Alpha 1 Antitrypsin Therapy in Patients with Alpha 1 Antitrypsin Deficiency: Perspectives from a Registry Study and Practical Considerations for Self-Administration During the COVID-19 Pandemic

Herth, Felix J.F.; Sandhaus, Robert A.; Turner, Alice; Sucena, Maria; Welte, Tobias; Greulich, Timm

doi:10.2147/copd.s325211

Cited by 10 publications

(10 citation statements)

References 60 publications

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“…The direct administration of hAAT to the lungs has been explored to overcome some limits of intravenous infusions [14,15]. Liquid aerosols are currently under clinical investigation as a non-invasive alternative.…”

Section: Introductionmentioning

confidence: 99%

Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

et al. 2022

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Alpha-1 antitrypsin (AAT) deficiency is a genetic disorder associated with pulmonary emphysema and bronchiectasis. Its management currently consists of weekly infusions of plasma-purified human AAT, which poses several issues regarding plasma supplies, possible pathogen transmission, purification costs, and parenteral administration. Here, we investigated an alternative administration strategy for augmentation therapy by combining recombinant expression of AAT in bacteria and the production of a respirable powder by spray drying. The same formulation approach was then applied to plasma-derived AAT for comparison. Purified, active, and endotoxin-free recombinant AAT was produced at high yields and formulated using L-leucine and mannitol as excipients after identifying compromise conditions for protein activity and good aerodynamic performances. An oxygen-free atmosphere, both during formulation and powder storage, slowed down methionine-specific oxidation and AAT inactivation. This work is the first peer-reviewed report of AAT formulated as a dry powder, which could represent an alternative to current treatments.

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Section: Introductionmentioning

confidence: 99%

Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

et al. 2022

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“…Patients with identified pathogenic variants of the SERPINA1 gene are recommended to periodically determine the level of AAT protein to determine the expedience of an appropriate therapy. In the case of diagnosis of AATD you should exclude the influence of external risk factors, the main of which is smoking, as well as the possible appointment of treatment with alpha one antitrypsin [26].…”

Section: Resultsmentioning

confidence: 99%

Genetic testing of allelic variants of PIZ (GLU342Lys, RS28929474) and PIS (GLU264Val, RS17580) of SERPINA1 gene in children with bronchial asthma

et al. 2022

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According to world publications, mutations in the SERPINA1 gene may be a genetic risk factor for severe chronic obstructive pulmonary disease and, consequently, rapid progression of respiratory dysfunction. This disease leads to a decrease in the level of alpha-1-antitrypsin protein. It is inherited by autosomal recessive type, but there are registered cases of codominance. In the absence of treatment, diseases of the respiratory system become chronic and lead to disability in adulthood. Early diagnosis of AAT deficiency is important to prevent complications and reduce mortality among people with this pathology. Due to these factors, genetic testing of SERPINA1 gene mutations in children with chronic lung diseases is appropriate to detect and prevent severe complications, associated with AATD. The aim of this work is to improve the effectiveness of early diagnosis of AAT deficiency in children with bronchial asthma and recurrent obstructive bronchitis by identifying different genotypes and phenotypes of A1AT deficiency, studying their relationship with the clinical course of respiratory diseases in children

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“…To alleviate these burdens, users of other IV therapies, such as hereditary angioedema and hemophilia, have successfully transitioned to self-infusion regimens [ 27 , 28 ]. In a recent review, Herth and colleagues outline the practical considerations of self-infusion for AATD patients, in light of the COVID-19 pandemic [ 29 ]. They assert that the pandemic has offered an opportune time to expand self-administration of AAT, which can improve safety for such at-risk patients [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

“…In a recent review, Herth and colleagues outline the practical considerations of self-infusion for AATD patients, in light of the COVID-19 pandemic [ 29 ]. They assert that the pandemic has offered an opportune time to expand self-administration of AAT, which can improve safety for such at-risk patients [ 29 ].…”

Section: Discussionmentioning

confidence: 99%

Assessment of Patient Perspectives and Barriers to Self-Infusion of Augmentation Therapy for Alpha-1 Antitrypsin Deficiency During the COVID-19 Pandemic

et al. 2022

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Introduction Alpha-1 antitrypsin (AAT) deficiency is an autosomal co-dominant genetic condition that predisposes individuals to pulmonary and hepatic disease, and in severe cases is treated with augmentation by intravenous infusion. Our aim was to assess patient reluctance to transition to self-administered augmentation of alpha-1-antitrypsin, during the pandemic of SARS-CoV-2. Methods A phone questionnaire was administered to 22 patients with severe alpha-1-antitrypsin deficiency who were currently receiving AAT augmentation therapy. Inclusion criteria included patients 18 years old, diagnosed with AATD, and receiving intravenous AAT protein augmentation therapy. Information was gathered regarding demographics, perspectives on transitioning to self-administered treatment, and anxiety and depression prevalence. Results were collected anonymously using REDCap. Joint and marginal statistical analysis was done to quantify links between participants’ willingness to transition to self-infusion and correlations with sex, age, years of therapy, anxiety, and depression. Results Of 22 patients, 14 were male and eight were female. Ages ranged from 36 to 79 years, with an average of 62.5. Genotypes were ZZ (14), MZ (3), and SZ (2) among others. Average length of intravenous augmentation was 9.5 years. The majority, 16 participants, were aware self-infusion was an option. Eight participants were willing to consider transitioning to self-infusion if trained and educated. Eight patients reported that fear of COVID-19 transmission influenced their decision-making. Above-normal anxiety, and depression scores, were found in four, and six patients, respectively. Neither sex, age, years of treatment, anxiety, or depression were found to be associated with willingness to consider self-infusion therapy. Conclusions Although there are many reasons AATD patients may benefit from AAT self-infusion, including decreased exposure to SARS-CoV-2, the majority preferred home nurse-infused therapy. Supplementary Information The online version contains supplementary material available at 10.1007/s41030-022-00182-z.

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Alpha 1 Antitrypsin Therapy in Patients with Alpha 1 Antitrypsin Deficiency: Perspectives from a Registry Study and Practical Considerations for Self-Administration During the COVID-19 Pandemic

Cited by 10 publications

References 60 publications

Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

Recombinant Alpha-1 Antitrypsin as Dry Powder for Pulmonary Administration: A Formulative Proof of Concept

Genetic testing of allelic variants of PIZ (GLU342Lys, RS28929474) and PIS (GLU264Val, RS17580) of SERPINA1 gene in children with bronchial asthma

Assessment of Patient Perspectives and Barriers to Self-Infusion of Augmentation Therapy for Alpha-1 Antitrypsin Deficiency During the COVID-19 Pandemic

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