Alpha 1-Antitrypsin deficiency (AATD), though often under-diagnosed, is one of the most common genetic respiratory disorders worldwide, affecting from 1 in 2000 to 1 in 5000 individuals.1 AATD predisposes to lung and liver disease and some other conditions.2,3

Alpha 1-Antitrypsin is the prototype member of the serine protease inhibitor (serpin) superfamily of proteins, and is caused by mutations in the SERPINA1 gene located in the long arm of chromosome 14.1,4 This genetic defect results in decreased serum levels of α1-antitrypsin, leading to low alveolar concentrations and protease excess, causing emphysema.1,4

In chronic respiratory diseases, such as chronic obstructive pulmonary disease (COPD), measures of Health Related Quality of Life (HRQoL) are frequently used as descriptive instruments or as outcome measures.5 Since no cure has yet been found for most chronic respiratory diseases, a major goal of care is to improve HRQoL.

Given the lack of studies assessing HRQoL in patients with AATD and the increasing importance of HRQoL measures, the aim of this study was to assess the relationship between HRQoL and gender, functional parameters and history of hospitalizations (previous year) in patients with AATD.

Socio-demographic characteristics of AATD patients are presented in Table 1. The mean age of the sample population was 48.2 years, 73.1% (Standard Error, SE=0.09) of the patients were married and 19.2% (SE=0.08) single. Regarding the education level, 46.2% (SE=0.10) had more than basic education.

The main baseline clinical characteristics of patients are described in Table 2. The AAT phenotype was ZZ for 15 patients (57.7%, SE=0.10) and SZ for 11 (42.3%, SE=0.10). All patients had lung involvement with emphysema or bronchiectasis on chest tomography. The majority of patients (80.8%, SE=0.08) had respiratory symptoms: dyspnea in 18 (69.2%, SE=0.09), chronic bronchitis in 16 (61.5%, SE=0.10) and wheezing in 10 (38.5%, SE=0.10). Liver disease was found in 50% (SE=0.10) of patients.

Most patients had a ventilatory obstructive pattern, with a mean FEV1 of 64.9% predicted, and 38.5% (SE=0.10) of patients with a FEV1 of less than 50% predicted. The mean 6MWTD was 387.2 meters, and the mean desaturation was 8.2%.

During the study period, 23 patients (88.5%, SE=0.06) were treated with long-acting bronchodilators, whereas 19 (73.1%, SE=0.09) also received inhaled corticosteroids. Seven patients (26.9%, SE=0.09) were undergoing long-term oxygen therapy. Eight patients (30.8%, SE=0.09) were given augmentation therapy during the study period according to a 60mg/kg weekly administration regimen, in accordance with the guidelines published by the Sociedad Española de Neumología y Cirurgía Torácica (SEPAR).12 Patients receiving augmentation therapy had more severe airflow limitation than untreated patients (P<0.05), and all of them presented a ZZ phenotype.

The association between the SF-36 dimensions and gender, phenotype, hospitalizations (in the previous year) and treatment with augmentation therapy is shown in Tables 3 and 4. A statistically significant difference between genders was found in 3 dimensions of the questionnaire, bodily pain (89.0 vs 65.2; P=0.016), vitality (58.8 vs 39.6; P=0.043) and mental health (74.2 vs 52.9; P=0.027), with female gender presenting lower scores in both dimensions. Patients with at least 1 hospitalization in the previous year due to respiratory disease had significantly lower scores in several dimensions of the SF-36 questionnaire (physical functioning, P≤0.001; role limitation due to physical health problems, P=0.012, bodily pain, P=0.017; vitality, P<0.001; social functioning, P=0.046). ZZ patients receiving augmentation therapy had significantly higher scores in the change of health item than ZZ patients no receiving this therapy (2.0 vs 3.0, P=0.021).

Table 5 presents the correlation of the SF-36 score with age, FEV1, FVC, 6MWTD and mMRC score. Older age negatively influenced 3 dimensions of the score (physical functioning, β=−1.06, P=0.020; role limitation due to physical health problems, β=−1.8, P=0.038; role limitation due to emotional function, β=−1.42, P=0.021). A positive correlation between FEV1 and physical functioning (β=0.64, P<0.001), role limitation due to physical health problems (β=0.62, P=0.045) and general health perception (β=0.18, P=0.002) was found. A higher distance mark in the 6MWT positively influenced several dimensions of the SF-36 questionnaire (physical functioning, β=0.12, P=0.007; role limitation due to physical health problems, β=0.24, P=0.010; bodily pain, β=0.17, P<0.001; general health perception, β=0.12, P=0.020; vitality, β=3.32, P=0.002; social functioning, β=0.14, P=0.002; mental health, β=0.16, P=0.008). Higher mMRC scores negatively influenced the 8 dimensions of the SF-36 questionnaire, as shown in Table 5.

In this paper, we describe a cross-sectional study that analyses the relationship between HRQoL and social-demographic, clinical and functional parameters in patients with AATD. All the patients included in this study were routinely followed-up in the pulmonology outpatient clinic and had documented lung involvement, with most of them having a ventilatory obstructive pattern. The cross-sectional data available found some significant statistical correlations.

In this study, female patients had significantly lower scores in 2 dimensions of the SF-36 questionnaire. In COPD patients, published data shows that women have higher levels of anxiety and depression and worse symptom-related quality of life than their male counterparts; nevertheless, gender-related determinants of HRQoL in COPD are not fully understood.13

A higher score in the SF-36 change of health item was found in ZZ patients receiving augmentation therapy. However, the difference found is of little value outside a randomized controlled double-blinded trial.

A positive correlation between FEV1, 6MWTD and numerous dimensions of the SF-36 was found, and higher mMRC scores negatively influenced all dimensions of HRQoL. Additionally, we found significantly lower scores in several dimensions of the SF-36 questionnaire in patients with at least 1 hospitalization in the previous year due to respiratory disease. Thus, a significant association between different markers of respiratory disease progression and several domains of the SF-36 questionnaire was identified in this patient sample. In line with these findings, published data shows that the SF-36 questionnaire could be a useful instrument to predict exacerbations in COPD patients, and that it correlates with the mMRC score and the 6MWTD in these patients.14,15

As the present study relied on cross-sectional data, unequivocal determinations of cause-and-effect are not possible. Furthermore, a larger sample would be needed to gain a better understanding of the relationship between the different markers of disease progression and outcomes and the SF-36 domains in a multivariate analysis.

HRQoL questions about perceived physical and mental health and function are an important component of health surveillance, and are considered indicators of service needs and intervention outcomes.16 Measuring HRQoL in AATD patients can help determine the impact of the disease and provide valuable insight into intervention outcomes.16 What little data is available on this subject is based on AATD National Registries.17,18 Despite its limitations, the present study represents an important step forward, since it analyzes the relationship between several characteristics of AATD patients and HRQoL dimensions. The results also suggest that the SF-36 questionnaire could be useful as a patient reported outcome for AATD patients with lung involvement.

Older and female patients with AATD have worse HRQoL when assessed by the SF-36 questionnaire. The present study found an association between different markers of respiratory disease progression and worse HRQoL in patients with AATD and lung involvement. Despite these findings, correlations between HRQoL outcome measures and clinical data have to be further investigated with prospective studies.

Given the scarcity of studies in HRQoL in patients with AATD, our findings can play an important role in the management of these patients.

The authors declare they have received no funding.

MTR contributed to study design, data collection, and authorship. EC was involved in study design, performed data collection and reviewed the manuscript. LR contributed to authorship and reviewed the manuscript for important intellectual content. MS was involved in study design, performed data collection, contributed to authorship and reviewed the manuscript for important intellectual content. All authors contributed toward data analysis, drafting and critically revising the paper, and are accountable for all aspects of the manuscript.

The authors state that they have no conflict of interests.