Abstract
BACKGROUND: Alpha-1 antitrypsin deficiency is frequently underrecognized. Individuals with symptoms often experience long diagnostic delays. Although a delayed diagnosis is logically presumed to be associated with adverse effects, confirmatory evidence that a delay in diagnosis confers harm is sparse. The current study characterized the association between a delayed diagnosis and the clinical status at the time of diagnosis.
METHODS: Patients with newly diagnosed severe deficiency of alpha-1 antitrypsin received questionnaires that assessed self-reported diagnostic delay, the St George Respiratory Questionnaire (SGRQ) and COPD Assessment Test. Results of spirometry were retrieved and the relationship between the diagnostic delay interval and FEV1% predicted, SGRQ, and COPD Assessment Test were assessed.
RESULTS: Forty subjects were recruited (31 with PI*ZZ, 9 with PI*SZ). Values for FEV1% predicted, SGRQ, and COPD Assessment Test were available for 17, 40, and 32 subjects, respectively. The relationship between the diagnostic delay interval and all outcomes was directionally consistent with an adverse impact of increasing diagnostic delay. For each additional year of diagnostic delay, the subject's FEV1% predicted decreased by 0.3% (P = .66), The SGRQ Total score increased by 1.6 points (P < .001), and the COPD Assessment Test score increased by 0.7 points (P = .004).
CONCLUSIONS: The results of this analysis were consistent with a delayed diagnosis of alpha-1 antitrypsin deficiency being associated with worse COPD-related symptoms and functional status, and with a trend toward worsened air-flow obstruction. Given that alpha-1 antitrypsin deficiency is associated with accelerated emphysema progression, these findings underscore the importance of early detection of alpha-1 antitrypsin deficiency and reinforce guidelines that endorse alpha-1 antitrypsin deficiency testing in all adults with fixed air-flow obstruction and first-degree relatives of individuals with severe deficiency of alpha-1 antitrypsin.
Footnotes
- Correspondence: Vickram Tejwani MD, Division of Pulmonary and Critical Care, 1830 E. Monument Street, Fifth floor, Baltimore, MD 21205. E-mail: tejwani{at}jhmi.edu.
This study was supported by a grant from CSL-Behring.
Dr Tejwani, Dr Nowacki, Ms Fye, and Mr Sanders report grants from CSL-Behring during the conduct of the study. Dr Stoller serves as a consultant to various companies regarding alpha-1 antitrypsin deficiency, including Grifols, Shire, CSL Behring, Arrowhead Pharmaceuticals, 23andMe, InhibRx, and Vertex; has received grant funding from CSL Behring, the National Heart, Lung, and Blood Institute, and the Alpha-1 Foundation; and serves as a member of the board of directors of the Alpha-1 Foundation.
Dr Tejwani gave an oral presentation of the preliminary results at the American College of Chest Physicians conference, held October 29, 2017, Toronto, Canada.
Supplementary material related to this paper is available at http://www.rcjournal.com.
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