lipidomics; Tandem Mass Spectrometry; Pulmonary Disease, Chronic Obstructive; Metabolomics; Inflammation; Cell Differentiation; Biomarkers
PubMed: 37492573
DOI: 10.3389/fimmu.2023.1208480 -
NPJ Primary Care Respiratory Medicine Aug 2023This cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as...
This cross-sectional study of 136 patients with chronic obstructive pulmonary disease (COPD) investigated the mechanism underlying overlap syndrome, defined as coexisting COPD and obstructive sleep apnea (OSA). OSA was defined as a respiratory event index (REI) ≥ 5 events/h, determined using type-3 portable monitors. The mean REI was 12.8 events/h. Most participants (60.1%) had mild OSA (REI: 5-15 events/h). The REI was positively correlated with forced expiratory volume in one second (%FEV) (r = 0.33, p < 0.001), body mass index (BMI) (r = 0.24, p = 0.005), and fat-free mass index (r = 0.31, p = 0.005), and negatively correlated with residual volume divided by total lung capacity (r = -0.27, p = 0.003). Receiver-operating characteristic curve analysis revealed an optimal BMI cutoff of 21.96 kg/m for predicting moderate/severe OSA. A BMI ≥ 21.96 kg/m was associated with OSA among participants with %FEV ≥ 50%, but not those with %FEV < 50%. This study revealed an interaction between airflow limitation and hyperinflation, nutritional status, and OSA.
Topics: Humans; Cross-Sectional Studies; Body Mass Index; Pulmonary Disease, Chronic Obstructive; Sleep Apnea, Obstructive; Lung
PubMed: 37582926
DOI: 10.1038/s41533-023-00351-w -
Clinical Medicine (London, England) Sep 2023Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT)...
Long-term pulmonary sequelae of Coronavirus 2019 (COVID-19) remain unclear. Thus, we aimed to establish post-COVID-19 temporal changes in chest computed tomography (CT) features of pulmonary fibrosis and to investigate associations with respiratory symptoms and physiological parameters at 3 and 12 months' follow-up. Adult patients who attended our initial COVID-19 follow-up service and developed chest CT features of interstitial lung disease, in addition to cases identified using British Society of Thoracic Imaging codes, were evaluated retrospectively. Clinical data were gathered on respiratory symptoms and physiological parameters at baseline, 3 months, and 12 months. Corresponding chest CT scans were reviewed by two thoracic radiologists. Associations between CT features and functional correlates were estimated using random effects logistic or linear regression adjusted for age, sex and body mass index. In total, 58 patients were assessed. No changes in reticular pattern, honeycombing, traction bronchiectasis/bronchiolectasis index or pulmonary distortion were observed. Subpleural curvilinear lines were associated with lower odds of breathlessness over time. Parenchymal bands were not associated with breathlessness or impaired lung function overall. Based on our results, we conclude that post-COVID-19 chest CT features of irreversible pulmonary fibrosis remain static over time; other features either resolve or remain unchanged. Subpleural curvilinear lines do not correlate with breathlessness. Parenchymal bands are not functionally significant. An awareness of the different potential functional implications of post-COVID-19 chest CT changes is important in the assessment of patients who present with multi-systemic sequelae of COVID-19 infection.
Topics: Adult; Humans; Pulmonary Fibrosis; COVID-19; Retrospective Studies; Follow-Up Studies; Lung; Tomography, X-Ray Computed; Bronchiectasis; Disease Progression; Dyspnea
PubMed: 37775167
DOI: 10.7861/clinmed.2023-0059 -
Cureus Oct 2023Pulmonary sequestration is a congenital lung malformation characterized by a mass of nonfunctioning lung tissue that receives its arterial supply from an aberrant...
Pulmonary sequestration is a congenital lung malformation characterized by a mass of nonfunctioning lung tissue that receives its arterial supply from an aberrant systemic artery. If symptomatic, most newborns present with respiratory distress. Recurrent infection is the most common presentation after the neonatal period. It is often diagnosed prenatally and is treated with elective surgical resection between ages six and twelve months. We present a case of an infant diagnosed with congenital pulmonary airway malformation prenatally revealed to be pulmonary sequestration at the age of six months, emphasizing the need for appropriate postnatal imaging.
PubMed: 37954799
DOI: 10.7759/cureus.46794 -
The Journal of Heart and Lung... Oct 2023Inflammatory injury in the donor lung remains a persistent challenge in lung transplantation that limits donor organ usage and post-transplant outcomes. Inducing...
BACKGROUND
Inflammatory injury in the donor lung remains a persistent challenge in lung transplantation that limits donor organ usage and post-transplant outcomes. Inducing immunomodulatory capacity in donor organs could address this unsolved clinical problem. We sought to apply clustered regularly interspaced short palindromic repeats (CRISPR)-associated (Cas) technologies to the donor lung to fine-tune immunomodulatory gene expression, exploring for the first time the therapeutic use of CRISPR-mediated transcriptional activation in the whole donor lung.
METHODS
We explored the feasibility of CRISPR-mediated transcriptional upregulation of interleukin 10 (IL-10), a key immunomodulatory cytokine, in vitro and in vivo. We first evaluated the potency, titratability, and multiplexibility of the gene activation in rat and human cell lines. Next, in vivo CRISPR-mediated IL-10 activation was characterized in rat lungs. Finally, the IL-10-activated donor lungs were transplanted into recipient rats to assess the feasibility in a transplant setting.
RESULTS
The targeted transcriptional activation induced robust and titrable IL-10 upregulation in vitro. The combination of guide RNAs also facilitated multiplex gene modulation, that is, simultaneous activation of IL-10 and IL1 receptor antagonist. In vivo profiling demonstrated that adenoviral delivery of Cas9-based activators to the lung was feasible with the use of immunosuppression, which is routinely applied to organ transplant recipients. The transcriptionally modulated donor lungs retained IL-10 upregulation in isogeneic and allogeneic recipients.
CONCLUSIONS
Our findings highlight the potential of CRISPR epigenome editing to improve lung transplant outcomes by creating a more favorable immunomodulatory environment in the donor organ, a paradigm that may be extendable to other organ transplants.
Topics: Humans; Animals; Rats; Interleukin-10; Gene Editing; Cell Line; Lung; Immunomodulation
PubMed: 37315746
DOI: 10.1016/j.healun.2023.06.001 -
Microbiology Spectrum Aug 2023Influenza A virus (IAV)-methicillin-resistant Staphylococcus aureus (MRSA) coinfection causes severe respiratory infections. The host microbiome plays an important role...
Influenza A virus (IAV)-methicillin-resistant Staphylococcus aureus (MRSA) coinfection causes severe respiratory infections. The host microbiome plays an important role in respiratory tract infections. However, the relationships among the immune responses, metabolic characteristics, and respiratory microbial characteristics of IAV-MRSA coinfection have not been fully studied. We used specific-pathogen-free (SPF) C57BL/6N mice infected with IAV and MRSA to build a nonlethal model of IAV-MRSA coinfection and characterized the upper respiratory tract (URT) and lower respiratory tract (LRT) microbiomes at 4 and 13 days postinfection by full-length 16S rRNA gene sequencing. Immune response and plasma metabolism profile analyses were performed at 4 days postinfection by flow cytometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The relationships among the LRT microbiota, the immune response, and the plasma metabolism profile were analyzed by Spearman's correlation analysis. IAV-MRSA coinfection showed significant weight loss and lung injury and significantly increased loads of IAV and MRSA in bronchoalveolar lavage fluid (BALF). Microbiome data showed that coinfection significantly increased the relative abundances of Enterococcus faecalis, Enterobacter hormaechei, Citrobacter freundii, and Klebsiella pneumoniae and decreased the relative abundances of Lactobacillus reuteri and Lactobacillus murinus. The percentages of CD4/CD8 T cells and B cells in the spleen; the levels of interleukin-9 (IL-9), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), IL-6, and IL-8 in the lung; and the level of mevalonolactone in plasma were increased in IAV-MRSA-coinfected mice. L. murinus was positively correlated with lung macrophages and natural killer (NK) cells, negatively correlated with spleen B cells and CD4/CD8 T cells, and correlated with multiple plasma metabolites. Future research is needed to clarify whether mediates or alters the severity of IAV-MRSA coinfection. The respiratory microbiome plays an important role in respiratory tract infections. In this study, we characterized the URT and LRT microbiota, the host immune response, and plasma metabolic profiles during IAV-MRSA coinfection and evaluated their correlations. We observed that IAV-MRSA coinfection induced severe lung injury and dysregulated host immunity and plasma metabolic profiles, as evidenced by the aggravation of lung pathological damage, the reduction of innate immune cells, the strong adaptation of the immune response, and the upregulation of mevalonolactone in plasma. was strongly correlated with immune cells and plasma metabolites. Our findings contribute to a better understanding of the role of the host microbiome in respiratory tract infections and identified a key bacterial species, , that may provide important references for the development of probiotic therapies.
Topics: Mice; Animals; Methicillin-Resistant Staphylococcus aureus; Influenza A virus; Coinfection; Lung Injury; CD8-Positive T-Lymphocytes; Chromatography, Liquid; RNA, Ribosomal, 16S; Mice, Inbred C57BL; Tandem Mass Spectrometry; Lung; Respiratory Tract Infections; Microbiota; Immunity
PubMed: 37318361
DOI: 10.1128/spectrum.05247-22 -
The Journal of Allergy and Clinical... Sep 2023Asthma is conventionally stratified as type 2 inflammation (T2)-high or T2-low disease. Identifying T2 status has therapeutic implications for patient management, but a...
BACKGROUND
Asthma is conventionally stratified as type 2 inflammation (T2)-high or T2-low disease. Identifying T2 status has therapeutic implications for patient management, but a real-world understanding of this T2 paradigm in difficult-to-treat and severe asthma remains limited.
OBJECTIVES
To identify the prevalence of T2-high status in difficult-to-treat asthma patients using a multicomponent definition and compare clinical and pathophysiologic characteristics between patients classified as T2-high and T2-low.
METHODS
We evaluated 388 biologic-naive patients from the Wessex Asthma Cohort of difficult asthma (WATCH) study in the United Kingdom. Type 2-high asthma was defined as 20 parts per billion or greater FeNO , 150 cells/μL or greater peripheral blood eosinophils, the need for maintenance oral corticosteroids, and/or clinically allergy-driven asthma.
RESULTS
This multicomponent assessment identified T2-high asthma in 93% of patients (360 of 388). Body mass index, inhaled corticosteroid dose, asthma exacerbations, and common comorbidities did not differ by T2 status. Significantly worse airflow limitation was found in T2-high compared with T2-low patients (FEV/FVC 65.9% vs 74.6%). Moreover, 75% of patients defined as having T2-low asthma had raised peripheral blood eosinophils within the preceding 10 years, which left only seven patients (1.8%) who had never had T2 signals. Incorporation of sputum eosinophilia 2% or greater into the multicomponent definition in a subset of 117 patients with induced sputum data similarly found that 96% (112 of 117) met criteria for T2-high asthma, 50% of whom (56 of 112) had sputum eosinophils 2% or greater.
CONCLUSIONS
Almost all patients with difficult-to-treat asthma have T2-high disease; less than 2% of patients never display T2-defining criteria. This highlights a need to assess T2 status comprehensively in clinical practice before labeling a patient with difficult-to-treat asthma as T2-low.
Topics: Humans; Leukocyte Count; Asthma; Eosinophils; Lung; Adrenal Cortex Hormones; Sputum
PubMed: 37245729
DOI: 10.1016/j.jaip.2023.05.028 -
International Journal of Chronic... 2024To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
To present the preliminarily findings regarding the effects of a herbal medicine, Ninjin'yoeito, on comorbid frailty and sarcopenia in patients with chronic obstructive pulmonary disease (COPD).
PATIENTS AND METHODS
Patients with COPD (GOLD II or higher) and fatigue were randomly assigned to Group A (n = 28; no medication for 12 weeks, followed by 12-week administration) or B (n= 25; 24-week continuous administration). Visual analog scale (VAS) symptoms of fatigue, the COPD assessment test (CAT), and the modified Medical Research Council (mMRC) Dyspnea Scale were examined. Physical indices such asknee extension leg strength and walking speed, skeletal muscle mass index (SMI), and respiratory function test were also measured.
RESULTS
VAS fatigue scales in Group B significantly improved after 4, 8, and 12 weeks compared to those in Group A (each p<0.001, respectively). Right and left knee extension leg strength in Group B significantly improved after 12 weeks compared to that in Group A (p=0.042 and p=0.037, respectively). The 1-s walking speed for continued to increase significantly over 24 weeks in Group B (p=0.016, p<0.001, p<0.001, p=0.004, p<0.001, and p<0.001 after 4, 8, 12, 16, 20, and 24 weeks, respectively); it also significantly increased after the administration of Ninjin'yoeito in Group A. In Group B, the SMI significantly increased at 12 weeks in patients with sarcopenia (p=0.025). The CAT scores in Group B significantly improved after 12 weeks compared to those in Group A (p=0.006). The mMRC scores in Group B also significantly improved after 8 and 12 weeks compared to those in Group A (p= 0.045 and p <0.001, respectively). The changes in %FEV1.0 in Group B were significantly improved at 12 and 24 weeks (p=0.039 and p=0.036, respectively).
CONCLUSION
Overall, Ninjin'yoeito significantly improved patients' quality of life, physical activity, muscle mass, and possibly lung function, suggesting that Ninjin'yoeito may improve frailty and sarcopenia in patients with COPD.
Topics: Humans; Sarcopenia; Pulmonary Disease, Chronic Obstructive; Male; Female; Aged; Treatment Outcome; Drugs, Chinese Herbal; Middle Aged; Muscle Strength; Lung; Time Factors; Exercise Tolerance; Frailty; Comorbidity; Fatigue; Recovery of Function; Functional Status; Frail Elderly; Walking Speed
PubMed: 38737191
DOI: 10.2147/COPD.S441767 -
Journal of Applied Physiology... Nov 2023Increased intrapulmonary shunt (Q/Q) and alveolar dead space (V/V) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients...
Increased intrapulmonary shunt (Q/Q) and alveolar dead space (V/V) are present in early recovery from 2019 Novel Coronavirus (COVID-19). We hypothesized patients recovering from severe critical acute illness (NIH category 3-5) would have greater and longer lasting increased Q/Q and V/V than patients with mild-moderate acute illness (NIH 1-2). Fifty-nine unvaccinated patients (33 males, aged 52 [38-61] yr, body mass index [BMI] 28.8 [25.3-33.6] kg/m; median [IQR], 44 previous mild-moderate COVID-19, and 15 severe-critical disease) were studied 15-403 days postacute severe acute respiratory syndrome coronavirus infection. Breathing ambient air, steady-state mean alveolar Pco, and Po were recorded simultaneously with arterial Po/Pco yielding aAPco, AaPo, and from these, Q/Q%, V/V%, and relative alveolar ventilation (40 mmHg/[Formula: see text], VArel) were calculated. Median [Formula: see text] was 39.4 [35.6-41.1] mmHg, [Formula: see text] 92.3 [87.1-98.2] mmHg; [Formula: see text] 32.8 [28.6-35.3] mmHg, [Formula: see text] 112.9 [109.4-117.0] mmHg, AaPo 18.8 [12.6-26.8] mmHg, aAPco 5.9 [4.3-8.0] mmHg, Q/Q 4.3 [2.1-5.9] %, and V/V16.6 [12.6-24.4]%. Only 14% of patients had normal Q/Q and V/V; 1% increased Q/Q but normal V/V; 49% normal Q/Q and elevated V/V; 36% both abnormal Q/Q and V/V. Previous severe critical COVID-19 predicted increased Q/Q (2.69 [0.82-4.57]% per category severity [95% CI], < 0.01), but not V/V. Increasing age weakly predicted increased V/V (1.6 [0.1-3.2]% per decade, < 0.04). Time since infection, BMI, and comorbidities were not predictors (all > 0.11). VArel was increased in most patients. In our population, recovery from COVID-19 was associated with increased Q/Q in 37% of patients, increased V/V in 86%, and increased alveolar ventilation up to ∼13 mo postinfection. NIH severity predicted Q/Q but not elevated V/V. Increased V/V suggests pulmonary microvascular pathology persists post-COVID-19 in most patients. Using novel methodology quantifying intrapulmonary shunt and alveolar dead space in COVID-19 patients up to 403 days after acute illness, 37% had increased intrapulmonary shunt and 86% had elevated alveolar dead space likely due to independent pathology. Elevated shunt was partially related to severe acute illness, and increased alveolar dead space was weakly related to increasing age. Ventilation was increased in the majority of patients regardless of previous disease severity. These results demonstrate persisting gas exchange abnormalities after recovery.
Topics: Male; Humans; Respiratory Dead Space; Acute Disease; COVID-19; Lung; Respiration
PubMed: 37767555
DOI: 10.1152/japplphysiol.00267.2023 -
Diagnostics (Basel, Switzerland) Apr 2024A 54-year-old woman presented to an outpatient clinic with a recurrence of triple-negative breast cancer and multiple bone metastases. The patient had a large mass...
A 54-year-old woman presented to an outpatient clinic with a recurrence of triple-negative breast cancer and multiple bone metastases. The patient had a large mass lesion of 10 cm on the sternum. She received the immune checkpoint inhibitors pembrolizumab and taxane. Initially, the patient responded excellently to treatment, but stopped pembrolizumab for grade IV skin toxicity with multiple ulcerative wounds over the bilateral leg and trunk. The lesions abated following administration of antibiotics and oral prednisolone for two months. After that, she was referred to the radiation oncology department for further treatment. She received radiotherapy for the sternum mass but stopped radiation at 42Gy/21 fractions for severe dyspnea and fever. Blood sampling found leukocytosis with neutrophil predominance. Chest radiography showed bilateral lung infiltration. Pulmonary CT scan yielded bilateral lung patchy consolidation compatible with radiation isodose-line. Bronchial lavage showed positive Pneumocystis jiroveci PCR. Dyspnea improved after titrating methylprednisolone within two days. The patient recovered well with TMP-SMX and glucocorticoids after the initiation of therapy.
PubMed: 38667495
DOI: 10.3390/diagnostics14080850