There is no fast track to identify fast decliners in alpha-1 antitrypsin deficiency by spirometry: A longitudinal study of repeated measurements this article was published in the following dove press journal

James A. Stockley; Robert A. Stockley; Elizabeth Sapey

doi:10.2147/COPD.S298585

There is no fast track to identify fast decliners in alpha-1 antitrypsin deficiency by spirometry: A longitudinal study of repeated measurements this article was published in the following dove press journal

James A. Stockley, Robert A. Stockley, Elizabeth Sapey^*

^*Corresponding author for this work

Inflammation and Ageing

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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Abstract

Background: It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease.

Methods: Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex-or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years.

Results: Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months’ data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%.

Conclusion: This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.

Original language	English
Pages (from-to)	835-840
Number of pages	6
Journal	International Journal of COPD
Volume	16
DOIs	https://doi.org/10.2147/COPD.S298585
Publication status	Published - 29 Mar 2021

Bibliographical note

Funding Information:
This work was funded by the Alpha-1 Foundation. Health data curation was supported by PIONEER, the Health data hub in acute care, which is funded by Health Data Research UK. W e thank all the patients with Alpha-1 Antitrypsin Deficiency for contributing to this study .

Professor Robert A Stockley is steering committee for Vertex, advisory board for Z factor , and chair of Data Safety Monitoring Board for Kamada; he also reports grants and/or personal fees from CSL Behring, Mereo biopharma, took part in the laboratory analyses for Takeda, during the conduct of the study . Professor Elizabeth Sapey reports grants from Alpha-1 Foundation, during the conduct of the study; grants from HDR-UK, The Wellcome Trust, MRC, British Lung Foundation, NIHR, and EPSRC, outside the submitted work. The authors report no other conflicts of interest in this work.

Publisher Copyright:
© 2021 Stockley et al.

Keywords

Alpha-1 antitrypsin deficiency
Decline
Lung function
Obstructive airways disease

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine
Health Policy
Public Health, Environmental and Occupational Health

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title = "There is no fast track to identify fast decliners in alpha-1 antitrypsin deficiency by spirometry: A longitudinal study of repeated measurements this article was published in the following dove press journal",

abstract = "Background: It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease. Methods: Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex-or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years. Results: Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months{\textquoteright} data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%. Conclusion: This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.",

keywords = "Alpha-1 antitrypsin deficiency, Decline, Lung function, Obstructive airways disease",

author = "Stockley, {James A.} and Stockley, {Robert A.} and Elizabeth Sapey",

note = "Funding Information: This work was funded by the Alpha-1 Foundation. Health data curation was supported by PIONEER, the Health data hub in acute care, which is funded by Health Data Research UK. W e thank all the patients with Alpha-1 Antitrypsin Deficiency for contributing to this study . Professor Robert A Stockley is steering committee for Vertex, advisory board for Z factor , and chair of Data Safety Monitoring Board for Kamada; he also reports grants and/or personal fees from CSL Behring, Mereo biopharma, took part in the laboratory analyses for Takeda, during the conduct of the study . Professor Elizabeth Sapey reports grants from Alpha-1 Foundation, during the conduct of the study; grants from HDR-UK, The Wellcome Trust, MRC, British Lung Foundation, NIHR, and EPSRC, outside the submitted work. The authors report no other conflicts of interest in this work. Publisher Copyright: {\textcopyright} 2021 Stockley et al.",

year = "2021",

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doi = "10.2147/COPD.S298585",

language = "English",

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There is no fast track to identify fast decliners in alpha-1 antitrypsin deficiency by spirometry: A longitudinal study of repeated measurements this article was published in the following dove press journal. / Stockley, James A.; Stockley, Robert A.; Sapey, Elizabeth.
In: International Journal of COPD, Vol. 16, 29.03.2021, p. 835-840.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - There is no fast track to identify fast decliners in alpha-1 antitrypsin deficiency by spirometry

T2 - A longitudinal study of repeated measurements this article was published in the following dove press journal

AU - Stockley, James A.

AU - Stockley, Robert A.

AU - Sapey, Elizabeth

N1 - Funding Information: This work was funded by the Alpha-1 Foundation. Health data curation was supported by PIONEER, the Health data hub in acute care, which is funded by Health Data Research UK. W e thank all the patients with Alpha-1 Antitrypsin Deficiency for contributing to this study . Professor Robert A Stockley is steering committee for Vertex, advisory board for Z factor , and chair of Data Safety Monitoring Board for Kamada; he also reports grants and/or personal fees from CSL Behring, Mereo biopharma, took part in the laboratory analyses for Takeda, during the conduct of the study . Professor Elizabeth Sapey reports grants from Alpha-1 Foundation, during the conduct of the study; grants from HDR-UK, The Wellcome Trust, MRC, British Lung Foundation, NIHR, and EPSRC, outside the submitted work. The authors report no other conflicts of interest in this work. Publisher Copyright: © 2021 Stockley et al.

PY - 2021/3/29

Y1 - 2021/3/29

N2 - Background: It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease. Methods: Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex-or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years. Results: Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months’ data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%. Conclusion: This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.

AB - Background: It is known that lung function decline in Alpha-1 Antitrypsin Deficiency (AATD) varies. Those with a rapid decline are at highest risk of poorer outcomes but may benefit most from targeted treatments including augmentation therapy. Current evidence suggests rapid decliners can be identified after 3 years of serial follow-up. It would be advantageous to identify these patients over a shorter time period, especially in mild disease. Methods: Post-bronchodilator spirometry was performed every 6 months for a total of 18 months (4 measurements) by PiZZ AATD patients (ex-or never-smokers) either without spirometric COPD or with mild COPD. Where possible, retrospective spirometry data were included. Decline was assessed using 2 (baseline and 6 month) or four measurements (including baseline, 6, 12 and 18 months) and compared to retrospective decline rates using annual measurements over 3 years. Results: Seventy-two PiZZ AATD patients were included, with 27 having at least three years of retrospective, annual spirometry. 18-month progression obtained by linear regression showed variable degrees of change with 29 showing no decline, 8 showing slow decline and 35 showing rapid decline. Bland-Altman plots showed that there was no overall agreement between predicted rate of decline using data obtained over 6 months and that obtained over 18 months. Furthermore, there was no agreement between rate of decline from either 6 or 18 months’ data when compared to data collected over 3 years. The positive predictive value for rapid decline with 18 months of data compared to 3 years was only 50.0%. Conclusion: This study suggests serial lung function over 18 months cannot identify AATD patients who have rapidly declining lung function. There is an urgent need for different biomarkers to help identify these patients at the earliest opportunity.

KW - Alpha-1 antitrypsin deficiency

KW - Decline

KW - Lung function

KW - Obstructive airways disease

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