Disease burden associated with alpha-1 antitrypsin deficiency: systematic and structured literature reviews

Abstract

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder characterised by reduced levels of circulating alpha-1 antitrypsin and an increased risk of lung and liver disease. Recent reviews of AATD have focused on diagnosis, epidemiology and clinical management; comprehensive reviews examining disease burden are lacking. Therefore, we conducted literature reviews to investigate the AATD disease burden for patients, caregivers and healthcare systems. Embase, PubMed and Cochrane libraries were searched for AATD publications from database inception to June 2021, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Most published AATD studies were small and short in duration, with variations in populations, designs, measures and outcomes, complicating cross-study comparisons. AATD was associated with significant pulmonary and hepatic morbidity. COPD, emphysema and bronchiectasis were common lung morbidities, where smoking was a key risk factor. Fibrosis and steatosis were the most common liver complications reported in patients with a PiZ allele. Health status analyses suggested a poorer quality of life for AATD patients diagnosed with COPD versus those with non-AATD-associated COPD. The burden for caregivers included loss of personal time due to caring responsibilities, stress and anxiety. AATD was also associated with high direct medical costs and healthcare resource utilisation.

Clinical and functional characteristics of individuals with alpha-1 antitrypsin deficiency: EARCO international registry

“…3 Respiratory Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK. 4 Institute of Applied Health Research, University of Birmingham, Birmingham, UK. 5 Servicio de Neumología.…”

“…Understanding the clinical characteristics and the natural history of a rare disease can be challenging due to the lack of large cohorts. This is even more challenging in the case of AATD because of the important influence of external factors, such as smoking, alcohol consumption or other toxic exposures, on the clinical manifestations in patients with the disease [1,4]. Traditionally, some European countries have organised national registries that have had different success in collecting prospective follow-up data of patients with AATD [5][6][7].…”

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

“…However, successful treatment of AATD patients is very relevant since no other lung function improving therapies are available at this moment, and lung transplantation is preferably postponed until the sixth decade of age. Burden of this disease for patients, caregivers, and healthcare systems has recently been shown, and the latter seems higher compared to non-AATD COPD patients [ 34 ].…”

“…The ZZ phenotype was confirmed in 20 (67%) patients, MZ in 1 patient (3%), and the mutation was unknown in 9 patients (30%) (shown in Table 1). The AATD patients were significantly younger (55 [46-62] versus 64 [59-68] years, p < 0.01) and smoked less (14 [8][9][10][11][12][13][14][15][16][17][18][19][20][21] versus 36 [26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45] pack-years, p < 0.001). There was no significant difference in FEV 1 , RV, or DL CO , but a less pronounced hyperinflation, based on a significant lower RV/TLC ratio, was present in the AATD group (60 [55-66] versus 64 [60-70], p < 0.05).…”

Proteomic Analysis of Human Sputum for the Diagnosis of Lung Disorders: Where Are We Today?

“…Finally, not to be underestimated are the indirect costs of the disease (i.e., within the profile of COPD/asthma patients) due to the loss of productivity and premature retirement of patients. The importance of these aspects is highlighted by the vast amount of literature dealing with the magnitude of resources needed to treat patients with these severe disorders, and with the public health measures taken by the world governments to face their impact on human psychology, the educational system, and the global economy [ 74 , 75 , 76 , 77 , 78 ]. How can proteomics alleviate these issues?…”