An analysis of the degree of concordance among international guidelines regarding alpha-1 antitrypsin deficiency

Abstract

Background

Practice guidelines (PGs) attempt to standardize practice to optimize care. For uncommon lung diseases like alpha-1 antitrypsin deficiency (AATD), a paucity of definitive studies and geographic variation in prevalence may hamper guideline generation. The current study assembled and assesses the degree of concordance among available PGs regarding AATD.

Methods

To assess concordance, 15 eligible guidelines focused on AATD were evaluated regarding recommendations surrounding 24 key clinical issues. A Delphi process achieved consensus on ratings for each statement among 3 reviewers. Agreement was quantified as the proportion of guideline comparisons with a matching rating.

Results

The overall level of agreement was 47% (1190/2520 comparisons). The overall “affirmative agreement percentage” (ie, when guidelines agreed in endorsing a practice), was 42% (501/1190 comparisons). The agreement for individual clinical statements ranged from 26% to 75%. A broad consensus was seen in the recommendation to test all patients with a history of fixed obstruction on pulmonary function testing (either from asthma or COPD). Given that AATD is an under-recognized disease and that diagnosis often occurs at a late stage, the authors are encouraged by this consensus. Where overall the guidelines were less explicit was when to refer to a specialist or AATD center. Deciding on a treatment strategy requires a thorough understanding of the alpha 1 serum level, genotype, pulmonary function testing, and imaging, and therefore the authors feel that all patients would benefit from a specialty referral if the diagnosis of AATD is being considered.

Conclusion

Available guidelines regarding AATD frequently disagreed in management recommendations. Possible explanations for discordance include differences in regional prevalence, availability of augmentation therapy, and insurance environments. Attempts to harmonize the various guidelines by empaneling a broadly representative international group of disease experts should be considered for AATD. Similar comparisons among guidelines for other diseases are recommended.

Keywords:

• alpha-1 antitrypsin deficiency
• practice guidelines
• chronic obstructive pulmonary disease
• clinical management

Acknowledgments

The authors would like to thank Shandra Knight for her assistance in article procurement for our manuscript. The paper was presented in abstract form at the 2019 American Thoracic Society meeting.

Abbreviations

AATD, alpha-1 antitrypsin deficiency; PG, practice guidelines; ATS, American Thoracic Society; ERS, European Respiratory Society; CTS, Canadian Thoracic Society; COPD, chronic obstructive pulmonary disease; FDA, Food and Drug Administration; EMA, European Medicines Agency.

Disclosure

Dr Robert A Sandhaus served in Advisory Board for Grifols, CSL Behring, and Shire, outside the submitted work. The authors report no other conflicts of interest in this work.