Role of neutralizing anti-murine interleukin-17A monoclonal antibody on chronic ozone-induced airway inflammation in mice.

Exposure to ozone has led to airway inflammation and airway hyperresponsiveness, which potential mechanisms relate to ozone-induced oxidative stress. IL-17 is a growing target for autoimmune and inflammatory diseases. The aim of the study was to examine the inhibitory effects of anti-murine interleukin-17A monoclonal antibody (IL-17mAb) on adverse effects of ozone which are noted above. After C57/BL6 mice were exposed to ozone (2.5ppm; 3h) for 12 times over 6 weeks, IL-17mAb, PBS was intraperitoneally injected into mice 1h after ozone or air exposure for 6 weeks and mice were studied 24h after final exposure, monitoring bronchial responsiveness, airway inflammatory cells, lung histology, levels of neutrophil-related chemokine and proinflammatory cytokines in bronchoalveolar lavage (BAL) fluid and serum, the expression of IL-17A mRNA and protein, glucocorticoid receptors (GR), and the phosphorylation of p38MAPK in lung tissues. The administration of IL-17mAb reduced the ozone-induced increases in total cells, especially neutrophils; decreased levels of cytokines, including IL-8 in BAL fluid, IL-8 and IL-17A in serum; mitigated the severity of airway hyperresponsiveness; attenuated lung inflammation scores and histologic analysis confirmed the suppression of lung inflammation, compared with the administration of a control PBS. Exposure to ozone results in increases in IL-17A production rate, mRNA and protein levels of IL-17A and the protein level of GR. These effects were halted and reversed by IL-17mAb treatment. Furthermore, IL-17mAb also reduced the phosphorylation of p38MAPK. Therefore, we conclude that IL-17mAb may be a useful therapy in ozone-related diseases, including COPD.

Aclidinium bromide inhalation powder for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease including chronic bronchitis and emphysema.

Aclidinium is a twice-daily long-acting muscarinic receptor antagonist (LAMA) with an interesting pharmacological profile. Recent evidence indicates that this LAMA, in addition to causing a significant improvement in lung function and other important supportive outcomes, such as health related quality of life, dyspnea and nighttime/early morning symptoms in patients suffering from COPD, is also able to significantly reduce the rate of exacerbations of any severity, is extremely effective in controlling the COPD symptoms, is able to reduce lung hyperinflation, and has an excellent cardiovascular safety profile. Consequently, aclidinium should be considered a first-line approach at least for the symptomatic treatment of COPD although there are still few head-to-head studies comparing this LAMA with other bronchodilators. In any case, aclidinium can be taken into account in the treatment of different COPD phenotypes (emphysema, chronic bronchitis, exacerbators and patients with overlap COPD asthma).

Severe bilateral panlobular emphysema and pulmonary arterial hypoplasia: unusual manifestations of Menkes disease.

Menkes disease is an X-linked recessive disorder of copper transport characterized by neurological deterioration, connective tissue, and vascular defects, abnormal hair, and death in early childhood. We report on a patient with Menkes disease in whom severe diffuse emphysema caused respiratory failure and death at 14 months of age. He had severe growth and developmental delays and other typical clinical manifestations of Menkes disease. He developed respiratory problems requiring continuous supplemental oxygen and a progressively enlarging soft tissue mass appeared on the neck. Imaging studies revealed cystic spaces in multiple lobes of the lung consistent with bullous emphysema. The neck mass was determined to be an internal jugular venous aneurysm. At autopsy, extensive emphysematous change was evident. Post-mortem barium injections of the pulmonary arterial system revealed marked dilatation and tortuosity of the preacinar pulmonary arteries and reduced numbers of intra-acinar arteries. Severe emphysema, presumably caused by abnormal elastin due to deficiency of the copper-dependent enzyme lysyl oxidase, may represent an underestimated clinical complication of Menkes disease and should be considered in the differential diagnosis of chronic respiratory disease in these patients.

Hypothalamic digoxin, hemispheric chemical dominance, and chronic bronchitis emphysema.

The isoprenoid pathway produces three key metabolites--endogenous digoxin (membrane sodium-potassium ATPase inhibitor, immunomodulator, and regulator of neurotransmitter/amino acid transport), dolichol (regulates N-glycosylation of proteins), and ubiquinone (free radical scavenger). This was assessed in patients with chronic bronchitis emphysema. The pathway was also assessed in patients with right hemispheric, left hemispheric, and bihemispheric dominance to find the role of hemispheric dominance in the pathogenesis of chronic bronchitis emphysema. All the 15 patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. In patients with chronic bronchitis emphysema there was elevated digoxin synthesis, increased dolichol, and glycoconjugate levels, and low ubiquinone and elevated free radical levels. There was also an increase in tryptophan catabolites and a reduction in tyrosine catabolites. There was an increase in cholesterol:phospholipid ratio and a reduction in glycoconjugate levels of RBC membrane in patients with chronic bronchitis emphysema. The same biochemical patterns were obtained in individuals with right hemispheric dominance. Endogenous digoxin by activating the calcineurin signal transduction pathway of T-cell can contribute to immune activation in chronic bronchitis emphysema. Increased free radical generation can also lead to immune activation. Endogenous synthesis of nicotine can contribute to the pathogenesis of the disease. Altered glycoconjugate metabolism and membranogenesis can lead to defective lysosomal stability contributing to the disease process by increased release of lysosomal proteases. The role of an endogenous digoxin and hemispheric dominance in the pathogenesis of chronic bronchitis emphysema and in the regulation of lung structure/function is discussed. The biochemical patterns obtained in chronic bronchitis emphysema is similar to those obtained in left-handed/right hemispheric chemically dominant individuals by the dichotic listening test. But all the patients with chronic bronchitis emphysema were right-handed/left hemispheric dominant by the dichotic listening test. Hemispheric chemical dominance has no correlation with handedness or the dichotic listening test. Chronic bronchitis emphysema occurs in right hemispheric chemically dominant individuals and is a reflection of altered brain function. Hemispheric chemical dominance can play a role in the regulation of lung function and structure.

A novel oral neutrophil elastase inhibitor (ONO-6818) inhibits human neutrophil elastase-induced emphysema in rats.

We investigated the effects of a novel oral neutrophil elastase inhibitor (ONO-6818) on acute lung injury and pulmonary emphysema induced by human neutrophil elastase (HNE). Young male Wistar rats were divided into four treatment groups: (1) control group (saline); (2) HNE group (HNE 200 U + 0.5% carboxymethyl-cellulose [solution for ONO-6818]); (3) low-dose ONO-6818 group (HNE 200 U + ONO-6818 10 mg/kg); and (4) high-dose ONO-6818 group (HNE 200 U + ONO-6818 100 mg/kg). Saline and HNE were applied via the trachea using a microsprayer. ONO-6818 was administered orally 1 hour before HNE application. Six hours after HNE application, neutrophil counts and hemoglobin concentration in bronchoalveolar lavage fluid and lung tissue myeloperoxidase activity were determined. Eight weeks after the application, FRC, TLC, lung compliance, and mean linear intercept were estimated. ONO-6818 attenuated dose-dependently HNE-induced increases in lung myeloperoxidase activity, hemoglobin, and neutrophil count in bronchoalveolar lavage fluid. Furthermore, it significantly attenuated HNE-induced increases in FRC, TLC, lung compliance, and mean linear intercept. ONO-6818 inhibited acute lung injury induced by HNE by minimizing lung hemorrhage and accumulation of neutrophils in the lung. ONO-6818 also inhibited the development of HNE-induced emphysematous changes including lung hyperinflation, degradation of elastic recoil, and airspace enlargement.

Effects of guided imagery in patients with chronic bronchitis and emphysema.

Together, chronic bronchitis and emphysema (CBE) ranks as one of the top five leading health problems in the United States. Few nursing interventions have been tested that improve symptom management, functional status, and quality of life. This study tested the effects of guided imagery and maximal inspiratory muscle training (MITT) in a group of 10 males and 9 females, 56-75 years old, with moderate CBE. The research tested whether the independent variables, guided imagery and MITT, have significant independent and/or interaction effects on the dependent variables functional status, fatigue, dyspnea, depression, mastery, quality of life, perceived health status, and inspiratory muscle strength. Results showed that the psychologic intervention of guided imagery significantly improved subjects' perceived quality of life. The physiologic intervention of MITT could not be tolerated by subjects, which precluded testing the effects on the dependent variables. Application of study findings to clinical practice and the need for further research are discussed.

Quartz but not iron oxide causes air-flow obstruction, emphysema, and small airways lesions in the rat.

Recent epidemiologic studies have suggested that some workers exposed to inorganic dusts develop air-flow obstruction independent of or greater than that produced by cigarette smoke; the morphologic basis of this effect is unknown. To investigate this problem, we administered saline alone, 10 mg iron oxide (an inert dust), or 10 or 30 mg of quartz to rats by intratracheal instillation. Animals were killed after 30 days, and pulmonary function and morphologic changes were examined. The iron oxide group was similar to the saline control group in all functional and morphometric parameters. However, both quartz-exposed groups showed evidence of air-flow obstruction, with more severe abnormalities in the high dose group. These findings correlated with morphometric observations of emphysema and thickened airway walls, with changes again more severe in the high dose group. Early silicotic nodules were also present in the latter animals. We conclude that in addition to the classic lesions of nodular silicosis, quartz can produce morphologic and functional changes of air-flow obstruction; no such changes are seen with iron oxide. These observations may explain the air-flow obstruction seen in workers exposed to mineral dusts.