Disease relevance of COPD

• Glucocorticoids are the most effective antiinflammatory agents for the treatment of chronic inflammatory diseases even though some diseases, such as chronic obstructive pulmonary disease (COPD), are relatively glucocorticoid insensitive [1].
• Nontypeable Haemophilus influenzae (NTHi) is an important human pathogen that causes chronic otitis media with effusion (COME) in children and exacerbation of chronic obstructive pulmonary disease (COPD) in adults [2].
• Mucin overproduction, a hallmark of both diseases, has been shown to directly cause conductive hearing loss in COME and airway obstruction in COPD [2].
• CONCLUSION: Activation of the renin-angiotensin system is associated with the development of secondary erythrocytosis in chronically hypoxemic patients with COPD [3].
• (3) Emphysema involves elastolytic destruction of the alveolar wall; its overall severity, rather than type, appears to be an important determinant of chronic irreversible deterioration of airflow in COPD [4].

Psychiatry related information on COPD

• When subjects were divided according to their current smoking status, levels of sTNF-R55, sTNF-R75, and IL-8 in sputum were significantly elevated in ex-smoking versus currently smoking patients with COPD, suggesting ongoing inflammation in airways and circulation of patients with COPD after smoking cessation [5].
• Psychometric properties of the RAND-36 among three chronic diseases (multiple sclerosis, rheumatic diseases and COPD) in The Netherlands [6].
• Besides ineffective antibody-mediated defense mechanisms, it is likely that hiding of the bacteria in tissue contributes to the persistence of these bacteria in patients with COPD [7].
• These findings do not support an association between regular marijuana smoking and chronic COPD but do not exclude the possibility of other adverse respiratory effects [8].
• RESULTS: Compared with the controls, COPD affected functional status in most areas, not just those requiring physical activity [9].

High impact information on COPD

• In patients with chronic obstructive pulmonary disease (COPD) and hyperinflation of the lungs, dysfunction of the diaphragm may contribute to respiratory decompensation [10].
• We evaluated the contractile function of the diaphragm in well-nourished patients with stable COPD, using supramaximal, bilateral phrenic-nerve stimulation, which provides information about the strength and inspiratory action of the diaphragm [10].
• COPD is associated with a chronic inflammatory response, predominantly in small airways and lung parenchyma, which is characterized by increased numbers of macrophages, neutrophils, and T lymphocytes [11].
• In conclusion, we show that overexpression of HDAC2 in glucocorticoid-insensitive alveolar macrophages from patients with COPD is able to restore glucocorticoid sensitivity [1].
• COPD AMs also showed increased basal release of IL-8 and TNF-alpha, which was poorly suppressed by dexamethasone [12].

Chemical compound and disease context of COPD

• CONCLUSIONS: Theophylline may have a beneficial effect in treatment and prevention of erythrocytosis in patients with COPD [13].
• Activation of the adenosine A(2A) receptor has been postulated as a possible treatment for lung inflammatory diseases such as asthma and chronic obstructive pulmonary disease (COPD) [14].
• Twenty-two age- and sex-matched healthy volunteers (healthy controls) and 20 patients receiving supplemental O2 and with level of hypoxaemia similar to severe COPD due to other pulmonary diseases (disease controls) were also examined [15].
• Using radial immunodiffusion serum histidine-rich glycoprotein (HRG) levels were measured in acquired immune deficiency syndrome (AIDS) patients, in end-stage renal disease (ESRD) patients after renal transplantation and immunosuppressive steroid therapy, and in asthma and chronic obstructive pulmonary disease (COPD) patients treated with steroids [16].
• The aim of the present study was to evaluate the determinants of body mass and the value of serum tumour necrosis factor alpha (TNF-alpha) as a marker of weight loss in COPD patients, and to correlate this with the burden of oxidative stress as measured by serum malonyldialdehyde (MDA) levels [17].

Biological context of COPD

• Chronic obstructive pulmonary disease (COPD) is a common chronic inflammatory disease of the lungs with little or no response to glucocorticoids and a high level of oxidative stress [12].
• We measured the effect of theophylline on HDAC activity and inflammatory gene expression in alveolar macrophages (AM) from patients with COPD [12].
• OBJECTIVE: To determine whether theophylline may be used to lower the hematocrit in patients with COPD [13].
• METHODS: We studied nine nonsmoking healthy subjects, 20 nonsmoking patients with asthma, 10 nonatopic smoking patients with CB (forced expiratory volume in 1 second: 98.4% +/- 11.3%) and 17 patients with COPD (forced expiratory volume in 1 second: 51.2% +/- 14.3%) [18].
• The odds ratio for GSTP1/Ile105 homozygotes versus all other genotypes was 3.5 (95% CI 2.7 to 4.6) for COPD [19].

Anatomical context of COPD

• Theophylline restores histone deacetylase activity and steroid responses in COPD macrophages [12].
• MEASUREMENTS AND MAIN RESULTS: Exacerbation of COPD is associated with greater nasal, sputum, and serum inflammation than the stable state [20].
• CONCLUSION: The percentages of neutrophils in BALF were greater in patients with COPD than in those with CB, suggesting a role in the chronic airflow limitation [18].
• In patients with CB or COPD, eosinophil numbers in biopsy specimens were not significantly different from those of patients with asthma, but cells were not degranulated and eosinophil cationic protein levels in BALF were similar to those of normal subjects [18].
• These data suggest a role for TGF-beta1 in recruiting macrophages into the airway epithelium in COPD [21].

Associations of COPD with chemical compounds

• Therefore, theophylline might restore steroid responsiveness in COPD patients [12].
• Theophylline induced a sixfold increase in HDAC activity in COPD AM lysates and significantly enhanced dexamethasone suppression of induced IL-8 release, an effect that was blocked by the HDAC inhibitor trichostatin A [12].
• The polymorphisms in glutathione S-transferase P1 (GSTP1), a xenobiotic metabolising enzyme, were investigated in patients with COPD [19].
• By contrast, breathing air through the same face mask for 1 hour had no significant effects on 8-isoprostane or IL-6 concentrations in normal subjects or those with COPD [22].
• Retinoids may be one of the few potential treatments capable of reversing alveolar destruction in COPD, and a number of compounds are in clinical trial (e.g. all-trans-retinoic acid) [23].

Physical interactions of COPD

• Cigarette smoke disrupts VEGF165-VEGFR-2 receptor signaling complex in rat lungs and patients with COPD: morphological impact of VEGFR-2 inhibition [24].

Regulatory relationships of COPD

• Elevated MMP-12 protein levels in induced sputum from patients with COPD [25].
• DESIGN: PBECs from eight smokers without airflow limitation and eight patients with COPD were stimulated with 50 ng/mL of TNF and 200 U/mL of IFN-gamma for 4 h along with unstimulated time controls [26].
• CONCLUSIONS: Elevated oxidative stress levels and a reciprocal reduction of VEGF levels in induced sputum were prominent with increases in the severity of COPD [27].
• Increased activity of matrix metalloproteinase-8 and matrix metalloproteinase-9 in induced sputum from patients with COPD [28].
• Eosinophils in atopic asthma bronchitis in contrast to COPD bronchitis also expressed both VLA4 and ICAM3 [29].

Other interactions of COPD

• METHODS: Two hundred four patients with COPD were studied retrospectively and 10 patients prospectively (8 starting treatment with the drug [group 1] and 2 who suspended its long-term use [group 2]) for the correlation between theophylline therapy and hematocrit and erythropoietin level [13].
• LBP levels were increased in COPD patients as compared with controls (11.7 +/- 4.5 versus 8.6 +/- 1.0 mg/L, p < 0.05), and showed a positive correlation with REE (r = 0. 49, p = 0.03), a negative correlation with the SumAA in plasma (r = -0.76, p < 0.0001), and no correlation with muscle AA levels [30].
• In patients with CB or COPD neutrophils were not increased in the mucosa, but neutrophil numbers and myeloperoxidase levels in BALF were significantly increased [18].
• We have applied immunohistology and in situ hybridization to bronchial biopsies of patients with chronic obstructive pulmonary disease (COPD) to examine neutrophil recruitment and to determine neutrophil chemoattractant and CXC receptor (CXCR) 1 and CXCR2 gene expression associated with acute severe exacerbations [31].
• Some clinical aspects of COPD occur similarly in cystic fibrosis (CF), particularly in adult patients [32].

Analytical, diagnostic and therapeutic context of COPD

• To better understand the molecular basis of chronic obstructive pulmonary disease (COPD), we used serial analysis of gene expression (SAGE) and microarray analysis to compare the gene expression patterns of lung tissues from COPD and control smokers [33].
• To differentiate among the pathology of asthma, CB, and COPD eosinophils and neutrophils were studied in peripheral blood, bronchial biopsy specimens, and bronchoalveolar lavage fluid (BALF) [18].
• We therefore prospectively measured TNF-alpha serum levels (immunoradiometric assay) in patients with clinically stable COPD (n = 30; all male; mean age, 65 yr) whose weight was less (Group I; n = 16) or more (Group II; n = 14) than the lower limit of normal taken from Metropolitan Life Insurance Company tables [34].
• RESULTS: Serum CRP levels were significantly higher in patients with COPD (5.03 (1.51) mg/l) than in controls (adjusted odds ratio 9.51; 95% confidence interval 2.97 to 30.45) but were similar in the two control groups (S: 2.02 (1.04) mg/l; NS: 2.24 (1.04) mg/l) [35].
• METHODS: Cross sectional analyses comparing cohorts of 88 patients with COPD, 33 smokers (S), and 38 non-smoker (NS) controls were performed [35].

References