Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema - PubMed (original) (raw)

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Efficacy of alpha1-antitrypsin augmentation therapy in conditions other than pulmonary emphysema

Ignacio Blanco et al. Orphanet J Rare Dis. 2011.

Abstract

Up to now alpha 1-antitrypsin (AAT) augmentation therapy has been approved only for commercial use in selected adults with severe AAT deficiency-related pulmonary emphysema (i.e. PI*ZZ genotypes as well as combinations of Z, rare and null alleles expressing AAT serum concentrations <11 μmol/L). However, the compassionate use of augmentation therapy in recent years has proven outstanding efficacy in small cohorts of patients suffering from uncommon AAT deficiency-related diseases other than pulmonary emphysema, such as fibromyalgia, systemic vasculitis, relapsing panniculitis and bronchial asthma. Moreover, a series of preclinical studies provide evidence of the efficacy of AAT augmentation therapy in several infectious diseases, diabetes mellitus and organ transplant rejection. These facts have generated an expanding number of medical applications and patents with claims for other indications of AAT besides pulmonary emphysema. The aim of the present study is to compile and analyze both clinical and histological features of the aforementioned published case studies and reports where AAT augmentation therapy was used for conditions other than pulmonary emphysema. Particularly, our research refers to ten case reports and two clinical trials on AAT augmentation therapy in patients with both AAT deficiency and, at least, one of the following diseases: fibromyalgia, vasculitis, panniculitis and bronchial asthma. In all the cases, AAT was successfully applied whereas previous maximal conventional therapies had failed. In conclusion, laboratory studies in animals and humans as well as larger clinical trials should be, thus, performed in order to determine both the strong clinical efficacy and security of AAT in the treatment of conditions other than pulmonary emphysema.

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Figures

Figure 1

Figure 1

Timeline of clinical events in a case of leukocytoclastic vasculitis related to ZZ alpha-1-antitrypsin deficiency. AAT: alpha-1-antitrypsin.

Figure 2

Figure 2

Demographic and clinical data of 7 patients with relapsing panniculitis associated to ZZ alpha-1-antitrypsin deficiency treated with alpha-1-antitrypsin augmentation therapy. F: female. AAT: alpha-1-antitrypsin.

Figure 3

Figure 3

Effects of augmentation therapy in 2 ZZ Alpha-1-antitrypsin deficiency sisters with fibromyalgia (FM).

Figure 4

Figure 4

Effects of a 6-month trial with alpha-1-antitrypsin augmentation therapy and placebo in a Fibromyalgia and Chronic Fatigue Syndrome patient with intermediate MZ alpha-1-antitrypsin deficiency. FIQ: Fibromyalgia Impact Questionnaire. HAQ: Health Assessment Questionnaire.

Figure 5

Figure 5

Chronology of clinical events in an MZ-AAT patient with severe persistent asthma. AAT: Alpha1-antitrypsin. FEV1: Forced Expiratory Volume in 1 second.

Figure 6

Figure 6

Effects of long-term augmentation therapy with alpha-1 antitrypsin in an MZ-AAT severe persistent asthma. Forced Expiratory Volume (A), Alpha-1-antitrypsin (AAT) serum concentrations (B), and Asthma Quality of Life (C) scores after and before alpha-1-antitrypsin infusions.

References

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