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• When to test for alpha-1 antitryspin deficiency in patients with bronchiectasis
  David G Parr, Robert A Stockley
  Published on: 23 July 2020

• Published on: 23 July 2020

  When to test for alpha-1 antitryspin deficiency in patients with bronchiectasis

  • David G Parr, Respiratory Physician University Hospitals Coventry and Warwickshire NHS Trust
  • Other Contributors:
    • Robert A Stockley, Respiratory Physician

  Caretto et al’s brief communication[1] shines some additional light on an unresolved question of the role of alpha-1 antitrypsin deficiency (AATD) screening in patients with bronchiectasis. The authors conclude that testing of an unselected UK population (presumably with a primary diagnosis of bronchiectasis) identifies severe AATD in less than 1% of cases and that routine screening does not significantly impact on clinical management. Whilst these conclusions may be broadly applicable, it may be advisable to qualify the recommendation with some further detail to avoid potential misinterpretation and the consequent complete avoidance of AATD testing in patients with bronchiectasis.

  The study rationale originates from apparent conflicting recommendations of guidelines for bronchiectasis[2] and those for AATD[3]. It is stated by the authors that the latter advises AATD testing in all cases of bronchiectasis, whereas the guidelines (in recommendation 1c) in fact advocate testing in cases of ‘unexplained’ bronchiectasis. The use of the term ‘unexplained’ implies the use of a staged approach to the investigation of bronchiectasis with AATD testing reserved for a selected bronchiectasis population in which a diagnosis remains elusive despite clinically appropriate initial investigations.

  Studies of bronchiectasis in AATD are few in number and relatively small in size. Nevertheless, there is some consistency in the findings. In their conclusions from a study of t...

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  Caretto et al’s brief communication[1] shines some additional light on an unresolved question of the role of alpha-1 antitrypsin deficiency (AATD) screening in patients with bronchiectasis. The authors conclude that testing of an unselected UK population (presumably with a primary diagnosis of bronchiectasis) identifies severe AATD in less than 1% of cases and that routine screening does not significantly impact on clinical management. Whilst these conclusions may be broadly applicable, it may be advisable to qualify the recommendation with some further detail to avoid potential misinterpretation and the consequent complete avoidance of AATD testing in patients with bronchiectasis.

  The study rationale originates from apparent conflicting recommendations of guidelines for bronchiectasis[2] and those for AATD[3]. It is stated by the authors that the latter advises AATD testing in all cases of bronchiectasis, whereas the guidelines (in recommendation 1c) in fact advocate testing in cases of ‘unexplained’ bronchiectasis. The use of the term ‘unexplained’ implies the use of a staged approach to the investigation of bronchiectasis with AATD testing reserved for a selected bronchiectasis population in which a diagnosis remains elusive despite clinically appropriate initial investigations.

  Studies of bronchiectasis in AATD are few in number and relatively small in size. Nevertheless, there is some consistency in the findings. In their conclusions from a study of the distribution of AATD alleles in an unselected bronchiectasis population, the presence of bronchiectasis in PiZ patients was considered by Cuvelier et al[4] to be a consequence of emphysema rather than a primary effect. This association had been previously suggested by small case series[5,6] and, in our subsequent study of 74 individuals with the PiZ phenotype, we were able to demonstrate using quantitative CT imaging that there is a clear association between the severity of emphysema and the severity of bronchiectasis, and a tendency for co-location of the two pathologies[7] (comparable associations between emphysema and bronchiectasis are also seen in patients with non-deficient or usual COPD). Whilst this relationship held true for the majority of our study population, we identified a sub-group of 6 patients in whom the bronchiectasis was of the greatest severity but with a relative paucity of emphysema. This sub-group also included the only 3 patients with cystic bronchiectasis. Our interpretation of these findings was that the sub-group was representative of a distinct clinical phenotype, possibly with individuals who had an alternative underlying cause for their bronchiectasis, perhaps amplified by AATD. On the basis of our results, screening for AATD in patients who have bronchiectasis alone will likely not identify patients with severe AATD and other causes should first be sought. In the absence of any other cause, testing for AATD should then be considered. Testing for AATD in patients with bronchiectasis and co-existing emphysema, particularly when basal and panlobular in nature, should be undertaken according to the advice on testing for AATD in COPD guidelines for the investigation of patients with emphysema.

  It would, therefore, seem that AATD testing in patients with bronchiectasis would be best reserved for patients with unexplained bronchiectasis in whom initial investigations have failed to identify a cause, and particularly in patients with co-existing emphysema. Whether the bronchiectasis in such patients would respond positively to AAT augmentation therapy remains unknown but, since bronchiectatic change is relatively common in AATD patients with emphysema, review of sequential scans in those who are or have been taking part in the placebo-controlled trials of augmentation with a focus on sequential bronchiectatic changes may prove informative.

  References:

  1 Caretto L, Morrison M, Donovan J, et al. Utility of routine screening for alpha-1 antitrypsin deficiency in patients with bronchiectasis. Thorax 2020; 75:592-593.

  2 Hill AT, Sullivan AL, Chalmers JD, et al. British thoracic Society guideline for
  bronchiectasis in adults. Thorax 2019;74:1–69.

  3 Sandhaus RA, Turino G, Brantly ML, et al. The diagnosis and management of alpha-1
  antitrypsin deficiency in the adult. Chronic Obstr Pulm Dis 2016;3:668–82.

  4 Cuvelier A, Muir JF, Hellot MF, et al. Distribution of alpha(1)-antitrypsin alleles in patients with bronchiectasis. Chest 2000;117:415–9.

  5 Guest PJ, Hansell DM. High resolution computed tomography (HRCT) in emphysema associated with alpha-1 antitrypsin deficiency. Clin Radiol 1992; 45:260–266

  6 King MA, Stone JA, Diaz PT, et al. a1-Antitrypsin deficiency: evaluation of bronchiectasis with CT. Radiology 1996; 199:137–141

  7 Parr DG, Guest PG, Reynolds JH, et al. Prevalence and impact of bronchiectasis in
  alpha1-antitrypsin deficiency. Am J Respir Crit Care Med 2007;176:1215–21.

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  Conflict of Interest:
  None declared.

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