Measurement of soluble proteins in lung secretions.

Stockley, Robert A.

doi:10.1136/thx.39.4.241

Cited by 40 publications

(26 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Sputum IgG subclass values were divided according to the nature of the secretions (mucoid, mucopurulent, and purulent) and compared. Sputum: serum albumin ratios were calculated and compared with sputum:serum IgG subclass ratios to assess the contribution of transudation from plasma and hence the inferred degree of local production as described previously 15. All data were expressed as medians and ranges.…”

Section: Methodsmentioning

confidence: 99%

IgG subclasses in the serum and sputum from patients with bronchiectasis

Hill

Mitchell

Burnett

et al. 1998

Thorax

Self Cite

View full text Add to dashboard Cite

Background-IgG subclass deficiency is often associated with recurrent pulmonary infections. The prevalence of deficiency in a large well characterised group of patients with bronchiectasis has not previously been established. Methods-Serum IgG subclass concentrations in 89 patients with bronchiectasis were compared with those obtained from a group of 82 age and sex matched normal healthy controls. Sputum IgG subclass concentrations were also assessed in 44 of the patients. Albumin was measured as a marker of protein transudation from plasma to determine the degree of local IgG subclass production. Results-The serum concentrations of IgG 1 , IgG 2 and IgG 3 were increased in the patients compared with the control group whereas IgG 4 concentrations were not. There was an overall incidence of deficiency of 1% for subclasses 1-3 and 5% for subclass 4 in patients with bronchiectasis based on observed concentrations being below the lower limit of the control group range. The concentrations of IgG subclasses in sputum were partly dependent upon the degree of inflammation as assessed by the macroscopic appearance of purulence. A comparison of the ratio of sputum:serum subclass concentration and sputum:serum albumin, however, revealed that all of the subclasses were present at greater concentrations than could be accounted for by transudation alone. Conclusions-A new normal control range for serum IgG subclasses has been established and from this range it was found that IgG subclass deficiency in a group of unselected patients with bronchiectasis was comparatively rare. A significant degree of local IgG production was also suggested in the lungs of these patients.

show abstract

Section: Methodsmentioning

confidence: 99%

IgG subclasses in the serum and sputum from patients with bronchiectasis

Hill

Mitchell

Burnett

et al. 1998

Thorax

Self Cite

View full text Add to dashboard Cite

show abstract

“…a 1 AT concentration in sputum sol phase was measured by ELISA relative to a commercially available serum standard (The Binding Site Ltd., Birmingham, UK) as described previously [16] and a 1 AT in serum was measured by radial immunodiffusion (The Binding Site Ltd.). The ratio of sol/serum a 1 AT was calculated and expressed as a percentage to assess the degree of protein leakage from serum as described previously [25].…”

Section: Assay Analysismentioning

confidence: 99%

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

Hill¹,

Bayley²,

Campbell³

et al. 2000

Eur Respir J

104

View full text Add to dashboard Cite

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.

show abstract

“…As previously discussed, some of this secreted protein circulates in the form of polymers [33,100] in patients with a 1 -AT deficiency but not in healthy individuals nor in non-a 1 -AT-deficient subjects with ''usual'' COPD. a 1 -AT enters the lung from the circulation by passive diffusion [101]. It is supplemented by local synthesis, which may be stimulated by oncostatin M [102] and TGF-b [103] in pulmonary epithelial cells [11,12].…”

Section: Intrapulmonary Polymers Of a 1 -At Neutrophil Influx And Thmentioning

confidence: 99%

Mechanisms of emphysema in α₁-antitrypsin deficiency: molecular and cellular insights

Gooptu¹,

Ekeowa²,

Lomas³

2009

Eur Respir J

121

102

View full text Add to dashboard Cite

The severe, early onset emphysema that occurs in patients with circulating deficiency of a 1 -antitrypsin (a 1 -AT) attests to the importance of this protease inhibitor in maintaining lung parenchymal integrity. It has led to the powerful concept of protease:antiprotease balance being crucial to alveolar homeostasis.Pathogenic mutations cause a 1 -AT to self-associate into polymer chains that accumulate intracellularly rather than proceeding along the secretory pathway. Polymerisation of a 1 -AT abolishes antiprotease activity and confers toxic gain-of-function effects. Since a 1 -AT is predominantly synthesised in the liver, where it does not play a major homeostatic role, the directly toxic effects of polymerisation are clearest here. However, data from molecular, cellular, animal and ex vivo studies indicate that intrapulmonary polymerisation of a 1 -AT and inflammatory positive feedback loops may augment the destructive effects of decreased antiprotease levels in the lung.This review integrates the findings from these different approaches and highlights how multiple pathways may converge to give the severe, panacinar emphysema phenotype seen in a 1 -AT deficiency.

show abstract

Measurement of soluble proteins in lung secretions.

Cited by 40 publications

References 35 publications

IgG subclasses in the serum and sputum from patients with bronchiectasis

IgG subclasses in the serum and sputum from patients with bronchiectasis

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

Mechanisms of emphysema in α₁-antitrypsin deficiency: molecular and cellular insights

Contact Info

Product

Resources

About

Measurement of soluble proteins in lung secretions.

Cited by 40 publications

References 35 publications

IgG subclasses in the serum and sputum from patients with bronchiectasis

IgG subclasses in the serum and sputum from patients with bronchiectasis

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

Mechanisms of emphysema in α1-antitrypsin deficiency: molecular and cellular insights

Contact Info

Product

Resources

About

Mechanisms of emphysema in α₁-antitrypsin deficiency: molecular and cellular insights