Eosinophilic airway inflammation in COPD

Figures & data

Figure 1 Sputum eosinophil count in subjects with corticosteroid-naïve asthma and COPD. Data derived from Brightling, Monteiro, et al (2000); Green, Brightling, Woltmann, et al (2002).

Table 1 Studies monitoring effect of corticosteroids (inhaled and oral) on airway inflammation and lung function

Reference	Number of patients	Design of trial	Severity of COPD	Inflammatory cell outcome	Lung function outcome
Barnes et al 2005 Qui et al 2005 Zhu et al 2005	140	Randomized, double-blind; 12 weeks of inhaled combined salmeterol/ fluticasone therapy	FEV1 59%	Reduction in sputum neutrophils and eosinophils and nonsignificant reduction in submucosal mast cells from EBB. Also reduction in TNFα and IFNγ +ve cells in subepithelium	Increase in FEV1 (0.17 L) in treatment group. Reduction in exacerbations (treatment 16% vs 33% placebo)
Brightling et al 2005	60	Randomized, double-blind, crossover; 6 weeks of inhaled mometasone or placebo 800 μg daily	FEV144%	No change in sputum cell counts	No significant overall increase. Post BD FEV1 increase improved with increasing tertile of sputum eosinophil count
Gizycki et al 2002	24	Randomized, double-blind; 3 months of fluticasone 1000 μg daily	FEV150%	No change in inflammatory cells in EBB except for submucosal mast cells. Increase in neutrophils in EBB	No change in lung function
Hattotuwa et al 2002	30	Randomized, double-blind; 3 months of fluticasone 1000 μg daily	FEV145%	No significant change in CD8+, macrophages, neutrophils, and eosinophils in EBB. Reduction in submucosal mast cells	No change in lung function
Loppow et al 2001	19	Randomized, double-blind, crossover; 4 weeks of fluticasone or placebo 1000 μg daily in chronic bronchitis ± mild obstruction	FEV1 83% FEV1/VC 68%	Decrease in total number of cells in sputum in fluticasone group but not when compared against placebo. No change in differential counts, IL-8, ECP, and NPE. No change in lung function and exhaled NO	No change in lung function
Balbi et al 2000	8	Open clinical study; 6 weeks of inhaled BDP 1.5 mg daily	FEV170%	Reduction in IL-8, MPO, total cell numbers, neutrophils (59.7% vs 31.5% mean) in BAL	No change in lung function
Yildiz et al 2000	18	Randomized, double-blind; 1500μg fluticasone, in subgroup theophylline also added (not stated to which patients)	FEV142%	Reduction in total cell count and neutrophils with fluticasone with increase of neutrophils after washout period; no change in eosinophil count	No change in lung function
Culpitt et al 1999	13	Randomized, double-blind, crossover; 4 weeks of fluticasone or placebo 1000 μg daily	FEV1 50%	No change in sputum cell counts or IL-8, MMP-1, -9, SLPI, and TIMP-1.	No clinical benefit with lung function or symptom scores
Confalonieri et al 1998	34	Randomized, double-blind: 2 months of BDP 1500 μg daily	FEV1 60%	Reduction of total cell count and neutrophils in sputum (−42% and −27%, respectively). No change in eosinophils	No change in lung function
Keatings, Jatakanon, et al 1997	13	Open study with 2 weeks of budesonide 1600 μg with analysis of induced sputum followed by 2-week course of prednisolone 30 mg daily, compared against 10 atopic asthma subjects	FEV1 35%	No reduction in ECP, EPO, MPO, TNFα, and IL-8 in sputum with inhaled corticosteroids Sputum eosinophil numbers, ECP, EPO reduced in asthma but not in COPD subjects with oral prednisolone	No change in lung function
Brightling, Monteiro, et al 2000	67	Randomized, double-blind, crossover; 2 weeks of prednisolone 30 mg daily	FEV142%	Reduction in sputum eosinophil counts	No significant overall increase. Post BD FEV1 increase improved with increasing tertile of sputum eosinophil count. Increase in CRQ score
Fujimoto et al 1999	24	Open study of 2 weeks with prednisolone 20 mg daily	FEV141%	Sputum measurements of cell counts, ECP, NPE-PI complex, and IL-8. Reduction in ECP and eosinophils	Baseline eosinophil count correlated with post-treatment FEV1 increase
Pizzichini et al 1998	18	Randomized, double-blind; 2 weeks of oral prednisolone 30 mg daily	FEV1 29%	Reduction in sputum eosinophil and ECP count	Eosinophilia indicated reduction in dyspnea and small increase in FEV1 of 0.1 1 L
Chanez et al 1997	25	Open study with 15 days of prednisolone 1.5 mg/kg daily; eosinophilic inflammation characterized by peripheral blood, BAL, and EBB	FEV1 51%	Increased levels of eosinophils and ECP in BAL seen in steroid responders	12/25 subjects showed increase of FEV1 >12% and 200 mL

Abbreviations: BAL, bronchoalveolar lavage; BD, bronchodilator; BDP, beclomethasone dipropionate; CRQ, Chronic Respiratory Disease Questionnaire; EBB, endobronchial biopsies; ECP, eosinophil cationic protein; EPO, eosinophil peroxidase; IFN, interferon; IL, interleukin; MMP, matrix metalloproteinase; MPO, myeloperoxidase; NPE, neutrophil elastase; NPE PI, neutrophil elastase-α-protease inhibitor; NO, nitric oxide; SLPI, secretory leukocyte proteinase inhibitor; TIMP, tissue inhibitor of metalloproteinase; TNF, tumor necrosis factor.

Figure 2 Improvement in post-bronchodilator FEV₁, health status (Chronic Respiratory Disease Questionnaire; CRQ), and shuttle walk distance in subjects with COPD with or without a sputum eosinophilia (>3% non-squamous cells). *p < 0.05; Δ represents change after prednisolone compared with placebo. Data derived from Brightling, Monteiro, et al (2000).

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