Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0206061 (interstitial pneumonia)
 6,105 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was designed to clarify the role of neutrophil elastase in the pathogenesis of idiopathic interstitial pneumonia (IIP). To accomplish this, elastase: alpha 1-antitrypsin complexes in plasma and bronchoalveolar lavage fluids (BALF) were measured in 19 patients with IIP and compared to 15 normal smokers. Cell differentiation counts showed that there was no difference in percent neutrophils in BALF between IIP patients and normal smokers. However, elastase: alpha 1-antitrypsin complexes were significantly increased in both plasma and BALF in patients with IIP compared to normal smokers. In IIP patients with honeycombing demonstrated by high resolution CT, although elastase: alpha 1-antitrypsin complexes were not significantly increased in plasma, elastase: alpha-antitrypsin complexes in BALF were significantly increased compared to IIP patients without honeycombing. Western immunoblot analysis showed that although the native 80-KD elastase: alpha-antitrypsin complex was detected in BALF, the molecular weight of elastase: alpha 1-antitrypsin complex in plasma was 60-KD.
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PMID:[Evaluation of the elastase burden in patients with idiopathic interstitial pneumonia]. 825 16

A 66-year-old man was admitted to the hospital due to a rapidly progressing interstitial shadow in both lower fields on a chest roentgenogram taken on November 30 1993. The diagnosis was idiopathic interstitial pneumonia. A corticosteroid and a neutrophil elastase inhibitor were administered and the interstitial shadow resolved. A new infiltration shadow appeared in the right upper lung field one and a half months after the start of steroid therapy. This shadow gradually grew and Aspergillus fumigatus was detected in sputum cultures. In spite of treatment with FCZ+5-FC and 5-FC+AMPH, the abnormal shadow increased in size and mixed with the cavity, and the patient died of respiratory failure, with a pneumothorax caused by ruptures of the cavity formed by CNPA. The clinical and radiological course were considered to the indicative of chronic necrotizing pulmonary aspergillosis, which was described by Binder et al. in 1982.
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PMID:[Chronic necrotizing pulmonary aspergillosis complicated by pneumothorax]. 862 79

Almost all respiratory diseases except benign lung tumors and lung dysplasia entail acute lung injury. The many clinical conditions associated with acute lung injury include aspiration pneumonia, bacterial pneumonia, and sepsis. The fundamental cause of acute lung injury is pulmonary vascular hyperpermeability. Pulmonary vascular hyperpermeability can be attenuated by nitric oxide and cyclic GMP, and potentiated by oxygen radicals and elastase released from neutrophils. Adhesion molecule inhibition could become an effective therapy against acute lung injury, because the adhesion molecules are very important in the pathogenesis of this condition. Adhesion molecules could also be useful markers of disease activity in various lung diseases. Neutrophil elastase inhibitors may become important as therapeutic agents against acute exacerbations of idiopathic interstitial pneumonia, because this pathological condition is a type of acute lung injury. Similarly, N-acetyl cysteine could also become a useful therapeutic agent against idiopathic interstitial pneumonia, because it is a precursor of glutathione, which is the major antioxidant in the fluid lining of the bronchial epithelium.
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PMID:[Pathophysiology of acute lung injury]. 921 75

Levels of KL-6 in serum were measured in 17 patients during acute exacerbations of idiopathic interstitial pneumonia (IIP). The patients were divided into three groups: "effectively" treated (n = 4), "ineffectively" treated (n = 4), and "untreated" with steroid pulse therapy (n = 9). In the "ineffective" group, the level of KL-6 in serum was significantly higher than that in the "effective" group. These results suggest that KL-6 is useful for assessing patients with acute exacerbations of IIP. In a separate study ONO-5046, a specific neutrophil elastase inhibitor, was given in 40 institutions to find out if it is useful in treating IIP. The PaO2/FIO2 ratio after the administration of ONO-5046 was significantly improved in high-dose group, which suggests that this agent is useful in treating patients with IIP.
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PMID:[How can we monitor and treat patients with acute exacerbations of idiopathic interstitial pneumonia]. 921 15

Almost all of respiratory diseases except benign lung tumors and lung dysplasia entail acute lung injury (ALI). The many clinical conditions associated with acute lung injury include aspiration pneumonia, bacterial pneumonia and sepsis. Acute lung injury is the end results of common pathways initiated by a variety of local or systemic insults leading to diffuse damage to the pulmonary parenchyma. Despite the accumulation of abundant information regarding the physiological and cellular basis of lung injury and increasing sophisticated intensive care, an improvement in prognosis has lagged behind. It has become clear that there is not one mediator responsible for ALI, but rather a complex interplay exists between diverse proinflammatory (e.g., lipopolysaccharide, complement products, cytocains, chemocains, reactive oxygen species and arachidonic acid products) and anti-inflammatory (IL-10, IL-1-RA, PGI2) mediators. Early in the course of ALI, large numbers of neutrophils are sequestered in and emigrate from the pulmonary capillaries. The fundamental cause of ALI is pulmonary vascular hyperpermeability caused by the activated neutrophils which release oxygen radicals and proteases. In these processes several adhesion molecules play very important roles. Neutrophil elastase inhibitors become very useful therapeutic agents against acute exacerbation of idiopathic interstitial pneumonia (IIP), because this pathological conditions is a type of ALI. Similarly, N-acetyl cystein could also become a useful therapeutic agent against IIP, because it is a precursor of glutathione, which is the major antioxidant in the fluid lining of the bronchial epithelium.
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PMID:[The 74th Annual Meeting President Lecture. Pathogenesis and therapy of acute lung injury]. 1053 83

ONO-5046 (sivelestat) is a competitive inhibitor of human neutrophil elastase from Ono Pharmaceutical, which is awaiting FDA approval for the treatment of pulmonary fibrosis and idiopathic interstitial pneumonia [349488]. An NDA was filed in Japan in September 1998 [299667]. It is in phase II trials for the treatment of acute circulatory failure [171678]. It is also being investigated as a potential treatment of arthritis [230100]. In animal models of asthma, sivelestat decreased the level of hemorrhage and protein extravasation into the bronchoalveolar lavage fluid after the administration of a 40 mg/kg injection of phorbol myristate acetate [188186]. The compound also inhibited the growth of human lung cancer cell lines in SCID mice [269736]. Sivelestat inhibits gastric lesion formation in rats subjected to water immersion restraint stress. Low oral bioavailability in vivo is due to extensive hepatic first-pass metabolism. Endotoxin-induced lung injury in rabbits was attenuated by pretreatment with sivelestat [276401]. In 1996, analysts at Yamaichi estimated sivelestat would be launched in Japan between 1998/9 and peak annual sales would be less than 5 billion yen [216018].
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PMID:ONO-5046 (Ono Pharmaceutical). 1610 41

We encountered two patients with clinically diagnosed idiopathic interstitial pneumonia with acute respiratory distress syndrome (ARDS). Both patients required mechanical ventilation within 24 hours after admission. We managed these patients using lower tidal volume ventilation (tidal volume: 5-6 ml/kg), antibiotics, sivelestat sodium hydrate and steroid pulse therapy followed by oral prednisolone therapy. Respiratory failure was relieved within 2 weeks following treatment There was no four-fold rise in screen viral titers and screening investigations of autoantibodies were negative. Based on these findings, we diagnosed these cases as having acute interstitial pneumonia (AIP). AIP represents a small subset of patients with ARDS without any associated or predisposing factor. Sivelestat sodium hydrate is an anti-neutrophil elastase inhibitor and is used for the treatment of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). Therefore, sivelestat sodium hydrate may be one of the treatment options for acute respiratory failure due to idiopathic interstitial pneumonia.
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PMID:[Two cases of acute respiratory failure due to idiopathic interstitial pneumonia successfully treated with sivelestat sodium hydrate and steroid therapy]. 1650 63

A six month-old female infant developed dyspnea when she was treated with valproate sodium (VPA) and zonisamide (ZNS) for epileptic spasms. Two weeks after its onset, her dyspnea was exacerbated by respiratory syncytial virus (RSV) infection. We diagnosed interstitial pneumonitis (IP) based on her chest CT and high serum concentrations of KL-6 and surfactant protein D. Her dyspnea improved with the treatment which included steroids, neutrophil elastase inhibitor and discontinuation of VPA and ZNS. An allergic reaction probably explains the IP in our patient because steroids were effective. Her IP might have been exacerbated by several factors including the use of two anticonvulsants (VPA, ZNS), RSV infection, and physiological low serum IgA level of infants. Drug-induced interstitial lung disease should be remembered as a possible complication of anticonvulsant treatment, such as VPA and ZNS.
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PMID:[Valproate sodium and zonisamide associated interstitial pneumonitis in an infant]. 1722 18

The prognostic significance of a neutrophil elastase inhibitor, sivelestat sodium hydrate (SSH), was evaluated in patients on mechanical ventilation due to acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) associated with systemic inflammatory response syndrome (SIRS). We studied 20 consecutive patients in our hospital, where patients complicated with interstitial pneumonia (IP) were separately analyzed (ARDS group, n = 10; IP group, n = 10). There was no significance difference between the two groups in the average lung injury score (3.0 in the ARDS group versus 2.8 in the IP group), the mean P/F ratio (96.3 mmHg in the ARDS group versus 96.7 mmHg in the IP group), plateau pressure (30.5 mmHg in the ARDS group versus 27.0 mmHg in the IP group), ventilator-free days, the duration of intensive care unit stay, and the hospitalization period. Four ARDS patients and 5 IP patients were treated with SSH within 3 days from SIRS onset. In the ARDS group, 5 patients (50%) were complicated with 4 or more organ dysfunctions and 3 patients (30%) died. IP patients all received corticosteroid, but the mortality was significantly higher among patients with IP than among those with ARDS by Kaplan-Meier survival curves. Of the clinical variables, only the diagnosis of IP was found to be independently related to mortality by a multivariate Cox proportional-hazards analysis. We conclude that IP patients have poor life expectancy if they are treated with SSH.
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PMID:[Prognostic significance of neutrophil elastase inhibitor in patients with acute lung injury and interstitial pneumonia]. 1741 35

Idiopathic interstitial pneumonias (IIPs) may have an acute or subacute presentation, or acute exacerbation may occur in a previously subclinical or unrecognized chronic IIP. Acute or subacute IIPs include acute interstitial pneumonia (AIP), cryptogenic organizing pneumonia (COP), nonspecific interstitial pneumonia (NSIP), acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) and AE-NSIP. Interstitial lung diseases (ILDs) including connective tissue disease (CTD) associated ILD, hypersensitivity pneumonitis, acute eosinophilic pneumonia, drug-induced lung disease and diffuse alveolar haemorrhage need to be differentiated from acute and subacute IIPs. Despite the severe lack of randomized controlled trials for the treatment of acute and subacute IIPs, the mainstream treatment remains corticosteroid therapy. Other potential therapies reported in the literature include corticosteroids and immunosuppression, antibiotics, anticoagulants, neutrophil elastase inhibitor, autoantibody-targeted treatment, antifibrotics and hemoperfusion therapy. With regard to mechanical ventilation, patients in recent studies with acute and subacute IIPs have shown better survival than those in previous studies. Therefore, a careful value-laden decision about the indications for endotracheal intubation should be made for each patient. Noninvasive ventilation may be beneficial to reduce ventilator associated pneumonia.
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PMID:Acute and subacute idiopathic interstitial pneumonias. 2712 74


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