Neutrophil Retention in the Lungs of Patients with Chronic Obstructive Pulmonary Disease

Selby, C.; Drost, Ellen; Lannan, S.; Wraith, P. K.; MacNee, William

doi:10.1164/ajrccm/143.6.1359

Cited by 77 publications

(35 citation statements)

References 15 publications

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“…There are no published data that directly compare concentrations of MPO and neutrophil counts from which to draw comparison; however, the values gained for the other inflammatory mediators in this study are similar to previously published data for both patient groups [14,15,[30][31][32] suggesting our results are robust. It may be that the differences in neutrophilic inflammation reflect greater neutrophil retention in the tissues of A1ATD due to the local accumulation of polymers [33], or a greater chemotactic response of neutrophils from COPD patients [34]. Differences between groups were influenced by a subset of patients who displayed consistently higher pulmonary inflammation during the study than their matched peers.…”

Section: Discussionmentioning

confidence: 99%

Variability of sputum inflammatory mediators in COPD and α₁-antitrypsin deficiency

et al. 2012

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There is inherent daily variability of sputum inflammatory mediators in stable-state patients with usual chronic obstructive pulmonary disease (COPD). The variability of pulmonary inflammation in patients with a 1 -antitrypsin deficiency (A1ATD) is unknown. Our study aimed to quantify this variability, in comparison to patients with usual COPD, in order to facilitate power calculations for proof of concept trials of putative specific anti-inflammatory agents in both groups.Sputum interleukin (IL)-8, myeloperoxidase (MPO), leukotriene B 4 (LTB 4 ) and differential cell counts were measured in 12 usual COPD patients and 12 A1ATD patients on nine occasions over a 1-month period. All samples were obtained in the stable clinical state.There was significant daily variability in all mediators in all patients. A1ATD patients had higher sputum concentrations of IL-8 and LTB 4 compared with usual COPD, but lower levels of MPO and absolute neutrophil counts. Patients with usual COPD had more intra-patient variability, A1ATD patients demonstrated greater inter-patient variability.There are increased concentrations of pulmonary inflammatory mediators but fewer sputum neutrophils in A1ATD compared with usual COPD. The daily variability of inflammatory mediators and cell counts was significantly reduced in both groups by averaging sequential samples. This can be utilised to perform power calculations for future proof of concept studies; averaging three sequential samples appears optimum.

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Section: Discussionmentioning

confidence: 99%

Variability of sputum inflammatory mediators in COPD and α₁-antitrypsin deficiency

et al. 2012

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“…The expression of neutrophil adhesion molecules is increased, the release of neutrophils from the bone marrow is also raised and there are changes in neutrophil function and deformability. This may lead to increased sequestration of neutrophils in the pulmonary microcirculation [23][24][25]. During smoking or exacerbations of COPD, these changes are magnified [7][8][9].…”

Section: Copd As a Putative Cause Of Anaemia Of Chronic Diseasementioning

confidence: 99%

The potential impact of anaemia of chronic disease in COPD

Similowski

Agustí²,

MacNee³

et al. 2006

Eur Respir J

153

107

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Anaemia of chronic disease (ACD), with chronically low levels of circulating haemoglobin, is an immune driven abnormality that occurs in many inflammatory diseases, and also in chronic heart failure. Although chronic obstructive pulmonary disease (COPD) is ''traditionally'' associated with polycythaemia, the systemic inflammation that is now recognised as a feature of COPD makes it a possible cause of ACD. If present in COPD, anaemia could worsen dyspnoea and limit exercise tolerance.Preliminary evidence suggests that anaemia in COPD patients may be more prevalent than expected, concerning 10-15% of patients suffering from severe forms of the disease. A database study conducted in 2,524 COPD patients being prescribed long-term oxygen therapy has shown that a low haematocrit is a strong predictor of survival in this population, before body mass index, and is associated with more hospitalisations and a longer cumulative duration of hospitalisation. COPD patients with low haemoglobin levels have a poorer prognosis than COPD patients with normal haemoglobin levels in the event of acute gastrointestinal bleeding or after elective aneurysm repair. Raising haemoglobinaemia through transfusion decreases minute ventilation and work of breathing in COPD patients.These preliminary evidences point to the need to study the prevalence of anaemia, and its physiological and clinical impact in chronic obstructive pulmonary disease. When this body of knowledge is available, the question of the putative benefits of raising haemoglobinaemia in chronic obstructive pulmonary disease will have to be addressed.

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“…This also may play a role in the elevation of lung cell numbers. The increase in the numbers of neutrophils is particularly interesting because such a chronic inflammatory state is associated with the pathogenesis of emphysema (Selby et al, 1991). In lungs of ASMKO mice that were fixed at constant equal pressure, no histologic evidence of emphysema was observed, even in the oldest group of mice studied (24 weeks).…”

Section: Dhami Et Almentioning

confidence: 99%

Analysis of the Lung Pathology and Alveolar Macrophage Function in the Acid Sphingomyelinase–Deficient Mouse Model of Niemann-Pick Disease

Dhami

Gordon

et al. 2001

Laboratory Investigation

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SUMMARY:Types A and B Niemann-Pick disease (NPD) are lipid storage diseases caused by the deficient activity of the lysosomal enzyme, acid sphingomyelinase (ASM). Type B NPD is associated with progressive pulmonary function decline and frequent respiratory infections. ASM knock-out (ASMKO) mice are available as a model for NPD, but the lung pathology in these mice has not been adequately characterized. This study shows that by 10 weeks of age ASMKO mice have a significantly higher number of cells in their pulmonary airspaces than normal mice, consisting primarily of enlarged and often multinucleated macrophages. These mice also have much higher levels of sphingomyelin in their airspaces at 10 weeks of age, and both cell numbers and sphingomyelin concentrations remain elevated until 26 weeks of age. In these older mice an increased number of neutrophils is also seen. The alveolar cell population in the ASMKO mice produces less superoxide when stimulated, but this can be corrected by providing recombinant ASM to the culture media. Elevated levels of the chemokines macrophage inflammatory protein-2 and macrophage inflammatory protein-1␣ were also present in the bronchoalveolar lavage fluid of ASMKO mice, and this correlated with increased production of these chemokines by cultured macrophages and enhanced immunostaining in situ. Also, lung histology showed increased cellularity in the alveolar walls of ASMKO mice, but no evidence of fibrosis. Ultrastructural analysis of the lungs showed that the ASMKO mice have similar pathologic features to human NPD patients, with variable lipid storage evident in type I pneumocytes, endothelial cells, and airway ciliated epithelia. The alveolar macrophage, however, was the most dramatically affected cell type in both mice and humans. These studies indicate that the ASMKO mice can be used as a model to study the lung pathology associated with NPD, and demonstrate that the cellular and biochemical analysis of pulmonary airspaces may be a useful approach to monitoring disease progression and/or treatment. (Lab Invest 2001, 81:987-999).

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Neutrophil Retention in the Lungs of Patients with Chronic Obstructive Pulmonary Disease

Cited by 77 publications

References 15 publications

Variability of sputum inflammatory mediators in COPD and α₁-antitrypsin deficiency

Variability of sputum inflammatory mediators in COPD and α₁-antitrypsin deficiency

The potential impact of anaemia of chronic disease in COPD

Analysis of the Lung Pathology and Alveolar Macrophage Function in the Acid Sphingomyelinase–Deficient Mouse Model of Niemann-Pick Disease

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Neutrophil Retention in the Lungs of Patients with Chronic Obstructive Pulmonary Disease

Cited by 77 publications

References 15 publications

Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency

Variability of sputum inflammatory mediators in COPD and α1-antitrypsin deficiency

The potential impact of anaemia of chronic disease in COPD

Analysis of the Lung Pathology and Alveolar Macrophage Function in the Acid Sphingomyelinase–Deficient Mouse Model of Niemann-Pick Disease

Contact Info

Product

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Variability of sputum inflammatory mediators in COPD and α₁-antitrypsin deficiency

Variability of sputum inflammatory mediators in COPD and α₁-antitrypsin deficiency