Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0034067 (emphysema)
 11,506 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chronic exposure to several types of mineral dust particles induces an inflammatory reaction in the lung. Dust particles activate alveolar macrophages and prime leukocytes (neutrophils, eosinophils, and basophils), leading to an enhanced release of reactive oxygen species. Sometimes mineral dust particles also contain radicals. Reactive oxygen species (superoxide anion radical, hydrogen peroxide, hydroxyl radical, and singlet oxygen) may lead to tissue damage. These are able to break DNA strands, to destroy proteins, and to induce the process of lipid peroxidation. The effects of oxygen radicals on the beta-adrenergic and muscarinic receptor response of the guinea pig and rat tracheal strip are described. The beta-adrenergic receptor response appeared to be more susceptible to oxidative stress than the muscarinic receptor response. This may lead to an autonomic imbalance on exposure to oxygen radicals. The lipid peroxidation product 4-hydroxy-2,3-trans-nonenal diminished the beta-adrenergic responsiveness in guinea pig tracheal preparations. Histologic examinations indicated that at low concentrations of cumene hydroperoxide (10(-4) M) the epithelial layer of rat trachea was already destroyed, whereas no effect on the muscarinic response was found. Oxygen radical-mediated damage in lung tissue may lead to lung emphysema, hyperresponsiveness, and hypersensitivity. Pharmacotherapeutic interventions that prevent initiation or propagation of these free radical reactions may have a beneficial effect in mineral dust-associated lung disease.
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PMID:Mineral dust exposure and free radical-mediated lung damage. 240 28

The hypothesis of an increased muscarinic receptor sensitivity in airway musculature of patients with asthma, chronic obstructive bronchitis and emphysema was investigated through methacholine-induced contraction of isolated airway smooth muscle strips. Contractile responses were recorded isotonically in tracheal smooth muscle preparations of 5 patients with chronic obstructive bronchitis, 2 patients with emphysema and 1 patient with allergic asthma, as well as in bronchial tissue preparations of 7 patients with chronic obstructive bronchitis. The responses were compared to those obtained in airway tissue preparations of 25 control subjects. The sensitivity to methacholine was normal in all groups of patients. This suggests that muscarinic receptor behaviour is normal in airway smooth muscle of patients with obstructive airway disease.
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PMID:Muscarinic receptor sensitivity in airway smooth muscle of patients with obstructive airway disease. 324 39

Airway remodelling and emphysema are major structural abnormalities in chronic obstructive pulmonary disease (COPD). In addition, pulmonary vascular remodelling may occur and contribute to pulmonary hypertension, a comorbidity of COPD. Increased cholinergic activity in COPD contributes to airflow limitation and, possibly, to inflammation and airway remodelling. This study aimed to investigate the role of acetylcholine in pulmonary inflammation and remodelling using an animal model of COPD. To this aim, guinea pigs were instilled intranasally with lipopolysaccharide (LPS) twice weekly for 12 weeks and were treated, by inhalation, with the long-acting muscarinic receptor antagonist tiotropium. Repeated LPS exposure induced airway and parenchymal neutrophilia, and increased goblet cell numbers, lung hydroxyproline content, airway wall collagen and airspace size. Furthermore, LPS increased the number of muscularised microvessels in the adventitia of cartilaginous airways. Tiotropium abrogated the LPS-induced increase in neutrophils, goblet cells, collagen deposition and muscularised microvessels, but had no effect on emphysema. In conclusion, tiotropium inhibits remodelling of the airways as well as pulmonary inflammation in a guinea pig model of COPD, suggesting that endogenous acetylcholine plays a major role in the pathogenesis of this disease.
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PMID:Tiotropium inhibits pulmonary inflammation and remodelling in a guinea pig model of COPD. 2134 17

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).
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PMID:Aclidinium bromide inhalation powder for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease including chronic bronchitis and emphysema. 2699 25