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Orphanet J Rare Dis. 2013 Sep 24;8:149. doi: 10.1186/1750-1172-8-149.

Augmentation therapy for alpha-1 antitrypsin deficiency: towards a personalised approach.

Author information

1
Lung Investigation Unit, Queen Elizabeth Hospital Birmingham, Mindelsohn way, Edgbaston, Birmingham B15 2WB, UK. r.a.stockley@bham.ac.uk.

Abstract

BACKGROUND:

Intravenous augmentation therapy is the only specific treatment available for emphysema associated with alpha-1 antitrypsin deficiency. Despite large observational studies and limited interventional studies there remains controversy about the efficacy of this treatment due to the impracticality of conducting adequately powered studies to evaluate the rate of decline in lung function, due to the low prevalence and the slow progression of the disease. However, measurement of lung density by computed tomography is a more specific and sensitive marker of the evolution of emphysema and two small placebo-controlled clinical trials have provided evidence supporting a reduction in the rate of decline in lung density with augmentation therapy.

THE PROBLEM:

Where augmentation therapy has become available there has been little consideration of a structured approach to therapy which is often introduced on the basis of functional impairment at diagnosis. Data from registries have shown a great variability in the evolution of lung disease according to patient acquisition and the presence of recognised risk factors. Avoidance of risk factors may, in many cases, stabilise the disease. Since augmentation therapy itself will at best preserve the presenting level of lung damage yet require intravenous administration for life with associated costs, identification of patients at risk of continued rapid or long term progression is essential to select those for whom this treatment can be most appropriate and hence generally more cost-effective. This represents a major reconsideration of the current practice in order to develop a consistent approach to management world wide.

PURPOSE OF THIS REVIEW:

The current review assesses the evidence for efficacy of augmentation therapy and considers how the combination of age, physiological impairment, exacerbation history and rate of decline in spirometry and other measures of emphysema may be used to improve therapeutic decision making, until a reliable predictive biomarker of the evolution of lung impairment can be identified. In addition, individual pharmacokinetic studies may permit the selection of the best regimen of administration for those who need it.

SUMMARY:

The rarity and variable characteristics of the disease imply the need for an individualised approach to therapy in specialised centres with sufficient experience to apply a systematic approach to monitoring and management.

PMID:
24063809
PMCID:
PMC3852071
DOI:
10.1186/1750-1172-8-149
[Indexed for MEDLINE]
Free PMC Article

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