The connection between Alpha-1 Antitrypsin Deficiency (AATD) and bronchiectasis (BE) has been a point of ongoing discussion and investigation in medical research. For years, the question of whether AATD plays a role in the Aetiological Diagnosis of BE has remained unanswered.
Initial observations from case reports suggested a potential link, particularly in individuals with severe AATD, specifically the PI*ZZ phenotype. These reports noted a surprisingly consistent incidence of BE in AATD patients, estimated to be around 40%. However, it’s crucial to recognize that case reports alone cannot establish a causal relationship between AATD and BE. Furthermore, some patients in these reports presented with other underlying health conditions that could independently contribute to the development of BE.
To investigate further, a case-control study was conducted to compare AAT phenotype distribution and gene frequencies between patients with bronchiectasis and a control group. The findings indicated no significant difference in AAT distribution between the two groups. However, this study brought to light the importance of considering emphysema in conjunction with bronchiectasis. Researchers observed that bronchiectatic patients without emphysema did not show a different AAT distribution compared to controls. In contrast, bronchiectatic patients who also had emphysema did exhibit differences. This suggests that in PI*Z individuals, bronchiectasis might be a secondary condition resulting from emphysema, rather than a primary cause itself.
A smaller case-control study did suggest a possible increased frequency of the Z allele in patients with both bronchiectasis and common variable immunodeficiency. Additionally, other research indicates that immune deficiency, when combined with specific AATD phenotypes, may contribute to clinically significant bronchiectasis.
Further supporting the potential link, a study by Parr et al. demonstrated that 27% of AAT-deficient patients displayed HRCT evidence of BE. This study also noted a correlated distribution of airway disease and emphysema, with greater severity observed in the lower lungs. This correlation could be explained by a shared pathogenic mechanism influenced by a field effect, or it might indicate an interaction between the inflammatory processes implicated in both conditions. While it’s plausible that BE is a consequence of emphysema, as previously suggested, the reverse possibility – emphysema as a consequence of BE – is equally conceivable.
Despite these findings, current Canadian guidelines state that there is insufficient evidence to recommend routine AATD testing for all individuals with BE. Similarly, the REDAAT group from the Spanish registry of AATD patients suggests that AAT serum concentration assessment should be individualized in BE patients, rather than a routine procedure.
Ultimately, more extensive studies with larger patient cohorts are necessary to definitively confirm the relationship between AATD and BE. These studies are crucial for establishing evidence-based guidelines with greater certainty.
In light of the mixed findings in existing literature, the relatively high prevalence of deficient AAT alleles in certain populations (like the Portuguese population mentioned in the original context), and the advantages of early AATD detection (including lifestyle modifications, optimized clinical care, specific treatments for some patients, and genetic counseling), a consensus is emerging. It is increasingly considered that AATD should be evaluated in all individuals diagnosed with BE.
AATD may indeed be a contributing factor, acting cumulatively with other conditions in the aetiological diagnosis of bronchiectasis.
Recommendations:
- AATD screening should be considered for all patients with bronchiectasis.
- If the AAT protein level is below the normal range, further investigation with protein phenotyping or genotyping is recommended.
