Heterozygous Alpha-1 Antitrypsin Deficiency Causing Pulmonary Emboli and Pulmonary Bullae

Tannous, Toufic; Rosso, C; Keating, Matthew

doi:10.7759/cureus.14759

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…The results of the large cohort study carried out in 15 586 COVID-19 patients at a Cleveland clinic have shown that 9.2% of COVID patients suffered from COPD [ 186 , 190 ]. This fact is in agreement with the data of other authors showing that COPD patients without any other comorbidities run the higher risk of severe COVID-19 [ 187 ]. At the same time, the increased expression of ACE2 receptor in case of SARS-CoV-2 infection was not associated with the phenotype of the disease [ 191 , 192 ].…”

Section: α 1 -Proteinase Inhibitor Under Normal ...supporting

confidence: 93%

“…Protection against respiratory infections [4,19,50,146,160,193,209] "Acute phase" protein Increased content of α 1 -PI; is considered as a universal response to a pathological process. Increased levels of this protein have been detected in case of COVID-19 [17, 18, 160-162, 164, 202] Oxidative stress marker Increase in α 1 -PI correlates with the oxidative stress development [168][169][170][171] NET inhibition Inhibition of elastase involved in NET formation, the development of thrombosis [50,187,[203][204][205] α 1 -PI dysfunction Genetic and acquired deficiency of the inhibitor: the damage to the active center during oxidation, the effects of ecologically unfavorable environmental factors, smoking. Degradation by proteinases with the formation of proinflammatory peptides [171-174, 183, 184] Therapeutic effect of α 1 -PI Inhibition of membrane and plasma proteinases.…”

Section: Anti-apoptotic Effectmentioning

confidence: 99%

“…Moreover, it has been shown that in the northern regions of Italy with the higher level of environmental pollution compared to the southern regions there are more people with genetic α 1 -PI deficiency [185]. The active center of α 1 -PI is damaged by the toxic products of tobacco smoke; hence, smokers are in the risk group for the unfavorable course of COVID-19 [186,187].…”

Section: Genetic and Acquired Deficiency Of α 1 -Proteinase Inhibitormentioning

confidence: 99%

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Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Акбашева

Spirina

Dyakov

et al. 2022

Biochem. Moscow Suppl. Ser. B

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The SARS-CoV-2 pandemic had stimulated the emergence of numerous publications on the α 1 -proteinase inhibitor (α 1 -PI, α 1 -antitrypsin), especially when it was found that the regions of high mortality corresponded to the regions with deficient α 1 -PI alleles. By analogy with the data obtained in the last century, when the first cause of the genetic deficiency of α 1 -antitrypsin leading to elastase activation in pulmonary emphysema was proven, it can be supposed that proteolysis hyperactivation in COVID-19 may be associated with the impaired functions of α 1 -PI. The purpose of this review was to systematize the scientific data and critical directions for translational studies on the role of α 1 -PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a therapeutic target. This review describes the proteinase-dependent stages of viral infection: the reception and penetration of the virus into a cell and the imbalance of the plasma aldosterone–angiotensin–renin, kinin, and blood clotting systems. The role of ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases in the virus tropism, the activation of proteolytic cascades in blood, and the COVID-19-dependent complications is considered. The scientific reports on α 1 -PI involvement in the SARS-CoV-2-induced inflammation, the relationship with the severity of infection and comorbidities were analyzed. Particular attention is paid to the acquired α 1 -PI deficiency in assessing the state of patients with proteolysis overactivation and chronic non-inflammatory diseases, which are accompanied by the risk factors for comorbidity progression and the long-term consequences of COVID-19. Essential data on the search and application of protease inhibitor drugs in the therapy for bronchopulmonary and cardiovascular pathologies were analyzed. The evidence of antiviral, anti-inflammatory, anticoagulant, and anti-apoptotic effects of α 1 -PI, as well as the prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders, are presented.

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Section: α 1 -Proteinase Inhibitor Under Normal ...supporting

confidence: 93%

Section: Anti-apoptotic Effectmentioning

confidence: 99%

Section: Genetic and Acquired Deficiency Of α 1 -Proteinase Inhibitormentioning

confidence: 99%

See 1 more Smart Citation

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Акбашева

Spirina

Dyakov

et al. 2022

Biochem. Moscow Suppl. Ser. B

View full text Add to dashboard Cite

show abstract

“…In contrast, a meta-analysis of 17 studies on PI*MS heterozygotes has shown that, despite reduced plasma AAT levels, these subjects are not at risk of airway obstruction, COPD or greater FEV 1 decline [10]. However, a case report revealed an association between this genotype and the presence of lung bullae [11]. In asthmatic patients, heterozygosity for AAT with PI*MZ and PI*MS genotypes is associated with small airway dysfunction and with lung air trapping [12].…”

Section: Introductionmentioning

confidence: 94%

Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

Annunziata,

Fiorentino,

Balestrino

et al. 2024

JCM

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(1) Background: Few data are available on the risk of airway dysfunction in protease inhibitor (PI*) M heterozygotes carrying rare null or deficient allelic variants of the gene SERPINA-1 (PI*MR). (2) Methods: In this observational study, in a cohort of PI*MR heterozygotes, we evaluated respiratory functional parameters at baseline and at one-year follow-up. Moreover, we compared such parameters with those of the PI*MZ and PI*MS patients. (3) Results: A total of 60 patients were recruited; 35 PI*MR, 11 PI*MZ and 14 PI*MS. At the annual follow-up, the PI*MR and PI*MZ patients demonstrated a significantly higher FEV1 decline than the PI*MS group (p =0.04 and p =0.018, respectively). The PI*MR patients showed a significant increase in DLCO annual decline in comparison with the PI*MS group (p =0.02). At baseline, the PI*MR smoking patients, compared with nonsmokers, showed statistically significant lower values of FEV1, FEV1/FVC and DLCO (p =0.0004, p <0.0001, p =0.007, respectively) and, at the one-year follow-up,they displayed a significantly higher FEV1 and DLCO decline (p =0.0022, p =0.011, respectively). PI*MR heterozygotes with COPD showed a significantly higher FEV1, FEV1/FVC and DLCO annual decline in comparison with healthy PI*MR (p =0.0083, p =0.043, p =0.041). (4) Conclusions: These results suggest that PI*MR heterozygotes, particularly smokers with COPD, have a greater annual decline in respiratory functional parameters and need to be monitored.

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Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection

et al. 2022

View full text Add to dashboard Cite

The SARS-CoV-2 pandemia had stimulated the numerous publications emergence on the α1-proteinase inhibitor (α1-PI, α1-antitrypsin), primarily when it was found that high mortality in some regions corresponded to the regions with deficient α1-PI alleles. By analogy with the last century's data, when the root cause of the α1-antitrypsin, genetic deficiency leading to the elastase activation in pulmonary emphysema, was proven. It is evident that proteolysis hyperactivation in COVID-19 may be associated with α1-PI impaired functions. The purpose of this review is to systematize scientific data, critical directions for translational studies on the role of α1-PI in SARS-CoV-2-induced proteolysis hyperactivation as a diagnostic marker and a target in therapy. This review describes the proteinase-dependent stages of a viral infection: the reception and virus penetration into the cell, the plasma aldosterone-angiotensin-renin, kinins, blood clotting systems imbalance. The ACE2, TMPRSS, ADAM17, furin, cathepsins, trypsin- and elastase-like serine proteinases role in the virus tropism, proteolytic cascades activation in blood, and the COVID-19-dependent complications is presented. The analysis of scientific reports on the α1-PI implementation in the SARS-CoV-2-induced inflammation, the links with the infection severity, and comorbidities were carried out. Particular attention is paid to the acquired α1-PI deficiency in assessing the patients with the proteolysis overactivation and chronic non-inflammatory diseases that are accompanied by the risk factors for the comorbidities progression, and the long-term consequences of COVID-19 initiation. Analyzed data on the search and proteases inhibitory drugs usage in the bronchopulmonary cardiovascular pathologies therapy are essential. It becomes evident the antiviral, anti-inflammatory, anticoagulant, anti-apoptotic effect of α1-PI. The prominent data and prospects for its application as a targeted drug in the SARS-CoV-2 acquired pneumonia and related disorders are presented.

show abstract

Heterozygous Alpha-1 Antitrypsin Deficiency Causing Pulmonary Emboli and Pulmonary Bullae

Cited by 3 publications

References 17 publications

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Proteolysis and Deficiency of α1-Proteinase Inhibitor in SARS-CoV-2 Infection

Alpha-1 Antitrypsin PI M Heterozygotes with Rare Variants: Do They Need a Clinical and Functional Follow-Up?

Proteolysis and deficiency of α1-proteinase inhibitor in SARS-CoV-2 infection

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