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Specific IgA and metalloproteinase activity in bronchial secretions from stable chronic obstructive pulmonary disease patients colonized by Haemophilus influenzae

Laura Millares1234*, Alicia Marin234, Judith Garcia-Aymerich5678, Jaume Sauleda29, José Belda10, Eduard Monsó1123* and On behalf of the PAC-COPD Study Group

Author Affiliations

1 Fundació Parc Taulí, Sabadell/Badalona, Spain

2 CIBER de Enfermedades Respiratorias, CIBERES, Bunyola, Spain

3 Universitat Autonoma de Barcelona, Esfera UAB, Barcelona, Spain

4 Department of Respiratory Medicine, Hospital Universitari Germans Trias i Pujol, Badalona, Spain

5 Centre for Research in Environmental Epidemiology (CREAL), Barcelona, Spain

6 Municipal Institute of Medical Research (IMIM-Hospital del Mar), Barcelona, Spain

7 Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain

8 CIBER Epidemiología y Salud Pública (CIBERESP), Barcelona, Spain

9 Department of Respiratory Medicine, Hospital Universitari Son Espases, Palma de Mallorca, Spain

10 Hospital Arnau de Vilanova, Valencia, Spain

11 Department of Respiratory Medicine, Hospital Universitari Parc Taulí, Sabadell, Spain

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Respiratory Research 2012, 13:113  doi:10.1186/1465-9921-13-113

Published: 11 December 2012



Haemophilus influenzae is the most common colonizing bacteria of the bronchial tree in chronic obstructive pulmonary disease (COPD), and positive cultures for this potentially pathogenic microorganism (PPM) has been associated with local inflammation changes that may influence the relationships between H. influenzae and the bronchial mucosa.


A cross-sectional analysis of stable COPD patients enrolled in the Phenotype and Course of Chronic Obstructive Pulmonary Disease (PAC-COPD) Study, focusing on bronchial colonization by H. influenzae, was performed. Specific IgA against the PPM was measured by optical density, and metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinase-1 (TIMP-1) using ELISA in sputum samples. Levels in patients colonized by H. influenzae and non-colonized patients were compared.


Sputum supernatant for the measurement of specific IgA against H. influenzae was available from 54 stable COPD patients, who showed levels of specific IgA significantly lower in colonized (n=21) than in non-colonized patients (n=33) (15 [4-37] versus 31 [10-75], p=0.033, Mann-Whitney U test). Proenzyme MMP-9 was measured in 44 patients, and it was higher in colonized (n=12, 1903 [1488-6699] ng/ml) than in non-colonized patients (n=32, 639 [373-972] ng/ml) (p<0.001, Mann-Whitney U test). Active form of MMP-9 was also higher in colonized (126 [25-277] ng/ml) than in non-colonized patients (39 [14-68] ng/ml) (p=0.021, Mann-Whitney U test), and the molar ratio between proenzyme MMP-9 and TIMP-1 was above 1 (2.1 [0.1-12.5]) in colonized patients, significantly higher than the ratio found in non-colonized patients (0.2 [0.08-0.5]) (p=0.030, Mann-Whitney U test).


Clinically stable COPD patients colonized by H. influenzae had lower levels of specific IgA against the microorganism and higher values of the active form of MMP-9 in their sputum supernatant than non-colonized patients. Bronchial colonization by H. influenzae may cause structural changes in the extracellular matrix through a defective defense and the production of active metalloproteinases.

Chronic Obstructive Pulmonary Disease (COPD); Haemophilus influenzae; Secretory IgA; Metalloproteinase-9 (MMP-9); Tissue-inhibitor of metalloproteinases-1 (TIMP-1)