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Microvascular hyperpermeability in COPD airways
  1. Y Minakata,
  2. M Nakanishi,
  3. T Hirano,
  4. K Matsunaga,
  5. T Yamagata,
  6. M Ichinose
  1. Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan
  1. Correspondence to:
    Dr M Ichinose
    Third Department of Internal Medicine, Wakayama Medical University School of Medicine, 811-1 Kimiidera, Wakayama 641-0012, Japan;

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Chronic obstructive pulmonary disease (COPD) is characterised by an abnormal inflammatory response of the lungs. An increase in the albumin concentration in the sputum of COPD patients has previously been reported.1 This may suggest that the airway microvascular permeability is increased in COPD airways because the albumin comes from the vasculature via endothelial contraction at post-capillary venule lesions. However, measurement of sputum samples has some limitations such as contamination by saliva. We have measured the albumin concentration of the airway lumen in patients with COPD using a new direct technique for collecting airway epithelial lining fluid.2

Eighteen untreated patients with peripheral type lung cancer undergoing a bronchoscopic examination for the diagnosis were recruited to the study. Approval was obtained from the Wakayama Medical University ethics committee and the patients gave their written informed consent. The mean (SE) age of the patients was 70.4 (2.0) years. Eight patients were current smokers, seven ex-smokers, and three non-smokers. Five of the subjects did not have COPD, four were at risk (stage 0), six had moderate COPD (stage II), and three had severe COPD (stage III) according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification of the severity of COPD.3 Epithelial lining fluid was collected using a microsampling probe under bronchoscopy at the main or intermediate bronchus on the tumour absent side. The albumin concentration in the extracted ELF was measured and normalised by the values in the serum.

The normalised airway albumin values showed a strong correlation with the forced expiratory volume in 1 second % predicted (%FEV1) values (r = −0.727, p = 0.0006; fig 1). There was no significant difference in the airway albumin values according to smoking status (non-smokers: mean (SE) 1.21 (0.29)%, ex-smokers: 1.23 (0.28)%, current smokers: 1.14 (0.28)%) or age. These data suggest that an increase in airway microvascular permeability may be involved in the inflammatory and subsequent obstructive process of COPD.

Figure 1

 Relationship between normalised airway albumin and forced expiratory volume in 1 second % predicted (%FEV1). Normalised airway albumin values were calculated as values of epithelial lining fluid/values of serum.

The precise mechanism of the microvascular hyperpermeability observed in COPD has not been well characterised. We have recently reported that oxidative and nitrosative stress is exaggerated in COPD airways.4,5 Reactive oxygen/nitrogen species such as superoxide anion and peroxynitrite may participate in the microvascular hyperpermeability of COPD airways.

At present some airway/pulmonary cells (including epithelial cells, neutrophils, and macrophages) are considered therapeutic targets for future COPD treatment. In addition to these cells, the airway microvasculature may also be a target in the treatment of COPD. Furthermore, airway albumin values may be a good marker for the efficacy of COPD treatment.