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Background
Resistin is an immunometabolic mediator that is elevated in several inflammatory disorders. A ligand for Toll-like receptor 4, resistin modulates the recruitment and activation of myeloid cells, notably neutrophils. Neutrophils are major drivers of cystic fibrosis (CF) lung disease, in part due to the release of human neutrophil elastase- and myeloperoxidase-rich primary granules, leading to tissue damage. Here we assessed the relationship of resistin to CF lung disease.Methods
Resistin levels were measured in plasma and sputum from three retrospective CF cohorts spanning a wide range of disease. We also assessed the ability of neutrophils to secrete resistin upon activation in vitro. Finally, we constructed a multivariate model assessing the relationship between resistin levels and lung function.Results
Plasma resistin levels were only marginally higher in CF than in healthy control subjects. By contrast, sputum resistin levels were very high in CF, reaching 50–100 fold higher levels than in plasma. Among CF patients, higher plasma resistin levels were associated with allergic bronchopulmonary aspergillosis, and higher sputum resistin levels were associated with CF-related diabetes. Mechanistically, in vitro release of neutrophil primary granules was concomitant with resistin secretion. Overall, sputum resistin levels were negatively correlated with CF lung function, independently of other variables (age, sex, and genotype).Conclusions
Our data establish relationships between resistin levels in the plasma and sputum of CF patients that correlate with disease status, and identify resistin as a novel mechanistic link between neutrophilic inflammation and lung disease in CF. 相似文献BACKGROUND CONTEXT
Although 40% of adolescent idiopathic scoliosis (AIS) patients present with chronic back pain, the pathophysiology and underlying pain mechanisms remain poorly understood. We hypothesized that development of chronic pain syndrome in AIS is associated with alterations in pain modulatory mechanisms.PURPOSE
To identify the presence of sensitization in nociceptive pathways and to assess the efficacy of the diffuse noxious inhibitory control in patients with AIS presenting with chronic back pain.STUDY DESIGN
Cross-sectional study.PATIENT SAMPLE
Ninety-four patients diagnosed with AIS and chronic back pain.OUTCOME MEASURES
Quantitative sensory testing (QST) assessed pain modulation and self-reported questionnaires were used to assess pain burden and health-related quality of life.METHODS
Patients underwent a detailed pain assessment using a standard and validated quantitative sensory testing (QST) protocol. The measurements included mechanical detection thresholds (MDT), pain pressure threshold (PPT), heat pain threshold (HPT), heat tolerance threshold (HTT), and a conditioned pain modulation (CPM) paradigm. Altogether, these tests measured changes in regulation of the neurophysiology underlying the nociceptive processes based on the patient's pain perception. Funding was provided by The Louise and Alan Edwards Foundation and The Shriners Hospitals for Children.RESULTS
Efficient pain inhibitory response was observed in 51.1% of patients, while 21.3% and 27.7% had sub-optimal and inefficient CPM, respectively. Temporal summation of pain was observed in 11.7% of patients. Significant correlations were observed between deformity severity and pain pressure thresholds (p=.023) and CPM (p=.017), neuropathic pain scores and pain pressure thresholds (p=.015) and temporal summation of pain (p=.047), and heat temperature threshold and pain intensity (p=.048).CONCLUSIONS
Chronic back pain has an impact in the quality of life of adolescents with idiopathic scoliosis. We demonstrated a high prevalence of impaired pain modulation in this group. The association between deformity severity and somatosensory dysfunction may suggest that spinal deformity can be a trigger for abnormal neuroplastic changes in this population contributing to chronic pain syndrome. 相似文献Methods: Prospective study of nine outcomes for consecutively enrolled children in outpatient AB-LT. To evaluate sensitivity to change, linear-mixed models were constructed and adjusted for covariates: age at and time since SCI. To evaluate responsiveness, standardized response means and 95% confidence intervals were estimated per outcome.
Results: SATCo scores increased significantly (p < 0.05) regardless of chronicity, initial score, and injury level. The SATCo was the most responsive measure and the only outcome demonstrating a large effect size after 3 months of therapy.
Conclusions: Children with SCI receiving AB-LT improved trunk control regardless of chronicity, initial impairment, or prior experience. SATCo sensitivity and responsiveness support its usefulness in measuring trunk control in children with SCI. 相似文献