Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0034069 (pulmonary fibrosis)
 7,050 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic lung disease (CLD) of prematurity is associated with an initial increase in pulmonary neutrophils followed by pulmonary fibrosis. We determined whether the proinflammatory cytokines, IL-1 beta and IL-6, were increased in the bronchoalveolar lavage fluid obtained from nine infants (median gestation 25 wk, birthweight 820 g) who developed CLD, seven (28 wk, 1110 g) who recovered from the respiratory distress syndrome (RDS), and four (38 wk, 2690 g) control infants. IL-1 beta and IL-6 protein were both increased in the bronchoalveolar lavage fluid from the CLD groups when compared with the RDS and control groups. This difference for both the cytokines was most marked on d 10 of age, when results from infants with and without CLD were compared (IL-1 beta, 4.6 versus 1.1 ng/mL, p < 0.05; and IL-6, 9.5 versus 1.5 ng/mL, p < 0.05). Immunocytochemistry of lavage cells for IL-1 beta, IL-6, and IL-8 protein showed alveolar macrophages to contain all three cytokines, with lesser staining evident in neutrophils, and in epithelial cells occasionally obtained by lavage. The contribution of alveolar macrophages and luminal cells to the increase in IL-6 and IL-1 was determined by performing semiquantitative reverse transcription-polymerase chain reactions on RNA extracted from lavage cells. IL-6 mRNA expression was increased in lavage cells from the CLD infants when compared with the RDS group. However, the expression for IL-1 beta and IL-8 mRNA was similar in both groups. These results suggest that IL-1 beta, IL-6, and IL-8 may contribute to the pathogenesis of CLD, and that, in CLD, IL-6 may be produced by cells within the air spaces.
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PMID:Increase in interleukin (IL)-1 beta and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity. 882 73

Chronic lung disease due to interstitial fibrosis can be a consequence of acute lung injury and inflammation. The inflammatory response is mediated through the migration of inflammatory cells, actions of proinflammatory cytokines, and the secretion of matrix-degrading proteinases. After the initial inflammatory insult, successful healing of the lung may occur, or alternatively, dysregulated tissue repair can result in scarring and fibrosis. On the basis of recent insights into the mechanisms underlying acute lung injury and its long-term consequences, data suggest that proteinases, such as the matrix metalloproteinases (MMPs), may not only be involved in the breakdown and remodeling that occurs during the injury but may also cause the release of growth factors and cytokines known to influence growth and differentiation of target cells within the lung. Through the release of and activation of fibrosis-promoting cytokines and growth factors such as transforming growth factor-beta1, tumor necrosis factor-alpha, and insulin-like growth factors by MMPs, we propose that these metalloproteinases may be integral to the initiation and progression of pulmonary fibrosis.
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PMID:Metalloproteinase and growth factor interactions: do they play a role in pulmonary fibrosis? 1206 May 55

Chronic lung disease (CLD) or bronchopulmonary dysplasia is a recognized sequel of preterm birth. With improving survival of infants at lower gestational ages, the incidence is on the rise. Pathological features of CLD include alveolar maldevelopment, with or without areas of pulmonary fibrosis. Assisted ventilation, infection/inflammation, oxygen administration, and fluid overload are the major risk factors in the evolution of CLD.Interventions, including the treatment of maternal infection, administration of prenatal glucocorticoids, and postnatal surfactant replacement therapy, improve the survival of preterm infants; however, their effect on CLD is difficult to determine. Strategies that have been effective in reducing CLD are the administration of retinol (vitamin A), high frequency oscillatory ventilation, and administration of glucocorticoids. Previous concerns regarding neurological problems associated with high frequency ventilation have not been substantiated in recent studies. Current recommendations do not advise the routine use of glucocorticoids due to concerns regarding long-term neurodevelopment. Therapies that were found to be ineffective in reducing the incidence of CLD include prenatal thyrotropin, cromolyn sodium (sodium cromoglycate), alpha-1 antitrypsin, superoxide dismutase, tocopherol (vitamin E), ascorbic acid (vitamin C), allopurinol, ambroxol, inositol, inhaled bronchodilators, and fluid restriction. Strategies that may be effective in reducing lung injury and subsequent CLD include avoiding assisted ventilation, lung protective ventilatory maneuvers, permissive hypercapnia, prevention of infection, early aggressive nutrition, and the treatment of a patent ductus arteriosus. The use of inhaled glucocorticoids improves pulmonary dynamics but long-term effects are unknown. The management of infants with established CLD has not been studied adequately, and the role of various ventilatory strategies for infants with established CLD is not clear. Adequate oxygenation should be maintained to prevent hypoxic episodes. Diuretics are helpful during acute decompensation; however, their long-term impact has not been well studied. Provision of adequate nutrition, immunization (routine and against respiratory syncytial virus), follow-up, and monitoring are the key elements in the long-term management of infants with CLD. Future research priorities should be to identify strategies to prevent/treat inflammation and promote the healing processes in the injured lung. The long-term effects of lung-protective ventilation strategies need to be studied.
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PMID:Current perspectives on the prevention and management of chronic lung disease in preterm infants. 1283 19

Chronic lung disease (CLD), including pulmonary fibrosis (PF) and chronic obstructive pulmonary disease (COPD), is the fourth leading cause of mortality worldwide. Both are debilitating pathologies that impede overall tissue function. A common co-morbidity in CLD is vasculopathy, characterized by deregulated angiogenesis, remodeling, and loss of microvessels. This substantially worsens prognosis and limits survival, with most current therapeutic strategies being largely palliative. The relevance of angiogenesis, both capillary and lymph, to the pathophysiology of CLD has not been resolved as conflicting evidence depicts angiogenesis as both reparative or pathologic. Therefore, we must begin to understand and model the underlying pathobiology of pulmonary vascular deregulation, alone and in response to injury induced disease, to define cell interactions necessary to maintain normal function and promote repair. Capillary and lymphangiogenesis are deregulated in both PF and COPD, although the mechanisms by which they co-regulate and underlie early pathogenesis of disease are unknown. The cell-specific mechanisms that regulate lung vascular homeostasis, repair, and remodeling represent a significant gap in knowledge, which presents an opportunity to develop targeted therapies. We have shown that that ABCG2pos multipotent adult mesenchymal stem or progenitor cells (MPC) influence the function of the capillary microvasculature as well as lymphangiogenesis. A balance of both is required for normal tissue homeostasis and repair. Our current models suggest that when lymph and capillary angiogenesis are out of balance, the non-equivalence appears to support the progression of disease and tissue remodeling. The angiogenic regulatory mechanisms underlying CLD likely impact other interstitial lung diseases, tuberous sclerosis, and lymphangioleiomyomatosis.
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PMID:Deregulated angiogenesis in chronic lung diseases: a possible role for lung mesenchymal progenitor cells (2017 Grover Conference Series). 2904 10