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Health-related QoL in Alpha-1 Antitrypsin Deficiency-Associated COPD

—According to these findings, individuals with alpha-1 antitrypsin deficiency associated COPD report impairments in physical health but not mental health.

By Alexandra McPherron, PhD
Reviewed by Sejal Makvana Bhavsar, MD

Prior research on health-related quality of life (HRQoL) in individuals with alpha-1 antitrypsin deficiency-(AATD) seems to suggest that those with chronic obstructive pulmonary disease (COPD) have more impaired QoL.2 However, the association of HRQoL scores with specific clinical characteristics among the AATD population is less clear. Furthermore, the results have been mixed when comparing the HRQoL of individuals with AATD-associated COPD with those with non-AATD-related COPD.2

“Health-related quality of life is a key self-reported measure for assessing health status in AATD-related lung disease, particularly in the absence of a cure, emphasizing the significance of disease management,” said lead author Radmila Choate, PhD, MPH, in an interview with ѿapp. Dr. Choate is an assistant research professor in the Department of Epidemiology and Environmental Health at the University of Kentucky College of Public Health, Lexington, Kentucky.

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Charlie Strange, MD, a professor of pulmonary and critical care medicine at the Medical University of South Carolina, Charleston, South Carolina, and one of the new study’s investigators, told ѿapp that physicians and researchers need more information about what factors affect HRQoL. “Our community is having a difficult time finding good outcome measures that change over time because COPD is typically a very slowly progressive disease,” he said.

Most studies of HRQoL in AATD have used the lung disease-specific St. George’s Respiratory Questionnaire.2 An alternative is the 36-Item Short Form Survey (SF-36), which allows QoL comparisons to populations without the disease.3

While the SF-36 has a mental component, prior studies on the quality of life in AATD patients focus on the impact of physical health on QoL.2 In the new study, investigators used the SF-36 questionnaire to evaluate both mental and physical health. 

“We aimed to identify individual and disease-specific aspects of COPD associated with reduced self-perceived quality of life in this population,” said Dr. Choate.

Data source

In this cross-sectional study, the investigators used data from structured telephone interviews between 2008 and 2019. Participants were people with AATD who received augmentation therapy in AlphaNet, a health management organization for people with AATD. Those with lung transplants were excluded. 

After an initial screening call, AlphaNet Coordinators collected responses from participants for the modified Medical Research Council (mMRC) dyspnea scale and the SF-36 version 2. The scores for the 8 domains of SF-36 were analyzed as a physical component summary score and a mental component summary score. Participants were also asked about exacerbations, productive cough, and their use of supplemental oxygen.

Physical vs mental health

The investigators identified 4398 participants with a mean age of 57.6 ± 10.6 years and a mean mMRC score of 2.4 ± 1.3. A total of 56.4% reported 2 or more exacerbations in the previous year. Daily productive cough for at least 3 months in each of the past two years was reported by 44.0% of participants.

For the physical component of the SF-36 summary scores, participants had a mean score of 36.3 ± 9.8. Given that the normalized mean score of the general US population in 1998 is set at 50 ± 10, the investigators concluded that participants reported poorer physical HRQoL compared with the general population. General health, role physical, and vitality were the most affected physical functioning subscales. 

In contrast, the mental health summary score was 51.2 ± 10.8, similar to that of the general population. 

Younger age, higher mMRC score, and higher exacerbation frequency had negative dose-response relationships with physical and mental health component summary scores (P = .004 to P < .001). The physical and mental health component summary scores were also worse in those with daily productive cough compared with those without and those who used oxygen regularly compared with those who did not (P = .0034 to P < .001).

Factors associated with poorer reported physical and mental health

Using multivariable regression analysis, the investigators found that disease factors were associated with scores on the physical component summary of the SF-36. An mMRC grade greater than 0 (P = .001), 2 or more exacerbations in the previous year (P < .001), daily productive cough (P < .001), and the regular use of supplemental oxygen (P < .001) were associated with worse mean scores on the physical component summary. 

For the mental component summary, both patient and disease characteristics influenced the scores. Age younger than 50 years (P < .001), higher mMRC grade (P < .001), 2 or more exacerbations in the previous year (P < .001), and daily productive cough (P = .0003) were associated with worse mean mental component summary scores. Male sex was also modestly associated with worse mental component summary scores than female sex (P = .0117).

More to the story

“Our findings demonstrate that dyspnea, frequent exacerbations, and other aspects of disease severity associate with worse quality of life, particularly its physical component,” said Dr. Choate.

Dr. Strange concurred, saying that these results show that “Healthcare professionals should focus on exacerbation frequency and dyspnea as the two most important outcome measures that associate with physical impairment in quality of life in Alpha-1.”

Dr. Choate pointed out another intriguing finding: “One of the interesting, and perhaps, paradoxical findings of our study was higher quality of life observed in older compared to younger individuals, which may be associated to several factors, such as higher impact of dyspnea and related altered quality of life expectations among young adults.” Dr. Strange added, “Our hypothesis is that a genetic diagnosis in the prime of life carries fear that is tempered over time once patients see that disease is slowly progressive.” 

The investigators also pointed out in their paper that the factors they identified did not account for most of the variability in their multivariable fit model. Future studies are needed to understand how dyspnea, exacerbations, and other factors influence the mental and physical HRQoL of individuals with AATD across the lifespan.

The study's limitations included the cross-sectional design, potential for recall or reporting bias, lack of data on mental health and physical evaluations, and the use of participants who received resources from AlphaNet and who may, therefore, not be representative of the broader population of individuals with AATD-associated COPD.

Published:

Alexandra McPherron, PhD, is a freelance medical writer based in Washington, DC, with research experience in molecular biology and metabolism in academia and startup companies.

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