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BMJ Open Oct 2023Evidence shows that the conventional cardiometabolic risk factors do not fully explain the burden of microvascular complications in type 2 diabetes (T2D). One potential...
OBJECTIVE
Evidence shows that the conventional cardiometabolic risk factors do not fully explain the burden of microvascular complications in type 2 diabetes (T2D). One potential factor is the impact of pulmonary dysfunction on systemic microvascular injury. We assessed the associations between spirometric impairments and systemic microvascular complications in T2D.
DESIGN
Cross-sectional study.
SETTING
National Diabetes Management and Research Centre in Ghana.
PARTICIPANTS
The study included 464 Ghanaians aged ≥35 years with established diagnosis of T2D without primary myocardial disease or previous/current heart failure. Participants were excluded if they had primary lung disease including asthma or chronic obstructive pulmonary disease.
PRIMARY AND SECONDARY OUTCOME MEASURES
The associations of spirometric measures (forced expiratory volume in 1 s (FEV), forced vital capacity (FVC) and FEV/FVC ratio) with microvascular complications (nephropathy (albumin-creatinine ratio ≥3 mg/g), neuropathy (vibration perception threshold ≥25 V and/or Diabetic Neuropathy Symptom score >1) and retinopathy (based on retinal photography)) were assessed using multivariable logistic regression models with adjustments for age, sex, diabetes duration, glycated haemoglobin concentration, suboptimal blood pressure control, smoking pack years and body mass index.
RESULTS
In age and sex-adjusted models, lower Z-score FEV was associated with higher odds of nephropathy (OR 1.55, 95% CI 1.19-2.02, p=0.001) and neuropathy (1.27 (1.01-1.65), 0.038) but not retinopathy (1.22 (0.87-1.70), 0.246). Similar observations were made for the associations of lower Z-score FVC with nephropathy (1.54 (1.19-2.01), 0.001), neuropathy (1.25 (1.01-1.54), 0.037) and retinopathy (1.19 (0.85-1.68), 0.318). In the fully adjusted model, the associations remained significant for only lower Z-score FEV with nephropathy (1.43 (1.09-1.87), 0.011) and neuropathy (1.34 (1.04-1.73), 0.024) and for lower Z-score FVC with nephropathy (1.45 (1.11-1.91), 0.007) and neuropathy (1.32 (1.03-1.69), 0.029). Lower Z-score FEV/FVC ratio was not significantly associated with microvascular complications in age and sex and fully adjusted models.
CONCLUSION
Our study shows positive but varying strengths of associations between pulmonary dysfunction and microvascular complications in different circulations. Future studies could explore the mechanisms linking pulmonary dysfunction to microvascular complications in T2D.
Topics: Humans; Diabetes Mellitus, Type 2; Cross-Sectional Studies; Ghana; Lung; Retinal Diseases
PubMed: 37903605
DOI: 10.1136/bmjopen-2023-075209 -
Cellular and Molecular Life Sciences :... Jul 2023The human chemokine stromal cell-derived factor-1 (SDF-1) or CXCL12 is involved in several homeostatic processes and pathologies through interaction with its cognate G...
The human chemokine stromal cell-derived factor-1 (SDF-1) or CXCL12 is involved in several homeostatic processes and pathologies through interaction with its cognate G protein-coupled receptor CXCR4. Recent research has shown that CXCL12 is present in the lungs and circulation of patients with coronavirus disease 2019 (COVID-19). However, the question whether the detected CXCL12 is bioactive was not addressed. Indeed, the activity of CXCL12 is regulated by NH- and COOH-terminal post-translational proteolysis, which significantly impairs its biological activity. The aim of the present study was to characterize proteolytic processing of CXCL12 in broncho-alveolar lavage (BAL) fluid and blood plasma samples from critically ill COVID-19 patients. Therefore, we optimized immunosorbent tandem mass spectrometry proteoform analysis (ISTAMPA) for detection of CXCL12 proteoforms. In patient samples, this approach uncovered that CXCL12 is rapidly processed by site-specific NH- and COOH-terminal proteolysis and ultimately degraded. This proteolytic inactivation occurred more rapidly in COVID-19 plasma than in COVID-19 BAL fluids, whereas BAL fluid samples from stable lung transplantation patients and the non-affected lung of lung cancer patients (control groups) hardly induced any processing of CXCL12. In COVID-19 BAL fluids with high proteolytic activity, processing occurred exclusively NH-terminally and was predominantly mediated by neutrophil elastase. In low proteolytic activity BAL fluid and plasma samples, NH- and COOH-terminal proteolysis by CD26 and carboxypeptidases were observed. Finally, protease inhibitors already approved for clinical use such as sitagliptin and sivelestat prevented CXCL12 processing and may therefore be of pharmacological interest to prolong CXCL12 half-life and biological activity in vivo.
Topics: Humans; Proteolysis; COVID-19; Chemokine CXCL12; Peptide Hydrolases; Lung; Receptors, CXCR4; Protein Processing, Post-Translational
PubMed: 37505242
DOI: 10.1007/s00018-023-04870-0 -
American Journal of Obstetrics &... Oct 2023Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung...
BACKGROUND
Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung lesions. However, there remains a lack of consensus on which congenital pulmonary airway malformation volume ratio values have the best predictive value because of operator dependence, inherent changes in lung lesion size throughout gestation, and the widespread use of maternal steroids.
OBJECTIVE
This study sought to determine the association between serial congenital pulmonary airway malformation volume ratio measurements and neonatal outcomes among fetuses with lung malformations.
STUDY DESIGN
This was a retrospective cohort study of fetuses with a prenatally diagnosed lung malformation managed at 2 major fetal centers from January 2010 to December 2021. Prenatal variables, including prospectively measured congenital pulmonary airway malformation volume ratio measurements (initial, maximum, and final), were analyzed. The results were correlated with 3 outcome measures, namely surgical resection before 30 days of life, a need for supplemental O at birth, and endotracheal intubation at birth. Statistical analyses were performed using receiver operating characteristic curve analyses, Welch 2 sample t tests, and multivariable logistic regressions (P<.05).
RESULTS
There were 123 fetuses with isolated lung lesions identified. Eight (6.5%) had hydrops. The mean initial congenital pulmonary airway malformation volume ratio was 0.67±0.61 cm at 22.9±3.9 weeks' gestation. The mean maximum congenital pulmonary airway malformation volume ratio was 1.08 ± 0.94 cm at 27.0 ± 4.0 weeks' gestation. The mean final congenital pulmonary airway malformation volume ratio was 0.58±0.60 cm at 33.2±4.1 weeks' gestation. At a mean gestational age at delivery of 38.3±2.6 weeks, 15 (12.2%) underwent neonatal lung resection for symptomatic disease. In a multivariable regression, all 3 congenital pulmonary airway malformation volume ratio measurements showed a significant correlation with neonatal lung resection (P<.001). Optimal congenital pulmonary airway malformation volume ratio cutoffs were established based on an initial congenital pulmonary airway malformation volume ratio of ≥0.8 cm, maximum congenital pulmonary airway malformation volume ratio of ≥1.5 cm, and a final congenital pulmonary airway malformation volume ratio of ≥1.3 cm with associated areas under the curve of 0.89, 0.97, and 0.93, respectively. The final congenital pulmonary airway malformation volume ratio had the highest specificity for predicting surgical lung resection in the early postnatal period.
CONCLUSION
Measuring congenital pulmonary airway malformation volume ratios throughout pregnancy in fetuses with pulmonary malformations has clinical value for prenatal counseling and planning care transition after delivery. Fetuses with a final congenital pulmonary airway malformation volume ratio of more than 1.3 cm are likely to require neonatal surgery and therefore should be delivered at tertiary care centers with a neonatal intensive care unit and pediatric surgical expertise.
Topics: Pregnancy; Infant, Newborn; Female; Child; Humans; Infant; Prognosis; Retrospective Studies; Fetal Diseases; Ultrasonography, Prenatal; Lung; Cystic Adenomatoid Malformation of Lung, Congenital; Fetus; Morbidity
PubMed: 37572880
DOI: 10.1016/j.ajogmf.2023.101128 -
Journal of Ethnopharmacology Jan 2024Pulmonary injury and fibrosis can be caused by various factors because of their inflammatory nature, both can lead to serious clinical consequences. Inula japonica...
ETHNOPHARMACOLOGICAL RELEVANCE
Pulmonary injury and fibrosis can be caused by various factors because of their inflammatory nature, both can lead to serious clinical consequences. Inula japonica Thunb. is used in traditional Chinese medicine for the treatment of lung diseases. However, the effect and mechanism of action of the essential oil of I. japonica (EOI) on pulmonary injury and fibrosis are not well understood.
AIM OF THE STUDY
To investigate the therapeutic effects of EOI on mice with bleomycin (BLM)-induced acute pulmonary injury and chronic fibrosis formation, as well as its potential mechanism.
MATERIALS AND METHODS
A short-term mouse model of pulmonary injury was established by intratracheal injection of BLM to investigate the anti-inflammatory effect of EOI, and a long-term model of pulmonary fibrosis was used to explore the anti-fibrosis effect of EOI. High-dose EOI (200 mg/kg) was administered intragastrically, and low-dose (50 mg/kg) was administered by intratracheal injection. Gas chromatography-mass spectrometry (GC-MS) was used to identify the ingredients in EOI, and high-performance liquid chromatography (HPLC) was performed for the preparation of EOI compounds. Western blot and real-time qPCR were used to verify the effects of EOI and its active composition on inflammation, oxidative stress and fibrosis signaling pathway.
RESULTS
Treatment with EOI significantly reduced the inflammation and oxidative stress by reducing the levels of inflammatory and oxidative cytokines such as tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and malondialdehyde in BLM-treated mice with acute pulmonary injury. EOI treatment could also suppress the formation of fibrous tissue in mice with BLM-induced pulmonary fibrosis through inhibiting TGF-β/Smad and PI3K/Akt pathways. Chromatographic analysis and preparation suggested that fatty acid and phenol derivatives are present in EOI. Based on cellular inflammation and fibrosis models, the phenolic compounds in EOI can represent the anti-inflammatory and anti-fibrotic effects of EOI by regulating pro-inflammatory and pro-fibrotic cytokines such as NO, TNF-α, IL-6, TGF-β1, and α-SMA.
CONCLUSION
EOI ameliorated BLM-induced pulmonary injury and fibrosis in mice by inhibiting the inflammatory response and regulating the redox equilibrium, as well as by mediating TGFβ/Smad and PI3K/Akt, which suggested that EOI has potential to treat pulmonary diseases.
Topics: Mice; Animals; Pulmonary Fibrosis; Bleomycin; Inula; Lung Injury; Tumor Necrosis Factor-alpha; Interleukin-6; Oils, Volatile; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Fibrosis; Inflammation; Cytokines; Anti-Inflammatory Agents; Transforming Growth Factor beta; Phenols; Lung
PubMed: 37704119
DOI: 10.1016/j.jep.2023.117169 -
Pediatric Pulmonology Oct 2023This case report describes the presentation, diagnosis, and treatment of a 13-year-old boy with pulmonary cystic echinococcosis. The patient presented with low-volume...
This case report describes the presentation, diagnosis, and treatment of a 13-year-old boy with pulmonary cystic echinococcosis. The patient presented with low-volume hemoptysis, and lung imaging revealed a large cystic mass, as well as smaller pseudo-nodular lesions, suggesting a large intrathoracic hydatid cyst and ruptured cysts. The diagnosis was confirmed by a positive echinococcosis Western Blot assay, despite equivocal serology. The treatment consisted of surgical removal of the large cyst using thoracoscopy, along with a two-week course of albendazole and praziquantel, followed by albendazole alone for two years. Analysis of the cyst membrane revealed an Echinococcus granulosus protoscolex. The patient had a successful recovery.
Topics: Male; Animals; Humans; Child; Adolescent; Albendazole; Echinococcosis; Echinococcus granulosus; Cysts; Lung; Echinococcosis, Pulmonary
PubMed: 37401873
DOI: 10.1002/ppul.26579 -
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 -
Journal of Ethnopharmacology Sep 2023Shiwei Qingwen decoction (SWQ), a Chinese herbal formula based on the classic traditional Chinese medicine prescription Yu Ping Feng San, has shown efficacy in...
ETHNOPHARMACOLOGICAL RELEVANCE
Shiwei Qingwen decoction (SWQ), a Chinese herbal formula based on the classic traditional Chinese medicine prescription Yu Ping Feng San, has shown efficacy in preventing and treating early pneumonia with good clinical outcomes. However, its underlying mechanism is yet unclear.
AIM OF THE STUDY
To clarify the preventive and therapeutic effects of SWQ on lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore the underlying mechanism by which SWQ influences pneumonia.
MATERIALS AND METHODS
First, the chemical composition of SWQ was preliminarily determined by high performance liquid chromatography (HPLC), and the impact of SWQ (3.27, 6.55, and 13.1 g/kg) was assessed in the LPS-induced ALI rat model. Next, its inflammatory pathway was determined via network pharmacology. Finally, the molecular mechanism of SWQ was validated using a rat ALI model and a THP-1 cell inflammation model.
RESULTS
HPLC identified chlorogenic acid, prime-O-glucosylcimifugin, calycosin, and 5-O-methylaminoside in the chemical profile of SWQ. In the ALI model, SWQ alleviated ALI by reducing lung wet/dry weight ratio (W/D) and preventing histopathological damage to the lungs. At the same time, SWQ decreased penetration of inflammatory mediators by upregulating AQP1 and AQP5 and endothelial nitric oxide synthase (eNOS). Pretreatment with SWQ downregulated white blood cells and neutrophils count in BALF and suppressed LPS-induced expression levels of MPO, NE, and pro-inflammatory factors (TNF-α, IL-1β, IL-6, and iNOS). Network pharmacology showed that SWQ was associated with TLR4/NF-κB inflammation pathway. Moreover, pretreatment with SWQ reduced the expression level of TLR4/NF-κB signaling pathway-associated proteins (TLR4, Myd88, p-IκB, and p-p65) and NLRP3 inflammasome (NLRP3, ASC, caspase-1, and cleaved-IL-1β) in vivo and vitro.
CONCLUSIONS
The present study demonstrates that SWQ can reduce inflammation in ALI by inhibiting TLR4/NF-κB and NLRP3 inflammasome activation.
Topics: Rats; Animals; NF-kappa B; Inflammasomes; Lipopolysaccharides; NLR Family, Pyrin Domain-Containing 3 Protein; Toll-Like Receptor 4; Signal Transduction; Acute Lung Injury; Lung; Inflammation; Pneumonia
PubMed: 37164255
DOI: 10.1016/j.jep.2023.116615 -
The Journal of Investigative Dermatology Oct 2023Microneedle array has proven more efficient in stimulating humoral immunity than intramuscular vaccination. However, its effectiveness in inducing pulmonary CD8+ T cells...
Microneedle array has proven more efficient in stimulating humoral immunity than intramuscular vaccination. However, its effectiveness in inducing pulmonary CD8+ T cells remains elusive, which is essential to the frontline defense against pulmonary viral infections such as influenza and COVID-19 viruses. The current investigation reveals that superior CD8+ T-cell responses are elicited by immunization with a microneedle array over intradermal or intramuscular immunization using the model antigen ovalbumin, irrespective of whether or not the antigen is provided in the lung. Mechanistically, microneedle array-mediated immunization targeted the epidermal layer and stimulated predominantly Langerhans cells, resulting in increased expression of α4β1 adhesion molecules on the CD8+ T-cell surface, which may play a role in T-cell homing to the lung, whereas CD8+ T cells induced by intramuscular immunization did not express the adhesion molecule sufficiently. CD8+ T cells with a lung-homing propensity were also seen after intradermal vaccination, yet to a much lesser extent. Accordingly, microneedle array immunization provided stronger protection against influenza viral infection than intradermal or intramuscular immunization. The observations offer insights into a strong cross-talk between epidermal immunization and lung immunity and are valuable for designing and delivering vaccines against respiratory viral infections.
Topics: Humans; Influenza, Human; COVID-19; CD8-Positive T-Lymphocytes; Vaccination; Lung; Influenza Vaccines; Immunization
PubMed: 37044258
DOI: 10.1016/j.jid.2023.03.1672 -
Scientific Reports Oct 2023Studies considering the relationship between non-obesity-related body composition and lung function are few; therefore, this study aimed to explore these correlations...
Studies considering the relationship between non-obesity-related body composition and lung function are few; therefore, this study aimed to explore these correlations and effects. This cross-sectional study conducted in rural Qingtongxia City and Pingluo County, Ningxia, China, included 776 participants aged 30-75 years. Body composition and lung function were measured using direct segmental multifrequency bioelectrical impedance analysis and a digital spirometer, respectively. Their correlation was assessed using partial correlation analysis, controlling for age and smoking status, and the body composition effect on lung function was analyzed using binomial logistic regression analysis. The body components total body water content, protein content, mineral content, muscle mass, fat-free mass (FFM), skeletal muscle mass, basal metabolic volume, and chest circumference (CC) positively correlated with pulmonary function (forced vital capacity and forced expiratory volume in one second) in both sexes. Neck circumference and hip circumference positively correlated with pulmonary function in women. Additionally, lung function declines more slowly in women (odds ratio [OR] = 0.66, 95% confidence interval [CI] = 0.44-0.98, p = 0.04); CC (OR = 0.92, 95% CI = 0.86-0.98, p = 0.01) increased as a protective factor for decreased lung function. Increased waist circumference (OR = 1.04, 95% CI = 1.00-1.09, p = 0.04) was a risk factor for reduced lung function. FFM contains body composition indicators positively correlating with lung function, excluding fat-related body composition. Abdominal obesity increases the risk of decreased lung function.
Topics: Male; Humans; Female; Cross-Sectional Studies; Body Mass Index; Body Composition; Lung; Obesity
PubMed: 37857639
DOI: 10.1038/s41598-023-44486-9 -
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