Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma.
BACKGROUND
Matrix metalloproteinase-9 (MMP-9) is capable of degrading elastin, whereas tissue inhibitor of metalloproteinase-1 (TIMP-1) can inhibit MMP-9 activity. We observed reduced airway tissue elastin volume density in six subjects with nocturnal asthma (NA) as compared with seven subjects with nonnocturnal asthma (NNA) and seven normal controls (NL) when endobronchial biopsies were evaluated morphometrically at 4:00 PM and 4:00 AM.


OBJECTIVE
We hypothesized that increased metalloproteinases and decreased tissue inhibitors of metalloproteinases in the airways of subjects with NA may be responsible for reduced elastin volume density.


METHODS
Ten additional subjects with NA, 10 subjects with NNA, and 7 normal control subjects underwent bronchoscopy with bronchoalveolar lavage at 4:00 PM and 4:00 AM. Levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in bronchoalveolar lavage by enzyme-linked immunosorbent assay.


RESULTS
There was a fourfold circadian increase in bronchoalveolar lavage levels of MMP-9, and there was a twofold increase in MMP-9:TIMP-1 ratio in NA subjects from 4:00 PM to 4:00 AM. There were no circadian changes in the NNA and NL subjects. At 4:00 AM, MMP-9 levels and the MMP-9:TIMP-1 ratio were highest in NA subjects. At 4:00 PM, no significant group differences were observed. The MMP-9 levels positively correlated with the overnight fall in forced expiratory volume in 1 second and the MMP-9/TIMP-1 ratio negatively correlated with the 4:00 AM % predicted forced expiratory volume in 1 second.


CONCLUSIONS
Our results from these two pilot studies suggest that increased MMP-9 and decreased TIMP-1 at night in NA may lead to reduced elastin density.
Pham
David N
DN
Department of Medicine, National Jewish Medical and Research Center, Denver, Colorado 80206, USA.
Chu
Hong Wei
HW
Martin
Richard J
RJ
Kraft
Monica
M
D000328:Adult; D001249:Asthma / Q000378:metabolism* / Q000503:physiopathology; D001706:Biopsy; D001980:Bronchi / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003120:Colorado; D004549:Elastin / Q000378:metabolism*; D005260:Female; D005541:Forced Expiratory Volume / Q000502:physiology; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D012129:Respiratory Function Tests; D013223:Statistics as Topic; D013997:Time Factors; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism
D019714:Tissue Inhibitor of Metalloproteinases; D004549:Elastin; D020780:Matrix Metalloproteinase 9