ABSTRACT

Figure 5.1 Percentage of neutrophils in sputum (median, 25% and 75% percentiles) in subjects with declines in forced expiratory volume (FEV1) of < 20 ml/year, 20-30 ml/year, and > 30 ml/year. R, Spearman rank correlation coefficient. Reproduced with permission from the BMJ Publishing Group from Stanescu D, Sanna A, Maestrelli P et al. Airways obstruction, chronic expectoration, and rapid decline of FEV1 in smokers are associated with increased levels of sputum neutrophils. Thorax 1996;51:267-71

Figure 5.2 Concentrations of interleukin (IL)-8 in the fluid phase of induced sputum from control, smoking, COPD and asthmatic subjects. Mean values ± standard error of the mean are shown. Reproduced with permission from Keatings VM, Collins PD, Scott DM, Barnes PJ. Differences in interleukin-8 and tumor necrosis factoralpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996; 153:530-4

Figure 5.3 Concentrations of tumor necrosis factor (TNF)-α in the fluid phase of induced sputum from control, smoking, COPD and asthmatic subjects. Mean values ± standard error of the mean are shown. Reproduced with permission from Keatings VM, Collins PD, Scott DM, Barnes PJ. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996; 153:530-4

Figure 5.4 Relationship between FEV1 : VC ratio and expression of CDllb on granulocytes in subjects with smoking history. The Spearman rank correlation coefficient (R) was calculated for all 33 subjects. Reproduced with permission from Maestrelli P Calcagni PG, Stanescu D, et al. Integrin upregulation on sputum neutrophils in smokers with chronic airway obstruction. Am J Respir Crit Care Med 1996; 154:1296-300

In most COPD patients, corticosteroids are ineffective at modifying the airway pathology that is more commonly characterized by neutrophilic airway inflammation and detectable by examination of induced sputum. However, eosinophilic airway inflammation, exhibited by some COPD patients, is associated with a significant response to short-term effects of corticosteroid treatment as measured by changes in post-bronchodilator FEV1, health status and symptom scores. Therefore, sputum eosinophilia may predict a beneficial response to steroid treatment (Figures 5.10 and 5.11). While these observations are interesting, further, larger studies are needed to provide more definitive answers that would be of relevance to routine clinical practice. Other drugs used in the treatment

Figure 5.5 Levels of IL-1O in sputum obtained from healthy non-smokers, healthy smokers and patients with asthma and COPD. Horizontal bars represent mean values. Reproduced with permission from Takanashi S, Hasegawa Y, Okamura K, et al. Interleukin-10 level in sputum is reduced in bronchial asthma, COPD and in smokers. Eur Respir J 1999; 14:309-14

Figure 5.6 Differential cell counts in induced sputum in different subject groups. *p < 0.05 versus COPD, smoking, and non-smoking control groups; **p < 0.001 versus asthma, smoking, and non-smoking control groups. Reproduced with permission from Keatings VM, Collins PD, Scott DM, Barnes PJ. Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am J Respir Crit Care Med 1996; 153:530-4

Figure 5.7 Characteristics of sputum inflammatory cells in healthy control subjects and COPD patients with (COPD rev) and without (COPD non-rev) reversibility of airway obstruction, i.e. an increase of FEV1 > 200 ml after 200 (µg of salbutamol. Horizontal bars represent median values. *p < 0.02 versus control. Reproduced with permission from Papi A, Romagnoli M, Fabbri LM, et al. Partial reversibility of airflow limitation and increased exhaled NO and sputum eosinophilia in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2000; 162:1773-7

Figure 5.8 Percentage of sputum eosinophils in subjects with COPD with or without hyperresponsiveness to adenosine 5'-monophosphate. Reproduced with permission from Rutgers SR, Timens W, Postma DS, et al. Airway inflammation and hyperresponsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease. Clin Exp Allergy 2000;30:657-62

Figure 5.9 Concentrations of myeloperoxidase (MPO) (left panel) and human neutrophil lipocalin (HNL) (right panel) in the subject groups. Reproduced with permission from Keatings VM, Barnes PJ. Granulocyte activation markers in induced sputum: comparison between chronic obstructive pulmonary disease, asthma, and normal subjects. Am J Respir Crit Care Med 1997; 155:449-53

of COPD have also been shown to be effective at reducing inflammatory indices in COPD: low doses of theophylline have reduced neutrophil counts and IL-8, myeloperoxidase (MPO) and lactoferrin levels in sputum; suggesting that this drug has anti-inflammatory properties that may be useful in the long-term treatment of COPD (Figure 5.12).