Bronchoscopic Lung Volume Reduction in Patients with Emphysema due to Alpha-1 Antitrypsin Deficiency

Abstract

<b><i>Background:</i></b> Bronchoscopic lung volume reduction using one-way endobronchial valves (EBVs) is a valid therapy for severe emphysema patients. However, alpha-1 antitrypsin (AAT)-deficient patients were excluded from the majority of clinical trials investigating this intervention. <b><i>Objectives:</i></b> The aim of this study was to investigate the feasibility, efficacy, and safety of EBV treatment in patients with AAT deficiency (AATD) or a reduced AAT level. <b><i>Method:</i></b> A retrospective analysis was performed of all patients treated with EBV with confirmed AATD or with a reduced AAT serum level at the University Medical Center Groningen between 2013 and 2021. Baseline and 6-month follow-up assessment included chest CT, pulmonary function measurement, 6-min walking distance (6MWD), and St. George’s Respiratory Questionnaire (SGRQ). <b><i>Results:</i></b> In total, 53 patients were included, 30 patients in the AATD group (AAT <0.6 g/L or confirmed ZZ phenotype) and 23 patients in the reduced AAT group (AAT 0.6–1 g/L). In both groups, all response variables improved significantly after treatment. There was a median increase in forced expiratory volume in 1 s of 105 mL (12% relative) and 280 mL (31% relative) in the AATD and reduced AAT groups, respectively. 6MWD increased by 62 min and 52 min, and SGRQ decreased by 12.5 patients and 18.7 patients, respectively. A pneumothorax occurred in 10% and 13% of patients, and no patients died. <b><i>Conclusions:</i></b> EBV treatment in patients with emphysema and AATD or a reduced AAT level is feasible and results in significant improvements in pulmonary function, exercise capacity, and quality of life and has an acceptable safety profile.

Surgical and bronchoscopic pulmonary function-improving procedures in lung emphysema

“…In case of ɑ 1- antitrypsin deficiency, results of LVRS in older studies were poor [ 138 , 139 ], but results of more recent surgical approaches are not available. However, BLVR with EBV seems an efficient and safe treatment in ɑ 1 -antitrypsin-deficient patients [ 140 ]. Patients with infection-related COPD will presumably present with airway disease rather than emphysema.…”

Bronchoscopic lung volume reduction in emphysema: a review

“…EBV should not be limited to patients with COPD/emphysema phenotype and are a welcome strategy for patients with native lung hyperinflation after single lung transplantation and alpha-1-antitrypsin deficiency (AATD) [40–42,43 ▪ ,44 ▪ ]. A recent retrospective review of BLVR via endobronchial valves in patients with AATD and low alpha-antitrypsin levels showed improvement in FEV1 (12–31%) and improvement in SGRQ scores (−12.5 to −18.7 points), providing an additional treatment option for this rare genetic disorder [44 ▪ ].…”

Impact of PNPLA3 I148M on alpha-1 antitrypsin deficiency-dependent liver disease progression

“…Mutations in the SERPINA1 gene can lead to its retention in the liver and thereby cause a toxic “gain of function.” The clinically most relevant variant of SERPINA1 is characterized by a substitution of a single amino acid, Glu342Lys, termed the PiZ variant 10,12 . The heterozygous occurrence of this variant, termed the PiMZ genotype, is relatively common (frequency 1:40 in Caucasians), while the homozygous PiZZ genotype is rare (1:3000 in Caucasians), but is the predominant cause of classic severe AAT deficiency (AATD) 10,12,13 …”

“…[10,12] The heterozygous occurrence of this variant, termed the PiMZ genotype, is relatively common (frequency 1:40 in Caucasians), while the homozygous PiZZ genotype is rare (1:3000 in Caucasians), but is the predominant cause of classic severe AAT deficiency (AATD). [10,12,13] The severe PiZ variant decreases the amount of secreted protein by ~85% and leads to hepatic retention of the misfolded Z-AAT protein, especially in hepatocytes. [14,15] Mice carrying the human PiZ variant (termed PiZ mice) were developed as the tool to study AATD and reflect the human phenotype with chronic liver injury and the accumulation of periodic acid-Schiff-positive diastase-resistant globules consisting of AAT.…”