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)

Cigarette smoke, a toxic collection of more than 4000 chemicals generated from combustion of tobacco plant leaves, is known to cause several respiratory ailments, including chronic bronchitis, emphysema and lung cancer, and is associated with an increase in respiratory infections. In addition, cigarette smoking is considered a principal aetiological factor responsible for the development of certain diffuse interstitial and bronchiolar lung diseases, namely respiratory bronchiolitis-interstitial lung disease (RB-ILD), desquamative interstitial pneumonia (DIP) and adult pulmonary Langerhans' cell histiocytosis (PLCH). Although not exclusively seen in cigarette smokers, substantial clinical and epidemiological data support a central role for smoking as the primary causative agent of most RB-ILD, DIP and PLCH. Additional evidence in support of cigarette smoke as a primary aetiological agent in RB-ILD, DIP and PLCH is the observation that smoking cessation may lead to disease improvement, while recurrence of these disorders has been observed to occur in the transplanted lung upon re-exposure to tobacco smoke. Furthermore, histopathological changes of respiratory bronchiolitis, DIP and PLCH (with or without co-existent emphysema) may be found on lung biopsy in the same individual, implicating smoking as a common inciting agent of these diverse lesions. Recent studies also suggest a role for cigarette smoking as a potential co-factor in the development of acute eosinophilic pneumonia, usual interstitial pneumonia and rheumatoid arthritis-associated interstitial lung disease. In the current review, we propose a novel classification that takes into account the complex relationship between cigarette smoking and diffuse lung diseases. Investigation on the role of smoking as a potential causative factor or modifier of these diverse diffuse lung diseases is important, as smoking cessation utilizing state-of-the-art tobacco cessation efforts should be a central part of therapy, while pharmacotherapy with corticosteroids or other immune modifying agents should be reserved for selected patients.
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PMID:Cigarette smoking and diffuse lung disease. 1862 8

Idiopathic pulmonary fibrosis has been associated with emphysema in cigarette smokers as a new clinical entity: combined pulmonary fibrosis and emphysema (CPFE). In order to compare histomorphometrical, roentgenological and immunohistochemical aspects of usual interstitial pneumonia (UIP) with and without associated pulmonary emphysema, 17 patients with biopsy-proven UIP were evaluated. Morphometrical evaluation of lung parenchyma destruction was used to divide patients in two subgroups: emphysema/UIP (n=9) and UIP alone (n=8); four patients with biopsy-proven emphysema without fibrosis were also evaluated. At HRTC scan, emphysematous lesions were prevalent in the upper fields of both emphysema/UIP and emphysema groups and the distribution of fibrotic lesions was similar in emphysema/UIP compared to UIP alone. The semiquantitative histopathological fibrotic score was also similar in emphysema/UIP and UIP alone. In addition, the expression of tumor necrosis factor (TNF)-alpha, matrix metalloproteinase (MMP)-2, MMP-9, MMP-7 and membrane type 1-metalloproteinase (MT1-MMP) by fibroblasts of myofibroblastic foci was similar in emphysema/UIP and UIP alone patients. In contrast, fibroblasts in areas of parenchymal destruction of emphysema/UIP expressed MMP-2, MMP-9, MMP-7 and MT1-MMP at variable but significantly higher levels when compared to emphysema subjects, in the presence of similar levels of TIMP-1, TIMP-2 and TNF-alpha. Fibrotic and emphysematous lesions in emphysema/UIP patients appear to follow the roentgenological and histopathological patterns expected for either UIP or emphysema. Interstitial fibroblast activation is more pronounced in the areas of lung destruction in emphysema/UIP compared to those with emphysema alone, as for exaggerated tissue remodeling.
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PMID:HRCT and histopathological evaluation of fibrosis and tissue destruction in IPF associated with pulmonary emphysema. 1872 34

Cigarette smoking is a recognized risk factor for development of interstitial lung disease (ILD). There is strong evidence supporting a causal role for cigarette smoking in development of respiratory bronchiolitis ILD (RB-ILD), desquamative interstitial pneumonitis (DIP), and pulmonary Langerhans cell histiocytosis (PLCH). In addition, former and current smokers may be at increased risk for developing idiopathic pulmonary fibrosis (IPF). The combination of lower lung fibrosis and upper lung emphysema is being increasingly recognized as a distinct clinical entity in smokers. High-resolution computed tomography is sensitive for detection and characterization of ILD and may allow recognition and classification of the smoking-related ILDs (SR-ILDs) into distinct individual entities. However, the clinical, radiologic, and histologic features overlap among the different SR-ILDs, and mixed patterns of disease frequently coexist in the same patient. The overlap is most significant between RB-ILD and DIP. Macrophage accumulation is bronchiolocentric in RB-ILD, producing centrilobular ground-glass opacity, and more diffuse in DIP, producing widespread ground-glass changes. The coexistence of upper lung nodules and cysts in a smoker allows confident diagnosis of PLCH. Final diagnosis of an SR-ILD and identification of the specific entity can be achieved with certainty only after the pulmonologist, radiologist, and pathologist have reviewed all of the clinical, radiologic, and pathologic data.
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PMID:Smoking-related interstitial lung disease: radiologic-clinical-pathologic correlation. 1879 14

Lymphangioleiomyomatosis is a rare and progressive lung cystic disease, caused by the infiltration of lung parenchyma by mesenchymal cells characterized by co-expression of contractile proteins and melanocytic markers. The pathogenesis of lymphangioleiomyomatosis is determined by mutations affecting tuberous sclerosis complex (TSC) genes, with eventual deregulation of the Rheb/mTOR/p70S6K pathway, and the potential therapeutic activity of mTOR inhibitors is currently under investigation. To better understand the molecular mechanisms involved in the pathogenesis of lymphangioleiomyomatosis, we investigated the expression of cathepsin-k (a papain-like cysteine protease with high matrix-degrading activity). The rationale of this choice was based on the recent demonstration that mTOR inhibitors can regulate major functional activities of osteoclasts, including the expression of cathepsin-k. The immunohistochemical study included 12 cases of lymphangioleiomyomatosis. Twelve angiomyolipomas and several lung diseases (sarcoidosis, organizing pneumonia, usual interstitial pneumonia, emphysema) were investigated as controls. In all lymphangioleiomyomatosis cases, strong cathepsin-k immunoreactivity was demonstrated, restricted to lymphangioleiomyomatosis cells. Similar expression levels were observed in renal angiomyolipomas. These observations extend the knowledge regarding the immunophenotypic profile of lymphangioleiomyomatosis cells, and provide a useful new marker for diagnosis in difficult cases (eg, in small transbronchial biopsies). The strong expression of such a potent papain-like cysteine protease in lymphangioleiomyomatosis cells can significantly contribute to the progressive remodelling of lung parenchyma observed in this deadly disease, with eventual formation of lung cysts. It is possible to speculate that mTOR inhibitors may exert part of their action by limiting the destructive remodelling of lung structure.
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PMID:Cathepsin-k expression in pulmonary lymphangioleiomyomatosis. 1906 Aug 45

The goal of this study was to seek indirect evidence that smoking is an aetiological factor in some patients with non-specific interstitial pneumonia (NSIP). Ten current and eight ex-smokers with NSIP were compared to controls including 137 current smokers with no known interstitial lung disease and 11 non-smokers with NSIP. Prevalence and extent of emphysema in 18 smokers with NSIP were compared with subjects meeting GOLD criteria for chronic obstructive pulmonary disease (COPD; group A; n = 34) and healthy smokers (normal FEV(1); group B; n = 103), respectively. Emphysema was present in 14/18 (77.8%) smokers with NSIP. Emphysema did not differ in prevalence between NSIP patients and group A controls (25/34, 73.5%), but was strikingly more prevalent in NSIP patients than in group B controls (18/103, 17.5%, P < 0.0005). On multiple logistic regression, the likelihood of emphysema increased when NSIP was present (OR = 18.8; 95% CI = 5.3-66.3; P < 0.0005) and with increasing age (OR = 1.04; 95% CI = 0.99-1.11; P = 0.08). Emphysema is as prevalent in smokers with NSIP as in smokers with COPD, and is strikingly more prevalent in these two groups than in healthy smoking controls. The association between NSIP and emphysema provides indirect support for a smoking pathogenesis hypothesis in some NSIP patients.
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PMID:Non-specific interstitial pneumonia in cigarette smokers: a CT study. 1921 21

Addiction is a chronic relapsing disorder characterized by repetitive and compulsive drug-seeking behavior and drug abuse despite negative health or social consequences. Cocaine addiction is a significant worldwide public health problem, which has somatic, psychological, psychiatric, socio-economic and judicial complications. Some of the most frequent complications are cardiovascular effects (acute coronary syndrome, cardiac arrhythmias, increased blood pressure); respiratory effects (fibrosis, interstitial pneumonitis, pulmonary hypertension, alveolar haemorrhage, asthma exacerbation; emphysema), neurological effects (strokes, aneurysms, seizures, headaches); risk for contracting HIV/AIDS, hepatitis B and C, sexual transmitted disease and otolaryngologic effects. Other complications are not discussed here. The vast majority of studies indicate that there are cognitive deficits induced by cocaine addiction. Attention, visual and working memories, executive functioning are affected in cocaine users. Psychiatric complications found in clinical practice are major depressive disorders, cocaine-induced paranoia, cocaine-induced compulsive foraging and panic attacks.
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PMID:[Complications of cocaine addiction]. 1964 39

Most cases of hypersensitivity pneumonitis develop only after many years of inhaling allergens, which include microbes, animal or plant proteins, and certain chemicals that form haptens. The initial clinical presentation is either episodes of acute illness with dyspnea and prominent constitutional symptoms, such as fever, or an insidious onset of dyspnea, coughing, and weight loss, sometimes with superimposed acute episodes. The histopathologic process consists of chronic inflammation of the bronchi and peribronchiolar tissue, often with poorly defined granulomas and giant cells in the interstitium or alveoli. Fibrosis and emphysema may develop. The radiologic findings include diffuse ground-glass opacification, centrilobular ground-glass opacities, air trapping, fibrosis, lung cysts, and emphysema. The histologic and radiologic features in some cases may resemble those of usual interstitial pneumonia or nonspecific interstitial pneumonia. The diagnosis usually rests on a variable combination of findings from history, serology, radiography, lung biopsy, and bronchoalveolar lavage, which characteristically reveals a lymphocyte content of more than 30%, often with an increased CD4-to-CD8 ratio of T cells. Treatment includes avoiding the allergen, if possible, and, in severe cases, systemic corticosteroids. The long-term prognosis is usually good, but some patients develop severe respiratory insufficiency, and a few die of the disease.
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PMID:Hypersensitivity pneumonitis: a historical, clinical, and radiologic review. 1992 54

This study reports the presence of surprisingly frequent and often severe interstitial fibrosis in cigarette smokers with no clinical evidence of interstitial lung disease. Twenty-three lobectomy specimens excised for neoplasms, including 20 from smokers, were extensively sampled, and examined semi-quantitatively for interstitial fibrosis, fibroblast foci, peribronchiolar metaplasia, honey-comb change, emphysema, and respiratory bronchiolitis. Interstitial fibrosis involving greater than 25% of slides was identified in 12 of 20 smokers (60%), but in none of the three never-smokers. Three cases were classified as specific forms of interstitial lung disease, including one each of usual interstitial pneumonia, Langerhans cell histiocytosis, and asbestosis. The remaining 9 cases did not fit with a named interstitial lung disease and were considered to represent examples of smoking-related interstitial fibrosis. This lesion was characterized by varying degrees of alveolar septal widening by collagen deposition along with emphysema and respiratory bronchiolitis. The fibrosis occurred both in subpleural and in deeper parenchyma. It surrounded enlarged airspaces of emphysema, but it also involved non-emphysematous parenchyma. Clinical progression was not documented in any case, although follow-up was short. These observations highlight the spectrum of unexpected fibrosis that is frequently encountered in lobectomy specimens from cigarette smokers. Additional investigation will be required to determine the clinical significance of smoking-related interstitial fibrosis and its relationship, if any, to other smoking-related diseases. It is important, however, that smoking-related interstitial fibrosis be distinguished from specific forms of fibrosing lung disease that may be associated with poor prognoses, especially usual interstitial pneumonia.
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PMID:Clinically occult interstitial fibrosis in smokers: classification and significance of a surprisingly common finding in lobectomy specimens. 2000 53

Advances in computed tomography (CT) scanner technology have made isotropic volumetric, multiplanar high-resolution lung imaging possible in a single breath-hold, a significant advance over the incremental high-resolution CT (HRCT) technique in which noncontiguous images sampled the lung, but lacked anatomic continuity. HRCT of the lungs is an established imaging technique for the diagnosis and management of interstitial lung disease, emphysema, and small airway disease, providing a noninvasive detailed evaluation of the lung parenchyma, and providing information about the lungs as a whole and focally. In addition to having a high degree of specificity for diagnosing conditions such as emphysema, sarcoidosis, usual interstitial pneumonitis, Langerhans cell histiocytosis, and small airway disease, there is a growing body of medical evidence to support the use of HRCT findings or diagnosis to predict patient prognosis. In this article, we review the technique, advantages, and clinical applications of the current HRCT technique.
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PMID:Multidetector high-resolution computed tomography of the lungs: protocols and applications. 2046 32

The purpose of this study is to evaluate the feasibility of and treatment plans for helical tomotherapy (HT) for solitary lung tumors. Nine patients with stage IA non-small-cell lung cancer (NSCLC) and three patients with solitary lung metastasis were treated with HT. All patients were immobilized with the BodyFIX system, and the target volume shown on computed tomography in the 3 respiration phases were superimposed onto the 3-dimensional radiation treatment planning system to represent the internal target motion. All patients were treated with 54-60 Gy in 12 fractions over 8 to 13 days. The median follow-up time was 14 months (range: 3-16 months). The overall response rate was 92%. The local control rate at 1 year was 100% with no difference between NSCLC and metastasis. Of 12 patients, one patient experienced Grade 2 radiation pneumonitis (RP), and the other patient with severe interstitial pneumonia and emphysema experienced Grade 5 RP. The mean lung dose (MLD) and the dose-volume histogram (DVH) for the normal lung volumes were converted into normalized total dose with an alpha/beta ratio of 3 Gy. The DVH of the normal lung volumes demonstrated that the mean volumes of V(10), V(30), V(50), and V(70) were 40.4 +/- 9.4%, 21.3 +/- 6.4%, and 12.8 +/- 4.6%, and 9.3 +/- 4.2% in all patients, 28.8%, 18.7%, 12.3%, and 10.5% in the patient with Grade 2 RP, and 29.3%, 17.9%, 7.7%, and 5.4% in the patient with Grade 5 RP. The mean MLD of all patients was 13.5 +/- 3.9 Gy, and those values of patients with Grade 2 and 5 RP were 12.9 and 21.8 Gy, respectively. Our study found that only the MLD was significantly correlated with RP >Grade 2 (p = 0.030) using the Student's t-test. Our study found the conformity index value of 1.48 +/- 0.15 and the homogeneity index value of 1.066 +/- 0.023, which suggested the feasibility of using HT to treat lung tumors with hypofractionation. In conclusion, HT is a feasible non-invasive technique for treating solitary lung tumors and achieves high accuracy in terms of dose conformity and homogeneity. The decision of the indications for HT might be required caution in cases in which a severe pulmonary toxicity is predicted from the high MLD, especially in cases involving a severe pulmonary comorbidity.
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PMID:Helical tomotherapy for solitary lung tumor: feasibility study and dosimetric evaluation of treatment plans. 2062 6


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