Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy

Campos, Michael; Alazemi, Saleh; Zhang, Guoyan; Wanner, Adam; Salathé, Matthias; Baier, H.; Sandhaus, Robert A.

doi:10.1016/j.rmed.2009.04.008

Cited by 41 publications

(47 citation statements)

References 25 publications

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“…Interestingly, the results observed in the previously mentioned studies in individuals with COPD www.copdjournal.com associated with AATD were similar to those obtained in previous studies in non-AATD COPD. Th e scores of the SGRQ were worse in patients experiencing frequent exacerbations, either while on augmentation therapy (23) or not (24). Th e scores of the SGRQ were also worse in patients with more severe impairment in lung function, as observed in non-AATD COPD (24), and more interestingly, the changes in SGRQ scores correlated with changes in lung density over time (25), suggesting that monitoring health status would be a good way of monitoring the progression of the disease in patients with emphysema due to AATD.…”

Section: Discussionmentioning

confidence: 96%

Usefulness of the CAT, LCOPD, EQ-5D and COPDSS Scales in Understanding the Impact of Lung Disease in Patients with Alpha-1 Antitrypsin Deficiency

Manca

Rodrı́guez

Huerta

et al. 2014

COPD: Journal of Chronic Obstructive Pulmonary Disease

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Alpha-1-antitrypsin deficiency (AATD) is an inherited disorder responsible for early onset emphysema associated with a significant impairment of health-related quality of life (HRQoL). Our aim was to assess the usefulness of different instruments to evaluate the HRQoL in patients with AATD compared to non-AATD COPD. Observational, cross-sectional study in which all patients filled out a series of questionnaires: the COPD severity score (COPDSS), the EuroQoL 5-Dimensions (EQ-5D), the Living with COPD (LCOPD) and the COPD Assessment Test (CAT). A total of 96 patients were included, 35 with AATD (mean age 56.5 yrs, 57.1% male and mean FEV1(%) 48.7% and 61 non-AATD COPD (70.3 yrs, 80.3% men and FEV1(%) 47%. The questionnaire scores were similar, with a tendency towards worse scores in AATD for the EQ-5D (VAS) (64.8 (20.2) vs. 71.6 (17.1); p = 0.08). The correlations between the different scores and FEV1(%) were significant in both groups for COPDSS and LCOPD, but not for CAT and EQ-5D. In general, the correlations of scores with FEV1(%) were stronger for AATD compared with non-AATD COPD patients: COPDSS r = -0.570, p < 0.01 for AATD and r = -0.260, p < 0.05 for COPD; LCOPD r = -0.502, p < 0.001 for AATD and r = -0.304, p < 0.05 for non-AATD COPD. Patients with AATD have a similar degree of HRQoL impairment as older subjects with non-AATD COPD and showed a stronger correlation between HRQoL measurements and lung function impairment compared with non-AATD COPD. This may be related to the characteristics of the disease in these patients who are usually younger, with less co-morbidity and lower smoking consumption.

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Section: Discussionmentioning

confidence: 96%

Usefulness of the CAT, LCOPD, EQ-5D and COPDSS Scales in Understanding the Impact of Lung Disease in Patients with Alpha-1 Antitrypsin Deficiency

Manca

Rodrı́guez

Huerta

et al. 2014

COPD: Journal of Chronic Obstructive Pulmonary Disease

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“…Augmentation therapy was FDA approved and is now widely used in Europe and North America in the treatment of AATD individuals with lung disease (Abboud et al 2001). Documented studies on the clinical efficiency of infused AAT augmentation therapy have reported on patient outcome measures including the rate of decline in forced expiratory volume in one second (FEV 1 ) (Seersholm et al 1997;Wencker et al 2001), the incidence of acute exacerbations (Campos et al 2009) and the change in lung density (Dirksen et al 1999) calculated by computed tomography scanning (Dirksen et al 2009). …”

Section: The Use Of Aat Augmentation Therapy In Treatment Of Lung Dismentioning

confidence: 99%

“…Reduced exacerbations or lung infections is an important endpoint in clinical studies of pulmonary disease and recent data from a German AATD registry (455 with the ZZ and SZ genotype) suggests that a reduction of exacerbations is directly associated with health-related quality of life of patients (Koczulla et al 2008). Clinicians have attempted to address this important endpoint (Campos et al 2009;Lieberman 2000;Needham and Stockley 2005) with Lieberman (2000) conducting an internet survey of patient-reported respiratory infections in individuals with the ZZ phenotype, which were markedly decreased after the introduction of augmentation therapy (Lieberman 2000). Post hoc analysis of the EXACTLE study, adjusted for exacerbation severity showed that the treatment group had fewer severe exacerbations than the control group.…”

Section: The Use Of Aat Augmentation Therapy In Treatment Of Lung Dismentioning

confidence: 99%

Alpha-1 Antitrypsin: A Potent Anti-Inflammatory and Potential Novel Therapeutic Agent

Bergin

Hurley

McElvaney

et al. 2012

Arch. Immunol. Ther. Exp.

120

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Alpha-1 antitrypsin (AAT) has long been thought of as an important anti-protease in the lung where it is known to decrease the destructive effects of major proteases such as neutrophil elastase. In recent years, the perception of this protein in this simple one dimensional capacity as an anti-protease has evolved and it is now recognised that AAT has significant anti-inflammatory properties affecting a wide range of inflammatory cells, leading to its potential therapeutic use in a number of important diseases. This present review aims to discuss the described anti-inflammatory actions of AAT in modulating key immune cell functions, delineate known signalling pathways and specifically to identify the models of disease in which AAT has been shown to be effective as a therapy.

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“…The global dysfunction of AM engulfment in smokers and COPD patients may be most damaging during acute infectious exacerbations, episodes of increased airway infection and inflammation during which AM have to scavenge an increased load of both bacterial and apoptotic targets [3]. Given the high morbidity and mortality, as well as healthcare cost associated with COPD and COPD exacerbations [4, 5], therapies aimed at improving AM scavenging functions are of clinical importance.…”

Section: Introductionmentioning

confidence: 99%

Alpha-1 antitrypsin supplementation improves alveolar macrophages efferocytosis and phagocytosis following cigarette smoke exposure

et al. 2017

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Cigarette smoking (CS), the main risk factor for COPD (chronic obstructive pulmonary disease) in developed countries, decreases alveolar macrophages (AM) clearance of both apoptotic cells and bacterial pathogens. This global deficit of AM engulfment may explain why active smokers have worse outcomes of COPD exacerbations, episodes characterized by airway infection and inflammation that carry high morbidity and healthcare cost. When administered as intravenous supplementation, the acute phase-reactant alpha-1 antitrypsin (A1AT) reduces the severity of COPD exacerbations in A1AT deficient (AATD) individuals and of bacterial pneumonia in murine models, but the effect of A1AT on AM scavenging functions has not been reported. Apoptotic cell clearance (efferocytosis) was measured in human AM isolated from patients with COPD, in primary rat AM or differentiated monocytes exposed to CS ex vivo, and in AM recovered from mice exposed to CS. A1AT (100 μg/mL, 16 h) significantly ameliorated efferocytosis (by ~50%) in AM of active smokers or AM exposed ex vivo to CS. A1AT significantly improved AM global engulfment, including phagocytosis, even when cells were simultaneously challenged with apoptotic and Fc-coated (bacteria-like) targets. The improved efferocytosis in A1AT-treated macrophages was associated with inhibition of tumor necrosis factor-α converting enzyme (TACE) activity, decreased mannose receptor shedding, and markedly increased abundance of efferocytosis receptors (mannose- and phosphatidyl serine receptors and the scavenger receptor B2) on AM plasma membrane. Directed airway A1AT treatment (via inhalation of a nebulized solution) restored in situ airway AM efferocytosis after CS exposure in mice. The amelioration of CS-exposed AM global engulfment may render A1AT as a potential therapy for COPD exacerbations.

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Exacerbations in subjects with alpha-1 antitrypsin deficiency receiving augmentation therapy

Abstract: COPD exacerbations occur frequently and are associated with significant disease burden in subjects with AATD receiving augmentation therapy.

Cited by 41 publications

References 25 publications

Usefulness of the CAT, LCOPD, EQ-5D and COPDSS Scales in Understanding the Impact of Lung Disease in Patients with Alpha-1 Antitrypsin Deficiency

Usefulness of the CAT, LCOPD, EQ-5D and COPDSS Scales in Understanding the Impact of Lung Disease in Patients with Alpha-1 Antitrypsin Deficiency

Alpha-1 Antitrypsin: A Potent Anti-Inflammatory and Potential Novel Therapeutic Agent

Alpha-1 antitrypsin supplementation improves alveolar macrophages efferocytosis and phagocytosis following cigarette smoke exposure

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