The Chemotactic Activity of Sputum from Patients with Bronchiectasis

201

148

Neutrophils recruited to the airways in chronic obstructive pulmonary disease (COPD) are thought to mediate tissue destruction. Neutrophil recruitment is increased during bacterial exacerbations. The inflammatory process was studied in patients with an acute exacerbation of COPD in order to ascertain the role of leukotriene B 4 (LTB 4 ).The sputum of eight subjects with a bacterial exacerbation of COPD was analysed for neutrophil products (myeloperoxidase, elastase) and chemoattractants (interleukin-8 (IL-8) and LTB 4 ). The contribution of LTB 4 to the chemotactic activity of the sputum sol phase was determined using the LTB 4 receptor antagonist LY293111. The concentrations of the serum acute phase proteins a 1 -proteinase inhibitor, a 1 -antichymotrypsin and C-reactive protein were measured. All patients received appropriate broad-spectrum antibiotic treatment for 7±14 days.Initially, the sputum myeloperoxidase activity was high, indicating neutrophil influx; this was associated with high levels of IL-8 and LTB 4 . All these concentrations fell with treatment (p<0.01). The chemotactic activity of the sputum was raised on presentation and fell with treatment (p<0.01). LTB 4 contributed~30% of the total chemotactic activity on presentation; this diminished with therapy. All acute phase proteins were raised on presentation and fell with therapy (p<0.01).These findings suggest that leukotriene B 4 contributes to neutrophil influx into the airway in chronic obstructive pulmonary disease and may influence disease progresgression. Eur Respir J 2000; 15: 274±280.

Section: Discussionsupporting

confidence: 93%

Bronchial inflammation in acute bacterial exacerbations of chronic bronchitis: the role of leukotriene B4

Crooks¹,

Bayley²,

Hill³

et al. 2000

201

148

“…Further studies after the resolution of the exacerbation may resolve this issue. However, it should be noted that the increased levels of DES and IDES excretion during the exacerbation are similar to those for the CF and Bx patients in the stable state, in whom the neutrophil burden is also markedly increased [25,26], although lung function is better (table 1).…”

Section: Discussionsupporting

confidence: 58%

MEKC of desmosine and isodesmosine in urine of chronic destructive lung disease patients

Viglio¹,

Iadarola²,

Lupi³

et al. 2000

Degradation of extracellular matrix components is central to many pathological features of chronic destructive lung disorders. Desmosine and isodesmosine are elastin-derived cross-linked amino acids whose urine levels are considered representative of elastin breakdown.The aim of this study was to apply a novel methodology, based on high-performance capillary electrophoresis, to the quantification of desmosine and isodesmosine in 11 patients with stable chronic obstructive pulmonary disease (COPD), 10 with an exacerbation of COPD, nine with a 1 -antitrypsin deficiency, 13 with bronchiectasis, and 11 adults with cystic fibrosis, in comparison to 24 controls.It was found that, in patients with stable COPD, urinary desmosine levels were higher than in controls (p=0.03), but lower than in COPD subjects with an exacerbation (p#0.05). The highest desmosine levels were found in subjects with a 1 -antitrypsin deficiency, bronchiectasis and cystic fibrosis (p<0.001 versus stable COPD). In a shortterm longitudinal study, five stable COPD patients showed a constant rate of desmosine excretion (mean coefficient of variation <8% over three consecutive days).In conclusion, the present method is simple and suitable for the determination of elastin-derived cross-linked amino acid excretion in urine, giving results similar to those obtained using other separation methods. In addition, evidence is presented that urinary desmosine excretion is increased in conditions characterized by airway inflammation, such as exacerbations of chronic obstructive pulmonary disease, bronchiectasis and cystic fibrosis. Results obtained in subjects with a 1 -antitrypsin deficiency suggest that this method might be used to evaluate the putative efficacy of replacement therapy. Eur Respir J 2000; 15: 1039±1045. Chronic obstructive pulmonary disease (COPD), with or without inherited deficiency of a 1 -antitrypsin (AAT), disseminated bronchiectasis (Bx) and cystic fibrosis (CF) are destructive lung disorders characterized by chronic and irreversible airflow limitation. Irrespective of the aetiological factors implicated, there is a solid body of evidence suggesting that degradation of the extracellular matrix component, mainly elastin, due to an imbalance between proteinases and their naturally occurring inhibitors, is central to many of the pathological features of these conditions [1±4].Excess lung elastin degradation results in the excretion of elastin-derived peptides containing desmosine (DES) and isodesmosine (IDES) in urine [5]. Since these crosslinked amino acids are unique to mature elastin, their urine levels are considered to be representative of body elastin breakdown. Urinary excretion of DES and IDES has been reported to be increased in patients with COPD, current smokers with normal lung function [6] and adults with CF [7] compared to appropriate controls.There are two validated means of detecting DES and IDES in body fluids: a separation method, based on isotope -dilution/high -performance liquid chromatography (HPLC) [8], and ...

“…The present data shows evidence of inflammation in the larger airways in patients with COB with a wide range of neutrophil influx (as reflected in the MPO concentration) in response to the chemoattractants IL-8 and LTB 4 which are thought to play a key role in neutrophil recruitment [28]. Elastase activity was absent or low even though these samples are known to contain the enzyme [29] probably due to inhibition by the natural inhibitors, especially SLPI.…”

Section: Discussionmentioning

confidence: 83%

Airways inflammation in chronic bronchitis: the effects of smoking and alpha1-antitrypsin deficiency

Hill¹,

Bayley²,

Campbell³

et al. 2000

104

Airways inflammation in chronic bronchitis is thought predominantly to be a direct consequence of neutrophil recruitment and release of elastase in response to factors such as cigarette smoke. The aims of this study were to assess the role of smoking and determine whether the serum elastase inhibitor α1‐antitrypsin (α1AT) influenced the process. Airways inflammation was compared between patients with chronic obstructive bronchitis with (n=39) and without (n=42) severe α1AT deficiency. The authors assessed the sputum concentration of the neutrophil chemoattractants interleukin‐8 (IL‐8) and leukotriene (LT)B4, myeloperoxidase (MPO) as a marker of neutrophil influx, neutrophil elastase activity and its natural inhibitors, α1AT and secretory leukoprotease inhibitor (SLPI). Finally serum α1AT was measured to determine the degree of protein leakage (sputum sol serum α1AT ratio). Compared to current smokers, the exsmokers had a lower concentration of the chemoattractant IL‐8 (p<0.05) and a lower MPO concentration, although this failed to reach conventional statistical significance (p=0.06). Patients with α1AT deficiency had greater inflammation in the larger airways with increased LTB4 (p<0.005), MPO (p<0.001), neutrophil elastase activity (p<0.01), protein leak (p<0.001), and were found to have a lower anti‐proteinase screen with both reduced sputum α1AT (p<0.001) and SLPI concentrations (p<0.05). The reduction in sputum interleukin‐8 levels in exsmokers may decrease neutrophil influx and thus explain the slower rate of neutrophil mediated progression of lung disease compared to subjects who continue to smoke. Patients with α1‐antitrypsin deficiency had greater inflammation suggesting that α1‐antitrypsin plays an important role in protecting the larger airways from the inflammatory effects of elastase activity and may explain their more rapid progression of disease.