Matrix metalloproteinase-9 predicts pulmonary status declines in α1-antitrypsin deficiency.

Matrix metalloproteinase-9 (MMP-9) may be important in the progression of emphysema, but there have been few longitudinal clinical studies of MMP-9 including pulmonary status and COPD exacerbation outcomes. We utilized data from the placebo arm (n=126) of a clinical trial of patients with alpha1-antitrypsin deficiency (AATD) and emphysema to examine the links between plasma MMP-9 levels, pulmonary status, and COPD exacerbations over a one year observation period. Pulmonary function, computed tomography lung density, incremental shuttle walk test (ISWT), and COPD exacerbations were assessed at regular intervals over 12 months. Prospective analyses used generalized estimating equations to incorporate repeated longitudinal measurements of MMP-9 and all endpoints, controlling for age, gender, race-ethnicity, leukocyte count, and tobacco history. A secondary analysis also incorporated highly-sensitive C-reactive protein levels in predictive models. At baseline, higher plasma MMP-9 levels were cross-sectionally associated with lower FEV1 (p=0.03), FVC (p<0.001), carbon monoxide transfer factor (p=0.03), resting oxygen saturation (p=0.02), and ISWT distance walked (p=0.02) but were not associated with radiographic lung density or total lung capacity (TLC). In longitudinal analyses, MMP-9 predicted a further decline in transfer factor (p=0.04) and oxygen saturation (p<0.001). MMP-9 also predicted worsening lung density (p=0.003), increasing TLC (p=0.02), and more frequent COPD exacerbations over follow-up (p=0.003). Controlling additionally for hs-CRP levels did not substantively change the longitudinal associations between MMP-9 and these outcomes. Increased plasma MMP-9 levels generally predicted pulmonary status declines, including worsening transfer factor and lung density as well as greater COPD exacerbations in AATD-associated emphysema.

Omachi TA ，Eisner MD ，Rames A ，Markovtsova L ，Blanc PD ... -  《RESPIRATORY RESEARCH》

Treatment of lung disease in alpha-1 antitrypsin deficiency: a systematic review.

Edgar RG ，Patel M ，Bayliss S ，Crossley D ，Sapey E ，Turner AM ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Relationship between plasma matrix metalloproteinase levels, pulmonary function, bronchodilator response, and emphysema severity.

Koo HK ，Hong Y ，Lim MN ，Yim JJ ，Kim WJ ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Individualized lung function trends in alpha-1-antitrypsin deficiency: a need for patience in order to provide patient centered management?

Stockley RA ，Edgar RG ，Pillai A ，Turner AM ... -  《International Journal of Chronic Obstructive Pulmonary Disease》

Exacerbations and duration of smoking abstinence are associated with the annual loss of FEV(1) in individuals with PiZZ alpha-1-antitrypsin deficiency.

Alpha-1-antitrypsin deficiency (AATD) is a genetic disorder that is associated with a higher risk of chronic obstructive pulmonary disease (COPD) and emphysema. The annual declines in lung function (FEV1) and transfer factor of the lung for carbon monoxide (TLCO) predict all-cause mortality. We investigated the longitudinal follow-up data over 11 years (mean follow-up period of 4.89 years) from the German AATD registry and analyzed the relationship between annual loss of FEV1 and TLCO and sex, age, body mass index (BMI), nicotine consumption, occupational dust exposure, St. George's Respiratory Questionnaire (SGRQ) score, baseline FEV1 or TLCO, alpha-1-antitrypsin (AAT) serum level, exacerbation frequency and the duration of smoking abstinence by multiple linear generalized estimating equations models (GEE-models). We evaluated the data of 100 individuals with post-bronchodilator FEV1 measurements and from 116 individuals with TLCO measurements. The mean overall decline was -54.06 ± 164.62 ml/year in FEV1 and -0.17 ± 0.70 mmol/min/kPa/year in TLCO. Accelerated deterioration of FEV1 was associated with occupational dust exposure (p = 0.026), shorter duration of smoking abstinence (p = 0.008), higher baseline FEV1 (p = 0.003), higher annual exacerbation frequency (p = 0.003) and higher frequency of glucocorticoids intake (p = 0.004). Furthermore, patients with an elevated decline in TLCO showed significant impaired health-related quality of life at baseline (p = 0.039) and lower AAT serum levels (p < 0.001) in multivariate analysis. Annual decline in FEV1 is related to the exacerbation rate, occupational dust exposure and the duration of smoking abstinence.

Fähndrich S ，Bernhard N ，Lepper PM ，Vogelmeier C ，Seibert M ，Wagenpfeil S ，Bals R ... -  《-》