Exacerbations in α₁-antitrypsin deficiency

Abstract

This study aimed to investigate the nature and effect of exacerbations in patients with a 1 -antitrypsin deficiency and to assess the impact of exacerbations on health status. Furthermore, the relationship of exacerbations to changes in lung function and health status was investigated.In total, 265 patients with severe deficiency (PiZ phenotype) were assessed over 12 months and a subgroup of 87 patients was studied for 3 yrs. Exacerbations were recorded and patients underwent full lung function testing and health status measurement.Exacerbations occurred in 142 patients (54%) over 12 months, with a median duration of 14 days (interquartile range 7-21). Health status was significantly worse in patients with exacerbations, especially those with frequent exacerbations. Neither the presence nor the frequency of exacerbations showed a relationship to decline in forced expiratory volume in one second, but the number of exacerbations was weakly associated with decline in gas transfer of the lung for carbon monoxide. Despite lung function decline, health status did not change significantly over 3 yrs.In conclusion, exacerbations occur commonly in patients with a 1 -antitrypsin deficiency and are associated with worse health status. Exacerbations were associated with a decline in the gas transfer of the lung for carbon monoxide over time, but show no relationship to changes in forced expiratory volume in one second. Despite lung function decline, patients do not show a progressive loss in health status.

Exploring the role of CT densitometry: a randomised study of augmentation therapy in α1-antitrypsin deficiency

“…These episodes are associated with greater neutrophilic inflammation and more free elastase activity in a 1 -AT deficiency compared with usual COPD [28], and retrospective data have suggested that exacerbations in a 1 -AT deficiency were less frequent once augmentation therapy was started [29]. The average annual exacerbation rate in the present study was similar in both the treated and placebo groups and was comparable with results for patients with a 1 -AT deficiency from the UK Registry who were not receiving augmentation therapy [30]. The number of patients included was too small to draw any conclusion on the treatment effect on the rate of exacerbations.…”

Rate of progression of lung function impairment in α1-antitrypsin deficiency

“…Exacerbation frequency is known to relate to a speedier decline in lung function in a 1 -ATD [27] and usual COPD [26]. However, the relationship with better physical health status may at first seem counter-intuitive.…”

“…Most data were determined objectively, but the exacerbation data relied upon subjective recall, and, since the patients were visiting the centre from all parts of the country, independent verification of exacerbations and hospitalisations from health records was impossible. Nevertheless, when diary card identification and primary care records have been assessed, such recall has proven reasonably reliable [27], suggesting that the associations found here are likely to be valid.…”

Alpha-1 Antitrypsin: A Potent Anti-Inflammatory and Potential Novel Therapeutic Agent

“…Reduced exacerbations or lung infections is an important endpoint in clinical studies of pulmonary disease and recent data from a German AATD registry (455 with the ZZ and SZ genotype) suggests that a reduction of exacerbations is directly associated with health-related quality of life of patients (Koczulla et al 2008). Clinicians have attempted to address this important endpoint (Campos et al 2009;Lieberman 2000;Needham and Stockley 2005) with Lieberman (2000) conducting an internet survey of patient-reported respiratory infections in individuals with the ZZ phenotype, which were markedly decreased after the introduction of augmentation therapy (Lieberman 2000). Post hoc analysis of the EXACTLE study, adjusted for exacerbation severity showed that the treatment group had fewer severe exacerbations than the control group.…”