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)

A case of histiocytosis X (Langerhans type) associated with bullous pulmonary emphysema and acquired immune deficiency, regarding CD4 positive cells, is described. Previous history was remarkable for skin lesions which first appeared in 1981 and progressively worsened, diabetes insipidus diagnosed in 1986, and bullous pulmonary emphysema detected in 1988. Biopsy results of skin lesions were consistent with histiocytosis X. Thyroid gland involvement was found by means of cytological examination. The search for HIV infection (also performed by means of immunoblotting and PCR) was negative. To our knowledge the immunodeficiency detected in histiocytosis X affects the T suppressor lymphocyte subset, so we thought this peculiar case was worth describing.
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PMID:A case of Langerhans histiocytosis with HIV-like immunodeficiency. 135 92

The tight skin (Tsk/+) mouse represents a murine model of heritable fibrosis with some similarities to the skin fibrosis seen in human scleroderma. Tsk/+ animals display alterations in connective tissue in some internal organs. Skin fibrosis can be adoptively transferred to normal recipients with Tsk/+ bone marrow or spleen cells and older Tsk/+ animals develop autoantibodies against topoisomerase suggesting that some of the pathogenesis in the Tsk/+ mouse may be mediated by autoimmunity. To determine the role of T cell subsets in the pathogenesis of fibrotic disease, Tsk/+ mice were bred with CD4- and CD8-deficient (CD4-/- and CD8-/-) mice. Tsk/+ CD4-/- mice showed a marked reduction in skin fibrosis as well as decreased cellularity and only mild collagen disorganization as compared to Tsk/+ CD4+ CD8+ control mice yet did not differ from Tsk controls in the level of serum anti-topoisomerase activity. In contrast, Tsk/+ CD8-/- mice exhibited the same histology in the skin as Tsk/+ controls yet had significantly reduced levels of serum anti-topoisomerase activity. Lung pathology, i.e. emphysema, was unaffected by both the CD4 or CD8 mutations. These data show that only some of the pathological effects of the Tsk mutation are T cell dependent and that different T cell subsets affect different parameters in this multi-organ model of fibrotic disease.
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PMID:A role for CD4+ T cells in the pathogenesis of skin fibrosis in tight skin mice. 791 25

Chronic obstructive pulmonary disease (COPD) is a cytotoxic T lymphocyte (CD8)- and macrophage (CD68)-predominant chronic inflammatory disorder of the conducting airways and alveoli. This is often associated with a neutrophilia, inflammation of small airways and destruction of tissue beyond the terminal bronchiolus, i.e. emphysema. In contrast, asthma is a helper T cell (CD4; type 2)-predominant chronic inflammatory disorder of the conducting airways in which there is T lymphocyte-derived gene expression for interleukin (IL)-4 and IL-5 but not interferon gamma. There is fragility of airway surface epithelium, thickening of the reticular basement membrane, bronchial vessel congestion and (when severe) an increase in the mass of bronchial smooth muscle. This is usually (but not always) associated with tissue and peripheral blood eosinophilia rather than a neutrophilia and there is exudative plugging of the airways. These differences of inflammatory profile, remodelling and lung function are seen when smokers with COPD are compared with non-smoking mild asthmatics. However there may be important similarities and overlap, particularly in more severe asthma when neutrophils predominate and in the older and or smoking asthmatic when reversibility of airflow is less obvious. We have recently demonstrated gene expression for IL-4 and IL-5 in and around the mucus-secreting glands of airways resected from smokers without a history of asthma. Also exacerbations of bronchitis may be associated with a tissue eosinophilia. On examination of bronchial biopsies from these patients we show surprisingly strong gene expression for IL-4, IL-5 and even human eotaxin and RANTES (regulated on activation normal T cell expressed and secreted). Whilst CD4 T lymphocytes of the Th2 phenotype might be expressing these cytokines in bronchitis, CD8 T lymphocytes are also capable of secreting IL-4 and IL-5. Viruses may modulate these changes in distinct lymphocyte functional phenotypes. The relevance and importance of CD4/CD8 T lymphocyte ratio to the development of COPD is discussed.
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PMID:Lymphocytes, chronic bronchitis and chronic obstructive pulmonary disease. 1119 94

The local increase in the secretion of extracellular proteases, allowing cleavage of the extracellular matrix and thereby facilitating the infiltration of T cells, monocytes and neutrophils, is a hallmark of chronic inflammation and autoimmunity. In pulmonary genetic diseases, such as emphysema and cystic fibrosis, proteases can also favour the development of local immunodeficiency by degrading key regulators of the immune response, such as CD4, CD8, IgG, ICAM-1 and C3b receptors. Since several infectious agents can give rise to severe pulmonary disorders associated with opportunistic infections, we sought to determine whether an increase in proteolytic activity occurred during infection with porcine reproductive and respiratory syndrome virus (PRRSV), the causative agent of a new disease in swine characterized by severe respiratory problems in young pigs. Piglets were infected with the virus and bronchoalveolar lavages were collected at various times post-infection to measure the net proteolytic activity. It was shown that PRRSV infection leads to a significant increase in proteolytic activity in pulmonary fluids. Maximal activity was found at 7 and 14 days post-infection, with a return towards normal levels at day 42. Zymographic analyses showed a significant increase in the secretion of matrix metalloproteases (MMPs) 2 and 9, two enzymes involved in tissue remodelling. Histological analyses showed a correlation between the increase in proteolytic activity and the appearance of lesions that were characterized by massive lymphomononuclear cell infiltration. These results suggest that virus infection of the lungs can lead to a transient increase in proteolytic activity that could favour opportunistic infection.
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PMID:Increased proteolytic activity and matrix metalloprotease expression in lungs during infection by porcine reproductive and respiratory syndrome virus. 1136 68

This study examines the hypothesis that the cigarette smoke-induced inflammatory process is amplified in severe emphysema and explores the association of this response with latent adenoviral infection. Lung tissue from patients with similar smoking histories and either no (n = 7), mild (n = 7), or severe emphysema (n = 7) was obtained by lung resection. Numbers of polymorphonuclear cells (PMN), macrophages, B cells, CD4, CD8 lymphocytes, and eosinophils present in tissue and airspaces and of epithelial cells expressing adenoviral E1A protein were determined using quantitative techniques. Severe emphysema was associated with an absolute increase in the total number of inflammatory cells in the lung tissue and airspaces. The computed tomography (CT) determined extent of lung destruction was related to the number of cells/m(2) surface area by R(2) values that ranged from 0.858 (CD8 cells) to 0.483 (B cells) in the tissue and 0.630 (CD4 cells) to 0.198 (B cells) in the airspaces. These changes were associated with a 5- to 40-fold increase in the number of alveolar epithelial cells expressing adenoviral E1A protein in mild and severe disease, respectively. We conclude that cigarette smoke-induced lung inflammation is amplified in severe emphysema and that latent expression of the adenoviral E1A protein expressed by alveolar epithelial cells influenced this amplification process.
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PMID:Amplification of inflammation in emphysema and its association with latent adenoviral infection. 1187 25

This study was designed to test the hypothesis that cigarette smoke-induced inflammation and emphysema are amplified by the presence of latent adenoviral (Ad) infection, and to determine whether this emphysematous process can be reversed by all-trans-retinoic acid (RA) treatment. The results confirm that in guinea pigs, chronic cigarette-smoke exposure caused lesions similar to human centrilobular emphysema. They also show that latent Ad infection combined with cigarette-smoke exposure caused an excess increase in lung volume (P < 0.001), air-space volume (P < 0.001), and lung weight (P < 0.01), and further decrease in surface-to-volume ratio (P < 0.001) compared with smoke exposure alone. RA treatment failed to reverse these emphysematous changes. Analysis of inflammatory response in parenchymal and airway tissue showed that smoking caused an increase of polymorphonuclear leukocytes (PMNs) (P < 0.0002), macrophages (P < 0.001), and CD4 cells (P < 0.0009), and that latent Ad infection independently increased PMNs (P < 0.001), macrophages (P = 0.003), and CD8 cells (P < 0.001). We conclude that latent Ad infection amplifies the emphysematous lung destruction and increases the inflammatory response produced by cigarette-smoke exposure. In this study, the increase in CD4 was associated with cigarette smoke and the increase in CD8 cells with latent Ad infection.
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PMID:Emphysematous lung destruction by cigarette smoke. The effects of latent adenoviral infection on the lung inflammatory response. 1175 Dec 3

The lung pathology of severe chronic obstructive pulmonary disease (COPD) has been poorly investigated. We examined surgical specimens obtained from patients with severe (forced expiratory volume in 1 second [FEV(1)] = 29 +/- 3% predicted, n = 9) or mild/no airflow limitation (FEV(1) = 86 +/- 5% predicted, n = 9) and similar smoking history. With histochemical and immunohistochemical methods we quantified the structural changes and the inflammatory cells in small airways and in muscular pulmonary arteries. As compared with smokers with mild/no COPD, smokers with severe COPD had an increased number of leukocytes in the small airways, which showed a positive correlation with the radiologic score of emphysema and with the value of residual volume, and a negative correlation with the values of FEV(1) and carbon monoxide diffusing capacity. The inflammatory process was characterized by an increase in CD8(+) and CD4(+) T-lymphocytes in the airway wall and by an increase in macrophages in the airway epithelium. When all smokers were considered together, the smoking history was correlated with both the airway wall and smooth muscle thickness, suggesting that smoking itself may play a role in the development of structural changes. No structural and cellular differences were observed in pulmonary arteries between smokers with severe COPD and smokers with mild/no COPD. In conclusion, in the small airways of smokers with severe COPD, there is an increased number of leukocytes, which is correlated with reduced expiratory flow, lung hyperinflation, carbon monoxide diffusion impairment, and radiologic emphysema, suggesting a role for this inflammatory response in the clinical progression of the disease.
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PMID:Airway inflammation in severe chronic obstructive pulmonary disease: relationship with lung function and radiologic emphysema. 1209 Nov 79

T lymphocytes modulate the pulmonary inflammatory response. The aim of this study was to evaluate the clonality within the interstitial lung and peripheral blood T cell receptor (TCR) repertoire in smokers. Interstitial T lymphocytes were isolated from surplus tissue of 16 patients (63 +/- 9 [+/- SD] yr old, 11 male) undergoing surgery due to lung cancer (n = 15) or emphysema. TCR clonality was assessed by PCR amplification followed by spectratyping. Nearly all TCR of interstitial lung lymphocytes showed oligoclonal bands (CD4(+) subset 13/16 patients, 81%; CD8(+) 100%) indicating a specific differentiation. Peripheral blood T lymphocytes (PBL) TCR (especially CD4(+)) had less oligoclonal bands (CD4(+) 31%, CD8(+) 88%). Likewise, more oligoclonal bands were seen in lung TCR (total of 168 bands; 37 CD4(+); 131 CD8(+)), compared with 59 bands in PBL TCR (13 CD4(+); 46 CD8(+)). Intraindividual comparison revealed a more prominent difference in TCR oligoclonality between lung and blood in CD8(+) T cells (median of difference lung minus blood 5; interquartile range 1-10; P = 0.002) compared with CD4(+) T cells (median 2, 0-3, P = 0.039). Thus, TCR oligoclonality is preferentially found in the CD8(+) T cell subset, most distinctive in the lung. These findings indicate a specific interstitial T cell differentiation in response to local stimuli.
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PMID:Characterization of the interstitial lung and peripheral blood T cell receptor repertoire in cigarette smokers. 1553 58

Mice develop pulmonary emphysema after chronic exposure to cigarette smoke (CS). In this study, the influence of gender, exposure duration, and concentration of CS on emphysema, pulmonary function, inflammation, markers of toxicity, and matrix metalloproteinase (MMP) activity was examined in A/J mice. Mice were exposed to CS at either 100 or 250 mg total particulate material/m(3) (CS-100 or CS-250, respectively) for 10, 16, or 22 weeks. Evidence of emphysema was first seen in female mice after 10 weeks of exposure to CS-250, while male mice did not develop emphysema until 16 weeks. Female mice exposed to CS-100 did not have emphysema until 16 weeks, suggesting that disease development depends on the concentration and duration of exposure. Airflow obstruction and increased pulmonary compliance were observed in mice exposed to CS-250 for 22 weeks. Decreased elasticity was likely the major contributor to airflow obstruction because substantial remodeling of the conducting airways, beyond mild mucous cell hyperplasia, was lacking. Exposure to CS increased the number of macrophages, neutrophils, lymphocytes (B cells and activated CD4- and CD8-positive T cells), and activity of MMP-2 and -9 in the bronchoalveolar lavage fluid (BALF). Treatment with antioxidants N-acetylcysteine or epigallocatechin gallate (EGCG) did not decrease emphysema severity, but EGCG slightly decreased BALF inflammatory cell numbers and lactate dehydrogenase activity. Inflammation and emphysema persisted after a 17-week recovery period following exposure to CS-250 for 22 weeks. The similarities of this model to the human disease make it promising for studying disease pathogenesis and assessing new therapeutic interventions.
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PMID:Modulators of cigarette smoke-induced pulmonary emphysema in A/J mice. 1669 68

Bird fancier's lung (BFL) is one of the most common types of hypersensitivity pneumonitis. Nevertheless, the criteria for diagnosing this condition are not standardized. The current study is an in-depth investigation into the clinical characteristics of BFL in the largest series examined for this purpose by a single group, to our knowledge, taking into account the acute, subacute, or chronic clinical presentation. From 1977 to 2003, BFL was diagnosed in 86 patients using a homogeneous protocol. Data from the clinical history and physical examination were analyzed, as well as the results from the following complementary examinations: laboratory analyses, specific serum IgG antibodies determination, chest X-ray, chest computed tomography (CT), pulmonary function testing, immediate hypersensitivity skin testing, delayed cutaneous hypersensitivity testing, bronchofibroscopy with bronchoalveolar lavage (BAL) and/or transbronchial biopsy, bronchial challenge testing, and surgical lung biopsy. In addition, clinical and epidemiologic characteristics were determined in a control group of 60 pigeon breeders who did not meet the diagnostic criteria of BFL. Eighty-six patients (21 men and 65 women) with a mean age of 47 years were studied. Seven (8%) patients were younger than 15 years of age at the time of the diagnosis. In 3 cases, the disease was caused by exposure to feather-filled bedding. Nearly 1 in 5 patients was diagnosed in the chronic phase of the disease. The mean diagnostic delay was 1.6 years overall, and 3.2 years in patients diagnosed in the chronic phase of the disease. Among the 17% of patients with chronic disease, the mean interval from initiation of exposure to diagnosis was 16 years, a higher value than in the acute or subacute presentation forms. Dyspnea and cough were the most common clinical symptoms (98% and 82%, respectively), and nearly 25% had grade III or IV dyspnea at diagnosis. Only 18% of patients experienced chest tightness, a symptom classically considered to be frequent in this condition. Erythrocyte sedimentation rate was elevated (>30 mm/h) in 44% of patients. Urinary calcium was elevated in 20% of patients. Angiotensin-converting enzyme was not elevated in any of the patients in which it was measured. Lactate dehydrogenase increases were found in 51% of patients. Specific IgG antibodies to avian antigens were documented in 92% of BFL patients, but also in 87% of pigeon breeder controls. The most frequent radiologic finding was an interstitial pattern in 79% of patients. Common chest CT features were ground glass areas (68%) and a mosaic pattern (61%); areas of emphysema were found in 7/41 (17%) patients, 5 of whom had never smoked. Two patients had a CT pattern of pulmonary fibrosis indistinguishable from idiopathic pulmonary fibrosis. Immediate hypersensitivity skin testing with bird sera and pigeon bloom was positive in 78% and 100% of BFL patients, respectively, and in 64% and 88% of control pigeon breeders, respectively. Almost one-third of the patients (29%) presented an anergic response on delayed cutaneous hypersensitivity testing. Restrictive ventilatory impairment was the most frequent functional pattern (77%), although 9% and 4% showed a pure obstructive and mixed pattern, respectively. The carbon monoxide diffusing capacity was decreased (<80% of the predicted value) in 85% of cases. Forty-one percent of patients had PaO2 <60 mm Hg at diagnosis when blood gas analysis was performed. Lymphocytosis (>20% lymphocytes) was documented in 83% of patients who underwent BAL, with a similar frequency in the 3 presentation forms: 70% acute, 89% subacute, and 85% chronic. In addition, inversion of the CD4/CD8 ratio (<1) was observed in 62% of the patients, but 38% of cases showed a CD4 predominance. The characteristic triad of histopathologic findings in hypersensitivity pneumonitis was found in only 9% of patients undergoing transbronchial biopsy, but at least 1 of these findings was seen in 69%. Surgical lung biopsy was undertaken in 14/86 (16%) patients; the complete triad was observed in 50% and at least 1 finding in 100%. In 54/86 (63%) patients, the diagnosis was confirmed by bronchial challenge testing, a test with a sensitivity of 92% and specificity of 100%. BFL is a potentially severe disease that can progress to respiratory failure secondary to pulmonary fibrosis or chronic obstructive pulmonary disease, as a form of chronic occupational respiratory disease. Respiratory symptoms in exposed patients, including children and adults who have only 1 pet bird at home, should raise the suspicion of BFL. Diagnosis in the chronic phase is frequent, and the delay to diagnosis was greatest in these cases. Elevated urinary calcium, lactate dehydrogenase, and erythrocyte sedimentation rate in a bird fancier may constitute a combined marker for suspected BFL. Chest CT frequently discloses emphysema and a pattern of idiopathic pulmonary fibrosis in some patients. An anergic response on delayed cutaneous hypersensitivity testing is not infrequent. The presentation with respiratory failure and the predominance of CD4 T lymphocytes in some patients' BAL are both remarkable. Lymphocytosis on BAL also persists in the chronic phase of the disease. Bronchial challenge testing has a high diagnostic yield, and surgical lung biopsy is not needed to reach the final diagnosis in the vast majority of cases.
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PMID:Bird fancier's lung: a series of 86 patients. 1834 8


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