To what extent does the delay between symptom onset and diagnosis of AATD affect patient survival?
The risk of chronic obstructive pulmonary disease (COPD) is increased, among other things, by a deficiency of alpha-1-antitrypsin (AATD). However, there is often a delay between the onset of symptoms and the diagnosis of AATD, which is associated with worse clinical and functional status and a more advanced stage of the disease. The study presented below examined how this fact further affects patient survival.
Study Methods and Population
The study included a total of 268 adults with AATD from the Austrian prospective multicenter registry Alpha-1 Lung. They were followed up until April 15, 2020, and patients with the Pi*MM genotype were not included.
The majority (n = 220; 82.1%) had the Pi*ZZ genotype. The median time from the diagnosis of AATD to enrollment in the registry was 8.8 months. At the time of diagnosis, 90.2% of patients had an AAT level < 0.6 g/l (i.e., increased risk of developing emphysema). A total of 28.2% were non-smokers, 68.0% former smokers, and 3.8% active smokers. Lung disease was diagnosed in 98.5% of patients in the registry, most commonly emphysema (63.8%) and/or COPD (44.0%).
The aim of the study was to determine the impact of the delay between the onset of symptoms (i.e., cough or dyspnea) and the diagnosis of AATD on overall survival (OS) and lung transplantation-free survival (TFS).
Findings
During follow-up (median 85.2 months), a total of 24 patients (9.0%) died. Overall survival was 96.2% at 5 years, 92.0% at 10 years, and 85.5% at 15 years. A total of 5 patients (1.9%) underwent lung transplantation.
The median delay between symptom onset and the diagnosis of AATD was 5.3 years (interquartile range [IQR] 2.2–11.5). In univariable analysis, patients with a diagnostic delay > 2 years had worse OS (15-year survival 81.7 vs. 95.2%; p = 0.08). In the group with a delay > 10 years, there was a higher proportion of patients with a history of pneumonia (42.4 vs. 24.1%; p = 0.002) and COPD exacerbations (50.0 vs. 28.7%; p = 0.008).
Increasing diagnostic delay was associated with significantly worse OS (hazard ratio [HR] 1.61; 95% confidence interval [CI] 1.09–2.38; p = 0.016) and TFS (HR 1.43; 95% CI 1.08–1.89; p = 0.011), independent of age, smoking, body mass index (BMI), forced expiratory volume in one second (FEV1), and long-term oxygen therapy. Moreover, BMI, age, and smoking were associated with significantly worse OS, and BMI, smoking, and FEV1 with worse TFS.
Conclusion
The delayed diagnosis of alpha-1-antitrypsin deficiency is significantly associated with worse overall survival and lung transplantation-free survival, independent of age and other parameters. AATD screening should be improved to enable timely initiation of augmentation therapy. Patients with COPD, emphysema, difficult-to-treat asthma with late onset, and relatives of patients with AATD should be tested.
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Source: Meischl T., Schmid-Scherzer K., Vafai-Tabrizi F. et al. The impact of diagnostic delay on survival in alpha-1-antitrypsin deficiency: results from the Austrian Alpha-1 Lung Registry. Respir Res 2023; 24 (1): 34, doi: 10.1186/s12931-023-02338-0.
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